ELEMENTS OF PRECAUTION: RECOMMENDATIONS FOR THE REGULATION O

[admin]

Part 2 of 4

PART 2: GM PLANTS

Environmental Risks

One of the most commonly perceived risks associated with GM crops concerns the possibility that transgenes will escape from the confines of agriculture with serious environmental consequences. Indeed, the US NRC report (1989, p. 3) considered that “the potential for enhanced weediness is the major environmental risk perceived for introductions of GM plants.” Two questions that relate to this issue are commonly asked. Will crops that have been GM become invasive? Could the transfer of genes from transgenic crops to their wild relatives through natural hybridization result in the origin of more aggressive weedy types? Under both scenarios, so called “superweeds” are predicted as the unintended results of biotechnology, resulting in the genesis of novel biological invasions. Such invaders would not only reduce crop yields but could also cause serious disruptions in the functioning of natural ecosystems and losses in biodiversity. Because of the potential ecological hazards posed by transgene escape, a considerable literature on this topic has developed during the past decade (reviewed in Tiedje et al., 1989; Crawley, 1990; Ellstrand and Hoffman, 1990; Raybould and Gray, 1994; Snow and Palma, 1997; Warwick and Small, 1998). Recent theoretical and empirical work concerning the potential escape of transgenes from the crop environment enables some assessment of the likely environmental risks posed by GM crops. In this section, we review this work and also consider other ways in which GM crops may have undesirable environmental consequences.

Could GM Plants Become Invasive?

The likelihood that GM crop plants will become invasive and constitute serious weed problems is often considered fairly remote. This is because most of today’s major crop species (e.g. corn, rice, wheat, beans) have been subjected to intense artificial selection over long periods of time for traits with low survival value under most natural conditions. Traits such as nonshattering of grain in cereals, weakly developed chemical defences, lack of seed dormancy, and high fertilizer requirements restrict the ability of most domesticated species to thrive outside the crop environment. Indeed, although crops are grown over vast areas of the globe today there are relatively few cases in which they persist without deliberate cultivation for more than a few seasons. Such volunteer plants are usually confined to agroecosystems and rarely if ever invade undisturbed natural plant communities. Domesticated crop plants are not represented among the world’s serious plant invaders. This is because persistence in wild communities results from the combined effects of many genes working in cooperation to produce a functioning phenotype adapted to local ecological conditions. Therefore, in most cases insertion of specific transgenes into a crop species already possessing a syndrome of domesticated traits is unlikely to alter its ecology so that it becomes converted into an aggressive invading species. Such targeted genetic modifications are unlikely to nullify many generations of artificial selection involving countless genetic loci.

This argument clearly depends on the extent to which a particular domesticated species has been subjected to artificial selection. Many cultivated species, especially those involved in horticulture, forestry and rangeland agriculture, have only recently been brought under cultivation and consequently have been subjected to relatively little genetic alteration through conventional breeding. In this case, the degree of domestication may be quite minor and cultivated genotypes may resemble their wild ancestors in many respects. In these cases, cultivars are more likely to persist outside of cultivation, and under certain circumstances could become invasive (see below). GM species with a short domestication history are more likely to pose environmental problems than our major crop plants. However, invasiveness will occur only if the genetic modifications increase the survival and reproduction of cultivars in natural ecosystems. Little work in this area has been conducted. In the future, as the range of target organisms for genetic modification widens, it may not be safe to assume that all cultivated species have been genetically crippled through intense artificial selection. Indeed, recent experience in Canada with herbicide-tolerant canola (oil seed rape), discussed next, provides a warning that some crop plants have the potential to become serious weeds of agriculture.

Canola is a relatively recent plant domesticate compared with many of our major cereals (e.g. corn, wheat, rice). Unfortunately, two wild traits that persist in many canola cultivars are weak seed dormancy and a degree of seed shattering. As a result of these traits, large numbers of seeds enter the soil after cropping and can persist in the seed bank to emerge in subsequent seasons as volunteer plants (Pekrun et al., 1998; Derksen and Watson, 1999; Downey, 1999). Traditionally, volunteer crop plants occur at relatively low densities and are eliminated from crops by selective herbicides. However, this management tool is complicated if volunteers are herbicide resistant. Unfortunately, herbicide-resistant volunteer canola plants are beginning to develop into a major weed problem in some parts of the Prairie Provinces of Canada. Indeed, some weed scientists predict that volunteer canola could become one of Canada’s most serious weed problems because of the large areas of the Prairie Provinces that are devoted to this crop. Of particular concern is the occurrence of gene exchange via pollen among canola cultivars resistant to different herbicides. This can occur through crosses between volunteer plants and the crop, or between different volunteer plants. Three classes of herbicide-resistant canola (resistant to glyphosate, glufosinate and imidazolinone) are currently grown in western Canada. Recent evidence indicates that crosses among these cultivars have resulted in the unintentional origin of plants with multiple resistance to two, and in some cases three, classes of herbicide (Derksen and Watson, 1999; Downey, 1999; Topinka et al., 1999). Such “gene stacking” represents a serious development because, to control multiple herbicide-resistant volunteer canola plants, farmers are forced to use older herbicides, some of which are less environmentally benign than newer products. This example involving the origin of multiple herbicide-resistant canola serves to illustrate the dynamic nature of weed evolution within managed agroecosystems. It also demonstrates that crops plants are not immune from becoming weeds of agriculture under the appropriate selection regimes.

Because of the large areas devoted to herbicide-resistant canola in the Prairie Provinces, it is not surprising that opportunities for the genetic mixing of different varieties occur. Despite the best efforts of growers, seeds may often be transported accidentally between fields containing different herbicide-tolerant canola varieties by farm machinery, or simply be blown from trucks transporting seeds to and from fields (Gray and Raybould, 1998). Indeed, it has been argued that seed spillage, a form of gene dispersal, may be a much more common mechanism resulting in hybridization between varieties than is likely by long-distance pollen flow by animal pollinators (McHughen, 2000, p. 166). Regardless of the mechanisms giving rise to multiple herbicidetolerant canola varieties, this example illustrates the problems in trying to predict the likelihood of gene flow from small-scale test plots involving relatively small numbers of plants. In addition, it emphasizes the inherent difficulties in the containment of genetic material in the context of normal farming practices in which literally millions of small seeds are produced and harvested over large areas of the landscape. Industry argues that as long as “good farming practices” are followed, these problems should not occur. This perspective may be unduly naïve. Environmental assessments associated with the release of GM crops should take account of the fact that in the real world human error and expediency may often compromise guidelines for the growing of such crops.

Gene Flow Between GM Crops and Wild Plants

In contrast to many animal species, reproduction in plants can be quite promiscuous. Individuals can mate simultaneously with many partners including themselves and, in addition, hybridization with related taxa commonly occurs. Mating complexity is promoted by a fundamental feature of plant reproduction — plants are immobile and therefore require vectors (e.g. mostly animals or wind) to transport their gametes from plant to plant to ensure crossfertilization. The process of pollen dispersal is inherently imprecise and only a small fraction of the large number of male gametes produced by a plant (usually < 1%) reach conspecific stigmas resulting in successful pollination. The majority of gametes are lost to the vagaries of the pollination process while a small fraction is dispersed to stigmas of other plant species. If the pollen donor and recipient are related, an opportunity is provided for inter-specific hybridization. Most inter-specific hybrids are genetically sterile or possess maladapted trait combinations and are soon eliminated by natural selection. Others persist through clonal propagation, while a small minority can become successful new forms because they possess novel phenotypes. Historically, inter-specific hybridization has played an important role in the evolution of flowering plants, with a significant proportion (estimates range from 30% – 50%) of all species arising in this manner.

A major environmental concern associated with agricultural biotechnology is that gene flow from GM crops to related weeds will result in the formation of novel weed phenotypes that have the potential to become highly invasive. Considerable effort in recent years has been directed toward understanding how likely this process is to occur for particular crops, and how to mitigate any negative environmental consequences that might result from such accidental gene transfer (Ellstrand and Hoffman, 1990; Jorgensen and Andersen, 1994; Kareiva et al., 1994; Raybould and Gray, 1994; Snow and Palma, 1997; Lavigne et al., 1998; Rieseberg et al., 1999). Indeed, one of the primary motivations for the use of maternally inherited genetic constructs has been that these technologies will reduce transgenic escape routes through pollen (Daniell et al., 1998; Gray and Raybould, 1998).

It is worth recognizing at the outset that gene flow between crops and weeds has been known for over a century and is not a unique characteristic of the technique of genetic modification per se. Inter-specific or inter-racial hybrids between crops and weeds are commonplace and have been well studied by weed scientists (e.g. carrots, oats, rice, oilseed rape, sorghum, sugarbeet, sunflower; see Table 2.2 in the US NRC report (2000) and similar tables in Snow and Palma, 1997; Rieseberg et al., 1999). Indeed, this phenomenon has resulted in the evolution of a special class of agricultural weeds known as crop mimics that resemble crops in appearance and/or behaviour and thereby evade detection (Barrett 1983, 1988).

The experimental study of pollen dispersal and gene flow in plants generally indicates that the distribution of pollen dispersal distances is highly leptokurtic (most pollen is dispersed short distances with a steadily declining fraction involved with long-distance dispersal). For example, most pollen in herbaceous plants is dispersed within two to three metres of source plants, with a small fraction being transported up to one kilometre or more (Levin and Kerster, 1974; Lavigne et al., 1998). The two most important determinants of pollen dispersal are the mating system of the plant and dispersion of pollen by wind or animals. In general, predominantly selfing species produce far less pollen than outcrossers, and little of this finds its way to other plants. In contrast, outcrossing species produce significantly more pollen and maximum dispersal distances can be considerable, especially in wind-pollinated species. There is no a priori reason why these general principles of pollen dispersal should be different for GM crops; so transgenic pollen should not behave in a manner different from the pollen of non-GM plants. However, comparative studies on this issue need to be conducted to confirm this assumption.

Crops can be roughly divided into three groups with respect to the likely incidence of the natural transfer of genes. 1) No possibility — where wild relatives are absent from the region where the crop is grown (e.g. GM maize, soybean, tomato in Canada). 2) Low possibility — GM crops that are either predominantly autogamous (many cereals) or propagated largely by asexual reproduction and flower rather infrequently (sweet potato, sugar cane). 3) Moderate to high possibility — where the crop is an outbreeder and is being grown in an area where cross-compatible wild relatives occur (e.g canola in many parts of Europe and North America; rice in South East Asia). Current guidelines for the field testing of GM crops recognize these distinctions and recommendations for the size and isolation of test plots reflect the likelihood of gene exchange with wild relatives. A major issue here concerns the issue of scale. Opportunities for gene transfer will be considerably greater for large-scale commercial plantings of GM crops than for small test plots. Hence, generalizations about pollen dispersal distances of commercial planting based on experimental studies of small plots should be treated with some caution.

How is hybridization between cultivated and wild plants studied, and is there evidence for the natural transfer of transgenes from GM crops to weeds? The frequency of hybridization events between crops and weeds has usually been detected by simply observing the occurrence of putative hybrids in close proximity to agricultural fields. The presence of plants with “intermediate phenotypes”, or character combinations predicted from hybridization, signal the occurrence of gene transfer. However, there are two reasons why this approach may greatly underestimate the true frequency of gene transfer. First, many products of hybridization are selected against during the establishment phase and hence do not give rise to viable offspring (see below). Second, hybrids can go undetected because of similarities in phenotype to parental forms. This is especially likely where backcrossing and advanced generation crosses result in hybrid swarms composed of plants spanning the entire spectrum of phenotypic variation encompassed by crop and weed. To avoid these difficulties in estimating the true frequency of gene transfer, researchers have recently used simply inherited genetic markers diagnostic for the parental forms to detect hybridization between crops and weeds (e.g. Luby and McNicol, 1995; Whitton et al., 1997, Wilkinson et al., 2000). Assays of seed families collected from individual plants enable the quantitative analysis of gene transfer.

While there is considerable evidence for crop–weed hybridization, only a few cases have been reported involving experimental trials of GM crops. To our knowledge, there are no known cases involving the escape of a transgene into weed populations from commercial scale plantings. To date, most work has involved the insect-pollinated outbreeder, Brassica napus (oilseed rape or canola), which can hybridize with several congeneric species (B. rapa, B. oleracea) as well as the related wild radish (Raphanus raphanistrum). It has been suggested that this species can potentially hybridize with up to nine related taxa (Stewart et al., 1997). Since several of these are also cross-compatible with other wild Brassica species, the pool of species that transgenes could potentially infiltrate is quite large. Chèvre et al. (1997) produced F1 inter-specific hybrids between oilseed rape and radish, and after four generations in field plots, herbicide-resistant plants with a similar morphology and chromosome number to the weed were established. The authors concluded that under normal agricultural conditions this process is likely to occur only rarely. Wilkinson et al. (2000) used remote sensing to identify areas of sympatry between non-GM oilseed rape and wild B. rapa over an extensive area (15,000km2) of South England. Flow cytometry and molecular markers were used to screen for hybrids. Only one naturally occurring hybrid was found. This was a much lower rate of hybridization than anticipated based on earlier predictions from hybridization rates in adjacent populations of the two species and presumed areas of sympatry (Scott and Wilkinson, 1998).

While the available data are sparse and limited to experimental plots of a single GM crop (oilseed rape) it does indicate that transgenes, not unexpectedly, can be transferred to wild plant species, albeit at a low frequency. Other crop–weed systems in which hybridization occurs more frequently (e.g. rice, Langevin et al., 1990) could pose greater risks. Where crops and interfertile wild plants co-exist in the same area, it is probably safest to assume that some degree of gene transfer will occur over time. It is important to recognize, however, that the process of gene flow from GM crops to weeds by itself does not pose an environmental risk. It is the potential consequences of such an event that is the cause for concern. The ecological outcome of hybridization will depend entirely on whether wild plants with newly acquired transgenes have sufficiently enhanced fitness to cause their numbers to increase in frequency. We address this issue below.

Finally, our focus in this section has been on the transfer of transgenes from GM crops to wild plants. As discussed above for canola, another potential escape route involves the transfer of transgenes to other crops of the same species that are not GM. Where GM crops are grown in the same region as non-GM cultivars, opportunities for cross-pollination exist. Indeed, the likelihood of this process occurring is likely to be higher than for most crop–weed transfers because of the very large population sizes involved in crop plantings and the complete absence of breeding barriers that are likely between conspecific cultivars. Recent reports from various European countries of the contamination of canola originating from Canada with small quantities of GM DNA seem likely to have arisen in this manner. Both GM and non-GM canola are grown over extensive areas of western Canada, facilitating insect-mediated cross-pollination between cultivars. While such cross-contamination is unlikely to pose environmental hazards to wild plant and animal communities, it does raise economic and political problems because of concerns in Europe over the food safety of GM crops discussed elsewhere in this report. In addition, the contamination of non-GM crops with transgenes represents a serious problem for low-input farming (organic agriculture) and may require much larger isolation distances than have been used to now to ensure the purity of non-GM produce (Moyes and Dale, 1999).

Spread of Transgenes in Wild Plants

Predicting the fate of transgenes in wild plant populations is considerably more difficult than determining whether gene flow between crops and weeds is likely to occur. This is because diverse ecological and evolutionary processes will govern the survival and spread of transgenes once they are incorporated into the genetic backgrounds of wild plants. Determining the ecological and evolutionary consequences of transgene spread in wild populations is one of the central issues in assessing the environmental impact of GM crops. While analytical tools have been developed by evolutionary biologists to measure the strength and direction of natural selection (reviewed in Endler, 1986), these approaches have yet to be applied to GM traits. Our ability to predict the spread of transgenes into wild plant communities is hampered by a lack of empirical data on the fitness costs and benefits of transgenic traits in non-crop species. Moreover, it is important to stress that such information is meaningful only when obtained from diverse ecological contexts. Because weedy plants, the likely first recipients of transgenes, have the potential to migrate to diverse habitats through natural dispersal, genotypes containing engineered traits have the opportunity to be tested by natural selection in countless environmental settings. While in many situations weedy genotypes are likely to be poorly adapted, it would be foolhardy to suggest that appropriate conditions do not exist in nature for successful spread. Indeed, experience suggests that novel phenotypes often succeed in circumstances not predicted based on simple demographic models that do not incorporate ecological variation.

Once transgenes are transferred to wild gene pools, their subsequent fate will be strongly influenced by population size. Because transgenes will initially be present at low frequency, they may often be lost from populations through stochastic processes such as genetic drift. Weed populations are especially vulnerable to stochastic processes since population sizes are often small and frequent colonizing episodes lead to an erosion of genetic diversity (Barrett, 1992). Repeated reintroduction through gene flow from GM crops may be necessary for establishment in some weed populations that are subject to frequent fluctuations in population size. The mating system of the weed species will be critical for determining how frequent the introgression of transgenes into wild gene pools is likely to be. Many weeds of agricultural land are predominantly selfing, reducing the likelihood of gene transfer. However, Bergelson et al. (1998) and Bergelson and Purrington (2002) reported that some herbicide resistant transgenic lines of the annual selfing weed Arabidopsis thaliana were roughly 20 times more likely to outcross than mutant plants of the same species. Therefore it may not be safe to assume that all selfing plants are immune from genetic contamination since even predominant selfers usually exhibit low levels of outcrossing.

The spread of transgenes into wild populations will be governed by the benefits that they confer to their carriers in terms of enhanced survival and reproductive success. This will depend on the types of transgene under consideration and their effects on plant phenotype. The first generation of GM crops largely involved genes conferring resistance to herbicides and to various pests and diseases, but new genes associated with stress tolerance (e.g. salt, drought and temperature tolerance) are also likely to become commercially available in the near future. It is not difficult to imagine that the escape of such genes could have potential influences on the ecology of wild plant communities. However, the potential ecological impacts of other targeted genes in the second generation of GM crops (e.g. vitamin-rich rice and increased floral longevity in ornamental species) are more difficult to assess.

Most engineered genes are likely to be ecologically neutral and some may carry fitness penalties to their carriers. In these cases, they are likely to be lost from populations quite rapidly through genetic drift or natural selection. Alternatively, some transgenes may provide a selective advantage within wild populations but predicting which constructs these are likely to be is not an easy task. To assess the ecological impacts of transgene escape, recent attempts (reviewed below) have been made to measure the fitness of GM varieties by assessing the costs and benefits of various transgenes in comparison with unmodified varieties. It is particularly important to determine whether transgenes persist in wild plant populations in the absence of selection to maintain engineered traits (e.g. continued herbicide sprays or pest and disease outbreaks). Alternatively, such genes may be selected against because of the costs that they can exert on plant fitness. Such costs can be caused by pleiotropy, linkage to deleterious genes, disruption of coding regions during insertion or the physiological costs associated with maintaining engineered traits.

Not surprisingly, the results of comparative studies of GM versus non-GM plants have been mixed. Some investigators have found no significant differences in performance, whereas others have demonstrated both costs and benefits to the possession of GM traits. For example, Snow et al. (1999) found no significant differences between transgenic herbicide resistant and non-transgenic plants of Brassica napus x B. rapa hybrids in both survival or seed production in growth chamber experiments. They concluded that the costs associated with herbicide resistance in the hybrids were probably negligible. Similar conclusions were also reached by Lavigne et al. (1995) following competition experiments conducted under field conditions between herbicideresistant and non-resistant lines of white chicory (Cichorium intybus). In contrast, Bergelson et al. (1996) demonstrated a strong cost to herbicide resistance in the weed Arabidopsis thaliana, with a 34% reduction in seed production of transgenic plants compared to susceptible genotypes sown into field plots. One of the only studies demonstrating increased fitness of transgenic plants involves Brassica napus containing Bt cryIAc, an insecticidal transgene that confers resistance to various caterpillars (Stewart et al., 1997). Insect attacks causing defoliation of non-transgenic plants favoured Bt plants in plots that were initially cultivated but were allowed to naturalize. This study is particularly significant because it involved fitness comparisons in natural vegetation.

To fully understand the dynamics of transgenic escape, large-scale demographic studies are required in which the complete life histories of populations are monitored over several successive years. Crawley et al. (1993) estimated demographic parameters of transgenic and nontransgenic Brassica napus in a variety of habitats and climatic conditions over a three-year period in the UK. Despite considerable variation in performance among sites and treatments, they found no evidence that transgenic lines were more or less likely to persist in disturbed habitats than plants that were not GM [and see Linder and Schmitt (1995) and Hails et al. (1997) for additional studies demonstrating similar results in B. napus]. Ecological comparisons of other GM crops and their associated weed complexes are urgently needed to assess the likelihood that transgene escape could result in negative environmental consequences.

While most studies to date have failed to demonstrate any strong ecological advantage to transgenic plants in comparison with conventional varieties, this should not be taken as evidence that the ecological risks associated with transgene escape will be always be minimal. Too few GM species have been examined for any broad generalizations to be made. Indeed, given the complex nature of many ecological interactions it may not be easy to make firm predictions in this area. Most workers that have considered the problem of transgene escape in any depth agree that each GM crop and transgene combination has to be considered separately, taking into account both the life history attributes of GM crop–weed complexes and the ecological context in which they occur.

GM Crops and Biodiversity

One of the least understood issues associated with GM organisms is their potential impact on biodiversity. For GM plants we have already considered the escape of transgenes into wild populations resulting in the origin of potentially aggressive weeds. While these weeds would impact agroecosystems first, causing yield reductions and economic losses, they could also lead to losses in biodiversity if they subsequently invaded natural plant communities. Most agricultural weeds are rather poor colonizers of undisturbed vegetation and seem unlikely candidates to invade plant communities. However, as discussed above, future genetic modification of a broader range of plant species, including trees, shrubs and clonal perennials, could potentially lead to the transfer of transgenes into plants with competitive life histories. These types of plants are more likely to be capable of moving into communities that up to now have resisted invasion.

While biodiversity is commonly thought to signify the number and kinds of species in a community, it is important to also recognize that biodiversity includes an intra-specific component, specifically the genetic diversity within species. How might large-scale introduction of GM crops influence this component of biodiversity? One potential impact involves genetic alterations in wild plant populations associated with changing agricultural practices. For example, the widespread introductions of herbicide-resistant crops (HR crops) will undoubtedly influence the spectrum of weeds occurring in and around arable fields. If herbicide usage increases because of HR crops, we might also expect more cases of the evolution of weeds that are genetically resistant to herbicides (HR weeds). Warwick et al. (1999) review this issue for the Canadian situation and point out that selection of HR weed biotypes is highest when a single class of herbicide is used repeatedly and is highly efficacious. There are now over 200 reported cases worldwide of herbicide-resistant weed biotypes since resistance was first reported in 1968 (reviewed in Heap, 1999); of these, nearly 30 have been reported in Canada (see Table 6 in Warwick et al., 1999).

Another serious biodiversity concern is the contamination of wild gene pools of the world’s major crop plants by genetic constructs engineered through biotechnology. Because, as discussed earlier, many crops have wild and weedy relatives with which they are fully interfertile, the potential for gene transfer into crop gene pools is a serious possibility. This is especially worrisome where crops are grown in regions of the world where they have originated and are thus in contact with a range of close relatives. For example, in South East Asia where rice originated, several cross-compatible wild and weedy species of rice inhabit wetland environments in and around rice fields. In contrast, the majority of crops that are grown in Canada were domesticated elsewhere and the number of cross-compatible relatives vulnerable to this form of so-called “genetic pollution” is more restricted than in many other regions of the world. Nevertheless, the weedy relatives of several crops grown in Canada, such as canola, carrot, sunflower and sorghum, occur in agricultural fields, a situation that creates opportunities for transgene escape.

Agriculture has resulted in the large-scale global destruction of natural ecosystems with concomitant losses in biodiversity. For example, it has been estimated that 70% of the land surface in the UK is under some form of agriculture, and in Canada and the US equivalent figures are 11% and 52%, respectively (reviewed in Maguire, 2000). A question that is often asked is whether the introduction of GM crops will exacerbate the problem of biodiversity loss or alternatively whether the impacts will be minimal. In Europe, this concern has received much greater public attention than in other parts of the world, presumably because farming and wildlife have co-existed for a much longer period and this has resulted in the development of a distinctive flora and fauna associated with farmland. In Europe, many species are adapted to the habitats associated with agricultural practices such as hedgerows, ditches, hayfields and meadows. The widespread use of broad-spectrum herbicides associated with herbicide-resistant crops could potentially reduce plant biodiversity with direct and indirect influences on vertebrate and invertebrate species. For example, a recent report by Watkinson et al. (2000) drew attention to the possibility that the use of GM herbicide-tolerant crops could result in severe reductions in weed populations with subsequent negative effects on seed-eating birds. Agricultural land in North America is also important for wildlife (Best et al., 1995; Boutin et al., 1999) and detailed studies are urgently needed to assess the impact of the large-scale growing of GM crops on the maintenance of biodiversity in agricultural ecosystems. We support the view taken by Maguire (2000) that conserving biodiversity is an essential part of sustainable agriculture that is beneficial from both an economic and ecological perspective. Agroecosystems that are sterile wastelands not only have little aesthetic appeal but are unlikely to be ecologically sustainable over the long term.

Perhaps the least appreciated way in which the biodiversity of natural plant and animal communities could be threatened by biotechnological change is through genetic alterations in the ecological amplitude of domesticated plants. As discussed above, one of the most potent forces resulting in the erosion of biodiversity is the replacement of natural ecosystems by agriculture and forestry. In the future, because of increasing pressures on land for food, it may be possible to engineer crops to grow in environments that up to now have been considered unsuitable or at best marginal for arable cropping systems (e.g. salt marshes, deserts, rainforests, mangrove swamps). The expansion of the range of conditions in which agriculture can be practised because of advances in genetic engineering could potentially lead to the extensive loss of wildlands and their constituent biodiversity.

Regulatory Implications

Predicting the environmental risks associated with GM crops is difficult because of the diverse ecological interactions that can potentially occur in agricultural and natural plant communities. Serious ecological impacts could arise following very rare events that would be hard to predict from data collected in conventional ecological experiments conducted at restricted spatial and temporal scales. The sparse knowledge base available concerning the ecology and genetics of GM crops is a major hurdle for sound risk assessment, with important regulatory implications. We recommend that before GM crops are released they should be subjected to a more thorough ecological risk assessment than has been conducted to date. In particular, more effort should be given to following the intent of the current Canadian Environmental Protection Agency guidelines with respect to potential adverse environmental impacts. Industry submissions often satisfy current guidelines through reliance on literature reviews without collecting their own experimental data on ecological impacts. Moreover, the whole focus of environmental assessment occurs within the context of agroecosystems only, with little effort paid on assessing likely impacts on the biodiversity of natural ecosystems. In future, we suggest a staged approach in which any new GM variety is subjected to a series of experimental comparisons with conventional varieties, including the unmodified variety from which it originated. These comparisons should be conducted under various sets of conditions (e.g. glasshouse, growth chamber, field plots, disturbed natural habitats) reflecting increasing ecological realism. The basic goal of these experimental comparisons is to determine whether the new GM crop differs from conventional varieties in any life-history attribute that is likely to have fitness implications for survival in the wild.

These experimental comparisons should provide the necessary information to make informed judgments related to regulation on whether a new GM variety, or its transgenes, are likely to pose an environmental threat by resulting in an invasion scenario. Another series of experiments is also required to determine the likelihood of pollen-mediated gene flow to related species. In these experiments, plots of various sizes of the GM crop should be established at different distances from target colonies (also of different size) of cross-compatible relatives. This will allow quantitative assessment of how gene flow interacts with distance. These experiments differ from those currently used to determine isolation distances of crop varieties from one another. This is because in the proposed experiments the target organism is a related species, not the crop. The wild species chosen should include all related species that are known to be cross-compatible with the cultivar and occur in the area in which the GM crop is likely to be grown.

Future Research

To address public concern about the potential environmental impacts of GMOs, a sound body of ecological research on this topic is required. While Canadian ecological research ranks highly by international standards, very little research currently being conducted by leading ecologists and evolutionary biologists in the country concerns GMOs. Moreover, in our opinion the quantity and the quality of research on the potential environmental impacts of GMOs is not sufficient to address many of the pressing questions that concern the environmental impacts of GMOs. The reasons for limited study in this area are complex and involve a variety of factors. These include: 1) limited funding from government agencies and industry for basic research on the ecology of GMOs (see our discussion of this in Chapter 9); 2) a failure by industry to recognize and take seriously potential environmental problems; 3) an early lack of interest by academic ecologists in what was seen as an uninteresting and perhaps even trivial research question; 4) the reluctance of the research community to commit limited research dollars to the kind of long-term ecological monitoring required in this area. For these and other reasons, the research capability required to answer satisfactorily the questions that are repeatedly raised by the environmental community and the general public is at present severely compromised.

The initial types of investigation that should be conducted on the environmental impacts of GMOs should grow out of research associated with regulation (see previous section). However, it is hoped that once routine protocols are in place for these environmental assessments more basic research will be addressed. It seems more likely that novel insights will be obtained if scientists are not constrained by the regulatory framework and are free to ask novel questions about the ecology and evolution of GMOs. Below are suggestions for future research on the potential ecological impacts of GMOs.

1. Glasshouse and growth chamber studies: The experimental material (GM crop and immediate ancestor) should initially be compared under uniform growing conditions in the glasshouse and in growth chambers using standard randomized block designs with sufficient replication. An important philosophy behind these comparisons not evident in the current guidelines is that investigators look beyond the normal agronomic traits associated with productivity and consider traits likely to have ecological significance in the context of potential escape scenarios. These comparisons could include several experimental treatments to simulate environmental variation, for example, various nutrient, light or temperature treatments. Traits measured should involve standard life-history variables, including growth rate, timing of reproductive events, reproductive and vegetative allocation, seed production, dispersal potential and seed dormancy. Of particular significance is the search for any unanticipated pleiotropic effects of transgene insertion on fitness traits.

2. Field trials: Field trials at several locations within Canada with contrasting climate and environmental conditions should be conducted. Once again, it is important that not just agronomic traits are compared but that a range of life-history variables related to fitness are assessed. Of particular interest for these comparisons is the detection of Genotype X Environment interactions in which the life-history traits of the GM crop vary depending on location. Evidence of these interactions can provide useful information on the plasticity of traits and how they might respond to novel environments. More ecological realism could be built into these field trials by introducing biotic interactions with competitors, parasites, predators and mutualists (see section on insect interactions).

3. Wild communities: There are obviously inherent dangers in introducing GM plants into wild communities because of the possibilities of escape. However, unless these types of experiments are undertaken it will not be possible to provide an answer to the question of whether GM plants could invade natural ecosystems. We suggest that in the future researchers consider how these types of comparison could be conducted with safety using isolated sites, quarantine procedures and restricted access to the general public to prevent inadvertent escape. Seeds of the GM plants could be sown into a range of disturbed and undisturbed plant communities and their demography monitored for as long as colonies persist. This approach was used by Crawley et al. (1993) in their studies of transgenic Brassica napus in habitats throughout the UK. By measuring standard demographic parameters, projection matrices can be used to predict population growth and likely invasiveness. It is particularly important to determine whether the GM crop has any capacity for persistence through seed dormancy and the maintenance of a seed bank. Most crops possess no dormancy (although see earlier discussion of volunteer canola) so this seems unlikely. However, since dormancy can have an environmental component, and this trait is critical for survival in most wild communities, it is important that this feature of the life history is subjected to the closest scrutiny.

We also recommend that researchers consider conducting a parallel series of comparative experiments on selected cross-compatible relatives containing transgenes. Here the idea is to introduce the transgene artificially into the wild relative and then observe how these plants differ from other individuals of the same species without the gene. Once again, to ensure ecological realism these fitness comparisons should be made under field conditions in a range of disturbed and undisturbed wild communities that would be carefully monitored to prevent escape. These comparisons are time consuming and clearly cannot be conducted on all cross-compatible relatives of GM crops. The choice of which species to examine should be based on their distribution relative to the potential range of the GM crop and the likelihood of escape.

RECOMMENDATIONS

6.5 The history of domestication, and particularly the time period and intensity of artificial selection, of GM plants should be taken into account when assessing potential environmental impacts. Species with a short history of domestication should receive particularly close scrutiny because they are more likely to pose environmental risks.

6.6 Environmental assessments of GM plants and their particular genetic constructs should pay particular attention to reproductive biology, including consideration of mating systems, pollen flow distances, fecundity, seed dispersal and dormancy mechanisms. Information on these life-history traits should be obtained from specific experiments on the particular GM cultivar to be assessed, not solely from literature reports for the species in general.

6.7 Environmental assessments of GM plants should not be restricted to their impacts on agroecosystems but should include an explicit consideration of their potential impacts on natural and disturbed ecosystems in the areas in which they are to be grown.

6.8 Research data from experiments conducted by industry on the potential environmental impacts of GM plants used in Canadian Environmental Protection Agency assessments should be made available for public scrutiny.

6.9 The Panel recommends that a federally funded multidisciplinary research initiative be undertaken on the environmental impacts of GM plants. Funds should be made available to scientists from all sectors (industry, government and university) with grant proposals subject to rigorous peer review.

REFERENCES

Barrett, S.C.H. 1983. Crop mimicry in weeds. Econ. Bot. 37: 255–82.

Barrett, S.C.H. 1988. Genetics and evolution of agricultural weeds. In M.A. Altieri, M. Liebman (eds.), Weed Management in Agroecosystems: Ecological Approaches, 57–75. Boca Raton: CRC Press.

Barrett, S.C.H. 1992. Genetics of weed invasions. In S.K. Jain, L.W. Botsford (eds.), Applied Population Biology, 91–119. Dordrecht, The Netherlands: Kluwer Academic Publishers.

Bergelson, J., C.B. Purrington, C.J. Palm, J.-C. Lopez-Gutierrez. 1996. Costs of resistance: a test using transgenic Arabidopsis thaliana. Proc. Royal Soc. London B. 263: 1659–63.

Bergelson, J., C.B. Purrington, G. Wichmann.1998. Promiscuity in transgenic plants. Nature 395: 25.

Bergelson, J., C.B. Purrington. 2002. Factors influencing the spread of resistant Arabidopsis thaliana populations. In D. Letourneau, B. Burrows (eds.), Genetically Engineered Organisms: Assessing Environmental and Health Impacts. (In Press). Boca Raton: CRC Press.

Best, L.B., K.E. Freemark, J.J. Dinsmore, M. Camp. 1995. A review and synthesis of habitat use by breeding birds in agricultural landscapes of Iowa. Am. Midland Nat. 123: 1–29.

Boutin, C., K.E. Freemark, D.A. Kirk.1999. Farmland birds in southern Ontario: field use, activity patterns and vulnerability to pesticide use. Agric. Ecosyst. Environ. 72: 239–54.

Chevre, A.-M., F. Eber, A. Baranger, M. Renard. 1997. Gene flow from transgenic crops. Nature 389: 924.

Crawley, M.J. 1990. The ecology of genetically engineered organisms: assessing the environmental risks. In H.A. Mooney, G. Bernardi (eds.), Introduction of Genetically Modified Organisms into the Environment, 133–50. Chichester, UK: John Wiley & Sons.

Crawley, M.J., R.S. Hails, M. Rees, D. Kohn, J. Buxton. 1993. Ecology of transgenic oil seed rape in natural habitats. Nature 363: 620–23.

Daniell, H., R. Datta, S. Varma, S. Gray, S.B. Lee. 1998. Containment of herbicide resistance through genetic engineering of the chloroplast genome. Nat. Biotechnol. 16: 345–48.

Derksen, D.A., P.R. Watson. 1999. Volunteer Crops: The Gift That Keeps on Giving. Poster, Expert Committee on Weeds. Ottawa: ECW.

Downey, R.K. 1999. Gene flow and rape – the Canadian experience. In Gene Flow and Agriculture: Relevance for Transgenic Crops, 109–16. Farnham, Surrey, UK: British Crop Protection Council.

Ellstrand, N.C., C.A. Hoffman. 1990. Hybridization as an avenue of escape for engineered genes. BioScience 40: 438–42.

Endler, J.A. 1986. Natural Selection in the Wild. Princeton, NJ: Princeton University Press.

Gray, A.J., A.F. Raybould. 1998. Reducing transgene escape routes. Nature 392: 653–54.

Hails, R.S., M. Rees, D.D. Kohn, M.J. Crawley. 1997. Burial and seed survival in Brassica napus subsp. oleifera and Sinapsis arvensis including a comparison of transgenic and nontransgenic lines of the crop. Proc. Royal Soc. London B. 264: 1–7.

Heap, I.M. 4 Feb 1999. International Survey of Herbicide Resistant Weeds. At: <www.weedscience.com>

Jorgensen, R.B., B. Andersen. 1994. Spontaneous hybridization between oilseed rape (Brassica napus) and weedy B. campestris (Brassicaceae): a risk of growing genetically modified oilseed rape. Am. J. Bot. 81: 1620–26.

Kareiva, P.R., W. Morris, C.M. Jacobi. 1994. Studying and managing the risk of cross-fertilization between transgenic crops and wild relatives. Mol. Ecol. 3: 15–21.

Langevin, S.A., K. Clay, J. Grace. 1990. The incidence and effects of hybridization between cultivated rice and its related weed rice. Evolution 44: 1000–08.

Lavigne, C., H. Manac’h, C. Guyard, J. Gasquez. 1995. The cost of herbicide resistance in whitechicory: ecological implications for its commercial release. Theor. Appl. Genet. 91: 1301–08.

Lavigne, E., K. Klein, P. Vallee, J. Pierre, B. Godelle, M. Renard. 1998. A pollen-dispersal experiment with transgenic oil seed rape. Estimation of the average pollen dispersal of an individual plant within a field. Theor. Appl. Genet. 96: 886–96.

Levin, D.A., H.W. Kerster. 1974. Gene flow in seed plants. Evol. Biol. 7: 139–220.

Linder, C.R., J. Schmitt. 1995. Potential persistence of escaped transgenes: performance of transgenic, oil-modified Brassica seeds and seedlings. Ecol. Appl. 5: 1056–68.

Luby, J.J., R.J. McNicol. 1995. Gene flow from cultivated to wild raspberries in Scotland: developing a basis for risk assessment for testing and deployment of transgenic cultivars. Theo. Appl. Genet. 90: 1133–37.

Maguire, R.J. 2000. Report of the Environment Canada Workshop on the Potential Ecosystem Effects of Genetically-Modified Organisms. NWR Contribution No. 00-034. Burlington, ON.

McHughen, A. 2000. Pandora’s Picnic Basket: The Potential and Hazards of Genetically Modified Foods. Toronto: Oxford University Press.

Moyes, C.L., P.J. Dale. 1999. Organic Farming and Gene Transfer from Genetically-modified Crops. MAFF Research Project OF0157. Norwich, UK: John Innes Centre.

NRC (National Research Council). 1989. Field Testing Genetically Modified Organisms: Framework for Decision. Washington, DC: National Academy Press.

NRC. 2000. Genetically Modified Pest-Protected Plants: Science and Regulation. Washington, DC: National Academy Press.

Pekrun, C., J.D.J. Hewitt, P.J.W. Hewitt. 1998. Cultural control of volunteer rape. J. Agric. Sci. 130: 150–63.

Raybould, A.F., A.J. Gray. 1994. Will hybrids of genetically modified crops invade natural communities. Trends Ecol. Evol. 9: 85–89.

Rieseberg, L.H., M.J. Kim, G.J. Seiler. 1999. Introgression between the cultivated sunflower and a sympatric wild relative, Helianthus petiolaris (Asteraceae). Int. J. Plant Sci. 160: 102–08.

Scott, S.E., M.J. Wilkinson. 1998. Transgene risk is low. Nature 393: 320.

Snow, A.A., P.M. Palma. 1997. Commercialization of transgenic plants: potential ecological risks. BioScience 47: 86–96.

Snow, A.A., B. Andersen, R.B. Joegensen. 1999. Costs of transgenic herbicide resistance introgressed from Brassica napus into weedy B. rapa. Mol. Ecol. 8: 605–15.

Stewart, C.N. Jr., J.N. All, P.L. Raymer, S. Ramachandran. 1997. Increased fitness of transgenic insecticidal rapeseed under insect selection pressure. Mol. Ecol. 6: 773–79.

Tiedje J.M., R.K. Colwell, Y.L. Grossman, R.E. Hodson, R.E. Lenski, R.N. Mack, P.J. Regal. 1989. The planned introduction of genetically engineered organisms: ecological considerations and recommendations. Ecology 70: 298–315.

Topinka, K., J. Huffman, L. Hall. 1999. Pollen flow between herbicide tolerant canola (Brassica napus) is the cause of multiple resistant canola volunteers. Poster, Expert Committee on Weeds, ECW, Ottawa.

Warwick , S.I., E. Small. 1998. Invasive plant species: evolutionary risks from transgenic crops. In L.W.D. van Raams donk, J.C.M. den Nijs (eds.), Plant Evolution in Man-Made Habitats, 235–56. Proceedings of the VIIth International Symposium of the International Organization of Plant Biosystematists. University of Amsterdam, Hugo de Vries Laboratory.

Warwick, S.I., H.J. Beckie, E. Small. 1999. Transgenic crops: new weed problems for Canada? Phytoprotection 80: 71–84.

Watkinson, A.R., R.P. Freckleton, R.A. Robinson, W.J. Sutherland. 2000. Predictions of biodiversity response to genetically modified herbicide-tolerant crops. Science 289: 1554–57.

Whitton, J., D.E. Wolfe, D.M. Arias, A.A. Snow, L.H. Rieseberg. 1997. The persistence of cultivar alleles in wild populations of sunflowers five generations after hybridization. Theor. Appl. Genet. 95: 33–40.

Wilkinson, M.J., I.J. Davenport, Y.M. Charters, A.E. Jones, J. Allainguillaume, H.T. Butler, D.C. Mason, A.F. Raybould. 2000. A direct regional scale estimate of transgene movement from genetically modified oilseed rape to its wild progenitors. Mol. Ecol. 9: 983–92.

[admin]

Part 3 of 4

PART 3: ENVIRONMENTAL IMPACT: AN ENTOMOLOGICAL PERSPECTIVE

Many species of transgenic plants currently available have been specifically modified to include genes to increase their resistance to major insect pests. To date, about 40 different genes conferring resistance have been incorporated into plants of economic importance (Schuler et al., 1998). Certain species, such as cotton, have been transformed to produce the delta endotoxins of Bacillus thuringiensis (Bt), a pathogenic bacterium that has been used as a microbial insecticide for over 50 years (Koziel et al., 1993). Other species, such as potatoes, have been transformed to produce proteinase inhibitors, which may be of plant or animal origin (Ryan, 1990).

Their use offers the potential benefits of increased yields and decreased ecological perturbations caused by the traditional application of chemical insecticides. Furthermore, it has also been argued that increased yields could lead to smaller surfaces being used for agriculture, and that the reclaiming of these lands for natural habitats would favour biodiversity.

However, there are a number of potential ecological/environmental costs that must be evaluated before these crops will be widely accepted for general use, including resistance in the target pest species, as well as the impact on other secondary pest species attacking the host plant, the natural enemies of these herbivores, and other non-target entomo-fauna in the ecosystem.

Resistance in the Targeted Pest Species

The effective lifetime of resistant plant varieties, selected through traditional breeding techniques, is often limited by the appearance of pest strains capable of overcoming these defences. Similarly, the indiscriminate use of chemical insecticides has resulted in the selection of very resistant strains of many major pest species (e.g. Metcalf, 1980), thereby limiting the use of these compounds as effective control measures. There is clear evidence that insects have evolved resistance when Bt is sprayed as a biological insecticide (Tabashnik, 1994) so there is no reason to expect anything different with a wide-scale, intensive use of transgenic plants (Gould, 1998). The Bt toxin is incorporated directly into the plant through genetic manipulation and the herbivores may be exposed for considerably longer periods during their development than with conventional Bt spraying. The appearance of Bt-resistant pest populations due to the widespread use of transgenic plants could have at least two undesirable effects: i) Bt is the most effective biological insecticide available to organic farmers; the loss of this means of control seriously jeopardizes their livelihood and an expansion of this more ecologically friendly form of agricultural practice, and ii) the possibility of a serious environmental impact if conventional farmers resorted to increased applications of chemical insecticides to control populations when the GM plants no longer offer sufficient levels of protection against pest species. These could be seen as points pertaining to altered pest potential, potential impact on non-target organisms (in this case, organic growers) and potential impact on biodiversity (items 2.1.3, 2.1.4 and 2.1.5 of the substantial equivalency for GM plants).

It is, therefore, essential that a well-developed resistance management program be implemented whenever the use of transgenic plants is a component of any production system. One approach relates directly to the GM plants. For example, the production of plants expressing very high levels of the toxin/antifeedant (known as the high-dose approach ensuring 100% mortality) would markedly decrease the possibility of resistance evolving. However, while this approach may be theoretically sound, 100% mortality may prove unrealistic under natural conditions. If some pests did survive there would be strong selection for resistance, since one would be eliminating all but the most resistant individuals in the target population. Furthermore, even if the high-dose approach were successful in controlling the pest species, it would be essential to ensure that these high levels of toxin/antifeedant do not result in negative effects at some other level in the system, such as increased toxicity to consumers (see elsewhere in this report) or on other species associated with the agroecosystem (see below).

Another approach is ensuring the existence of refuge populations of the pest species. These populations are not subjected to selection for pesticide resistance, so mating between resistant and susceptible individuals would also slow the process of selection for resistance. However, if developmental asynchrony occurs between susceptible and resistant strains, then assortative mating (mating of like phenotypes: resistant with resistant and susceptible with susceptible) may accelerate the evolution of resistance (see Liu et al., 1999). The practice of planting susceptible host plants in association with GM ones has been employed in the cottonproducing areas of Australia (see Fitt and Wilson, 2000). In this case, the number of hectares planted with non-transformed, unsprayed refuge crops is determined as a function of the land areas planted with GM plants (Bt) and non-transformed plants treated with conventional insecticides. However, insect movement is a confounding factor that may modify the effectiveness of resistance management. When highly mobile species are involved, any resistance management strategy must be viewed from a regional rather than local scale, since efforts to manage resistance at one site may be compromised through the immigration of individuals from another area where there has been strong selection for resistance. For example, some of the moth species targeted by the use of the Bt-expressing cotton plants in Australia migrate over considerable distances (Fitt, 1989), so the control means deployed at one site may have considerable influence at sites hundreds of kilometres away. An influx of resistant individuals would be a component of the “gene flow” criterion, which is specifically mentioned in the procedure for the determination of substantial equivalence for GM plants.

The idea of insects developing resistance to “insecticidal GM plants” is not a trivial matter, and it is essential that the question of resistance monitoring be addressed immediately to establish meaningful guidelines for the monitoring of resistance (see Roe et al., 2000). In establishing guidelines one must not only consider the question of migration from other sites, but also movement of the target species between different host plants species within the habitat. For example, if an insect attacks three agricultural crops (corn, beans and potatoes), as well as several uncultivated species, then the introduction of one transgenic crop (e.g. corn) could have a very different impact on potential problems of resistance than if the pest species attacked only corn.

Impact on Other Herbivores Attacking the Same Host Plant

It is very rare that a given plant will be attacked by only one species of herbivore so the possibility that the biology of non-target herbivores may be significantly modified when feeding on transgenic plants cannot be overlooked. In many cases, one would expect similar effects against the different species of herbivore, especially if they have the same feeding strategies (i.e. chewing), although varying susceptibility to Bt toxins is known among different species of lepidopteran larvae.

A recent study looked at the performance of the potato aphid, Macrosiphum euphorbiae, a secondary pest problem in potato production, on two GM potato lines whose transgene conferred resistance against the Colorado potato beetle (Ashori, 1999). He found that, when compared with control plants, aphids did very poorly on plants expressing the Bt toxin. However, on a GM line expressing a proteinase inhibitor, aphids not only survived (as well as on controls) but also had significantly better reproductive success than on control plants. Thus, the use of this GM line potentially could result in higher aphid populations, which would not only increase the risk of reduced host plant performance due to aphid feeding but could also increase the probability of increased spread of plant diseases vectored by aphids.

There are now a number of examples (oral presentations at the 2000 joint meeting of the Entomological Societies of Canada, the United States and Quebec at Montreal) where the use of Bt transgenic crops has decreased the number of sprays used against the target pest but has increased problems with secondary pests. In the past, these “minor” pests were controlled by the repeated applications of insecticides against the primary pest but now, in the absence of these sprays, the “minor” pests are able to develop, since they are unaffected by the toxin.

Impact on the Natural Enemies of Herbivores

One of the problems associated with the use of traditional chemical insecticides is the negative impact of these compounds on natural enemies. A decline in natural enemies following spraying frequently allows the subsequent resurgence of the pest species following the initial knockdown effect of the treatment and/or outbreaks of secondary pests (van den Bosch, 1978). The use of GM plants will eliminate the direct negative influence of natural enemies coming into contact with the toxin/inhibitor on the plant surface as it will be contained within the plant tissues. Thus, the deployment of GM plants could result in higher densities of natural enemies than in plots treated with conventional insecticides (Hoy et al., 1998). However, the acquisition of the toxin/inhibitor by all natural enemies is still possible through the ingestion of herbivore tissue. Some studies testing that hypothesis have shown negative effects (e.g. Hilbeck et al., 1998a, b) while others have not (e.g. Hough-Goldstein and Keil, 1991). A number of explanations exist for these apparently conflicting findings with respect to the impact of GM plants on natural enemies.

One obvious source of difference is the type of GM plant being tested, as previously noted with the performance of the potato aphid on different transgenic potatoes. In a laboratory study on Aphidius nigripes, the major parasitoid of the potato aphid (Cloutier et al., 1981), mortality from egg to adult was higher in aphids reared on a Bt potato line but on an oryzacystatin I (OCI) line was similar to controls (Ashouri, 1999). Furthermore, while their developmental time did not vary, parasitoids from hosts on the OCI line were significantly bigger than controls, thus having a potentially higher reproductive success. However, no clear trends were observed under field conditions (Ashouri, 1999), as the incidence of parasitism was very low during the two years of the study (in part due to the widespread use of traditional insecticides against the Colorado potato beetle in recent years).

There will also be obvious interspecific differences of sensitivity to the toxins, even when the same GM host plant is tested. These may relate to differences in the life histories of the species under consideration: for example, effects may be more pronounced for endoparasitoids, which actually live within the host, than for ectoparasitoids or predators that are external feeders.

The environmental conditions under which the experiments are carried out and the actual assays used could also influence the results obtained. For example, a laboratory study was carried out looking at the possible effects of the ingestion of the cysteine proteinase inhibitor, OCI (from rice and expressed in potato) on the two-spotted stinkbug, Perillus bioculatus, a predator of the Colorado potato beetle (Ashouri et al., 1998). In this experiment, the stinkbug females were fed beetle larvae injected with different chronic concentrations of OCI (1–16:g/day). While survivorship was not affected, there were negative dose-related effects on reproduction (longer pre-reproductive period, lower daily fecundity, lower egg mass size and reduced eclosion of eggs). Furthermore, these effects continued for some time after females were provided control food only, and at the highest doses the effect was non-reversible (Ashouri et al., 1998). However, in another series of experiments the growth of two-spotted stinkbug larvae was studied but in this case the prey (Colorado potato beetle larvae) were actually fed OCI plants rather than being artificially injected with the proteinase inhibitors. No significant differences were observed in survivorship, developmental time or weight gain between predatory larvae attacking hosts fed on OCI or control plants (Bouchard, 1999). Thus, in this system, the quantities of proteinase inhibitors a small predator would ingest via the herbivore had no detrimental effects on the parameters studied.

One must also place the parameters evaluated in any given bioassay within a broader context. For example, as noted above, Ashouri et al. (1998) reported some negative impact on stinkbug females that were fed beetle larvae that had been injected with different chronic concentrations of OCI. However, the authors also carried out feeding assays and found that individuals fed on OCI-injected prey showed a significantly higher incidence of attack than controls. This suggests that the ingestion of the OCI changes gut biochemistry and affects the feedback loop modulating “hunger”(Ashouri et al., 1998). Thus, while having a lower reproductive output, these stinkbugs might have a significantly higher predatory activity. If this occurred under natural conditions, then an increased attack rate by individual predators might compensate for an overall lower population density of natural enemies.

Some natural enemies are omnivores, and thus could ingest the products of transgenes through direct feeding on plant tissues as well as through the ingestion of prey feeding on GM plants. The predatory two-spotted stinkbug may feed directly on the plant, especially early in larval development. Young two-spotted stinkbug nymphs confined on plants without prey did feed on plant juices, with no differences being detected between those feeding on OCI and control plants (Bouchard, 1999). There was clear evidence that the ingestion of OCI did influence digestive protease activity in the predator but, at the concentrations encountered, the animals could compensate (Bouchard, 1999). This is not particularly surprising, since some proteinase inhibitors are also found in non-transformed plants, so some exposure to these compounds will occur under natural conditions.

Other natural enemies may feed on host plant products in specific parts of their life cycle. This is particularly true for adult parasitoids; they use pollen and nectar as food sources which may significantly impact on both their longevity and reproductive success. Given that these species directly ingest plant products, the potentially negative effects of feeding on GM plants must also be evaluated. Does active feeding influence the population dynamics of parasitoids and could this lead to the resurgence of pest populations in a manner similar to that observed when chemical insecticide sprays reduce natural enemy populations?

Furthermore, in order to determine the impact on natural enemies under field conditions one must also consider the number of different host species exploited by a given parasitoid or predator. For example, if a major parasitoid of a cotton pest also exploits many other insect species within the habitat, one must determine the relative importance to the parasitoid of hosts feeding on the GM crop relative to those hosts feeding on non-GM plants. It is clear from the preceding discussion that evaluating the potential impact of GM plants on natural enemies is a complex issue and that a real understanding will only be obtained from well-esigned, ecologically meaningful experiments focused on this issue.

Impact on Other Non-Target Insects in the Habitat

One major plant–insect interaction relates to pollination, since many plant species depend on insects for successful reproduction. The honey bee, Apis mellifera, is a major pollinator of many agronomic crops and, while no detrimental effects have been reported from their exploitation of pollen from current GM plants (Poppy, 1998),additional studies should be conducted. For any given crop there may be a highly diverse guild of pollinator species, but very little work has been carried out investigating the potential impact of GM plants on other pollinators (e.g. bumblebees, solitary bees, syrphids) that use pollen and/or nectar as food. It should be realized that any potential impact will probably not be described by a yes-no response, as possible effects may vary in time and/or space depending on the ecological conditions.

Other plant species are wind pollinated and the direct impact on pollinators of pollen from GM plants using this pollination strategy could be considered negligible. However, the very nature of wind pollination results in pollen being found at different sites throughout the ecosystem. Losey et al. (1999) addressed the potentially negative effects of windborne pollen on non-target species by examining the impact of pollen from Bt corn on the survivorship of monarch larvae feeding on milkweed, its normal host plant, which is commonly found near corn fields. This paper attracted considerable public attention but also received considerable criticism concerning the validity of the experimental protocol used (e.g., the high pollen density used). A second study has also reported a negative impact of pollen from Bt corn on monarch larvae, this time using pollen loads similar to those found on milkweed plants growing near corn fields (Hansen and Obrycki, 2000). In contrast, a similar study on the black swallowtail showed no detrimental effects when caterpillars ingested ecologically relevant concentrations of pollen from most GM corn plants (Wraight et al., 2000).

Together, the results of these experiments underline two important points: i) one cannot rule out potentially negative impacts of pollen from wind-pollinated GM crops if the pollen is ingested by non-target organisms feeding on other plants in the ecosystem; and ii) there are important species differences in susceptibility. It should also be noted that the susceptibility of a particular herbivore species to a fixed dose of pollen may be affected by many factors, such as the insect’s developmental stage and overall physical condition, and the chemistry of the host plant. For example, would one observe similar levels of mortality of a polyphagous herbivore (one that eats several different species of host plant) when it consumes GM pollen in combination with foliage from two different host plants with very different chemical profiles?

Thus, considerable research will be required to elucidate possible effects of pollen from GM plants, whether they be insect or wind ollinated, if the expression of the transgene is not restricted to those specific parts of the plant (e.g. leaves or roots) attacked by the important pest species. Particular attention is required when wind-pollinated GM plants are grown near habitats of lepidopteran species that are rare or endangered, for if there was a negative impact it could directly contribute to a reduction in biodiversity. For example, in the US the Environmental Protection Agency has called for data examining the potential impact of Bt corn pollen on the endangered Karner blue butterfly (Hansen and Obrycki, 2000).

General Conclusions

It is clear from available information that the impact of GM plants on both target and nontarget insect species is extremely variable, so rigorous experimentation will have to be carried out on a case-by-case basis to determine potentially negative effects. In the future, it may be possible to draw broader generalizations by considering insects that are closely related phylogenetically or that share similar life-history strategies. For example, are polyphagous species more likely to develop resistance to proteinase inhibitors than monophagous ones, as a result of their normal exposure to a wider variety of naturally occurring enzymes and plant defence compounds? For the moment, however, there are not enough available data to determine if such broader predictions concerning potential outcomes with respect to pests, natural enemies and/or non-target species are possible.

The implementation of rigorous field testing of previously released GM plants, and any coming on line, will help develop the necessary data sets that will permit us to look for possible general trends. It must be borne in mind that data from small field trials may not always provide a realistic picture of the situation that prevails under full commercial production. Therefore, it is essential that there be continued monitoring for those GM crops currently being used on a commercial scale with careful comparisons with conventional agricultural practices. The parameters measured would be similar to those suggested in the protocol for small plots but should be expanded to include monitoring of bird and small mammal populations. Such studies will provide information on the changes, if any, in the biological systems where GM plants are being intensively used.

Other GM Organisms for Insect Control

While insect pathogens (bacteria, viruses, fungi and protozoa) are a component of integrated pest management programs against many insect species, their sales (a reflection of use) pale when compared with those of chemical insecticide (Federici, 2000). In part, this is due to low and variable efficacy, which may be influenced by a wide array of both biotic and abiotic factors. Recombinant DNA technology is seen as one approach that could significantly increase pathogen efficacy, and already field-scale trials of GM pathogens are being carried out in certain countries. However, as with the use of GM plants there are/will be a series of ecological, economic and social questions that must be addressed as these products become available commercially (see Richards et al., 1998).

Biological control agents (parasitoids, predators) are seen as a highly desirable alternative to traditional insecticides although, like pathogens, their efficacy is affected by many environmental factors. Again, although research is ongoing with respect to GM “natural enemy” control agents, there are questions relating to the long-term effects that the presence of these organisms might have on different ecosystems (see Hoy, 2000).

To date, there are no GM microbial pest control agents registered in Canada. However, the information officer at the Pest Management Regulatory Agency (PMRA) indicated to the Panel that registration of these products would follow the same guidelines currently deployed for the registration of conventional microbial pesticides. With respect to natural enemies, permits for importation and release are currently studied by PMRA on a case-by-case basis, with input from the Canadian Food Inspection Agency (CFIA)and Agriculture and Agri-Food Canada. If and when there are genetically altered biological control agents presented for regulatory approval, PMRA indicated there would be a case-by-case review (by PMRA and CFIA) to determine if these organisms were acceptable for use in Canada.

Given the ecological complexity of pest–natural enemy/pathogen interactions, the Expert Panel believes the appropriate governmental agencies should start immediately to consider how the evaluation of these GM organisms will be carried out, specifically addressing questions relating to potential long-term ecological consequences once these organisms are released in nature.

RECOMMENDATIONS

Given the need for transparency in the registration process of GMOs, it is recommended that, when considering applications for registration of new plants with novel traits:

6.10 Companies applying for permission to release a GMO into the environment should be required to provide experimental data (using ecologically meaningful experimental protocols) on all aspects of potential environmental impact as outlined in the current guidelines relating to “substantial equivalence” (e.g. CFIA Step 2 on page 12 of the document Regulatory Directive 95- 01 and in Appendix 3 of Regulatory Directive 2000-07).

6.11 An independent committee should evaluate both the experimental protocols and the data sets obtained before approvals are granted.

6.12 Standard guidelines should be drawn up for the long-term monitoring of development of insect resistance when GMOs containing “insecticidal” products are used, with particular attention to pest species known to migrate over significant distances.

REFERENCES

Ashouri, A. 1999. Interactions de la resistance aux ravageurs primaires avec les ravageurs secondaires et leurs ennemis naturels: le cas des pucerons (Homoptera: Aphididae) sur la pomme de terre (Solanaceae). Ph.D. Thesis. Université Laval.

Ashouri, A., S. Overney, D. Michaud, C. Cloutier. 1998. Fitness and feeding are affected in the two-spotted stinkbug, Perillus bioculatus, by the cysteine proteinase inhibitor, oryzacystatin I. Arch. Insect Biochem. Physiol. 38: 74–83.

Bouchard, E. 1999. Interactions tritrophiques entre une plante de pomme de terre transgenique et Perillus bimaculatus, un predateur du doryphore de la pomme de terre. M.Sc. Thesis. Université Laval.

Cloutier, C., J.N. McNeil, J. Régnière. 1981. Fecundity, longevity and sex ratio of Aphidius nigripes (Hymenoptera: Aphidiidae) parasitising different stages of its host Macrosiphum euphorbiae (Homoptera: Aphididae). Can. Ent. 113: 193–98.

Federici, B.A. 2000. Genetically engineered pathogens of insects for IPM: concepts and status. In G.G. Kennedy, T.B. Sutton (eds.), Emerging Technologies for Integrated Pest Management: Concepts, Research and Implementation, 163–76. St. Paul: ASP Press.

Fitt, G.P. 1989. The ecology of Heliothis species in relation to agroecosystems. Annu. Rev. Entomol. 34: 17–52.

Fitt, G.P., L.J. Wilson. 2000. Genetic engineering in IPM: Bt cotton. In G.G. Kennedy, T.B. Sutton (eds.), Emerging Technologies for Integrated Pest Management: Concepts, Research and Implementation, 108–25. St. Paul: ASP Press.

Gould, F. 1998. Sustainability of transgenic insecticidal cultivars: integrating pest genetics and ecology. Annu. Rev. Entomol. 43: 701–26.

Hansen, L.C., J.J. Obrycki. 2000. Field deposition of Bt transgenic corn pollen: lethal effects on the monarch. Oecologia. 125: 241– 48.

Hilbeck, A., M. Baumgartner, P.M. Fried, F. Bigler. 1998a. Effects of transgenic Bacillus thuringensis corn-fed prey on mortality and developmental time of immature Chrysoperla carnea (Neuroptera: Chrysopidae). Environ. Entomol. 27: 480–87.

Hilbeck, A., M.J. Moar, M. Pusztai-Carey, A. Filippini, F. Bigler. 1998b. Toxicity of Bacillus thuringensis Cry 1 Ab toxin to the predator Chrysoperla carnea (Neuroptera: Chrysopidae). Environ. Entomol. 27: 1255–63.

Hough-Goldstein, J., C.B. Keil. 1991. Prospects for the integrated control of the Colorado potato beetle (Coleoptera: Chrysomelidae) using Perillus bioculatus (Hemiptera: Pentatomidae) and various pesticides. J. Econ. Entomol. 84: 1645–51.

Hoy, C.W., J. Feldman, F. Gould, G.G. Kennedy, G. Reed, J.A. Wyman. 1998. Naturally occurring biological control in genetically engineered crops. In P. Barbosa (ed.), Conservation Biological Control, 185–205. New York: Academic Press.

Hoy, M.A. 2000. Current status of biological control of insects. In G.G. Kennedy, T.B. Sutton (eds.), Emerging Technologies for Integrated Pest Management: Concepts, Research and Implementation, 210–25. St. Paul: ASP Press.

Koziel, M.G., N.B. Carozzi, T. Currier, G.W. Warren, S.V. Evola. 1993. The insecticidal crystal proteins of Bacillus thuringensis: past, present and future uses. Biotech. Genet. Engineer Rev. 11: 171–227.

Liu, Y.-B., B.E. Tabashnik, T.J. Dennehy, A.L. Patin, A.C. Bartlett. 1999. Developmental time and resistance to BT crops. Nature 400: 519.

Losey, J.E, L.S. Rayor, M.E. Carter. 1999. Transgenic pollen harms monarch larvae. Nature 399: 214.

Metcalf, R.L. 1980. Changing role of insecticides in crop protection. Ann. Rev. Entomol. 25: 219–56.

Poppy, G. 1998. Transgenic plants and bees: the beginning of the end or a new opportunity? Bee World 79: 161– 6.

Richards, A., M. Matthews, P. Christian. 1998. Ecological considerations for the environmental impact evaluation of recombinant baculovirus insecticides. Ann. Rev. Ent. 43: 493–517.

Roe, R.M., W.D. Bailey, F. Gould, C.E. Sorenson, G.G. Kennedy, J.S. Bachler, R.L. Rose, E. Hodgson, C.L. Sutula. 2000. Detection of resistant insects in IPM. In G.G. Kennedy, T.B. Sutton (eds.), Emerging Technologies for Integrated Pest Management: Concepts, Research and Implementation, 67–84. St. Paul: ASP Press.

Ryan, C.A. 1990. Potease inhibitors in plants: genes for improving defences against insects and pathogens. Annu. Rev. Phytopath. 28: 425–49.

Schuler, T.H., G.M. Poppy, B.R. Kerry, I. Denholm. 1998. Insect-resistant transgenic plants. Trends Biotechnol. 16: 168–175.

Tabashnik, B.E. 1994. Evolution of resistance to Bacillus thuriengensis. Annu. Rev. Entomol. 39: 47–79.

van den Bosch, R. 1978. The Pesticide Conspiracy. New York: Doubleday.

Wraight, C.L., A.R. Zangeri, M.J. Carroll, M.R. Berenbaum. 2000. Absence of toxicity of Bacillus thuriengensis pollen to black swallowtails under field conditions. PNAS Early Edition (www.pnas.org/cgi/doi/10.1073/pnas.130202097)

[admin]

Part 4 of 4

PART 4: POTENTIAL ENVIRONMENTAL RISKS RESULTING FROM INTERACTIONS BETWEEN WILD AND CULTURED FISH

To date, the assessment of environmental risks associated with GM foods in Canada has been restricted to those resulting from transgenic plants and microbes (see Parts 1 and 2). As of November 2000, the Canadian Food Inspection Agency (CFIA) had not received a request for approval of a GM animal for commercial food production. However, when the Canadian government does receive such a request, it will almost certainly be for a GM fish. Given the high probability that CFIA will receive such a request within the next 10 years, the Panel considered it appropriate to examine the potential risks to the environment posed by the commercial production of transgenic fish. To this end, it is important to note the comparatively short history of domestication of farmed fish in Canada, relative to that of crop plants and terrestrial animals. For this reason, coupled with the paucity of environmental and ecological assessments of transgenic fish, the Panel considered it necessary to draw upon research on interactions between wild fish and their non-transgenic, farmed counterparts to provide an empirical basis upon which the potential environmental risks posed by GM fish can be assessed. Also, given its predominance in Canada today and in the foreseeable future, this section focuses primarily on the aquaculture of salmonids, that is, salmon, trout and char.

Salmonid Aquaculture and the Incidence of Escape Events in Canada

By any metric, the Canadian aquaculture industry has experienced impressive growth over the past two decades. By 1998, the Canadian aquaculture industry was producing approximately 92,000 tonnes of product valued at $443 million (DFO, 2000c). By 1999, the farming of salmonid fish alone accounted for 68,000 t (74%) of the total aquaculture tonnage and 92% of the industry’s value (DFO, 2000c). Among these fish, Atlantic salmon was by far and away the most highly farmed species, with production estimates of 22,610 t in Atlantic Canada (Whoriskey, 2000) and 30,165 t in British Columbia (Noakes et al., 2000) in 1998. Worldwide, the production of farmed Atlantic salmon has exceeded that of all other organisms reared in aquaculture facilities, experiencing a rate of increase of 22.4% per annum (Naylor et al., 2000).

With reference to Atlantic and Pacific salmon, fish farming involves two main phases, both of which may have consequences for interactions between wild and domesticated species. During the initial freshwater phase, individuals are spawned artificially from broodstock and reared in land-based tanks for usually one to two years. The second phase of the rearing period begins with the transfer of fish to aquatic netpens, or sea cages, where the fish are maintained until they attain a size at which they can be marketed. During both phases of this rearing period, farmed fish are exposed to environmental conditions that differ greatly from those they would normally experience in the wild. To a greater or lesser degree, then, the unnatural environment results in domestication selection (i.e. differential mortality among farmed individuals), with the greatest survival experienced by those individuals whose physiology, morphology and behaviour provide them with a survival advantage in the farm environments.

Risks to wild fish populations arise from the escape of cultured fish from aquaculture facilities.

Without a remarkable improvement in containment capabilities, the number of escaped domesticated fish interacting with wild fish can be expected to increase significantly if Canada’s aquaculture industry maintains its current 15% annual rate of growth (DFO, 2000c). In the only Canadian river (Magaguadavic River, New Brunswick) for which annual data on escaped cultured fish and wild fish exist, the number of cultured fish entering the river between 1992 and 1999 has been two to eight times that of the wild salmon returning to the same river to spawn (Carr et al., 1997; Whoriskey, 2000). On the Pacific coast, the numbers of Atlantic salmon escaping into British Columbia waters averaged 43,863 per annum between 1994 and 1998 (Noakes et al., 2000); an estimated 32,000 to 86,000 farmed Atlantic salmon escaped from netpens between January and September 2000 (Mickleburgh, 2000; Sullivan, 2000). Concomitant with the increased aquaculture production of Atlantic salmon in Pacific waters is evidence of natural spawning by escaped members of this exotic species in British Columbia rivers (Gross, 2000; Volpe et al., 2000).

Genetic and ecological factors will influence the extent to which native populations are affected by interactions between wild and escaped aquaculture fish, whether the latter are transgenic or not. Genetic interactions can result in the exchange of genetic material, or introgression, between wild and cultured forms of the same species, or less frequently between cultured fish of one species and wild fish of another species. Intra- and inter-specific ecological interactions involve those related to predation, competition for food, space and mates, and the transmission of disease and parasites between cultured and wild fish. Regarding the relative importance of ecological versus genetic factors, it is important to note that an absence of gene transfer between wild and cultured fish need not significantly reduce potentially negative population consequences to wild fish. The well-documented negative effects of exotic species introductions to wild ecosystems underscore the point that organisms need not interbreed for negative impacts to population persistence to be realized. This may be particularly important when intrusions by cultured fish are frequent, involve relatively large numbers of cultured fish, and when wild population sizes are near historically low levels.

Genetic Interactions Between Wild and Cultured Fish

The effect of genetic interactions on the viability and persistence of wild fish populations will depend on the degree to which individuals are adapted to their local environment, on the genetic differentiation between wild and cultured individuals, on the probability and magnitude of outbreeding depression (i.e. a fitness reduction in hybrids from matings between individuals from two genetically distinct populations), and on the size of potentially affected wild populations relative to their carrying capacities (Hindar et al., 1991; Hutchings, 1991a).

Local Adaptation in Fish

There is considerable evidence of adaptation by fish to their local environments (see reviews by Hindar et al., 1991; Taylor, 1991; Carvalho, 1993; Conover and Schultz, 1997; Lacroix and Fleming, 1998). This adaptive variation can be evident among fish inhabiting different lakes, rivers, or even tributaries of the same river. Notwithstanding suggestions to the contrary (Peterson, 1999), evidence of outbreeding depression (see below), population differences in resistance to disease, and adaptive variation in growth rate and life history (Table 2) are inconsistent with the hypothesis that the introduction of genes from one population is, in general, likely to increase the fitness of individuals within another population.

Most research on transgenic fish in Canada is directed toward the production of growth-enhanced fish for the aquaculture industry. Thus, of particular relevance to the question of whether genetic interactions between wild and transgenic fish may have deleterious consequences to native populations is the substantive evidence of adaptive, among-population variation in individual growth rate (Table 2).

Genetic Differences Between Wild and Cultured Fish

There is a high probability that non-transgenic cultured fish differ genetically from their wild counterparts (Crozier, 1993; Fleming and Einum, 1997; Clifford et al., 1998). These differences are generated by the very different environments, and corresponding selection pressures, in which wild and cultured fish spend their lives. Selection in the wild generally represents weak stabilizing selection for traits that optimize individual fitness in the natural environment. By contrast, selection in hatcheries and in farms is directional (e.g. selection for faster growth, larger body size, increased aggression), favouring traits, with unknown correlational effects, that optimize marketability, rather than the ability to produce offspring in the wild that they themselves will survive to reproduce successfully. It is improbable that selection in the natural and cultured environments will be similar. Selection on individual growth rate, for example, can be particularly intense in cultured environments and the response to selection has been remarkably high (e.g. 8–10% per generation in Atlantic salmon (Gjoen and Bentsen, 1997), and 50% over 10 generations in coho salmon (Hershberger et al., 1990).

Table 2. Selected examples of evidence for local adaptation in fish

Species / Trait / Reference

American shad / age at maturity / Leggett and Carscadden (1978)

brook trout / egg size / Hutchings (1991b)
-- / age at maturity / Hutchings (1993)

Atlantic salmon / age at maturity / Hutchings and Jones (1998)
-- / parasite/disease resistance / Bakke (1991)
-- / growth rate / Torrissen et al. (1993)

sockeye salmon / breeding time / Hendry et al. (1999)

coho salmon / parasite/disease resistance / Hemminsen et al. (1986)

sockeye salmon / migratory behaviour / Quinn (1982)

Atlantic cod / resistance to cold waters / Goddard et al. (1999)
-- / growth rate / Svasand et al. (1996)
-- / plasticity in growth rate / Purchase (1999)
-- / plasticity in behavioiur / Puvanendran and Brown (1998)

largemouth bass / growth rate / Philipp and Whitt (1991)

mummichog / growth rate / Schultz et al. (1996)

Atlantic silverside / growth rate / Conover and Present (1990)

striped bass / growth rate / Conover et al. (1997)

By definition, transgenic fish differ genetically from their wild counterparts. Although some of these differences will be manifest by obvious differences in phenotype, such as differences in size at age, others may not. The latter will be particularly important for physiological traits such as cold-water resistance, salinity tolerance, and ability to metabolize plant protein, characters of interest for future biotechnology research in fish. This is an important point when assessing the environmental risks of transgenic fish. Depending on the transgene, some transgenic individuals may be phenotypically, behaviourally or physiologically similar to their wild counterparts, increasing the difficulty of assessing potential risks of cultured fish escapees on wild fish populations.

Hybridization and Outbreeding Depression in Fish

Relative to other animals, fish tend to have relatively high levels of inter-specific hybridization, presumably because of their high propensity for external fertilization (Hubbs, 1955; Chevassus, 1979). Hybridization can be expected to be more frequent between species that have had a comparatively short history of cohabitation (e.g. between native and introduced fish). In the present context, Hindar and Balstad (1994) reported that, from 1980 to 1992, hybridization between Atlantic salmon and brown trout in Norway increased almost four-fold with increased production of farmed Atlantic salmon (escapees typically comprise 20%–40% of the size of wild populations in Norway, reaching as high as 80%; Fleming et al., 2000; Mork, 2000).

Although risks to wild fish resulting from inter-specific hybridization may be comparatively low, the potential consequences of mating between wild and cultured members of the same species merit close attention.

The fitness of offspring resulting from matings between wild and cultured fish of the same species can be reduced, relative to the fitness of pure-bred wild offspring from the same population, possibly because of the breaking up of co-adapted gene combinations found within the wild populations. Evidence of such outbreeding depression for characters such as survival, disease resistance and growth rate has been well documented in fish (Table 3). Within the present context, and based on experiments in the wild, differences in viability in early life and juvenile growth rate between farmed, first-generation hybrid, and wild Atlantic salmon have revealed negative influences of intra-specific hybridization between farmed salmon and wild salmon, a finding consistent with the hypothesis of outbreeding depression (McGinnity et al., 1997; Fleming et al., 2000). And in the only analogous study to date on transgenic fish, Muir and Howard (1999) documented a significant reduction in survival among the progeny of GM medaka relative to those produced by pure non-transgenic crosses.

It is also important to note that the fitness consequences of outbreeding depression may not be realized immediately in first-generation hybrids if these fish retain intact components of parental genomes, thus maintaining the inter-gene, or epistatic, interactions favoured by natural selection; these interactions may not be disrupted until the second generation, or later, after recombination has occurred.

Ecological Interactions Between Wild and Cultured Fish

Interactions Between Wild and Non-Transgenic Cultured Fish

Ecological interactions between wild fish and cultured fish that have escaped from aquaculture facilities can be broadly categorized as those resulting from competition for resources, such as food, space and mates, those resulting from predator–prey interactions, and those resulting from disease and parasites (Hindar et al., 1991; Hutchings, 1991a; Fleming et al., 1996; Gross, 1998; Lacroix and Fleming, 1998; Whoriskey, 2000).

Table 3. Evidence of outbreeding depression in fish

wild x wild / pink salmon / survival / Gharrett et al. (1999)
-- / coho salmon / parasite resistance / Hemmingsen et al. (1986)
-- / mosquito fish / growth rate / Leberg (1993)
-- / sockeye salmon / survival / Wood and Foote (1990)
-- / largemouth bass / survival / Philipp and Whitt (1991)

wild x farmed / Atlantic salmon / survival / Felming et al. (2000)

non-transgenic / Atlantic salmon / survival / McGinnity et al. (1997)
-- Atlantic salmon / growth rate / Fleming et al. (2000)

wild x transgenic / medaka / survival / Muir and Howard (1999)

Competition between cultured and wild fish for food and territories can negatively affect the growth and survival of the latter and can presumably occur at any age and size. During spawning, competition can be expected for nest sites and for mates, unless there are significant temporal differences in the timing of reproduction. Escaped cultured fish, if they are comparatively large, may prey upon wild fish of smaller size. Depending on the number and size of escaped fish, absolute increases in fish abundance have been hypothesized to increase the mortality of wild fish indirectly either because of increased attraction to natural predators or because of increased fishing pressure by anglers. Transfer of disease and parasites from cultured to wild fish can also represent a potential threat to the persistence of wild populations (although it would be incorrect to assume that all such pathogens have their origin in cultured fish). Of particular concern in North America are bacterial kidney disease (caused by the bacterium Reinebacterium salmoninarium), infectious salmon anemia (a disease that resulted in the government-ordered destruction of two million cultured Atlantic salmon in New Brunswick in the late 1990s), and the parasitic sea lice Lepeoptherius salmonis and Caligus elongatus.

Although the hypothesized consequences of interactions between wild and cultured salmon are many, the number of empirical evaluations of these are few. Nonetheless, it is known that:

• escaped farmed Atlantic salmon can spawn successfully in rivers in the North Atlantic and the Northeast Pacific (Webb et al. 1991; Volpe et al. 2000);
• escaped farmed Atlantic and Pacific salmon have destroyed the egg nests constructed by wild salmon (Gallaugher and Orr 2000);
• the breeding performance of farmed Atlantic salmon, particularly males, can be inferior to that of wild salmon (Fleming et al. 1996, 2000);
• the progeny of farmed Atlantic salmon (including hybrids with wild salmon) can experience lower survival in early life than progeny of wild salmon (McGinnity et al. 1997; Fleming et al. 2000); and
• as juveniles, the progeny of farmed Atlantic salmon can compete successfully with, and potentially competitively displace, the progeny of wild Atlantic salmon (McGinnity et al. 1997; Fleming et al. 2000).

Interactions Between Wild and Transgenic Fish

The pleiotropic consequences effected by insertion of single gene constructs in fish (see Chapter 5) presents a major difficulty in reliably assessing the environmental risks posed by transgenic fish. For example, growth hormone constructs in salmonids have been shown to influence smoltification (Saunders et al., 1998), swimming ability (Farrell et al., 1997), gill irrigation (Devlin et al., 1995a,b), feeding rates (Abrahams and Sutterlin, 1999; Devlin et al., 1999), risk-avoidance behaviour (Abrahams and Sutterlin, 1999), disease resistance (Devlin, 2000), muscle structure and enzyme production (Hill et al., 2000), cranial morphology (Devlin et al., 1995a, b), body morphometry (Ostenfield et al., 1998), pituitary gland structure (Mori and Devlin, 1999), life span (Devlin et al., 1995a, b), and larval developmental rate (Devlin et al., 1995b). These phenotypic changes to morphology, physiology and behaviour could theoretically have both positive and negative effects on fitness. Compounding this is the current inability to reliably predict the variation in phenotype that will be produced by insertion of any single gene construct.

Based on the limited research that has been published to date, the Panel concludes that there is little, if any, empirical basis upon which one can reliably predict the outcome of interactions between wild and GM fish. On the one hand, the introduction of gene constructs can be associated with morphological and physiological changes to transgenic fish that may negatively affect the ability of transgenic fish to compete successfully with wild fish. For example, transgenic coho salmon appear to have reduced abilities to irrigate their gills (Devlin et al., 1995a), thus reducing their respiratory capabilities. They have also been reported to have reduced swimming abilities (Farrell et al., 1997). By contrast, critical swimming speeds of growth hormone-enhanced Atlantic salmon appear not to differ from non-transgenic controls (Stevens et al., 1998), suggesting that transgenic Atlantic salmon would not be disadvantaged by reduced locomotory abilities. Increased ability by transgenic fish to compete for food (a positive effect on fitness), coupled with reduced vigilance to predators (a negative effect on fitness), has been suggested by two recent studies that have documented increased feeding rates by GM coho and Atlantic salmon in the presence and absence of non-transgenic conspecifics (Abrahams and Sutterlin, 1999; Devlin et al., 1999).

It is reasonable to predict that the threat to native populations posed by ecological interactions with either transgenic or non-transgenic fish will be greater for small populations than for large ones. In this respect, a small population may be numerically small, or it may be small relative to its historical abundance. Although it is the former characterization of small population size that is often of concern, the latter characterization may be of equal import.

Evaluating the Environmental Safety of Genetically Modified Fish

Experimental Facilities and Evaluation Protocol

Unlike many plants and terrestrial animals, it would be very difficult, if not unwise, to incorporate field trials in an evaluation process designed to assess the potential risks that genetically engineered fish might pose to native species. Once transgenic fish were placed into a natural ecosystem for a field trial (e.g. to compare growth rates and survival of juvenile transgenic and wild conspecifics), the probability of being able to then remove every transgenic fish from that lake or stream would be very low.

Nonetheless, under special circumstances, field trials of a sort could be undertaken in a facility, or even natural systems, devoted to such experimental study. One example of such an experimental facility would be a section of river or stream separated from the main stem of that river by barriers that would be impassable to fish and that would permit control of water flow through the experimental stream section (e.g. via stop-logs). However, while such a facility might allow one to evaluate potential risks to native riverine fish, it would be impractical to design a similar experimental facility in a lake, unless remote lake/river systems were designated as experimental systems solely for the study of the interactions between wild and transgenic fish, such as the Experimental Lakes Area established in Northwestern Ontario to study wholeecosystem effects of pollutants and fishing (Schindler, 2001).

If one were to conduct field trials in such an experimental facility, they could comprise a suite of experiments conducted during the final stage of a tiered experimental protocol to evaluate the environmental safety of GM fish. During the first stage of such an approach, there are a number of experiments that could be conducted, each of which would be designed to evaluate the probability that transgenic fish would negatively influence the population growth rate, and thus the persistence, of wild fish.

Following is a series of research questions that should be addressed when assessing the potential consequences of transgenic and non-transgenic cultured fish on the viability and persistence of wild fish. These can be grouped into four, non-mutually exclusive categories: genetic introgression, ecological interactions, fish health, and physical environmental health. These are broadly phrased questions that will apply to interactions between members of the same species as well as interactions between members of different species.

I. Genetic Introgression

1. What is the probability that cultured fish will reproduce with wild fish? Does this probability differ between sexes?

2. What is the probability that a transgenic fish will transmit its novel gene construct to offspring resulting from matings with other transgenic fish and with wild fish?

3. What is the range of pleiotropic effects on the phenotype that recombination of the novel gene construct might produce?

4. Is there a difference in the viability of offspring produced by crosses between cultured fish, pure wild crosses, and mixed crosses?

II. Ecological Interactions

In order of preference (i.e. increased similarity between experimental and natural conditions), experiments to address the following questions could be conducted in circular or longitudinal hatchery tanks, stream tanks or hatchery raceways, or experimental natural stream sections (as described above). Questions can be asked of offspring, notably during the juvenile stage, produced from matings (pure and hybrid) in the natural environment, and they can be asked of cultured fish that escape from aquaculture farms and enter the natural environment of wild fish.

1. Comparing cultured (pure and hybrid) and wild fish, are there significant differences in growth rate, survival, feeding rate, predator-avoidance behaviour, critical swimming speed, agonistic behaviour (e.g. aggression, territoriality), habitat selection, movement, migration, or dispersal?

2. Do escaped cultured fish compete with wild fish for food or space?

3. Do escaped cultured fish prey upon juvenile wild fish?

4. Do escaped cultured fish, sterile or not, negatively affect the reproductive success of wild fish (e.g. by nest superimposition, or by increased density on the spawning grounds)?

III. Fish Health

1. Is the disease and parasite profile of cultured fish likely to differ from that of wild fish?

2. What is the probability of disease/parasite transfer between cultured and wild fish?

IV. Changes to Environmental Health Effected by Aquaculture Farms

1. Do residues from factors such as antibiotics, high faeces concentration, vaccines and food accumulate near aquaculture sites and, if so, do they affect the microbial community in the bottom substrate?

2. Do aquaculture netpens serve as predator attractors, increasing predation risks to wild fish?

3. Do aquaculture farms influence the migratory behaviour of wild fish?

4. Do aquaculture farms allow for increased prevalence of diseases or parasites in cultured fish and, if so, does this increase the likelihood of their transmission to wild fish?

Density-dependent Effects and Population Viability

Critical to most of the questions posed above is the degree to which the consequences to wild population viability resulting from interactions between wild and cultured fish are likely to depend on density. Specifically, it is critical to note that the influence of cultured escapees on a wild population will depend on the number of farmed escapees, NF, the size of the wild population of interest, NW, and the size of the wild population relative to some conservation-based metric (i.e., N(W*C)).

In a general sense, and in the absence of detailed experimental studies, the probability of negative consequences to the viability and persistence of a wild population effected by intrusions of escaped cultured fish can be assessed from the following table of population size inequalities.

Probability of Negative Consequences to Wild Population / Abundance of Cultured Population Relative to That of a Wild Population

Very High / NF > NW < N(W*C)

High / NF > NW > N(W*C)

Medium / NF < NW < N(W*C)

Low / NF < NW > N(W*C)

The table draws attention to the premise that cultured fish will be more likely to have a negative impact on wild fish when the number of escapees potentially interacting with wild fish exceeds the size of the wild fish population(s), particularly when the wild population(s) is itself small relative to some conservation-based metric of population size.

Sterility of Genetically Modified Fish

Induction of Triploidy

One widely discussed means of reducing potentially negative consequences of genetic interactions between wild and cultured fish is to render the latter sterile before they are placed in sea cages. If cultured fish can be made sterile, it would eliminate the potentially deleterious consequences of interbreeding between wild and cultured fish. (Based on data from five studies of transmission of growth-hormone gene constructs to F1 progeny in salmonids, consisting of 25 crosses from founder transgenic parents, Devlin (1997) estimated that the probability of transmission of novel genes from parents to offspring averages 15.6% + 3.1%.)

The only effective method for mass producing sterility in most fish is to induce triploidy at the egg stage very early in development (Benfey, 1999). By exposing eggs to thermal or hydrostatic pressure shortly after fertilization, one can disrupt the normal movement of chromosomes during meiosis, essentially by making the eggs retain the second polar body (a package of maternal chromosomes which would normally leave the egg shortly after fertilization).

Triploid individuals, which possess three complete chromosome sets in their somatic cells, differ from conspecific diploids in three fundamental ways. Triploid fish are more heterozygous, they have larger although fewer cells in most tissues and organs, and their gonadal development is disrupted to some extent, depending on the sex (Benfey 1999). Females typically remain sexually immature, although Johnstone et al. (1991) reported a 0.1% rate of partial maturation in triploid Atlantic salmon. Triploid males, on the other hand, produce spermatozoa, exhibit normal spawning behaviour, and will mate with diploid females (Benfey, forthcoming). However, the development of offspring produced by matings between triploid males and diploid females is severely impaired, resulting in death during the embryonic and larval stages. Thus, all-female populations of triploids are better suited for aquaculture than mixed-sex, triploid populations.

Sterility as a Mitigative Tool to Minimize Potential Environmental Risks

In principle, triploidy would seem to be the ideal means of minimizing the potentially negative influences of interactions between cultured transgenic and non-transgenic fish and wild members of the same species. This is reflected by the DFO and International Council for the Exploration of the Sea (ICES 1995) endorsement of the recommendation that transgenic fish be permitted in aquatic netpens only if they are first rendered sterile.

However, there are three reasons why triploidy is unlikely to be an effective mitigative tool in the near future. These are based on the considerable uncertainty associated with the degree to which 100% sterility can be achieved in practice, the consequences of ecological interactions between triploid and wild fish, and the likelihood that the aquaculture industry would favour triploid fish over their diploid counterparts.

The effectiveness of the technology used to induce triploidy, and the incidence of sterility achieved, depends on a number of factors, perhaps most notably on the experience of the individual performing the technique (T.J. Benfey, Department of Biology, University of New Brunswick, pers. comm. 23 June 2000). Nonetheless, when undertaken properly, the technique can be quite effective. Benfey (unpublished data), for example, found that of 450 Atlantic salmon for which triploidy was induced by hydrostatic pressure, the ploidy of 17 (3.8%) individuals could not be ascertained and no individuals were confirmed as being diploid. Kapuscinski (2000) reports that triploidy can be successfully induced in more than 90% of offspring in large-scale production, noting however that this success rate will vary with fish strain, egg quality, the age of the breeding fish, and induction conditions. As a precautionary measure, even under ideal conditions, triploidy should always be verified (e.g. by flow-cytometric measurement of erythrocyte DNA content) among experimental fish before they are released into netpens (Benfey, 1999). Such individual screening is necessitated by the fact that variability in operator experience, induction conditions and biological factors, coupled with inevitable human error, will compromise the effectiveness of the sterility procedure.

However, the cost associated with confirming sterility in each fish before their transfer to netpens makes it unlikely that the aquaculture industry would find it economically worthwhile to rear triploid fish commercially as food. Additional disincentives to the industry include the greater mortality experienced by triploid fish and their higher incidence of morphological deformities, relative to diploid fish (O’Flynn et al., 1997; Benfey, forthcoming). These differences in mortality and morphology between diploid and triploid fish might be reduced if, and when, the optimal conditions for rearing the latter have been identified.

Notwithstanding the uncertainty associated with achieving 100% sterility and the present economic costs of rearing triploids, it is critical to determine the degree to which sterility would effectively mitigate potential negative consequences of interactions between wild and cultured fish. This is of concern from both a genetic and ecological perspective. Although sterile fish may not be able to transmit their genes, if their spawning behaviour is not severely impaired by triploidy, males in particular may be able to mate successfully, negatively influencing the fitness of affected wild individuals. From an ecological perspective, sterile fish require food and space. Given that triploid and diploid salmonids are behaviourally and morphologically similar in those aspects of non-reproductive behaviour that have received study (O’Flynn et al., 1997; O’Keefe and Benfey, 1997, 1999), it would seem reasonable to predict that escaped cultured fish will compete with wild fish for food and space, and that large cultured fish will prey upon smaller wild fish. Furthermore, there is no reason to believe that competition and predation would be restricted to members of the same species. The deleterious effects of exotic fish introductions on wild populations throughout the world is ample demonstration that a fish need not reproduce with another to negatively affect the other’s viability and persistence.

For some salmonids, it is possible that the reduced activity of reproductive hormones caused by sterility might suppress the migratory behaviour of affected individuals, reducing the probability that sterile individuals will enter rivers and interact with wild fish in those rivers. There is evidence, for example, that diploid coho salmon sterilized by androgen treatment have a very low probability of entering rivers from the ocean (e.g. Solar et al., 1986; Baker et al., 1989). Notwithstanding the need to verify such a hypothesis for triploid transgenic and non-transgenic individuals (Benfey, forthcoming), hormone-induced suppression of migratory behaviour may be of little consequence to salmonids that regularly enter rivers from the ocean in the absence of maturation (e.g. Arctic char, brook trout).

Nonetheless, if the incidence with which a wild population is exposed to escaped cultured fish is small, the number of escapees relative to the wild populations is low, and if the potentially affected wild populations are near their carrying capacities (or some other conservation-based metric of sustainability), then the influence of sterile cultured fish on wild fish populations is likely to be small.

Regulatory Implications

DFO National Code on Introductions and Transfers of Aquatic Organisms

The stated purpose of this proposed National Code (DFO, 2000b) is to establish scientific criteria for the intentional introduction and/or transfer of live aquatic organisms into Canada, between provinces and territories, and within provinces and territories. In Canada, the primary reasons for such introductions and transfers include the creation or maintenance of recreational angling fisheries and the rearing of fish for human food consumption. Predominant examples of the latter in Canada include the existing aquaculture netpen facilities for Atlantic salmon and rainbow trout on the east and west coasts. Because of rapidly developing research within the aquaculture industry and within academia, requests for fish transfers can be expected to increase as the industry expands its comparatively nascent efforts in the rearing of fish such as Arctic char, Atlantic cod (Gadus morhua), Atlantic halibut (Hippoglossus hippoglossus) and yellowtail flounder (Limanda ferruginea).

DFO Draft Policy on Research with, and Rearing of, Transgenic Aquatic Organisms

The motivation for this draft policy (DFO, 2000a) lies in the expectation that application for commercial production of a transgenic fish is imminent. Such an application was filed in the US in early 2000 for transgenic Atlantic salmon by a company (A/F Protein Canada) whose research laboratory is located in Prince Edward Island. In addition to fish, transgenic research has been undertaken on marine invertebrates. Examples include the insertion of a growth hormone gene construct into abalone, a slow-growing mollusc, and the insertion of a marker gene into giant prawn (Canada, 1998), although there is no strong indication that transgenic marine invertebrates will be submitted for approval to CFIA within the decade. The draft policy is to be used on an interim basis, until specific Regulations are enacted under the Fisheries Act. Provinces may establish provisions and requirements additional to those set out in this national policy (DFO, 2000a).

Notably, the Draft Policy on transgenic fish makes the observation that, “because escape from commercial aquaculture cages and netpens has been significant, fish placed in them must be treated the same as fish released into the natural ecosystem (italics added)”. Given the potentially negative consequences of introgression between transgenic and wild fish, the DFO has recommended that transgenic fish be sterilized before release into commercial aquatic rearing facilties. (A population is defined here as a group of potentially interbreeding individuals, found in a geographically limited area, that are members of the same species. Operationally, for fish, such a definition is often applied to conspecific individuals spawning in the same river or lake.)

Specifically, the DFO draft policy on transgenic aquatic organisms recommends that:

1. Initially, and until otherwise authorized, rearing of transgenic organisms outside a laboratory may be made only with functionally sterile organisms.

2. Requests to hold reproductively capable transgenic aquatic organisms in facilities such as dug-out, or by-pass natural or semi-natural ponds, netpens, etc., for broodstock development, or other purposes may be considered in exceptional circumstances and will be subject to a public consultation (italics added)”.

The document does not explain why the sterility requirement should be applied only when transgenic organisms are initially introduced outside a laboratory, nor does it specify the “exceptional circumstances” under which releases of non-sterile transgenic fish would be considered.

Proposed Aquatic Organism Risk Analysis

The Implementation Guidelines of the DFO proposed National Code on Introductions and Transfers and of the Draft Policy on Transgenic Aquatic Organisms detail an Aquatic Organism Risk Analysis that must be completed for most new applications for introductions or transfers of fish. An organism may be deemed exempt from the Code, by the Minister, if the importation of that organism “presents minimal risk of negative impact on fisheries resources, habitat, or aquaculture”. However, in the absence of a formal risk analysis, it is not clear how these exemptions would be justified scientifically.

Aquatic organism risk analyses are the responsibility of the DFO, unless the authorizing jurisdiction requires the risk analysis to be prepared by the proponent. The risk analyses for evaluating environmental consequences associated with the introduction of non-transgenic and transgenic aquatic organisms are identical, and consist of the following two parts, each of which comprises three steps:

# Part I – [Transgenic] Aquatic Organism Ecological and Genetic Risk Assessment Step 1: Determining the probability of establishment. The Probability of Establishment is subjectively assigned the category of High, Medium or Low. The Level of Certainty associated with this probability assessment is assigned one of the following categories: Very Certain (VC), Reasonably Certain (RC), Reasonably Uncertain (RU) or Very Uncertain (VU).

Step 2: Determining the consequence of establishment of an aquatic organism, with associated subjective estimates of Consequences of Establishment (High, Medium, Low) and Level of Certainty (categories are those given in Step 1).

Step 3: Estimating aquatic organism risk potential. The Final Risk Estimate is assigned a single probability rating (High, Medium, Low), with an associated level of certainty (VC to VU), based on the Probability of Establishment (Step 1) and the Consequences of Establishment (Step 2) assessments. The probability rating in assigning Final Risk is the higher of those delineated in steps 1 and 2; the level of certainty is that corresponding to the less certain of the two levels identified in steps 1 and 2.

Requirements for Approval: The requested Introduction or Transfer will be recommended for approval only if the overall estimated risk potential is Low and if the overall confidence level for which the overall risk was estimated is Very Certain or Reasonably Certain. However, the regional Introductions and Transfers Committees responsible for these evaluations can identify mitigative measures that would, in their opinion, reduce High and Medium risk potentials to a Low level. Possible mitigation measures identified by the Code include use of genetically similar stocks, sterilization, and use of containment facilities to prevent escapes.

# Part 2 – Pathogen, Parasite or Fellow Traveller Risk Assessment Process Step 1: Determining the probability of establishment, with associated subjective estimates of Probability of Establishment and Level of Certainty (see above).

Step 2: Determining the consequences of establishment of a pathogen, parasite or fellow traveller, with associated subjective estimates of Consequences of Establishment and Level of Certainty.

Step 3: Estimating pathogen, parasite or fellow traveller risk potential. The Final Risk Estimate is assigned a single value based on the Probability of Establishment (Step 1) and the Consequences of Establishment (Step 2), as described for the Ecological and Genetic Risk Assessment above.

Requirements for Approval: The requested Introduction or Transfer will be recommended for approval only if the overall estimated risk potential is Low and if the overall confidence level for which the overall risk was estimated is Very Certain or Reasonably Certain. However, the DFO’s Introductions and Transfers Committees can identify mitigative measures that would, in their opinion, reduce the risk potential to a Low level. Possible mitigation measures include health inspection and certification, pre-treatment for pathogens, diseases and parasites, and vaccination, among others.

Critique of Current Regulatory Framework and Proposed Risk Aquatic Organism Analysis

CEPA (Canadian Environmental Protection Act)

Until the DFO establishes regulations pertaining to transgenic organisms in the Fisheries Act, the environmental consequences associated with the commercial rearing of transgenic aquatic organisms will be assessed under CEPA. According to CEPA Regulations, in order for regulators to assess the potential risks to the environment posed by transgenic animals, the proponent must provide information on “the potential of the organism to have adverse environmental impacts that could affect the conservation and sustainable use of biological diversity” (Regulation 5(c) of Sections 29.16 and 29.19, Schedule XIX).

Despite the apparent breadth of this requirement, based on the Guideline (4.3.5.3) accompanying this Regulation, and based on interviews with Environment Canada officials, the Panel concludes that CEPA Regulations have no explicit data requirements for information pertaining to the potential effects on conservation and biodiversity posed by GM animals. The Panel views this to be a significant weakness in the current legislation and concludes that the existing regulatory framework is ill-prepared, from an environmental safety perspective, for imminent applications for the approval of transgenic animals for commercial production.

Sterility of Transgenic Fish

Upon initial consideration, it would appear that DFO’s position regarding sterility of transgenic fish is in accordance with that of ICES, whose Code of Practice on the Introductions and Transfers of Marine Organisms stipulates that GMOs be reproductively sterile prior to release (ICES, 1995). However, one should contrast this recommendation with that made by the Working Group of ICES that deals specifically with transgenic aquatic organisms. This Working Group, represented by scientists from Canada, the US and countries throughout northern Europe, recommended that:

“Until there is a technique to produce 100% sterilization effectiveness, GMO[s] should not be held in or connection with open water systems” (ICES, 1997).

It is the opinion of this ICES Working Group that existing techniques for effecting sterility are not 100% effective (ICES 1997, 1998), an opinion with which the Expert Panel agrees. Given, then, that 100% sterility cannot be ensured, transgenic fish should not be placed in aquatic netpens.

DFO’s Draft Policy recommendation that sterile GM fish be permitted in aquatic netpens does not appear to be shared by the North Atlantic Salmon Conservation Organization (NASCO), whose parties include Canada, Denmark (in respect of the Faroe Islands and Greenland), the European Union, Iceland, Norway, Russia and the US. (Subject to the approval of the Council, the Convention is open for accession by any State that exercises fisheries jurisdiction in the North Atlantic or is a State of Origin for salmon stocks subject to the Convention.)

The NASCO Guidelines on Transgenic Salmon (adopted by the Council) state that the Parties agree to “take all possible actions to ensure that the use of transgenic salmon, in any part of the NASCO Convention area, is confined to secure self-contained, land based facilities” (NASCO, 1997). This text is also reflected in the Revision to Protocols (paragraph 5.5 entitled Transgenic Salmon) of North American Commission document NAC(98)6, the Draft Discussion document for Revision to Protocols for the Introduction and Transfer of Salmonids (NASCO, 1998). It is worth noting, however, an internal inconsistency in the North American Commission document. In Section 2.2.1, the protocols state that “Transgenic salmonids may be used in marine or freshwater cages if they are reproductively sterile”. It is somewhat strange that there should be a different approach between the Council’s guidelines (agreed to by all Parties) and the North American Commission Protocols, although it should be borne in mind that the latter are still only in the form of a discussion document.

Aquatic Organism Risk Analysis

Despite its positive intent and potential breadth of information requirements, the Aquatic Organism Risk Analysis by which the DFO has proposed to evaluate the environmental safety of transgenic aquatic organisms has one primary weakness: the probabilities and consequences of establishment by GM fish, and their associated certainty levels, are based on subjective evaluations supported by existing scientific literature and by the opinions of those who are members of DFO Introductions and Transfers Committees. There is no requirement for either the Proponent or DFO to undertake scientific analyses, or to collect experimental data, in support of the risk analysis process.

DFO (2000a, b) does note that:

“The strength of the review process is not in the ratings but in the detailed biological and other relevant information statements that motivate them.”

Herein lies a paradox. The Code states, in effect, that the strength of the review process is reflected by the biological data underlying the risk probability assessments. Logically, then, the absence of biological data pertaining to a specific introduction/transfer request must necessarily be associated with a weak review.

In addition, the proposed Aquatic Organism Risk Analysis should account for changes to risk associated with changes to the population density and conservation status of potentially affected organisms (see above). This “conditional” nature of potential consequences to wild population viability and persistence underscores the points that:

1. risks to environmental health must be assessed on a case-by-case and population-by-population basis,

2. that these risks should be reviewed regularly (e.g. every 5 years), and

3. that it would be inconsistent with the precautionary approach to assign general environmental risk probabilities that will be applicable to all environments in all parts of the country.

Given the paucity of scientific data and information pertaining to the environmental consequences of genetic and ecological interactions between cultured and wild fish, DFO’s Aquatic Organism Risk Analysis, despite its laudable intentions, will be unable to provide strong, accurate, reliable assessments of potential risks to the environment posed by the introduction and transfer of GM fish. This dearth of comparative research, the difficulty (because of genotype by environment interactions) in being able to use laboratory research to predict environmental consequences reliably, and the unpredictable nature of complex pleiotropic phenotypic effects of gene insertions, lead the Expert Panel to conclude that it would be prudent and precautionary to impose a moratorium on the rearing of GM fish in aquatic facilities.

Future Research

Clearly, there is a need for research which addresses the consequences of interactions between wild and GM aquatic organisms. Examples of the questions that should be addressed by such research are identified earlier in this section. In this regard, the Canadian Biotechnology Strategy has recently provided support for research on transgenic Pacific salmon at DFO’s West Vancouver Laboratory and on triploid salmonids by researchers at the University of New Brunswick. In addition, within the next 10 years, research on interactions between wild and cultured salmonids, funded by AquaNet, a National Centre of Excellence, will be undertaken.

These research initiatives will complement the comparative research that has been done to date on wild and GM fish, notably by Devlin and colleagues at DFO’s West Vancouver Laboratory, but increasingly by academic scientists from various Canadian universities (e.g. Manitoba, Guelph, New Brunswick) in collaboration with industry. The greatest strength of this research lies in the scrutiny the work receives by the scientific community during the anonymous peer review of the manuscripts prior to publication and by continuous evaluation of the widely available published papers and associated data.

Public Perception of Environmental Risks Posed by Cultured Fish

One of the difficulties in assessing potential environmental risks posed by the introduction of cultured fish to natural ecosystems is the imprecise threshold of risk that different sectors of society are willing to accept. For some individuals, angling associations, aquaculture companies and government agencies, an absence of obviously negative consequences, even in the absence of relevant scientific studies to examine such consequences, appears to constitute evidence that cultured fish have negligible influences on wild populations. Indeed, depending on the individual or organization, the criterion for a negative influence effected by the presence of a cultured population probably ranges from any reduction in the abundance of a wild population to the commercial or biological extinction of a wild population.

The recreational fishing industry in Canada provides one example of the potential for extremely divergent perceptions of the potential environmental risks posed by cultured fish. Among the 92 fish species and 13 “forms” (subspecies, varieties, hybrids) identified by Crossman (1991) as having invaded Canadian freshwater lakes and rivers, 71 were authorized introductions (DFO, 2000b). Of the eight species of salmon and trout listed in the Government of Ontario’s 2000 Recreational Fishing Regulations (Ontario, 2000), only three (two if one excludes the reintroduced Atlantic salmon) are native to Ontario and one (brown trout) is not native to Canada. In the late 1990s and in 2000, non-native fish, such as rainbow trout and brown trout, continue to be stocked into Ontario’s lakes and rivers (OMNR, 2000). In fact, one of these intentionally introduced non-native fish (splake) is actually an inter-specific hybrid produced by artificially breeding lake trout (Salvelinus namaycush) with brook trout.

Furthermore, the Government of Ontario, and presumably most angling associations, do not consider pink salmon, chinook salmon, coho salmon, rainbow trout, brown trout, or the interspecific hybrid splake to be non-native species in Ontario — none of these three is identified as exotic species in the 2000 Ontario Fishing Regulations (Ontario, 2000). Oddly, of the 3 non-native fish that are mentioned, the rainbow smelt (Osmerus mordax) is actually native to eastern Ontario (Scott and Crossman, 1973).

Thus, to many sectors of society, cultured fish will be perceived to pose a threat to the environment only when they negatively influence the abundance of a commercially or recreationally exploited species.

RECOMMENDATIONS

The Panel concluded that there were significant scientific uncertainties associated both with the potential consequences of genetic and ecological interactions between transgenic and wild fish, and of the mitigative utility of rendering GM fish sterile in aquatic facilities. As a consequence, the Panel recommends that:

6.13. A moratorium be placed on the rearing of GM fish in aquatic netpens.

6.14 Approval for commercial production of transgenic fish be conditional on the rearing of fish in land-based facilities only.

6.15 Reliable assessment of the potential environmental risks posed by transgenic fish can only be addressed by comprehensive research programs devoted to the study of interactions between wild and cultured fish.

6.16 Potential risks to the environment posed by transgenic fish must be assessed not just case-by-case, but also on a population-by-population basis.

6.17 Identification of pleiotropic, or secondary, effects on the phenotype resulting from the insertion of single gene constructs be a research priority.

[admin]

REFERENCES

Abrahams, M.V., A. Sutterlin. 1999. The foraging and antipredator behaviour of growthenhanced transgenic Atlantic salmon. Anim. Behav. 58: 933–42.

Baker, I.J., I.I. Solar, K. Mulji, E.M. Donaldson, G.A. Hunter, E.T. Stone. 1989. Coded wire tag recoveries from the second release of sterile coho salmon (Oncorhynchus kisutch) into the marine environment. Can. Data Rep. Fish. Aquat. Sci. No. 775.

Bakke, T.A. 1991. A review of the inter- and intraspecific variability in salmonid hosts to laboratory infections with Gyrodactylus salaris Malmberg. Aquaculture 98: 303–10.

Benfey, T.J. In press. Use of sterile triploid Atlantic salmon (Salmo salar L.) for aquaculture in New Brunswick, Canada. ICES J. Mar. Sci.

Benfey, T.J. 1999. The physiology and behavior of triploid fish. Rev. Fish. Sci. 7: 39–67.

Canada. 1998. Aquatic Biotechnology. Discussion document – Renewal of the Canadian Biotechnology Strategy. Prepared by the Working Group on Aquatic Biotechnology, March 1998.

Carr, J., J.M. Anderson, F.G. Whoriskey, T. Dilworth. 1997. The occurrence and spawning of cultured Atlantic salmon (Salmo salar L.) in a Canadian river. ICES J. Mar. Sci. 54: 1064–73.

Carvalho, G.R. 1993. Evolutionary aspects of fish distribution: genetic variability and adaptation. J. Fish Biol. 43 (Suppl. A): 53–73.

Chevassus, B. 1979. Hybridization in salmonids: results and perspectives. Aquaculture 17: 113–28.

Clifford, S.L., P. McGinnity, A. Ferguson. 1998. Genetic changes in Atlantic salmon (Salmo salar) populations of Northwest Irish rivers resulting from escapes of adult farm salmon. Can. J. Fish. Aquat. Sci. 55: 358–63.

Conover, D.O., T.M.C. Present. 1990. Countergradient variation in growth rate: compensation for length of the growing season among Atlantic silversides from different latitudes. Oecologia 83: 316–24.

Conover, D.O., E.T. Schultz. 1997. Natural selection and the evolution of growth rate in the early life history: what are the trade-offs? In R.C. Chambers, E.A. Trippel (eds.), Early Life History and Recruitment in Fish Populations, 305–32. New York: Chapman and Hall.

Conover, D.O., J.J. Brown, A. Ehtisham. 1997. Countergradient variation in growth of young striped bass (Morone saxatilis) from different latitudes. Can. J. Fish. Aquat. Sci. 54: 2401–09.

Crossman, E.J. 1991. Introduced freshwater fishes: a review of the North American perspective with emphasis on Canada. Can. J. Fish. Aquat. Sci. 48 (Suppl. 1): 46–57.

Crozier, W.W. 1993. Evidence of genetic interaction between escaped farmed salmon and wild Atlantic salmon (Salmo salar L.) in a northern Irish river. Aquaculture 113: 19–29.

Devlin, R.H. 1997. Transgenic salmonids. In L.M. Houdebine (ed.), Transgenic Animals: Generation and Use. Amsterdam: Harwood Academic Publishers.

Devlin, R.H. 2000. Risk assessment of genetically-distinct salmonids: difficulties in ecological risk assessment of transgenic and domesticated fish. In P. Gallaugher, C. Orr (eds.), Aquaculture and the Protection of Wild Salmon, 63–69. Burnaby, BC: Simon Fraser University, Cont. Stud. Sci.

Devlin, R.H., T.Y. Yesaki, E.M. Donaldson, S.J. Du, C.-L. Hew. 1995a. Production of germline transgenic Pacific salmonids with dramatically increased growth performance. Can. J. Fish. Aquat. Sci. 52: 1376–84.

Devlin, R.H., T.Y.Yesaki, E.M. Donaldson, C.-L. Hew. 1995b. Transmission and phenotypic effects of antifreeze/GH gene construct in coho salmon (Oncorhynchus kisutch). Aquaculture 137: 161–69.

Devlin, R.H., J.I. Johnsson, D.E. Smailus, C.A. Biagi, E. Jönsson, B. Th. Björnsson. 1999. Increased ability to compete for food by growth hormone-transgenic coho salmon Oncorhynchus kisutch (Walbaum). Aquacult. Res. 30: 479–82.

DFO (Department of Fisheries and Oceans). 2000a. Draft Policy on Research with, and Rearing of, Transgenic Aquatic Organisms. Ottawa: DFO, Aquaculture and Oceans Science Branch.

DFO. 2000b. National Code on Introductions and Transfers of Aquatic Organisms. Ottawa: DFO.

DFO. 2000c. What Is Aquaculture? Backgrounder B-HQ-00-71(143). Ottawa: DFO.

Farrell, A.P., W. Bennett, R.H. Devlin. 1997. Growth-enhanced transgenic salmon can be inferior swimmers. Can. J. Zool. 75: 335–37.

Fleming, I.A., B. Jonsson, M.R. Gross, A. Lamberg. 1996. An experimental study of the reproductive behaviour and success of farmed Atlantic salmon (Salmo salar). J. Appl. Ecol. 33: 893–905.

Fleming, I.A., S. Einum. 1997. Experimental tests of genetic divergence of farmed from wild Atlantic salmon due to domestication. ICES J. Mar. Sci. 54: 1051–63.

Fleming, I.A., K. Hindar, I.B. Mjølnerød, B. Jonsson, T. Balstad, A. Lamberg. 2000. Lifetime success and interactions of farm salmon invading a native population. Proc. R. Soc. Lond. B 267: 1517–23.

Gallaugher, P., C. Orr (eds.). 2000. Aquaculture and the Protection of Wild Salmon. Burnaby, BC: Simon Fraser University, Cont. Stud. Sci.

Gharrett, A.J., W.W. Smoker, R.R. Reisenbichler, S.G. Taylor. 1999. Outbreeding depression in hybrids between odd- and even-broodyear pink salmon. Aquaculture 173: 117–29.

Gjoen, H.M., H.B. Bentsen. 1997. Past, present, and future of genetic improvement in salmon aquaculture. ICES J. Mar. Sci. 54: 1009–14.

Goddard, S.V., M.H. Kao, G.L. Fletcher. 1999. Population differences in antifreeze production cycle of juvenile Atlantic cod (Gadus morhua) reflect adaptations to overwintering environment. Can. J. Fish. Aquat. Sci. 56: 1991–99.

Gross, M.R. 1998. One species with two biologies: Atlantic salmon (Salmo salar) in the wild and in aquaculture. Can. J. Fish. Aquat. Sci. 55 (Suppl. 1): 131–44.

Gross, M.R. 2000. Will farmed Atlantic salmon invade the ecological niches of wild Atlantic salmon? In P. Gallaugher, C. Orr (eds.), Aquaculture and the Protection of Wild Salmon, 25–28. Burnaby, BC: Simon Fraser University, Cont. Stud. Sci.

Hemmingsen, A.R., R.A. Holt, R.D. Ewing, J.D. McIntyre. 1986. Susceptibility of progeny from crosses among three stocks of coho salmon to infection by Ceratomyxa shasta. Trans. Am. Fish. Soc. 115: 492–95.

Hendry, A.P., O.K. Berg, T.P. Quinn. 1999. Condition dependence and adaptation-by-time: breeding date, life history, and energy allocation within a population of salmon. Oikos 85: 499–514.

Hersberger, W.K., J.M. Myers, R.N. Iwamoto, W.E. Mcauley, A.M. Saxton. 1990. Genetic changes in the growth of coho salmon (Oncorhynchus kisutch) in marine net-pens, produced by ten years of selection. Aquaculture 85: 187–97.

Hill, J.A., A. Kiessling, R.H. Devlin. 2000. Coho salmon (Oncorhynchus kisutch) transgenic for a growth hormone gene construct exhibit increased rates of muscle hyperplasia and detectable levels of gene expression. Can. J. Fish. Aquat. Sci. 57: 939–50.

Hindar, K., N.F. Ryman, F. Utter. 1991. Genetic effects of cultured fish on natural fish populations. Can. J. Fish. Aquat. Sci. 48: 945–57.

Hindar, K., T. Balstad. 1994. Salmonid culture and interspecific hybridization. Conserv. Biol. 8: 881–82.

Hubbs, C.L. 1955. Hybridization between fish species in nature. Syst. Zool. 4: 1–20.

Hutchings, J.A. 1991a. The threat of extinction to native populations experiencing spawning intrusions by cultured Atlantic salmon. Aquaculture 98: 119–32.

Hutchings, J.A. 1991b. Fitness consequences of variation in egg size and food abundance in brook trout, Salvelinus fontinalis. Evolution 45: 1162–68.

Hutchings, J.A. 1993. Adaptive life histories effected by age-specific survival and growth rate. Ecology 74: 673–84.

Hutchings, J.A., M.E.B. Jones. 1998. Life history variation and growth rate thresholds for maturity in Atlantic salmon, Salmo salar. Can. J. Fish. Aquat. Sci. 55 (Suppl. 1): 22–47.

ICES (International Council for the Exploration of the Sea). 1995. Code of Practice on the Introductions and Transfers of Marine Organisms 1994. Copenhagen.

ICES. 1997. Report of the Working Group on the Application of Genetics in Fisheries and Mariculture. Copenhagen. C.M.1997/F:4.

ICES. 1998. Report of the Working Group on the Application of Genetics in Fisheries and Mariculture. Copenhagen. C.M.1998/F:1.

Johnstone, R., H.A. McLay, M.V. Walsingham. 1991. Production and performance of triploid Atlantic salmon in Scotland. Can. Tech. Rep. Fish. Aquat. Sci. 1789: 15–36.

Kapuscinski, A. 2000. Biosafety assessment of transgenic aquatic organisms: the case of transgenic salmon. In P. Gallaugher, C. Orr (eds.), Aquaculture and the Protection of Wild Salmon, 56–63. Burnaby, BC: Simon Fraser University, Cont. Stud. Sci.

Lacroix, G.L., I.A. Fleming. 1998. Ecological and Behavioural Interactions Between Farmed and Wild Atlantic Salmon: Consequences for Wild Salmon. Canadian Stock Assessment Secretariat Research Document 98/162.

Leberg, P.L. 1993. Strategies for population reintroduction: effects of genetic variability on population growth and size. Conserv. Biol. 7: 194–99.

Leggett, W.C., J.E. Carscadden. 1978. Latitudinal variation in reproductive characteristics of American shad (Alosa sapidissima): evidence for population specific life history strategies in fish. J. Fish. Res. Board Can. 35: 1469–78.

McGinnity, P., C. Stone, J.B. Taggart, D. Cooke, D. Cotter, R. Hynes, C. McCamley, T. Cross, A. Ferguson. 1997. Genetic impact of escaped farmed Atlantic salmon (Salmo salar L.) on native populations: use of DNA profiling to assess freshwater performance of wild, farmed, and hybrid progeny in a natural river environment. ICES J. Mar. Sci. 54: 998–1008.

Mickleburgh, R. 2000. B.C. tells fish farms to contain stocks. The Globe and Mail. 24 Aug.

Mori, T., R.H. Devlin. 1999. Transgene and host growth hormone gene expression in pituitary and nonpituitary tissues of normal and growth hormone transgenic salmon. Mol. Cell. Endocrinol. 149: 129–39.

Mork, J. 2000. Cultured/wild interactions in the east Atlantic salmon: a convergence of opinions on levels, effects and remedies. In P. Gallaugher, C. Orr (eds.), Aquaculture and the Protection of Wild Salmon, 18–21. Burnaby, BC: Simon Fraser University, Cont. Stud. Sci.

Muir, W.M., R.D. Howard. 1999. Possible ecological risks of transgenic organism release when transgenes affect mating success: sexual selection and the Trojan gene hypothesis. Proc. Nat. Acad. Sci. USA 96: 13853–56.

NASCO (North Atlantic Salmon Conservation Organization). 1997. NASCO Guidelines for Action on Transgenic Salmon. Edinburgh: NASCO. Document CNL(97)48.

NASCO. 1998. Discussion Document for Revision to Protocols for the Introduction and Transfer of Salmonids. Edinburgh: North American Commission, NASCO. Document NAC(98)6.

Naylor, R.L., R.J. Goldburg, J.H. Primavera, N. Kautsky, M.C.M. Beveridge, J. Clay, C. Folke, J. Lubchenco, H. Mooney, M. Troell. 2000. Effect of aquaculture on world food supplies. Nature 405: 1017–24.

Noakes, D.J., R.J. Beamish, M.L. Kent. 2000. On the decline of Pacific salmon and speculative links to salmon farming in British Columbia. Aquaculture 183: 363–86.

O’Flynn, F.M., S.A. McGeachy, G.W. Friars, T.J. Benfey, J.K. Bailey. 1997. Comparisons of cultured triploid and diploid Atlantic salmon (Salmo salar L.). ICES J. Mar. Sci. 54: 1160–65.

O’Keefe, R.A., T.J. Benfey. 1997. The feeding response of diploid and triploid Atlantic salmon and brook trout. J. Fish Biol. 51: 989–97.

O’Keefe, R.A., T.J. Benfey. 1999. Comparative growth and food consumption of diploid and triploid brook trout (Salvelinus fontinalis) monitored by radiography. Aquaculture 175: 111–20.

OMNR (Ontario Ministry of Natural Resources). 2000. Fish Stocking List – 1996 to 2000. Bracebridge Area Office, District of Parry Sound, OMNR.

Ontario. 2000. Year 2000 Recreational Fishing Regulations Summary. Queen’s Printer for Ontario.

Ostenfeld, T.H., E. McLean, R.H. Devlin. 1998. Transgenesis changes body and head shape in Pacific salmon. J. Fish Biol. 52: 850–54.

Peterson, R.G. 1999. Potential Genetic Interaction Between Wild and Farm Salmon of the Same Species. Report prepared for the Office of the Commissioner for Aquaculture Development, Department of Fisheries and Oceans, Ottawa.

Philipp, D.P., G.S. Whitt. 1991. Survival and growth of northern, Florida, and reciprocal F1 hybrid largemouth bass in central Illinois. Trans. Am. Fish. Soc. 120: 156–78.

Purchase, C.F. 1999. Inter-populational differences in growth and energy allocation of northwest Atlantic cod (Gadus morhua L.) revealed by common environment experiments. M.Sc. Thesis. St. John’s, NF: Memorial University.

Puvanendran, V., J.A. Brown. 1998. Effect of light intensity on the foraging and growth of Atlantic cod larvae: interpopulation difference? Mar. Ecol. Prog. Ser. 167: 207–14.

Quinn, T.P. 1982. Intra-specific differences in sockeye salmon fry compass orientation mechanisms. In E.L. Brannon, E.O. Salo (eds.), Salmon and Trout Migratory Behavior Symposium, 79–85. Seattle: University of Washington, School of Fisheries.

Saunders, R.L., G.L. Fletcher, C.-L. Hew. 1998. Smolt development in growth hormone transgenic Atlantic salmon. Aquaculture 168: 177–94.

Schindler, D.W. 2001. The cumulative effects of climate warming and other human stresses on Canadian freshwaters in the new millenium. Can. J. Fish. Aquat. Sci. 58.

Schultz, E.T., K.E. Reynolds, D.O. Conover. 1996. Countergradient variation in growth among newly hatched Fundulus heteroclitus: geographic differences revealed by common-environment experiments. Funct. Ecol. 10: 366–74.

Scott, W.B., E.J. Crossman. 1973. Freshwater fishes of Canada. Fish. Res. Board Can. Bull. 184.

Solar, I.I., I.J. Baker, I.I. Solar, K. Mulji, E.M. Donaldson, G.A. Hunter, E.T. Stone. 1986.

Coded wire tag recoveries from the first release of all-female and sterile groups of coho salmon (Oncorhynchus kisutch) into the marine environment. Can. Data Rep. Fish. Aquat. Sci. No. 609.

Sullivan, P. 2000. One fish, two fish, red fish, blue fish. The Globe and Mail. 24 Aug.

Stevens, E.D., A. Sutterlin, T. Cook. 1998. Respiratory metabolism and swimming performance in growth hormone transgenic Atlantic salmon. Can. J. Fish. Aquat. Sci. 55: 2028–35.

Svasand, T., K.E. Jorstad, H. Ottera, O.S. Kjesbu. 1996. Differences in growth performance between Arcto-Norwegian and Norwegian coastal cod reared under identical conditions. J. Fish Biol. 49: 108–19.

Taylor, E.B. 1991. A review of local adaptation in salmonidae, with particular reference to Pacific and Atlantic salmon. Aquaculture 98: 185–208.

Torrissen, K.R., R. Male, G. Naevdal. 1993. Trypsin isozymes in Atlantic salmon, Salmo salar L.: studies of heredity, egg quality and effect on growth of three different populations. Aquacult. Fish. Manage. 24: 407–15.

Volpe, J.P., E.G. Taylor, D.W. Rimmer, B.W. Glickman. 2000. Evidence of natural reproduction of aquaculture-escaped Atlantic salmon in a coastal British Columbia river. Conserv. Biol. 14: 899–903.

Webb, J.H., D.W. Hay, P.D. Cunningham, A.F. Youngson. 1991. The spawning behaviour of escaped farmed and wild adult Atlantic salmon (Salmo salar L.) in a northern Scottish river. Aquaculture 98: 97–110.

Whoriskey, F. 2000. The North American East Coast Salmon Aquaculture Industry: The Challenges for Wild Salmon. St. Andrews, NB: Atlantic Salmon Federation.

Wood, C.C., C.J. Foote. 1990. Genetic differences in the early development and growth of sympatric sockeye salmon and kokanee (Oncorhynchus nerka), and their hybrids. Can. J. Fish. Aquat. Sci. 47: 2250–60.

[admin]

7. SUBSTANTIAL EQUIVALENCE AS A REGULATORY CONCEPT

INTRODUCTION

One of the major challenges facing regulators of GM crop varieties world-wide has been deciding what comprises a meaningful difference between an existing crop variety and its GM derivatives. The genetic differences are apparently modest, and the GM derivatives retain most of the familiar characteristics of the parental variety, although the GM variety clearly possesses at least one additional novel (transgenic) trait. Regulators have generally taken the position that GM derivatives are so similar to the conventional varieties from which they have been derived that the two can be considered “substantially equivalent”.

It is clear that GM varieties and conventional varieties are indeed very similar. However, application of this term to a new GM variety has become, within the present regulatory environment, effectively a declaration of safety. The validity of this use of “substantial equivalence” as a regulatory decision tool has become a hotly debated issue.

In this chapter, we explore the origins and applications of “substantial equivalence”, and the basis of the debate. We also discuss what the Panel feels would be required to make this concept a valid metric for decisions regarding approval of new GM products.

THE ORIGINS OF “SUBSTANTIAL EQUIVALENCE”

The origins of “substantial equivalence” as an operational construct reside within the conventional breeding process. Plant breeders work primarily with highly refined breeding lines whose genetic heritage is known, and whose progeny have been evaluated from countless sexual recombination events. In effect, the existing gene pools are being shuffled into new combinations of alleles (the primary source of phenotypic variability) with additional variation often being created through incorporation of genetic material from distant relatives (wide crosses), and the ongoing appearance of spontaneous mutations in the genetic backgrounds in use. The expectation, borne out by years of successful crop variety development, is that “barley is barley is barley” (i.e. most, if not all, of the new gene combinations will produce a “barley” phenotype). Those that fail to meet that expectation are eliminated from the breeding program, and the most promising of the remaining lines are carried forward. The range of variability that appears in these progeny generations can be significant but, in general, such gene shuffling consistently recreates the same basic plant, and the expectation of “equivalence” has been fulfilled. The history of success in variety development through conventional breeding thus demonstrates that, despite occasional exceptions (Zitnak and Johnston, 1970; Hellenas et al., 1995), it is usually possible to recombine genes within a species in many ways and create broadly similar, non-hazardous, phenotypic outcomes.

The caveat to this conclusion, however, relates to the relative genetic uniformity of the material used in most crop breeding programs. Selection over millennia for enhancement of desirable traits, and for absence of undesirable properties, has converted most of our major crops into genetically homogeneous forms which have lost most, if not all, of their capacity to either harm consuming organisms or compete successfully outside of a managed agro-ecosystem. Given this general “disarming” of the original species, it is perhaps not surprising that shuffling of the remaining functional genes within contemporary breeding programs can be routinely undertaken without creation of harmful progeny.

HOW HAVE NEW CROP VARIETIES NORMALLY BEEN APPROVED?

For crop varieties developed through conventional breeding, the testing required for new genotypes being considered for commercial release follows a long-established model. The conventional crossing and selection process through which new varieties are produced will, by design, have created new gene combinations. At the level of the genome, such new combinations may involve only modest local differences in DNA sequence in comparison with existing varieties, but these small differences are likely to be numerous, and distributed non-uniformly across the genome. Their collective effects will be responsible for generation of the new phenotype, conditioned to some extent by interactions with the environment.

However, no straightforward method has been available for assessing, a priori, the specific contribution of each genetic difference to the new phenotype. It is therefore accepted practice to compare directly any new genotypes with existing varieties (referred to as “test” or “check” varieties) and to establish that the new candidate meets or exceeds specific standards for quality and performance. Such testing typically includes laboratory evaluation (e.g. chemical analysis) of the harvested plant parts, as well as comparative field performance data from test plots grown at multiple sites over a number of years.

Traditional breeding has frequently produced new crop varieties distinguished by possession of “novel traits”, including greater herbicide tolerance, increased disease resistance, different seed colour, altered oil profile, etc. Where a novel trait accompanies the new genotype, the validity and stability of this specific trait will also be monitored under field conditions. However, interactions of such a breeding-derived trait with other parts of the genome are assumed either to be of no functional significance, or, should a negative impact perchance be created, to be readily detected during the usual field testing.

It should be noted that tests for direct human impacts such as toxicity or allergenicity would not normally be included in such routine variety evaluation, unless there were a prior history of problems of this nature associated with the species in question (e.g. glucosinolates in canola, glycoalkaloid accumulation in potatoes). Otherwise, the implicit assumption behind this methodology is that, even where a breeding-derived novel trait is involved, new combinations of existing genes operating within highly selected germplasm are not expected to generate harmful outcomes. In other words, while the new variety will not be identical to existing germplasm (otherwise no improvement would have occurred), it does meet the expectations for the crop in question, and offers some enhancement of one or more traits.

HOW HAVE TRANSGENIC CROPS BEEN TREATED IN THIS CONTEXT?

When faced with the question of what testing should be required for new genotypes that result from genetic engineering of existing crop varieties, regulatory agencies in Canada and elsewhere have invoked a line of reasoning that tries to mirror the historical practice in conventional breeding. In the case of transgenic material, the assumptions implicit in the conventional breeding methodology have been made explicit by rolling them up in the term “substantial equivalence”. This concept was first described in a 1993 report from the Organisation for Economic Co-operation and Development (OECD), in which “substantial equivalence” was suggested as an operational mechanism to indicate that a GM organism was essentially similar to its traditional counterpart. The major conclusion of the OECD report was: “If a new food or food component is found to be substantially equivalent to an existing food or food component, it can be treated in the same manner with respect to safety”. Subsequently, the World Health Organization (1995) published a report in which the concept of “substantial equivalence” as a decision threshold was promoted as the basis for safety assessment decisions concerning GMOs.

HOW WELL HAS “SUBSTANTIAL EQUIVALENCE” BEEN ACCEPTED?

The adoption of “substantial equivalence” as a decision threshold has been criticized because of the ambiguity and lack of specificity of the term. The failure to define “substantial equivalence” clearly was emphasized by Millstone et al. (1999), who also stated that the “biotechnology companies wanted government regulators to help persuade consumers that their products were safe, yet they also wanted the regulatory hurdles to be set as low as possible”. Those using the concept as a screening tool immediately defended “substantial equivalence”, as shown by the subsequent correspondence to the journal Nature Biotechnology. For instance, Miller (1999) wrote that: “Substantial equivalence is not intended to be a scientific formulation; it is a conceptual tool for food producers and government regulators, and it neither specifies nor limits the kind or amount of testing needed for new foods”.

Reflecting this ongoing uncertainty, the Committee on Food Labelling (February 2000) of the Codex Alimentarius, created by the Food and Agriculture Organization and the World Health Organization, decided to remove the term “substantial equivalence” from its draft recommendations for food and food ingredients obtained through modern biotechnology. This commission had already made the decision to delete the word “substantial” in 1999, and in 2000, proposed to use such phrases as “no longer equivalent” or “differs significantly” in the text of its recommendations. It was suggested that “if the nutritional value of a food or food ingredient is no longer equivalent to the corresponding food or food ingredient”, certain conditions would apply, such as informing the consumer of a changed nutrient content. However, this negative approach to “equivalence” appears to constitute a rejection of the concept of “substantial equivalence” altogether, rather than a redefinition of it. The Codex ad hoc task force on Foods Derived from Biotechnology acknowledged this in its report of March 2000: “While recognizing that the concept of substantial equivalence was being used in safety assessment, several delegations and observer organizations stressed the need for further review of the concept and its applicability to safety assessment”.

THE ROLE OF THE “SUBSTANTIAL EQUIVALENCE” CONCEPT IN THE CANADIAN REGULATORY PROCESS

In practice, the designation of a candidate GM crop variety as “substantially equivalent” to other, non-GM, varieties essentially pre-empts any requirement in Canada to assess further the new variety for unanticipated characteristics. Thus, the Decision Documents issued by CFIA in approving new GM canola crops for commercial release state: “Unconfined release into the environment, including feed use... but without the introduction of any other novel trait, is ... considered safe”. Both in Canada and elsewhere, therefore, “substantial equivalence” is currently employed as an explicit rule stating the conditions under which it can be assumed that a new crop poses no more risks than a counterpart that is already considered safe. It represents one of the early criteria to be met in the regulatory decision trees (see Chapter 3). If a plant or food is judged to be substantially equivalent to one present in the Canadian diet, passage of this step in the decision tree spells success for its approval. Conceptual and practical implementation of “substantial equivalence” is thus the most critical element in the current approval process.

“NOVELTY” VERSUS “EQUIVALENCE”

The “substantial equivalence” concept is clearly rooted in the existing paradigm for new crop development through traditional methodologies. A breeder who has genetically manipulated a crop through crossing/selection takes it as a given that, despite the numerous small changes introduced into the genome of the new genotype, the species as an entity remains largely unmodified. The new variety is thus assumed to be “substantially equivalent” to other varieties of the same crop. It is worth emphasizing that this assumption applies even if “novel trait” genes have been introduced into the breeding lines at some point, through use of wide crosses or mutation.

On the face of it, however, there would appear to be an intrinsic contradiction between the presence of “novelty” in a new plant genotype and a designation of “equivalence”. This tension is reflected in the Seeds Regulations (under the administration of CFIA) which state that a “novel trait” introduced into cultivated seed “….[is one that] is not substantially equivalent, in terms of its specific use and safety for both the environment and for human health, to any characteristic of a distinct, stable population of cultivated seed of the same species in Canada, having regard to weediness potential, gene flow, plant pest potential, impact on non-target organisms and impact on biodiversity.” Also, in the Feeds Regulations, a novel trait introduced into an animal feed is similarly described as making the feed no longer substantially equivalent to similar feed without that trait. It is clear that this treatment of novel traits recognizes their potential to create a human or environmental health hazard, and that a designation of “substantial equivalence” would only be justified if and when a novel trait can be demonstrated to have no safety implications “…for both the environment and human health…”.

This framing of “substantial equivalence” links it intimately with the definition of “novel trait” in a way that leads to a logical impasse. If a “novel trait” can be demonstrated to have no safety implications “…for both the environment and human health…”, the above description implies that the genotypes being compared must be “substantially equivalent” and that there is, in fact, no “novel trait” at issue. Conversely, if two genotypes are deemed to be “substantially equivalent” then no “novel trait”, as defined above, can be present. The current language is thus unhelpful when it comes to describing the outcomes of transgenic variety evaluation.

This logical confusion is part of a larger ambiguity in the use of “substantial equivalence” in the regulatory world. The ambiguity can be seen in the original OECD formulation of the concept: “If a new food or food component is found to be substantially equivalent to an existing food or food component, it can be treated in the same manner with respect to safety”. This can be interpreted in very different ways.

In one interpretation, to say that the new food is “substantially equivalent” is to say that “on its face” it is equivalent (i.e. it looks like a duck and it quacks like a duck, therefore we assume that it must be a duck — or at least we will treat it as a duck). Because “on its face” the new food appears equivalent, there is no need to subject it to a full risk assessment to confirm our assumption. This interpretation of “substantial equivalence” is directly analogous to the reasoning used in approval of varieties derived through conventional breeding. In both cases, “substantial equivalence” does not function as a scientific basis for the application of a safety standard, but rather as a decision procedure for facilitating the passage of new products, GM and non-GM, through the regulatory process.

However, the OECD maxim cited above can be interpreted in quite a different manner, with the consequence that the need to establish scientifically that the new food is identical in its health and environmental impacts to its conventional counterpart is not so readily circumvented. This interpretation requires a scientific finding that the new food does not differ from its existing counterpart in any way other than the presence of the single new gene and its predicted phenotypic change. In every other way, phenotypically and in terms of its impacts on health and the environment, it will have been demonstrated to be identical to the existing food. Once this finding is made, the food can then be considered (i.e. “treated as”) safe, in as much as the existing food is already considered safe, with the caveat that the phenotypic expression of the added novel gene(s) must also be demonstrated to have no negative health or safety impacts. In this interpretation, the concept of “substantial equivalence” functions as a scientific finding or conclusion that in turn becomes the justification for an assumption of safety. In effect, “substantial equivalence” is invoked as a standard of safety.

“Substantial equivalence” is commonly used by government regulatory agencies under the first interpretation, although public statements defending the use of the concept often play upon its inherent ambiguity by suggesting the second interpretation. The CFIA Schematic Representation of the Safety Based Model for Regulation of Plants (Chapter 3) demonstrates how initial findings of “familiarity” and “substantial equivalence” are used to exempt new plants from the third step, which is the full environmental safety assessment. Step 2.1 in the schematic requires that scientific data and rationale support any conclusions that the new plant “will not result in altered environmental interaction compared to its counterpart(s)”. The question that concerns the Expert Panel is whether in actual practice these conclusions are based upon a full analysis of the new organism in question, or whether they are based upon unsubstantiated assumptions about the equivalence of the organisms, by analogy with conventional breeding. We have concluded that the latter is a consistent reading of the schematic, and is what often occurs in practice.

In summary, the Panel has identified two different uses of the concept of “substantial equivalence”:

1. A GM organism is “substantially equivalent” if, on the basis of reasoning analogous to that used in the assessment of varieties derived through conventional breeding, it is assumed that no changes have been introduced into the organism other than those directly attributable to the novel gene. If the latter are demonstrated to be harmless, the GM organism is predicted to have no greater adverse impacts upon health or environment than its traditional counterpart. We refer to this interpretation as the decision threshold interpretation.

2. A GM organism is “substantially equivalent” if rigorous scientific analysis establishes that, despite all changes introduced into the organism as a result of the introduction of novel genes, the organism poses no more risk to health or to the environment than does its conventional counterpart. We refer to this interpretation as the safety standard interpretation.

The Expert Panel accepts the validity of the concept when used in the “safety standard” interpretation. We have grave reservations about its validity when employed in the “decision threshold” interpretation.

In the Panel’s view, the use of “substantial equivalence” as a decision tool within the regulatory process would appear to demand a careful assessment of safety impacts associated with any “novel trait” being considered for deployment in a new transgenic variety. If the presence of the novel trait can be rigorously demonstrated to be harmless (or the harm does not surpass a certain agreed-upon threshold) in the tested genetic/environmental context, the new genotype can be considered to be as safe as the original variety from which it was derived during the genetic engineering process. The question then becomes one of defining “rigorous demonstration” and its implementation.

HOW DO THE PRODUCTS OF GENETIC ENGINEERING DIFFER FROM THE CONVENTIONALLY DERIVED PRODUCTS?

The current generation of GM crops differs in its genetic origins from crop varieties created through conventional breeding. Unlike the mixture of parental genes represented in a conventionally derived variety, a first-generation GM crop is distinguished from its parental variety by the incorporation into that original parental genome of a novel single gene trait. In the GM crops presently in production, these traits are controlled by gene sequences derived almost exclusively from non-plant sources (i.e. bacterial, viral or insect DNA). It has been pointed out that the resulting phenotypes may be functionally similar to naturally occurring examples of analogous genetic traits, such as herbicide, insect or virus disease tolerance. Nevertheless, there is little serious debate about the fact that the presence of any of these transgene DNA sequences in a GM crop variety represents an example of incorporation of a “novel trait”.

The fact that the “novel trait” is being controlled by a tract of DNA that makes up only an extremely small part of the plant genome, and that its introduction into the plant genome was not accompanied by transfer of large numbers of other genes (or, more accurately, other alleles) physically associated on the same chromosome, as would happen in conventional breeding, has led to genetic engineering for novel traits being characterized as “more precise”.

WHAT ARE THE ANTICIPATED CONSEQUENCES OF “PRECISE” SINGLE GENE MODIFICATIONS?

In the very simplest model, the term “precise” implies that the only changes resulting from such a genetic modification should be:

• presence at a defined site within the genome of one small novel stretch of DNA;
• expression of one new mRNA encoded by the inserted gene;
• expression of a new protein translated from the new mRNA, when the transgene encodes a protein;
• appearance of a new catalytic activity displayed by that protein (if the protein is an enzyme); and
• changes in the pools of relevant metabolic substrates/products affected by that catalysis in the transgenic tissues.

In other words, this linear sequence of outcomes would be predicted to occur without significantly perturbing the remaining transcriptional, translational and metabolic activities in the plant. The genotype and phenotype of the genetically engineered variety will thus differ from that of the original variety from which it was derived solely in terms of the “novel trait” represented by the transgene and its products. In all other respects, the transgenic variety will be identical to that parental variety. If this simple linear model is valid, the evaluation of the transgenic variety need only focus upon the predicted phenotypic characteristics conferred by the transgene, and their potential to cause harm. If that narrowly focused evaluation finds no grounds for concern, the transgenic variety can be considered “equivalent” to existing varieties because the genetic background within which the transgene is operating is identical to that of one of those existing varieties.

IS THIS SIMPLE LINEAR MODEL VALID?

As outlined above, the primary assumption operating within this simple linear model is that the action of one gene and its products will have no significant effects on other genes, gene products or metabolic functions in the tissues within which it is expressed. However, empirical evidence suggests that linear models are not good predictors of complex biological systems, which involve extensive interactions between cellular components at all levels. While our understanding of the intricacies of genetic interaction networks is still only poorly developed, it is clear that living cells are exquisitely tuned to both their internal and external environments. Perturbations in either will typically induce a spectrum of changes in gene expression, protein synthesis and metabolic patterns, all designed to enhance the organism’s ability to survive and thrive. Mutations in single genes have long been known usually to produce multiple effects (pleiotropic effects) within the mutated organism. Even when visual assessment detects no differences between mutant and wild-type forms, more detailed chemical analysis may reveal marked alterations in metabolism (Flehn et al., 2000).

The default prediction for the impacts of expression of a new gene (and its products) within a transgenic organism would therefore more logically be that this expression will be accompanied by a range of collateral changes in expression of other genes, changes in the pattern of proteins produced and/or changes in metabolic activities (Chavadev et al., 1994; Fischer et al., 1997; Burton et al., 2000; Eriksson et al., 2000; Flehn et al., 2000; Roessner et al., 2000). This is graphically demonstrated in the range of phenotypes displayed by transgenic salmon carrying a transgene encoding human growth hormone (see Chapters 5 and 6) or aspen trees expressing a transgene encoding a plant hormone modifier (Eriksson et al., 2000). It is, in fact, an accepted part of the process of genetic engineering of plants to screen for unusual phenotypes within the primary populations of transgenic crops generated in the laboratory (Matzke and Matzke, 2000). These will usually be discarded and only those lines displaying apparently normal phenotypes will be carried through for further analysis and/or breeding.

A related prediction, based on our appreciation of the complexity of biological systems, is that the nature of any such transgene-related changes is likely to be conditioned by:

• the genetic background within which the new gene is being expressed;
• the developmental and physiological status of the transgenic organism; and
• the environmental pressures impinging upon it.

In other words, an altered phenotype may only appear at a particular growth stage, or in response to specific environmental conditions.

It is important to recognise, however, that most, if not all, of these induced changes may be quite minor. In addition, biological systems are remarkably robust and flexible. The induced changes may therefore be readily accommodated within the normal dynamic range of cellular activities without apparently affecting the phenotype (Flehn et al., 2000). Nevertheless, the conclusions relevant to this discussion are that:

• unanticipated changes can be induced by expression of a novel gene; and
• their phenotypic consequences need to be assessed empirically across time and environments.

If unanticipated changes are likely to have been induced by transgene insertion, how might these be tracked, and how could their significance be assessed, in the context of a regulatory approval process?

ASSESSING THE SIGNIFICANCE OF DIFFERENCES

The obvious approach to analysis of the consequences of the presence of the transgene is to employ direct testing for harmful outcomes. In the case of food or feed products, this would mean testing for short-term and long-term human toxicity, allergenicity or other health effects (see Chapter 4). The environmental impacts of both local and landscape-scale deployment of the transgenic organism would also be assessed, over time and across relevant sites (see Chapter 6). At the end of this comparative analysis, an assessment must be made of the extent to which the transgenic variety deviates from the parental genotype, and whether any observed deviations are biologically significant. The absence of significant deviations would remove any regulatory barrier to variety approval (i.e. the transgenic variety would qualify as “substantially equivalent”).

This approach has the obvious merit of directly addressing the potential for harm, which is the primary motivation for the regulatory process, and from that perspective it must remain the cornerstone of the approval process. To some extent, it represents the model followed within the current Canadian regulatory system. However, this empirical approach presents some serious challenges.

First, the integrity of the final assessment is obviously dependent on the depth and rigour of the testing regimes implemented. Inadequate, inappropriate or improperly conducted tests inevitably compromise the validity of the conclusions, while the determination of any “significant deviation” needs to be based on sound science, appropriate statistical analysis, and reliable baseline data, a resource which is not always available for a given trait, species and/or ecosystem. Concerns of this nature have been voiced about the current Canadian regulatory process (Barrett, 1999), and the lack of transparency in that process makes it difficult to establish how valid such concerns might be. Recommendations for the design and execution of suitable testing regimes, and the need for appropriately focused research programs, have been presented in other chapters of this Report, while the necessity for greater transparency has been discussed in Chapter 9.

BUILDING BETTER EVALUATION CAPACITY

While empirical screening directly addresses the immediate needs of the regulatory system, by itself it creates little opportunity for improving our understanding of the ways in which transgenes affect phenotype. Unless we learn more about the ways in which a transgene has modified the inner workings of the transgenic organism, it is difficult to develop any predictive capacity that would allow informed judgments about the likely performance of similar transgenes in other genetic or environmental contexts. In the absence of improved knowledge, testing of future novel genotypes must inevitably remain a largely empirical process, with all the associated complexity and costs.

It would therefore be highly desirable to integrate empirical screening with detailed analysis of the molecular and cellular status of the transgenic organism. These analyses should draw upon the “full system” molecular tools now being developed for our major crop species. The first complete plant genome DNA sequence (Arabidopsis) is now available, and the first cereal genome sequencing project (rice) is also in its final stages. These resources are largely the result of major international public research efforts whose output is freely available. However, agbiotech companies have also invested heavily in this area, creating large proprietary genomic databases for crops that are of specific interest to them (e.g. maize, potato, wheat).

While these public and commercial resources are still incomplete, they point to a not-toodistant future when a detailed knowledge of the genome and proteome of each of our major food crops will be available as a routine research tool. With these tools in hand, it should be possible to define accurately the structural and functional differences between any two genotypes within a crop species at four levels.

Level One - DNA Structure

In the case of a transgenic versus non-transgenic comparison, it should be feasible to establish unequivocally the location, size and nature of any insertion of a novel gene and to verify whether any additional changes (e.g. somaclonal variation) have been induced at the DNA level during the process of developing the transgenic genotype.

Of particular interest in this regard would be evidence that the transgene insertion has disrupted either a gene coding region, or associated regulatory regions. Examination of the phenotypic consequences of such insertion events would be part of the overall assessment of the transgenic genotype, and these data would also provide useful insights into biological function of discrete regions of the crop genome. It is noteworthy that a more detailed examination of the DNA sequence structure in Roundup Ready soybean varieties that had been developed by Monsanto almost a decade ago recently revealed the presence of short, extra stretches of transgenic DNA. These unanticipated insertions had not been detected in the original evaluation and approval process, and their impact, if any, on the transgenic phenotype is uncertain (Palewitz, 2000).

Level Two - Gene Expression

Knowledge of the exact structure of the transgenic organism’s genome provides a concrete measure of the difference between the transgenic genotype and the parental variety from which it was derived. However, this knowledge does not, in itself, enable a prediction of phenotypic differences. Those differences will become manifest at the “downstream” levels of gene function, beginning with the expression of transcripts.

Thousands of genes are being expressed in a plant in an orchestrated manner at any given time. The rate and timing of transcript expression from any given gene in any particular cell represents an integrated response to many factors, internal and external, that impinge on that cell. The pattern of expression of all transcripts is thus an exquisitely sensitive monitor of cell and tissue status. In species where the effort has been made to assemble a complete set of the potential transcripts from the genome, it is possible to physically array DNA derivatives of these transcripts on high-density microarrays. The arrays can then be interrogated by hybridization with mRNA preparations derived from the plant tissues to be compared, and the identity and relative abundance of each transcript in each preparation assessed (Schenk et al., 2000; Wang et al., 2000). Carefully controlled DNA microarray analysis has the potential to reveal significant shifts in the overall pattern of gene expression associated with transgene insertion. For genomes that have been fully sequenced, other technologies can also provide a quantitative read-out of gene expression patterns (Velculescu et al., 1995).

The simple linear model discussed earlier predicts that only one new transcript will be detected in the transgenic line. However, should more extensive changes in transcript profiles be detected, microarray analysis immediately provides crucial information on the identity of the specific genes whose output is being affected. Knowledge of the biological role of those genes will allow a first estimate of the area(s) of metabolism or development in which a phenotypic change might be anticipated, and would thus help to focus the evaluation of the transgenic material on the most relevant issues. More sophisticated transcript profiling might explore differences on a tissue or organ basis, make comparative measurements over developmental time, and examine the interaction with different environments, all of which would improve the resolution and value of the resulting information (Aharoni et al., 2000).

Level Three - Protein Profiling

While the usual processing of genetic information predicts that a functional transcript will be translated to yield the corresponding protein, this correlation is neither perfect nor quantitative. Therefore, not all changes in gene transcript level in a particular cell will necessarily be reflected in predictable changes in the constellation of proteins synthesized and accumulated in that cell. Given that uncertainty, it would be desirable to determine whether transgene insertion has created any significant changes in the protein complement of the transgenic line, particularly since the great majority of food allergens are protein-based.

A comparative “proteomic” analysis of different plant tissues is a technically far more challenging exercise than transcript profiling. The methodologies available until recently have been limited in their throughput, reliability and sensitivity. However, new mass spectrometry-based techniques show promise of being able to distinguish differences between very small samples of complex protein mixtures (Oda et al., 1999; Gygi et al., 1999). As these techniques are further refined, we can anticipate being able to create detailed and quantitative protein “fingerprints” for the same range of tissue samples that would be examined for transcript differences (Natera et al., 2000). Any novel proteins can be identified by mass spectrometry sequencing combined with database searches. Most importantly, perhaps, recombinant versions of such proteins can then be produced in substantial quantities as pure proteins, which would allow thorough testing for their potential allergenicity or anti-nutritive activity in humans and animals.

Level Four - Metabolic Profiling

Changes in transcript profiles and protein accumulation in a tissue will often be reflected in altered metabolite profiles. Of particular concern in plants is the potential for induced alterations in their secondary metabolite patterns. Most plant-derived toxicity problems are associated with accumulation in the plant tissues of unusual species-specific metabolites. These “secondary” metabolites represent an extraordinarily rich chemical arsenal that enables plants to survive as immobile organisms in a challenging environment. Since many of these chemicals render plants unpalatable or even toxic, it is not surprising that one of the outcomes of crop breeding over the centuries has been to suppress much of the original secondary metabolic output. However, secondary metabolism is highly plastic, and changes in enzyme levels and/or input metabolite availability can have a marked effect on the final metabolite profile (Bate et al., 1994). It would therefore be important to establish that transgene insertion has not significantly altered the secondary metabolite profile of the food tissues, or that, if such changes have occurred, these are not associated with increased risks to human, animal or environmental health (Firn and Jones, 1999). The basic technology for such an analysis is already available in the form of various chromatographic methodologies (HPLC and GC operating with a range of detector modes) (Roessner et al., 2000; Flehn et al., 2000). This would complement the standard “proximate analysis” which is used to assess the content of major nutrients in new foodstuffs.

CAN “SUBSTANTIAL EQUIVALENCE” BECOME SCIENTIFICALLY RIGOROUS?

The integrated approach suggested above would see newly developed transgenic genotypes subjected to intense scrutiny at six relevant levels (genome, transcript, protein, metabolite, health impacts, environmental impacts) before they were approved for commercial production. The answers obtained from the molecular analyses, in particular (Levels 1 to 4 above), would speak directly to the validity of the simple linear model of “precise” genetic engineering. If these analyses are conducted on a range of existing transgenic varieties and the predictions of the simple linear model prove to be valid, that outcome would provide essential scientific support for the current regulatory view that the insertion of the transgene(s) has created no significant changes in the original variety, other than those predicted and desired. If, on the other hand, the molecular analyses demonstrate that the simple model is not valid, the data would provide immediate entry points for studying the impacts of the detected changes on human health and the environment. The outcome of those follow-up studies will then help determine whether the impacts create a significant risk.

The integrated approach would also enable the development of a better understanding of how genomes and their variants control phenotypes at many different levels. By carefully examining the environmental performance of transgenic organisms and correlating this with the activity and responses of the modified genome, a much more sophisticated understanding of the genotype/phenotype/safety linkage will be developed for each of our major food crop species. This cumulative experience will eventually allow more accurate predictions of trait expression, ecological fitness and potential risk, and thereby support reliable, a priori assessments of “substantial equivalence” with reduced levels of empirical testing. In the Panel’s view, the goal should be to move away from an assumption of “precise” genetic engineering to a knowledge-based precise analysis of the resulting transgenic organisms.

Implementation of such an integrated evaluation process would initially increase the cost of GM variety approvals. The new “full systems” technologies are expensive (although these costs are expected to decline as capacity increases), and appropriate tools and robust protocols need to be developed, refined and implemented for each major Canadian crop. Baseline ecological studies across our major crop production areas and adjoining unmanaged ecosystems also need to be undertaken. However, these development costs should be regarded as a necessary long-term investment, both in the future of the major Canadian crop systems and in the genetic technologies capable of adding value to them. The Panel notes that the recent federal funding provided to create a national genomics initiative in Canada (Genome Canada) is a positive step in this direction.

RECOMMENDATIONS

7.1 Approval of new transgenic organisms for environmental release, and for use as food or feed, should be based on rigorous scientific assessment of their potential for causing harm to the environment or to human health. Such testing should replace the current regulatory reliance on “substantial equivalence” as a decision threshold.

7.2 Design and execution of the testing regimes should be conducted in open consultation with the expert scientific community.

7.3 Analysis of the outcomes of these tests should be monitored by an appropriately configured panel of “arms-length” experts from all sectors, who report their decisions and rationale in a public forum.

7.4 Canada should develop and maintain comprehensive public baseline data resources that address the biology of both its major agroecosystems and adjacent biosystems.

7.5 Canada should develop state-of-the-art genomics resources for each of its major crops, farm animals and aquacultured fish, and use these to implement effective methodologies for supporting regulatory decision making.

REFERENCES

Aharoni, A., L.C.P. Keizer, H.J. Bouwmeester, Z. Sun, M. Alvarez-Huerta, H.A. Verhoeven, J. Blaas, A.M.M.L. van Houwelingen, R.C.H. De Vos, H. van der Voet, R.C. Jansen, M. Guis, J. Mol, R.W. Davis, M. Schena, A.J. van Tunene, A.P. O’Connell. 2000. Identification of the SAAT gene involved in strawberry flavor biogenesis by use of DNA microarrays. The Plant Cell 12: 647–61.

Barrett, K.J. 1999. Canadian Agricultural Biotechnology: Risk Assessment and the Precautionary Principle. Ph.D. Thesis. Vancouver: University of British Columbia.

Bate, N.J., J. Orr, W. Ni, A. Meromi, T. Nadler-Hassar, P.W. Doerner, R.A. Dixon, C.J. Lamb, Y. Elkind. 1994. Quantitative relationship between phenylalanine ammonia-lyase levels and phenylpropanoid accumulation in transgenic tobacco identifies a rate-determining step in natural product synthesis. Proc. Natl. Acad. Sci. USA 91: 7608–12.

Burton, R.A., D.M. Gibeaut, A. Bacic, K. Findlay, K. Roberts, A. Hamilton, D.C. Baulcombe, G.B. Fincher. 2000. Virus-induced silencing of a plant cellulose synthase gene. The Plant Cell 12: 691–705.

Chavadev, S., N. Brisson, J.N. McNeil, V. DeLuca. 1994. Redirection of tryptophan leads to production of low indole glucosinolate canola. Proc. Natl. Acad. Sci. USA 91: 2166–70.

Eriksson, M.E., M. Israelsson, O. Olsson, T. Moritz. 2000. Increased gibberellin biosynthesis in transgenic trees promotes growth, biomass production and xylem fiber length. Nat. Biotechnol. 18: 784–88.

Firn R.D., C.G. Jones. 1999. Secondary metabolism and the risks of GMOs. Nature 400: 13–14. Flehn, O., J. Kopka, P. Doermann, T. Altmann, R.N. Trethewey, L. Willmitzer. 2000. Metabolite profiling for plant functional genomics. Nat. Biotechnol. 18: 1157–62.

Fischer, R., I. Budde, R. Hain. 1997. Stilbene synthase gene expression causes changes in flower colour and male sterility in tobacco. The Plant J. 11: 489–98.

Gygi, S.P., B. Rist, S.A. Gerber, F. Turecek, M.H. Gelb, R. Aebersold. 1999. Quantitative analysis of protein mixtures using isotope coded affinity tags. Nat. Biotechnol. 17: 994–99.

Hellenas, K.E., C. Branzell, H. Johnsson, P. Slanina. 1995. High levels of glycoalkaloids in the established Swedish potato variety “Magnum Bonum”. J. Sci. Food Agric. 23: 520–23.

Matzke, M.A., A.J.M. Matzke. 2000. Cloning problems don’t surprise plant biologists. Science 288: 2318.

Miller, H.I. 1999. Substantial equivalence: its uses and abuses. Nat. Biotechnol. 17: 1042–43.

Millstone, E., E. Brunner, E., S. Mayer. 1999. Beyond “substantial equivalence”. Nature 401: 525–26.

Natera, S.H.A., N. Guerreiro, M.A. Djordjevic. 2000. Proteome analysis of differentially displayed proteins as a tool for the investigation of symbiosis. Mol. Plant Microbe Interactions 13: 995–1009.

Oda, Y., K. Huang, F.R. Cross, D. Cowburn, B.T. Chait. 1999. Accurate quantitation of protein expression and site-specific phosphorylation. Proc. Natl. Acad. Sci. USA 96: 6591–96.

Palewitz, B.A. 2000. Monsanto discovers extra sequences in its Roundup Ready soybeans. The Scientist 14: 20–21.

Roessner, U., C. Wagner, J. Kopka, R.N. Trethewey, L. Willmitzer. 2000. Simultaneous analysis of metabolites in potato tubers by gas chromatography-mass spectrometry. The Plant J. 23: 131–42.

Schenk, P.M., K. Kazan, I. Wilson, J.P. Anderson, T. Richmond, S.C. Somerville, J.M. Manners. 2000. Coordinated plant defence responses in Arabidopsis revealed by microarray analysis. Proc. Natl. Acad. Sci. USA 97: 11655–60.

Velculescu, V.E., L. Zhang, B. Vogelstein, K.W. Kinzler. 1995. Serial analysis of gene expression. Science 270: 484–86.

Wang, R., K. Guegler, S.T. LaBrie, N.M. Crawford. 2000. Genomic analysis of a nutrient response in Arabidopsis reveals diverse expression patterns and novel metabolic and potential regulatory genes induced by nitrate. The Plant Cell 12: 1491–1509.

Zitnak, A., G.R. Johnston. 1970. Glycoalkaloid content of B5141-6 potatoes. Am. Potato J. 47: 256–60.

[admin]

8. THE PRECAUTIONARY PRINCIPLE AND THE REGULATION OF FOOD BIOTECHNOLOGY

INTRODUCTION

The Precautionary Principle has become a widely invoked doctrine within the field of risk regulation around the world. Though widely invoked, it is equally widely disputed and interpreted (Anon, 2000). Its roots are in the environmental movements of the 1970s, where it arose as part of a growing scepticism about the ability of scientific risk assessment and management models to predict accurately the adverse consequences of complex technologies (McIntyre and Mosedale, 1997). In essence, the principle advises that, in the face of scientific uncertainty or lack of knowledge, it is better to err on the side of protecting human and environmental safety than to err on the side of the risks (i.e. “Better safe than sorry.”) (Barrett, 1999).

The Precautionary Principle has been the focus of much of the debate associated with biotechnology, as with other technological developments. Its proponents view it as a proactive and anticipatory approach to technology development essential to protecting human, animal and environmental health from potentially catastrophic harms that even the best science cannot always foresee (Gullett, 1997; Barrett, 1999). Its opponents view it as an unscientific attitude that seriously inhibits economic and technological development on the basis of unfounded fears (Miller and Conko, 2000). For example, it has been suggested that the recent adoption of the principle in the Cartagena Protocol on Biosafety (see below) has the potential to “lead to arbitrary unscientific rejection of some products” (Mahoney, 2000).

CURRENT STATUS

Since its introduction in European environmental policies in the late 1970s, the Precautionary Principle has emerged as one of the principal tenets of international environmental law (Shipworth and Kenley, 1999). Today, the principle is contained in over 20 international laws, treaties, protocols and declarations (Barrett, 1999), including the Protection of the North Sea (1984), the Montreal Protocol (1997), The Bangkok Declaration on Environmentally Sound and Sustainable Development in Asia (1990), The Climate Change Convention (1992), the Rio Declaration (1992), The European Union’s Maastricht Treaty (1994), and The Fish Stocks Agreement (1995, signed by over 100 countries) (McIntyre and Mosedale, 1997; Barrett, 1999). It has also been considered by the International Court of Justice (e.g. the case of New Zealand challenging France on nuclear tests, Hungary’s challenge to the Czech Republic regarding the Danube Dams Project, and in Ireland’s case against the UK regarding the risk of radioactive material entering the marine environment [the “NIREX” case]) (McIntyre and Mosedale, 1997). While the principle is not widely accepted in US law, American courts have upheld government regulatory decisions which are “precautionary like” (Cellular Telephone Co. v. Town of Oyster Bay, 166 F.3d 490, 494 (2d Cir. 1999) (Foster et al., 2000).

The Precautionary Principle has also been enshrined in international agreements affecting the regulation of plant and animal biotechnology in trade. For example, the principle is included in the Cartagena Protocol on Biosafety (agreed to in Montreal, January 2000). The treaty allows countries to use the Precautionary Principle to refuse import of GE food products. Article 11.8 states:

“Lack of scientific certainty due to insufficient relevant scientific information and knowledge regarding the extent of the potential adverse effects of a living modified organism on the conservation and sustainable use of biological diversity in the Party of import, taking also into account risks to human health, shall not prevent that Party from taking a decision, as appropriate, with regard to the import of that living modified organism intended for direct use as food or feed, or for processing, in order to avoid or minimize such potential adverse effects.”

However, because the treaty later states that a rejection must be based on “credible scientific evidence,” the exact impact of the treaty remains unclear (Helmuth, 2000). This proviso reflects a central unresolved issue in national and international invocations of the principle — namely, the issue of what level of scientific evidence of potential harm is required to trigger the application of precaution.

The 1992 United Nations Conference on Environment and Development (The Rio Declaration) adopted language similar to the Cartagena Protocol. Principle 15 states that “Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation.” The Rio and Cartagena formulations are widely cited as definitive statements of the Precautionary Principle by both supporters and critics.

CONTROVERSIES SURROUNDING THE PRECAUTIONARY PRINCIPLE

As noted above, the Precautionary Principle has been the subject of much debate. Despite a substantial amount of political support throughout the world, the principle has attracted much criticism. Some of the more commonly heard criticisms of the principle include the following:

1. The Precautionary Principle lacks a uniform interpretation (Barrett, 1999). One study found 14 different interpretations of the principle (Foster et al., 2000). Some treaties, such as that of the European Union, refer to the Principle but do not actually define it. Other international instruments, such as the Cartagena Protocol, adopt it in an ambiguous manner.

2. The Precautionary Principle marginalizes the role of scientists and can be applied in an arbitrary fashion (Chapman et al., 1998; Mahoney, 2000). This criticism is based upon the concern that the invocation of the principle usually involves the relaxation of the standards of proof normally required by the scientific community. In the face of evidence less rigorous than that required for “science-based” conclusions, decision making then invokes other, extra-scientific considerations.

3. The Precautionary Principle is used as a veiled form of trade protectionism. For example, it has been claimed that the “precautionary” decision by the European markets to ban American and Canadian beef (treated with growth hormone) had an element of protectionism (Adler, 2000; Foster et al., 2000). The essence of this criticism is that the principle is used to circumvent the fundamental rules established by trade agreements enforced by the World Trade Organization, which generally require a showing by an importing country of reliable scientific evidence that an exported product poses levels of risk not accepted in domestic products (e.g. the Sanitary and Phytosanitary Agreement adopted in the Uruguay Round of GATT). The Precautionary Principle, it is argued, inherently undermines the force of this requirement by taking the burden of scientific proof off the importing country and/or relaxing the rigour of the scientific evidence required to allege unacceptable risk. As alleged in Criticism 2, above, extra-scientific considerations then enter into a decision that should be “science-based”.

4. The use of the Precautionary Principle is a form of over-regulation that will lead to a loss of potential benefits. For example, a strong biosafety protocol that limits the use of GE crops worldwide may retard advances in agricultural productivity, which could lead to global food shortages (Adler, 2000).

The persuasiveness of the latter three criticisms are clearly all related to the problem alluded to in the first one — the lack of uniform interpretation of the Precautionary Principle. The various interpretations of the principle cited in criticism (1), above, range over a wide spectrum, involving disagreement at several levels. These include disagreements over: 1) who should bear the burden of proof — those who allege potential harm, or those who deny it, 2) what the standard of proof should be for the party who bears the burden, and 3) to what extent the costs of precautionary restraint should be taken into account.

The most stringent (maximally precautionary) interpretations of the principle place the burden of proof upon the promoters of new technologies to prove its safety (no unacceptable risk), and require a high standard of proof that such risks are not involved. They counsel restraint, even if the social or economic costs of restraint are high. Proving “no-risk” in this sense is generally considered a difficult, if not impossible, scientific task.

The most permissive (minimally precautionary) interpretations of the principle, on the other hand, place most of the burden of proof upon those who allege potential risks, while perhaps relaxing the standards of proof (this is the only “precautionary” aspect), but they insist that the social and economic costs of exercising restraint be balanced against the potential risks. They “open the door to cost-benefit analysis and discretionary judgement” (Foster et al., 2000). The formulations of the Precautionary Principle in the Rio Declaration and the Cartagena Biosafety Protocol are both examples of this kind of cost-effectiveness approach.

In between these two extremes, are formulations of the principle that do not require proof of safety, but rather counsel restraint when levels of scientific uncertainty about potential risks remain high, with the burden of proof being assigned to those who develop or stand to benefit from the technology. These more moderate formulations, however, share with the more stringent formulations, the suspicion of permitting the prospect of significant benefits to override precautionary concern about the potential risks.

INTERPRETING THE PRINCIPLE

Although there is a wide diversity in the interpretation of the Precautionary Principle, it is possible to state its fundamental tenets, and to identify the points of debate within each of these tenets.

Recognition of Scientific Uncertainty and Fallibility

As noted above, the Precautionary Principle has its roots in a sense of scepticism about the ability of science, or any system of knowledge, to understand and predict fully the function of complex biological and ecological systems. The principle is essentially a rule about how to manage risks when one does not have fully reliable knowledge about the identity, character or magnitude of those risks. It assumes that there is often the possibility of error in the assessment of risks, and the higher the potential for this error, the greater the precaution it prescribes in proceeding with actions that place certain values at risk.

Uncertainty is an endemic and unavoidable aspect of any regulatory science, especially risk assessment science (Salter, 1988; Brunk et al., 1992). There are different kinds of uncertainty (Barrett, 1999) and many reasons for them. They include, among other things, the incompleteness and fallibility of the scientific models that are used to predict events and relationships in complex systems (Funtowicz and Ravetz, 1994), the incompleteness and inconsistency of data obtainable within the constraints of time and resources that normally operate within a regulatory context, and the presence of unavoidable but controversial extra-scientific assumptions (Brunk et al., 1992). The laboratory scientist can, and must, take the time and effort to reduce these uncertainties before affirming or rejecting a scientific hypothesis. The regulatory scientist, however, often does not have the time or the resources to reduce this uncertainty.

The Precautionary Principle, however variously applied, is fundamentally a rule about how technology developers, regulators and users should handle these uncertainties when assessing and managing the associated risks. Having identified the potential for error in predicting all the outcomes, the rule identifies which of these outcomes it is most important to avoid (or protect) in the event that predictions turn out to be wrong. Is it best to have erroneously lost the potential benefits in order to avoid the potential harms, or to have erroneously suffered the harms in order to realize the benefits? The Precautionary rule tends to favour the former error.

One of the most commonly cited implications of the precautionary approach is the need to respect the distinction between “absence of evidence” and “evidence of absence” when assessing and managing technological risks. For example, the claim that “there are no known adverse health or environmental effects” associated with a particular technology can mean very different things. It can mean that rigorous and intensive scientific investigation of the potential harms that might be induced by the technology has failed to show any of those harms (and, in the best case, provided a reliable explanation why the harmful effects do not or will not occur). At the other extreme, this claim might mean simply that no studies to determine if the harmful effects occur have been carried out, in which case the claim is simply an admission of ignorance. In the first instance the claim would be “evidence of absence” (of risk); in the later instance it would be simply a veiled admission of the “absence of any evidence” relevant to the question. One simple expression of the Precautionary Principle is that it counsels restraint in proceeding with the deployment of a technology in the “absence of evidence”, and requires that the greater the potential risks, the stronger and more reliable be the “evidence of their absence”.

Presumption in Favour of Health and Environmental Values

The Precautionary Principle is a rule about handling uncertainty in the assessment and management of risk, and the rule recommends that the uncertainty be handled in favour of certain values — health and environmental safety — over others. Uncertainty in science produces the possibility of error in the prediction of risks and benefits. The Precautionary Principle makes the assumption that if our best predictions turn out to be in error it is better to err on the side of safety. That is to say, all other things being equal, it is better to have forgone important benefits of a technology by wrongly predicting risks of harm to health or the environment than to have experienced those serious harms by wrongly failing to predict them.

Understood in terms more familiar to scientists, the Precautionary Principle can be understood to require in general that, if an error in scientific prediction should occur, it is better that it erroneously predict an adverse effect where there is in fact none (false positive, or “Type I error”), than that it erroneously predict no such effect when in fact there is one (false negative, or “Type II error”) (Shrader-Frachette, 1991; Barrett, 1999). The standards of scientific research are often understood to require just the opposite value judgment — that it is far more grievous for a scientist to commit the Type I than the Type II error. The Type I error involves making a premature claim (rejection of the null hypothesis — e.g. that a GM food poses no significantly greater risk) without ample scientific evidence. Committing the Type II error merely reflects a scientifically perspicacious withholding of judgment in the face of incomplete evidence. This is what makes the Precautionary Principle appear “anti-scientific” (Criticism 2, above) to many scientists. It would appear to ask regulatory scientists to risk committing the unscientific error of affirming risks that turn out to be much lower or non-existent (rejecting the null hypothesis when it turns out to be true). [*]

The rules of evidence in courts of law reflect a preference with respect to uncertainty analogous to that of science. In modern democratic societies, criminal courts favour the Type II over the Type I error. It is considered far worse to convict erroneously an innocent person of a crime than to acquit erroneously a guilty person. “Better that 10 guilty persons go unpunished than that 1 innocent person be convicted” is the well-known legal axiom. In the face of legal uncertainty (“reasonable doubt” in law), the presumption should be in favour of the null hypothesis (“not guilty”).

Thus, the Precautionary Principle appears to violate the rules of presumption that govern both scientific research and criminal law. Its acceptance in the regulatory context involves the judgment that, when it comes to regulating technological risks, it is better to err on the side of wrongly assuming risk than of wrongly assuming safety. This is the basis of Criticism 4 (above) that the Precautionary Principle tends to restrict the development of new technologies, and thus to retard the enjoyment of the benefits they may promise. It prefers to avoid risks, even at the expense of lost benefits, than to take those risks in order to enjoy the benefits. This, indeed, is the central force of the tenet — that given the potential of at least certain kinds and magnitudes of harms, reasonable prudence would slow the development of technologies pending stronger assurances of their safety or the implementation of active measures to guarantee safety.

The Precautionary Principle, however, need establish only a presumption in favour of safety over the benefits of a technology. Only the most stringent interpretations of the principle would demand that avoidance of risk, no matter how slight, always take priority over the enjoyment of benefits, no matter how great. Most interpretations of the principle (Pearce, 1994; Barrett, 1999) build in some sort of “proportionality rule” (O’Riordin and Jordan, 1995), which takes into consideration the costs of exercising precaution. The greater the opportunity costs of precaution, the more significant the potential harms and the more demanding the standards of evidence for suspecting such harms. Most proponents of the Precautionary Principle hold that the presumption in favour of safety increases to the extent that the potential harm to health and environment have characteristics such as irreversibility, irremediability or catastrophic proportions. It decreases to the extent that the harms are reversible and less probable, and the costs of precaution become excessively high.

As stated earlier, the most permissive (least precautionary) interpretations of the principle hold that the costs of exercising precaution should always be balanced against the risks — that is, that a simple risk–cost–benefit analysis should determine the levels of precaution. Such an approach would in effect negate the central point of the principle, which is to create a presumption in favour of safety, since it would insist that risks and benefits be given equal weight. Even more importantly, a pure risk–cost–benefit approach is seen by many critics as anti-precautionary. This is because the usual methods by which it is carried out have a built-in bias in favour of technological benefits, which are immediate, highly predictable and quantifiable (otherwise, the technology would have no market), and against the risk factors, which are discounted because they tend to be long term, less certain and less easily quantified (Shrader-Frechette, 1991).

Proactive Versus Reactive Approaches to Health and Environmental Values

Another common feature of appeals to the Precautionary Principle is inherent in the concept of “precaution” itself. It involves a requirement that the measures one takes in the face of potential harms are proactive rather than reactive. It makes the assumption that, with respect to certain kinds of technological risks, it is better to design and deploy the technologies in ways that prevent or avoid the potential harms, or guarantees the management of these risks within limits of acceptability, than to move ahead with them on the assumption that unanticipated harms can be ameliorated with future revisions or technological “fixes”.

This proactive aspect of precaution entails certain norms for the development of technology, which include the responsibilities: a) to carry out the appropriate research necessary to identify potential unacceptable risks; b) to withhold deployment of technologies until levels of uncertainty respecting these risks are reduced, and reasonable confidence levels concerning acceptable levels of risk are achieved; and c) to design technologies in ways that minimize health and environmental risks.

Burden of Proof and Standards of Evidence

In most legal proceedings, the party that alleges harm or offence on the part of another must shoulder the burden of proof that such harm has occurred and that it has been caused by the accused. In the case of criminal allegations, the prosecution has the burden of proof, and the standard of proof it must meet is that the evidence must establish guilt “beyond all reasonable doubt”. In civil litigation, the plaintiff has the burden of proof, but the standard of proof the plaintiff must meet is usually less demanding — there must be merely a “balance of evidence” in support of the plaintiff’s allegations.

Technology proponents often argue that the legal regulation of risk should follow similar principles — a technology, too, should be considered safe until proven unsafe (Miller and Conko, 2000). If the proof of risk is to be science-based in the strongest sense, it would follow that the standards of evidence should be those of research science — normally defined in terms of a 95% confidence rule (probability of error is less than 5%). This standard of evidence is the analogue in science to the “beyond all reasonable doubt” standard of evidence in criminal law.

The Precautionary Principle challenges the assumption that the regulation of environmental and health risks should always follow the legal analogy by asking whether such an approach constitutes an irresponsible attitude toward these risks. It is reasonable to invoke the legal analogy in regulatory science only on the assumption that any and all significant risks of this type can be predicted with high confidence by scientific research, not only in theory, but in actual regulatory practice. And, of course, invoking the legal analogue in regulatory science creates a strong presumption in favour of technological benefits rather than health and environmental safety. To paraphrase the legal axiom, it implies that “it is better that 10 hazardous technologies be employed to the detriment of human and environmental health than that one safe technology be erroneously restricted”.

Consequently, the invocation of the Precautionary Principle nearly always involves an appeal either to shift at least some of the burden of proof (that the technology is safe) to those who propose the technology, or to relax in some way the standards of evidence required for the suspicion of unacceptable risk. Often it involves an appeal for both. Critics of the principle often argue that it puts the burden of proof upon promoters of a technology to prove (with low margins of error) its safety, which is simply unrealistic given the scientific impossibility of proving no risk (one can reject the null hypothesis, but not prove it using a standard statistical framework). There is no need to interpret the principle in such a manner, however. Proponents of the principle argue that it is equally unreasonable to place the burden of proof upon the claim of unacceptable risk, especially if the standard of proof is the normal high confidence rule required by research science. The uncertainties endemic in regulatory science are too great for this burden to be met. Such a requirement would imply that, in a case where the weight of evidence suggested the possibility of serious risk to human, animal or environmental health but confidence in the data was substantially less than the rigorous levels required for laboratory science, there would be insufficient basis for regulatory restriction of the technology.

The Precautionary Principle can be interpreted in a manner that avoids both these extremes. It can be understood to place at least a fair share of the burden of proof upon technology proponents to show that the technology will not cause unacceptable risks to health or the environment — with standards of evidence something less than the highest levels of confidence in the conclusion of “no harm”. Some proponents suggest that a better standard is the one analogous to that used in civil law — “balance of evidence”. A “balance of evidence” standard, in conjunction with a burden of proof to the promoter of a technology, would mean that the promoter (i.e. the applicant for registration) would have the burden of establishing that at least the weight of evidence does not support a prima facie case of serious risk. Such an approach is much more precautionary than giving the burden of higher standards of proof to the side that alleges serious risk. But, it can be argued that it still is too lenient, since it permits the approval of technologies where there is substantial, though not preponderant, evidence that unacceptable risk exists. A more precautionary approach would invoke the simple maxim that the more serious the magnitude and nature of the potential harm to health or environment, the less demanding should be the levels of confidence (the wider the margin for error) in the assumption of risk.

If there are scientific data (even though incomplete, contested, or preliminary) — plausible scientific hypotheses or models (even though contested) — together with significant levels of uncertainty, that establish a reasonable prima facie case for the possibility of serious harm (with respect to reversibility, remediation, spatial and temporal scale, complexity and connectivity), then precautionary action is justified (Barrett, 1999; Tickner, 1999). “Precaution”, as noted, does not mean paralysis; it means shifting the burden of narrowing the uncertainty range and removing the theoretical unknowns to those who wish to move forward with the technology.

Sometimes, a prima facie case of risk is established by preliminary evidence that is discounted by the scientific community. The British crisis over the link between BSE (“mad cow disease”) and the human nvCJD (new variant Creuzfeld-Jacob Disease) provides an instructive example of precisely this situation. The Report of the British BSE Inquiry (BSE Inquiry, 2000) documents the manner in which the scientists (The Southwood Working Party) advising the British Ministry of Agriculture, Fisheries and Food (MAFF) assessed the preliminary evidence that BSE posed a health risk to humans. The Southwood Report assessed the risk to humans as “remote”, but nevertheless made two recommendations it considered “precautionary” — that sick cows be taken out of the food chain and that bovine offal not be used in baby food. They did not recommend any further precautionary restriction on food use of subclinically infected animals (even though the long incubation period of BSE was well known). Because of the “remoteness” of the risk, such action was not considered “reasonably practical” (BSE Inquiry, 2000, Chapter 4). [1] The BSE Inquiry Report concluded that the scientific working group’s dismissal of the human health risks as “remote” was a significant factor in communicating to the government and to consumers that further precautionary measures were unnecessary. The Inquiry Report wondered why, if it was “reasonably practical” to be precautionary with respect to baby food, it is not also reasonable with respect to adult food, especially since the scientists had concluded their report with the caution that “if our assessment of these likelihoods are [sic] incorrect, the implications would be extremely serious.” Unfortunately, this caution was lost sight of by scientists and regulators, and was cited “as if it demonstrated as a matter of scientific certainty, rather than provisional opinion, that any risk to humans from BSE was remote” (BSE Inquiry, 2000).

What disturbed the BSE Inquiry most was the way the British MAFF responded to the preliminary assessment of the scientific work group. The Inquiry concluded that, rather than acting in an appropriately precautionary way, by taking steps to protect the British public against the potential “extremely serious” risks, the government became “preoccupied with preventing an alarmist over-reaction to BSE because it believed that the risk was remote.... The possibility of a risk to humans was not communicated to the public or to those whose job it was to implement and enforce the precautionary measures” (BSE Inquiry, 2000, Executive Summary). The implications of the BSE Inquiry Report are, therefore, clear: even when the available scientific evidence fails to establish a risk as anything other than “remote”, where there is a prima facie case of serious risk, significant (in this case highly costly) precautionary action is warranted.

Because the British government did not act early enough upon the growing evidence of human health risks, public confidence in both government and science was seriously eroded. As the Inquiry Report put it, “The public felt that they had been betrayed. Confidence in government pronouncements about risk was a further casualty of BSE” (BSE Inquiry, 2000, Executive Summary). The current moratorium on GM crops in the UK is widely seen as the only politically viable response to a public that has lost confidence in the ability of science, government or industry to protect public health.

Standards of Acceptable Risk (Safety)

Finally, the Precautionary Principle involves certain assumptions about what standards of safety are appropriately applied by risk regulators to different kinds of risk. The question of whether a technology is “safe” is widely recognized as a value judgment about whether a risk exceeds some level of acceptability. The acceptability of any given risk is determined by multiple factors, among the most important of which are the degree of voluntary choice involved in the risk taking, the off-setting benefits of the risk taking (and the fair distribution of the risks and benefits), the familiarity of the risk and the perceived ability to control it, the trustworthiness of the risk manager, and a whole range of highly subjective attitudes and fears associated with particular groups in particular circumstances (Fischhoff et al., 1981).

It is well known that risks associated with potentially catastrophic events (i.e. events involving dreaded harms occurring at high orders of magnitude, which are unforeseen and/or uncontrollable, and which may be irremediable) have extremely low levels of acceptability in public consciousness. When hazard magnitudes are catastrophic in nature, even extremely low probabilities of occurrence are often not sufficient to render the risk acceptable. These are the scenarios that typically invoke public demands for “zero-risk”. [2]

Other safety standards commonly invoked in the context of health risks in food (e.g. chemical residues, microbiological risks, artificial additives) include “threshold” standards (those that set levels of acceptability at certain specified limits) such as NOAEL (“No Observable Adverse Effect Level) and “No Higher than Background Levels”. In cases where risks and benefits tend to be evenly distributed among risk stakeholders (those who bear the risks also enjoy the benefits), so-called “balancing” standards such as risk–cost–benefit and cost-effectiveness standards tend to be more appropriate.

In Chapter 7, we identified a critical ambivalence in the concept of “substantial equivalence” as it is invoked in the regulatory environment of many countries and in international standards. We have expressed serious concerns about its use as a decision threshold for exempting new genetically engineered products from rigorous safety assessment, which, as noted above, may not always be consistent with a duly precautionary approach.

However, the concept also often serves a different function — that of establishing a standard by which a GM product can be considered safe for human and animal health and for the environment. Used in this way, it functions primarily as a “No Higher than Background Level” threshold safety standard. It sets a benchmark of risk acceptability, requiring that the health and environmental risks of GM products be no higher than those associated with their non-GM counterparts. It is based upon the assumption, not that traditional native and hybridized plants are entirely free of risks, but that whatever these risks may be, they are part of the normal background of risk that society has come to view as acceptable. If the employment of a new, GM food can be shown (not assumed) to be “substantially equivalent” in the types and magnitudes of health or environmental risks to those posed by the employment of its traditional, non-GM alternative, by this standard it, too, should be considered acceptable or “safe”.

Understood and applied in this way, “substantial equivalence” would appear to be a fairly rigorous precautionary safety standard. Consistently applied, it would question the safety of any GM food for which there was evidence of risks higher than those known to be posed by its traditional counterpart. It represents a more precautionary standard than the “balancing” standards (e.g. ALARA, Cost-Effectiveness, Risk–Cost–Benefit) typically employed by risk managers and regulators. These latter standards are all willing to “trade off” significant risks in order to limit the costs of safety or to realize certain economic and other benefits.

IMPLICATIONS FOR THE REGULATION OF FOOD BIOTECHNOLOGY

The debate over the meaning and proper application of the Precautionary Principle cannot be settled by this Expert Panel. However, because the principle has become deeply embedded in the many international agreements and protocols to which the Canadian government is a party, and is increasingly affirmed by European, North American and international regulatory bodies as a guiding principle for policy (CFIA, 1997; Barrett, 1999), it is appropriate that Canadian biotechnology regulatory policy reflect the basic sentiments and spirit of the principle. The recommendations contained in this Report assume that the fundamental tenets of the Precautionary Principle should be respected in the management of the risks associated with food biotechnology. All of these recommendations can be implemented within the existing regulatory framework. Our approach to the issues we consider within this Report is based upon what we consider the following precautionary rules:

RECOMMENDATIONS

8.1 In general, those who are responsible for the regulation of new technologies should not presume its safety unless there is a reliable scientific basis for considering it safe. This approach is especially appropriate for those who are responsible for the protection of health and the environment on behalf of the Canadian people. Any regulatory mechanism which assumes that a new product is safe on less than fully scientifically substantiated basis violates this fundamental tenet of precaution. The Expert Panel rejected the use of “substantial equivalence” as a decision threshold to exempt new GM products from rigorous safety assessments on the basis of superficial similarities (Chapter 7), because such a regulatory procedure is not a precautionary assignment of the burden of proof.

8.2 The proponents and developers of food biotechnology products bear a serious responsibility to subject these products to the most rigorous scientific risk assessment. In this sense, the primary burden of proof is upon those who would deploy these food biotechnology products to carry out the full range of tests necessary to demonstrate reliably that they do not pose unacceptable risks. The laws and regulations under which these products are regulated and approved in Canada already place this burden or proof upon producers of these technologies insofar as they require the producers or proponents to carry out the tests and submit data from these tests demonstrating that the products are safe.

8.3 Where there are scientifically reasonable theoretical or empirical grounds establishing a prima facie case for the possibility of serious harms to human health, animal health or the environment, the fact that the best available test data are unable to establish with high confidence the existence or level of the risk should not be taken as a reason for withholding regulatory restraint on the product. In such cases, regulators should impose upon applicants for approval of the technology the obligation to carry out further research which can establish on reasonable weight of evidence that unacceptable levels of risk are not imposed by the technology.

8.4 Serious risks to human health, such as the potential for allergens in genetically engineered foods, risks of extensive, irremediable disruptions to the natural ecosystems through emergence of highly aggressive or invasive weed species, or of serious diminution of biodiversity, demand that the best scientific methods be employed to reduce the uncertainties with respect to these risks. Approval of products with these potentially serious risks should await the reduction of scientific uncertainty to minimum levels. The Expert Panel supports the view of the British BSE Inquiry, as discussed above, in this regard. Even though the risks appeared remote on the basis of the available evidence, the potential seriousness of the health risks justified extraordinary precaution before a fuller scientific picture was available.

8.5 Regulatory action in accord with the Precautionary Principle means the imposition of more “conservative” safety standards with respect to certain kinds of risks. Where there are health or environmental risks involving catastrophe scenarios (e.g. the potential effects of global warming), the greater the case for more conservative safety standards such as “zero-risk” or low threshold standards, such as that of “substantial equivalence”, as articulated above. In the Panel’s view, when “substantial equivalence” is invoked as an unambiguous safety standard (and not as a decision threshold for risk assessment) it stipulates a reasonably conservative standard of safety consistent with a precautionary approach to the regulation of risks associated with GM foods.

REFERENCES

Adler, J. 2000. More sorry than safe: assessing the precautionary principle and the proposed international biosafety protocol. Tex. Int. Law J. 35: 173–205.

Anon. 2000. Harvard International Conference on Biotechnology in the Global Economy: Science and the Precautionary Principle, 22–23 September 2000. Sustainable Dev. 30(2).

Barrett, K.J. 1999. Canadian Agricultural Biotechnology: Risk Assessment and the Precautionary Principle. Ph.D. Thesis. Vancouver: University of British Columbia.

Brunk, C.G., L. Haworth, B. Lee. 1992. Value Assumptions Is Risk Assessment. A Case Study of the Alachlor Controversy. Waterloo, ON: Wilfrid Laurier Press.

The BSE Inquiry: The Report. 20 Nov 2000. The Inquiry into BSE and Variant CJD in the United Kingdom. At: <http://www.bseinquiry.gov.uk/>

CFIA (Canadian Food Inspection Agency). 1997. Comments on Mad Cows and Mothers’ Milk. At: <www.cfia-acia.agr.ca/english/ppc/biotech/madcow.html>

Chapman P., A. Fairbrother, D. Brown. 1998. A critical evaluation of safety (uncertainty) factors for ecological risk assessment. Environ. Toxicol. Chem. 17: 99–108.

Fischhoff, B., S. Lichtenstein, P. Slovic, S. Derby, R. Keeney. 1981. Acceptable Risk. Cambridge: Cambridge University Press.

Foster K.R., P. Vecchia, M. Repacholi. 2000. Science and the precautionary principle. Science 288: 979–81.

Funtowicz, S.O., J.R. Ravetz. 1994. Uncertainty and regulation. In F. Campagnari et al. (eds.), Scientific-Technical Backgrounds for Biotechnology Regulations. Brussels and Luxembourg: ECSC< EEC<EAEC.

Gullet W. 1997. Environmental protection and the “precautionary principle”: a response to scientific uncertainty in environmental management. Environ. Plann. Law J. 14: 52–69.

Helmuth L. 2000. Both sides claim victory in trade pact. Science 287: 782–83.

Mahoney, R. 2000. Opportunity for agricultural biotechnology. Science 288: 615.

McIntyre O., T. Mosedale. 1997. The precautionary principle as a norm of customary international law. J. Environ. Law 9: 221–41.

Miller, H., G. Conko. 2000. Letter to the editor. Nature Biotechnol. 18(July): 697–98.

O’Riordin T., A. Jordan, A. 1995. The precautionary principle in contemporary environmental politics. Environ. Values 4.

Pearce, D. 1994. The precautionary principle and economic analysis. In T. O’Riordin, J. Cameron (eds.), Interpreting the Precautionary Principle. London: Earthscan.

Salter, L., E. Levy, W. Leiss. 1988. Mandated Science. Science and Scientists in the Making of Standards. Boston: Kluwer Academic Publishers.

Shrader-Frechette, K.S. 1991. Risk and Rationality. Berkeley, CA: University of California Press. Shipworth D., R. Kenley. 1999. Fitness landscapes and the precautionary principle: the geometry of environmental risk. Environ. Manage. 24: 121–31.

Tickner, J. 1999. A map towards precautionary decision-making. In C. Raffensperger, J. Tickner (eds.), Protecting Public Health and the Environment: Implementing the Precautionary Principle. Washington, DC: Island Press.

_______________

Notes:

*. While many biologists focus on avoiding the Type I error (e.g. set at 5%), and ignore the probability of Type II error, this is a weak application of statistical method. Many refereed ecological journals now demand that researchers calculate the power (1-$) of the statistical tests performed in any given experiment. There are many statistical resources readily available for analyzing power in almost any experimental context, and many biologists have advocated abandoning slavish devotion to avoiding the Type I error and paying much more attention to avoiding the Type II error, especially in applied contexts like resource management and conservation. In focusing on the Type II error the Precautionary Principle is, therefore, fully in accord with the current application of statistics in science. It does not, as the critics often charge, necessarily ask regulatory scientists to risk committing the “unscientific error” of affirming unwarranted risk. The Expert Panel is indebted to one of the anonymous peer reviewers of this Report for making this important point.

1. The Working Group invoked the principle known as ALARP (As Low As Reasonably Practicable). It requires an exercise in proportionality. When deciding whether a precaution is “reasonably practicable”, it is necessary to weigh the cost and consequences of introducing the precaution against the risk which the precaution is intended to obviate.

2. The demand for “zero risk” is often viewed by risk experts as irrational, because there is no such thing as an absolute zero risk for any possible hazard occurrence. This is, strictly speaking, true. However, the demand for “zero risk” often can be interpreted as an expression of zero tolerance for any incremental increase in the already occurring background risk. For example, in the current debate about the impact of pollen from Bt-engineered crops upon the Monarch butterfly, there is evidence that these crops may pose some risk to the Monarch. But many argue that the risk is marginal in comparison with other greater risks imposed upon the species, such as destruction of its habitat. The question here is what level of risk is acceptably imposed upon this species. The insistence by some that no risk from Bt crops to the Monarch is acceptable is not a call for “zero risk” in any absolute form, but rather a call for zero increase in the cumulative risk burden already imposed upon the species.

[admin]

9. ISSUES IN THE SCIENCE-BASED REGULATION OF BIOTECHNOLOGY

PART 1: MAINTAINING THE INTEGRITY OF RISK ASSESSMENT SCIENCE

One of the concerns frequently voiced about the regulation of biotechnology in Canada and elsewhere involves the question of the independence, objectivity and transparency of the science involved in the assessment of the technologies. This issue was raised as a concern by many of the parties who made submissions to the Expert Panel. It is generally framed in terms of public trust in the objectivity and disinterestedness of the scientists who develop, test and regulate biotechnology products. But it also concerns the process by which the underlying science used to assess GM products is made transparent to independent validation.

Trust in those who develop and regulate technologies is a factor in public acceptance of these technologies and of the risks they may involve. Studies of risk perception are uniform in the finding that even the most minimal risks may be unacceptable if levels of trust in those who manage those risks are low or eroding (Slovik, 1992; Powell and Leiss, 1997). Most commentators agree that the high levels of public apprehension in Europe about food risks generally, and GM food risks specifically, are significantly coloured by the loss of trust in scientists and regulators resulting from the BSE crisis in Britain (cf. Chapter 8). This is only one of the most dramatic examples of what numerous commentators have identified as a general erosion of public confidence in science well beyond Europe (Angell, 1996).

International trade protocols as well as national regulatory practices rely upon the ostensible objectivity and reliability of science in the assessment and management of risks associated with food biotechnology. Practices that compromise this objectivity and reliability also seriously erode public confidence in the regulatory process. Thus, the Expert Panel wishes to underscore the critical importance of this for the regulation of food biotechnology in Canada, and call attention to practices and social trends that tend, in fact, to compromise the scientific assessment of biotechnology risks.

Regulatory Conflict of Interest

One of the broadest issues relates to government regulators and policy makers. Biotechnology is viewed by most Western governments as an important part of the new economy. Many governments, including the Canadian government, have formal programs specifically designed to facilitate the growth of biotechnology (e.g. Alberta Science and Research Authority, 1996; Barrett, 1999). Many statements by Agriculture and Agri-Food Canada and Canadian Food Inspection Agency (CFIA) officials and documents indicate that the official policy of the government regarding the regulation of agricultural biotechnology is two-fold — both the protection of the public from potential health and environmental hazards, and the ensuring of a viable and internationally competitive biotechnology industry (NBAC, 1987-88). As one Agriculture Canada official put it, the goal of regulatory agencies with respect to biotechnology must be to develop regulations that assure “that the products can be used without adversely affecting humans and animal health, and the environment”, and that are “not so restrictive or time-consuming to fulfill that industry loses its competitive advantage and seeks markets outside the country” (Hollebone, 1988). CFIA has engaged in active media campaigns promoting agricultural biotechnology, and seeking to allay public fears about risks associated with GM foods (CFIA, 2000).

If the same government agency that is charged with the responsibility to protect the public health and environmental safety from risks posed by technologies also is charged with the promotion of that same technology, and if its safety assessments are, by official policy, balanced against the economic interests of the industries that develop them, this represents, from the point of view of both the public and the industrial stakeholders, a significant conflict of interest. Each stakeholder is placed in the position of having to ask, with respect to each regulatory decision, whether its own interests have been unduly compromised by the interests of the other.

The concern of the Expert Panel in this issue is not primarily from the point of view of the legal or ethical issues it raises. These are vitally important, but beyond the scope of the Panel’s mandate. The Panel’s interest is primarily from the point of view of how such regulatory conflict of interest compromises the integrity of regulatory science and decision making, as well as public perception of that integrity. The claim that the assessment of biotechnology risks is “science based” is only as valid as the independence, objectivity and quality of the science employed. All the regulatory departments involved in the regulation of food biotechnology should seek to separate institutionally as much as possible the role of promoter from the role of regulator. The more the regulatory agencies are, or are perceived to be, promoters of the technology the more they undermine public trust in their ability to regulate the technology in the public interest.

Confidentiality Versus Transparency in Canadian Regulatory Science

Current regulatory practice in Canada protects the confidentiality of much of the test data submitted by developers of food biotechnology in support of the approval of their products. Data identified by such companies as Confidential Business Information (CBI) is protected under federal access to information laws. This information can be released only by application, and with approval of the owner of the proprietary information. This means that the full data in the risk assessments upon which approval (or non-approval) decisions are based are often not available for public scrutiny or for peer review in the community of science. The company applying for approval of a biotechnology product essentially gets to decide what counts as CBI. Presumably, the regulatory agency can, and often does, negotiate with the company applicant what test data the agency will consider confidential, and thus has the power to negotiate for relatively full disclosure.

The information that CFIA makes available to the public, contained in published Decision Documents, summarizes the assessment conclusions upon which the approval of the unconfined release of a genetically engineered plant into the environment was based. The actual data and scientific judgments leading to that assessment are not included in the Decision Document. Thus, the science behind the regulatory decision remains largely obscure unless there is an application to view it made under access to information laws. While one could make the argument that some of the data provided to regulators need to be protected (e.g. those related to genetic transformations and gene constructs), the Panel does not agree that data pertaining to environmental and ecological consequences should be proprietary.

It is important to note, however, that the amount of information the regulatory departments choose to disclose from the application and approval process is not set by any formal regulations. Rather, it is a policy judgment that seeks to balance the interests of industry against the desire for transparency in the regulatory process. Government could insist on more complete disclosure of the relevant data, but many consider that such a policy discourages industry research and development. In the extreme case, a company may decide not to seek approval if it fears that the application process would lead to the disclosure of valuable business information.

In meetings with senior managers from the various Canadian regulatory departments, the Expert Panel addressed questions related to their handling of the issues of transparency and confidentiality in dealing with applicants for licensing of new biotechnology. Their responses uniformly stressed the importance of maintaining a favourable climate for the biotechnology industry to develop new products and submit them for approval on the Canadian market. If the regulatory agencies do not respect industry interests in protecting the confidentiality of product information as well as data obtained from extensive health and environmental testing, industry in turn will be deterred from engaging in the regulatory approval process. Several of the managers referred to the importance of maintaining a relationship of trust between industry and the regulators. Only in an atmosphere of trust, they argued, can government and industry work together in the cooperative way necessary to generate the product and test data required for the protection of public safety.

Such concern with industry development, though understandable, highlights another aspect of the regulatory conflict. The conflict of interest involved in both promoting and regulating an industry or technology, discussed in the previous section, is also a factor in the issue of maintaining the transparency, and therefore the scientific integrity, of the regulatory process. In effect, the public interest in a regulatory system that is “science based” — that meets scientific standards of objectivity, a major aspect of which is full openness to scientific peer review — is significantly compromised when that openness is negotiated away by regulators in exchange for cordial and supportive relationships with the industries being regulated.

In the judgment of the Expert Panel, the more regulatory agencies limit free access to the data upon which their decisions are based, the more compromised becomes the claim that the regulatory process is “science based”. This is due to a simple but well-understood requirement of the scientific method itself — that it be an open, completely transparent enterprise in which any and all aspects of scientific research are open to full review by scientific peers (Kennedy, 2000). Peer review and independent corroboration of research findings are axioms of the scientific method, and part of the very meaning of the objectivity and neutrality of science.

Validation of the Science

In principle, the Regulations specified by CFIA, Food and Drugs Act, and Canadian Environment Protection Act for approval of GMOs, particularly those that pertain to microbes and plants, are comprehensive in their breadth of required information, ranging from the molecular nature of the novel gene construct to potential consequences to human health and the environment. However, despite this breadth, the Panel has concluded that there is no means of determining the extent to which these information requirements are actually met during the approval process, or of assessing the degree to which the approvals are founded on scientifically rigorous information. The Panel attributes this uncertainty to a lack of transparency in the process by which GMOs are approved within the present regulatory framework.

The Panel’s, and the public’s, lack of access to this information raises questions concerning the scientific rigor of the approval process. Based on the Guidelines that accompany the CEPA and FDA Regulations, and based on interviews with representatives of CFIA, Health Canada and Environment Canada, the Panel concluded that, although the proponents are required to provide new data in some areas, there is no means for independent evaluation of either the quality of the data or the statistical validity of the experimental design used to collect those data. Furthermore, it appears that a significant part of the decision-making process can be based on literature reviews alone.

Consider, for example, the sole Regulation under CEPA that deals with the potential risks of non-microbial transgenic organisms to the environment. Schedule XIX (Sections 29.16 and 29.19), paragraph 5c identifies the requirement for information on “the potential of the organism to have adverse environmental impacts that could affect the conservation and sustainable use of biological diversity.” The information necessary to meet the requirement stipulated by this Regulation is detailed in CEPA Guideline 4.3.5.3, which states:

“A brief summary of predicted ecological effects should be provided, including any effects on biodiversity. This should include a description of the expected beneficial or adverse ecological effects that result from the growth of the organism, as well as any other ecological effects likely to occur from its introduction.”

The Panel interprets this Guideline to mean that the CEPA Regulation pertaining to environmental risks associated with non-microbial transgenic organisms has no explicit data requirements for information pertaining to the potential effects of these GMOs on conservation and biodiversity. (This may reflect the fact that Regulations have yet to be developed for transgenic animals by CFIA and for transgenic fish by Department of Fisheries and Oceans.) It is the Panel’s opinion that a literature review alone is insufficient and that experimental data for the particular GMO under consideration should be part of the evaluation process.

Currently, there is no objective way for the public or independent scientists to evaluate fully the scientific rigor of these assessments. In the one example available to the Panel, the data used to evaluate the invasiveness of Monsanto’s Roundup Ready Canola (approved in 1995) were judged by Barrett (1999) to be scientifically inadequate for either a rational regulatory decisionmaking process or a peer-reviewed scientific publication. Based on available information, this is a judgment with which the Panel agrees. However, the generality of this conclusion cannot be assessed because all of the data sets used in the decision-making process, notably those pertaining to environmental safety, are not available for public scrutiny.

The Panel concludes that the lack of transparency in the current approval process, leading as it does to an inability to evaluate the scientific rigor of the assessment process, seriously compromises the confidence that society can place in the current regulatory framework used to assess potential risks to human, animal and environmental safety posed by GMOs.

Increasing Commercialization of University Scientific Research in Biotechnology

There is growing concern in the public and the scientific community that the increasing focus of government upon the promotion of biotechnology has an adverse impact on the allocation of research funds. As suggested by Varma, there is a growing perception that “Basic science is valued only if it contributes to the creation of products or processes for... industry. The government agencies are more and more supporting research which is geared to help industry” (Varma, 1999). In Canada, an Expert Panel on Commercialization of University Research has recently made strong recommendations to the Prime Minister’s Advisory Council on Science and Technology that governments and universities adopt policies encouraging the commercialization of university research with intellectual property potential (Expert Panel on Commercialization, 1999).

There are also numerous specific conflicts which have been associated with the research environment. Though academic science has always been affiliated with the private sector, the application of genetic engineering to food production is progressing at a time when universities and university researchers are building unprecedented ties with industry partners (Schultz, 1996; Angell, 2000; DeAngelis, 2000). Researchers, such as David Blumenthal, have noted that these commercial alliances can have a profound impact on the choice of research topics (Blumenthal, 1992). They also help to create an atmosphere of secrecy among researchers (Wadman, 1996; Blumenthal, 1997; Caulfield, 1998; Gold, 1999) and jeopardize the trust which the public places in academic science. As noted by Korn: “There is good reason for concern [that the] idealistic image of academic virtue and the public’s willingness to trust in it may be tottering” (Korn, 2000).

The pressures and opportunities for institutional and personal gain from research has a profound impact upon the willingness of researchers to share openly research plans, research results and relevant resources within the research community. This openness is one of the traditional strengths of the scientific enterprise. It is the traditional mechanism by which the potential risks and failures of certain technological designs and directions become widely known within the scientific and technological communities. This is true not just of biotechnology, but of other research disciplines with potential industrial applications as well. Increased secrecy and protection of intellectual property in the research community does not well serve the public interest in reliable scientific research on safety matters.

Academic/industry relationships are extremely widespread. Blumenthal’s 1997 study found 90% of the US life sciences companies surveyed had a “relationship with academia”. In such a climate, it may become increasingly difficult to find independent academic researchers with the motivation, or even the freedom, to evaluate the claims of industry. As argued by science historian Charles Weiner: “[T]he dual roles played by many leading biologists have begun to impair the credibility of scientists when they provide advice on matters of public concern relating to their research” (Weiner, 1988, at 32–33). Scientists who concentrate their research efforts on the environmental and health risks of new technologies, and who develop the expertise upon which competent regulation of these technologies must depend, are not likely to be prime candidates for research grants from industry partners.

In addition, academic scientists involved in the advancement of knowledge in the biotechnology area are increasingly enticed by the considerable commercial value of this knowledge, and increasingly involved in the patenting and marketing of new organisms and techniques. This situation is exacerbated by the emerging structures of intellectual property ownership and management by public universities. A university researcher wishing to release the results of his or her work in the interest of the public good may encounter tangible institutional or corporate pressure not to do so in order to capture the potential commercial value through patenting and licensing. In relation to food biotechnology, it is arguable that such a refocusing of the public research agenda makes it more difficult to find funds for research aimed at the critique or evaluation of GMO technology or scientific researchers with the independence and objectivity to carry it out.

This co-opting of biotechnology science by commercial interest contributes to the general erosion of public confidence in the objectivity and independence of the science behind the regulation of food biotechnology. It reduces significantly the scientific resources available to government regulators of the technology and, hence, the reliability of the “science base” of this regulation. This situation is one that goes well beyond the power of government regulatory agencies to remedy on their own. Instead, they suffer the consequences of these dynamics in the society insofar as the knowledge base they depend upon for the evaluation of technological risks is impoverished. The Expert Panel considers this to be a serious public policy issue related to the public funding of independent scientific research in the universities, and can be remedied only by those in government who formulate and implement these public policies.

RECOMMENDATIONS

9.1 The Panel recommends that Canadian regulatory agencies and officials exercise great care to maintain an objective and neutral stance with respect to the public debate about the risks and benefits of biotechnology in their public statements and interpretations of the regulatory process.

9.2 The Panel recommends that the Canadian regulatory agencies seek ways to increase the public transparency of the scientific data and the scientific rationales upon which their regulatory decisions are based.

9.3 The Panel recommends that the Canadian regulatory agencies implement a system of regular peer review of the risk assessments upon which the approvals of genetically engineered products are based. This peer review should be conducted by an external (non-governmental) and independent panel of experts. The data and the rationales upon which the risk assessment and the regulatory decision are based should be available to public review.

9.4 The Panel recommends that the Canadian Biotechnology Advisory Commission (CBAC) undertake a review of the problems related to the increasing domination of the public research agenda by private, commercial interests, and make recommendations for public policies that promote and protect fully independent research on the health and environmental risks of agricultural biotechnology.

REFERENCES

Angell, M. 1996. Science on Trial: The Clash of Medical Evidence and the Law in the Breast Implant Case. New York: W.W. Norton.

Angell, M. 2000. Is academic medicine for sale? New Eng. J. Med. 20: 1516–18.

Alberta Science and Research Authority. 1996. The Commercialization of Biotechnology in Alberta.

Barrett, K.J. 1999. Canadian Agricultural Biotechnology: Risk Assessment and the Precautionary Principle. Ph.D. Thesis. Vancouver: University of British Columbia.

Blumenthal, D. et al. 1997. Withholding research results in academic life science: evidence from a national survey of faculty. JAMA 277: 1224.

Blumenthal, D. 1992. Academic–industry relationships in the life sciences. JAMA 268: 3344.

Caulfield T. 1998. The commercialization of human genetics: a discussion of issues relevant to Canadian consumers. J. Consum. Policy 21: 483.

CFIA (Canadian Food Inspection Agency). 2000. What am I eating? Consumers, producers and genetically modified foods. CFIA Sponsored Supplement, Canadian Living 25(10): 240–47.

DeAngelis, C. 2000. Conflicts of interest and the public trust. JAMA 284 (online).

Expert Panel on the Commercialization of University Research. 1999. Public Investments in University Research: Reaping the Benefits. Prime Minister’s Advisory Council on Science and Technology.

Gold, R. 1999. Making room: reintegrating basic research, health policy, and ethics into patent law. In T. Caulfield, B. Williams-Jones B (eds.), Commercialization of Genetic Research: Ethical, Legal and Policy Issues. New York: Plenum Publishers.

Hollebone, J. 1988. An overview of the Canadian federal and agricultural regulatory frameworks for biotechnology. CARC Workshop on Biotechnology Regulation. Ottawa.

Kennedy, D. 2000. Science and secrecy. Science 289: 724.

Korn, D. 2000. Conflicts of interest in biomedical research. JAMA 284 (online).

NBAC (National Biotechnology Advisory Committee). 1987-88. Annual Report. Ottawa.

Powell, D., W. Leiss (eds.). 1997. Mad Cows and Mother’s Milk. Montreal: McGill-Queen’s University Press.

Schultz, J. 1996. Interactions between universities and industry. In F. Rudolph, L. McIntire (eds.), Biotechnology. Washington, DC: Joseph Henry Press.

Slovic, P. 1992. Perceptions of risk. In S. Krimsky, D. Golding (eds.), Social Theories of Risk. Westport, CT: Praeger.

Varma, R. 1999. Professional autonomy vs. industrial control? Science as Culture 8: 23.

Wadman, M. 1996. Commercialization interest delays publication. Nature 374: 574.

Weiner, C. 1988. Genetic engineering: when and where do we draw the line? MBL Science 3: 30.

PART 2: LABELLING OF GENETICALLY MODIFIED FOODS

A major issue in the public debate over food biotechnology has concerned the labelling of foods containing, or produced from, GM products (Pollara, 2000). In part this issue has been cast as a human health issue — if GMO foods pose risks to health, the consumer should have the right of “informed choice” about exposure to these risks. However, it is also in significant part a socioeconomic and political issue having to do with the alleged right of consumers to participate intelligently in the marketplace and to exercise the “power of the pocketbook” in support of the technologies and industries they prefer. Public opinion surveys (Leger and Leger poll, March 2000) report that consumers feel that they have not been sufficiently informed (67.7% of responses) to make educated decisions on the adoption of GM food.

Because the first generation of GM foods has been aimed largely at producing food industry benefits (e.g. increased yields, lower production costs), consumers have yet to perceive direct benefits to them from biotechnology in food production. This has contributed to the perception that GM plants benefit large corporations that bear few of the risks, while providing little or no benefit to consumers, who may bear the potential risks. The absence of labelling on GM products has reinforced the perception that companies are “hiding” important information from the public. The absence of justification for the need for GM food, combined with a perception of lack of transparency from regulatory agencies, and the absence of balanced risk/benefit analyses have all undermined the acceptance of these products.

The Expert Panel is compelled to address the labelling question because concerns about health and environmental risks form an important part of the arguments made in favour of various forms of labelling. As argued below, one of the functions of food labelling is to turn over certain risk management functions to the consumer — which Canada does currently with its labelling policies regarding known allergy risks or health-related nutritional changes. The question we address in this chapter is whether the genetic food technologies we have assessed in this Report involve potential hazards or risks whose effective management would require the use of food labels. If so, are those risks better addressed through the use of general mandatory labels (i.e. required labels for all GM foods and foods containing GM components) or voluntary labels (i.e. labels used voluntarily by producers to provide information that enhances the product for some consumers).

Current Labelling Policies on GM Foods

Many countries have introduced some form of mandatory labelling for GM foods (Nottingham, 1999). Mandatory labelling requirements have been implemented in the EU and are being implemented in Japan. The governments of Australia and New Zealand have agreed “in principle” that GM products should be labelled, including labelling that foods “may contain” GM ingredients (CFIA, 2000). The US, like Canada, currently requires only those GM food products that pose health and safety issues such as possible allergens or changed nutritional content from accepted levels to be labelled. However, there is currently legislation introduced in both houses of Congress to require labelling of food that “contains a genetically engineered material, or was produced with a genetically engineered material” (Goldman, 2000).

The primary forum at the international level for discussion of the labelling issue is the Codex Alimentarius Commission. The Codex Committee on Food Labelling (CCFL) has been carrying on this debate for several years, without resolution. It is divided between those member nations that believe that mandatory labelling should be product-based only and those that believe it should be based on differences of process, such as the rDNA technologies (IFT Report, 2000). One international agreement, however, does speak to the GM labelling issue. The Cartagena Protocol on Biosafety has been interpreted to provide that “living modified organisms” (LMOs) intended for “food, feed or processing” must be identified as LMOs (IFT Report, 2000). The US Department of State has interpreted this provision to require only “may contain” labels on international shipments of LMOs, and not to impose consumer product labelling requirements (IFT Report, 2000).

To date, Canada has taken no formal steps to introduce a mandatory labelling scheme, although the government is currently in the process of developing regulations governing the labelling of biotechnology products (Wilson, 2000). The Canadian government is supporting a joint initiative with the Canadian General Standards Board and the Canadian Council of Grocery Distributors to develop a Canadian standard for voluntary labelling of GM products, similar to the recently adopted voluntary labelling standard for organic products (CFIA, 2000).

Public support for labelling appears, in many respects, to be rooted in a widely held belief in the value of informed choice and the “right-to-know”. Several of the letters received by the Panel from interested parties raised a commonly heard public argument: that GM foods involve unknown or uncertain risks, and that consumers are being used as “human guinea pigs” in a large experiment to determine what these might be. If consumers are subjects of this experiment, the argument continues, they at least should have the right to informed consent to participation, and this can be exercised only if they have appropriate information (i.e. food labels).

Labelling is also usually defended as an important mechanism of risk management, in which the decision whether or not to be exposed to potential hazards in a product is shifted to the consumers or endusers, as is the responsibility to manage those hazards as they choose. If done using meaningful information, it allows individual consumers to make choices about the acceptability of a given risk to themselves. Labels warning consumers to “cook properly before serving” are examples of this type of risk management. Rather than removing products from the market that may contain hazards such as E. coli or Salmonella contamination, notification of the risk passes the effective management of that risk on to the consumer. Labels warning that a product contains ingredients that are known major allergens (e.g. peanuts) serve a similar purpose. Rather than removing the product, and thus also the risk, from the market entirely, the management of the risk is left to those who purchase and consume the product.

In Western regulatory jurisdictions, labelling has generally been thought to be mandated only when there is some feature of the product itself that is worthy of being brought to consumers’ attention, such as a specific health risk or nutritional issue (CFIA, 2000). The process by which a food product is produced (e.g. by genetic modification) has generally been considered to be irrelevant.

In the US, the courts and the Food and Drug Administration (FDA) have generally considered it a requirement that a mandatory food label refer to a “material fact” about the product that is relevant to nutritional value or safety (IFT Report, 2000). In this regard, the issue is closely tied to the concept of substantial equivalence. If a food product is “substantially equivalent” to an existing product, it is assumed that no labelling is required. This philosophy toward labelling was consistently expressed to the Panel by representatives from the CFIA and Health Canada. In the context of GM foods, a new and identifiable health safety risk, such as the presence of a new allergen, or a substantial alteration in the nutritional properties, would need to exist in order to justify labelling under the current Canadian and US regimes (Miller, 1999; CFIA, 2000).

The recent response by many countries to GM food products, particularly in the EU, appears to be a departure from this general rule of product-based, health risk labelling. The decision to mandate labelling of these products in Europe is considered by its critics to be a political response to a broad range of public concerns rather than a reflection of scientific evidence calling into question the actual safety of GM foods. Others argue that it is the result of European governments having been more responsible about informing their citizens of the potential risks and their taking a more precautionary approach toward uncertain risks (Le Monde, 2000). Throughout the 1990s, there was growing pressure in the EU to introduce some form of labelling of all foods and ingredients produced by genetic engineering, regardless of whether they were demonstrably different from those derived from traditional, non-GM plants (Nottingham, 1999). This poses the question whether Canadian regulators should adopt a similar approach to labelling for some or all products associated with the genetic modification process.

In both Canada and the US, there is an important exception to the general rule that labelling should be product-based, which could be seen as a precedent for GM foods. Both countries have a mandatory labelling requirement for foods that have been subjected to the process of irradiation (Food and Drug Regulations, B.01.035; IFT Report, 2000). As with GM food products, there has always been a degree of public and consumer suspicion about the safety of food irradiation — a process used to reduce the presence of pathogens in food products (Lutter, 1999). Though there are many agencies, including the World Trade Organization, that support the use of irradiation for food preservation (Nightingale, 1998; Lutter, 1999), it remains a relatively tightly regulated food preparation process. In the US, the labelling requirement is justified by defining the irradiation process itself as a “food additive” (Pauli, 1999). The rationale behind this regulatory approach is that irradiation is a process that “can render food materially different organoleptically, e.g. taste, smell and texture”. Although the USFDA no longer considers this rationale to have any firm scientific basis, the labelling requirement has been maintained (IFT Report, 2000). However, even if it had such a basis, it is clear that these “material facts” about irradiated foods have no scientifically established relation to health or nutrition risks.

In Canada, the regulatory requirement for labelling of irradiated foods is laid out in Section B.01.035 of the Food and Drug Regulations. This regulation requires that both non-pre-packaged and pre-packaged foods carry a label stating that the food has been irradiated and carrying the international symbol for irradiation. Even pre-packaged foods containing more than 10% of irradiated ingredients must list every such ingredient on the label, preceded by the statement “irradiated” (Section B.01.035.6). Thus, the argument that there is no precedent for process-based labelling in Canada is not accurate. Nor is the claim of no precedent for the labelling of processed foods containing only a percentage of ingredients subjected to a specific process such as irradiation (or, presumably, genetic engineering). Indeed, it could be argued that the case for labelling of GM food products is stronger than for irradiated ones, because genetic engineering may produce “material changes” in the product itself. In the case of quality-enhanced products (e.g. improved appearance, longer shelf-life), this is the whole point of the genetic engineering.

Socio-Political and Ethical-Philosophical Concerns

As noted, the dominant argument for mandatory labelling of GM foods rests upon the claim that it enhances informed choice among consumers. Critics of biotechnology often point out that, while the biotechnology industry argues that the market should be allowed to decide whether GM food products are acceptable, it at the same time often opposes the very labelling necessary for consumers to exercise informed choice. In response, the opponents of labelling point out the myriad of complications involved in formulating a labelling policy that would actually provide accurate and meaningful information to consumers (see below), and conclude that labelling does not solve the problem.

The complicating factor in this debate is that, as the situation in the EU illustrates, the issues about which many consumers wish to exercise informed choice go well beyond the restricted range of health concerns. They involve a much broader range of religious/philosophical, ethical, social and political issues. These are summarized in Chapter 1. These broader dimensions of the labelling debate are beyond the mandate of the Panel. We will, therefore, withhold comment on the question of whether mandatory (or voluntary) labelling would provide a feasible means of enhancing consumer choice with respect to these issues, or whether it would be a socially desirable means of achieving this goal. However, policy makers need to recognize that public demand for the labelling of GM products is not based solely on health considerations.

Health Basis for Mandatory Labelling

The Expert Panel is unanimous in its support for mandatory labelling of GM food products where there are clear, scientifically established health risks or significant nutritional changes posed by the product itself. The Panel sees several kinds of justification for the mandatory labelling of these products.

• The first justification stems from the fact that certain changes introduced into food products, regardless of the means by which they are introduced, pose clear, scientifically established risks only to some consumers and not others (e.g. pregnant women or persons with allergies to peanuts or fish). In such cases, there is a non-controversial case for relying upon the consumers themselves to manage these risks. In other words, providing the consumers with a clear warning label permits those at risk to protect themselves by not consuming the product, while at the same time permitting those who are not at risk to consume the product.
• The second justification rests upon the recognition that there are some kinds of hazards in food products that place all consumers of those products at risk to some degree, but the consumers have the right to decide for themselves whether, or at what levels, they wish to be exposed to the risk. In other words, risk management is transferred to consumers in order to allow them to determine their own levels of acceptable risk, rather than having these determined for them by regulatory standards. Warnings on tobacco and alcohol products are examples of this rationale for labelling.
• There is a third, more controversial, justification for food labelling that is rooted in the well-documented fact that consumer perceptions of the acceptability of certain risks are strongly related to the levels of uncertainty in the assessment of these risks. Risks fraught with high levels of uncertainty, but associated with catastrophic outcome scenarios or “dreaded” hazards (e.g. cancer in our society) are usually less acceptable (Slovic, 1991). Therefore, an argument can be made that in cases where there are recognized uncertainties in the identification or evaluation of certain risks, labels warning of the existence of these uncertainties are useful and prudent. They allow the consumer to decide whether the risks, however minimal, are acceptable. For example, labels stating that a food contains genes engineered into it from sources that are known to be allergenic (e.g. a peanut gene spliced into soybean) may be advisable, even though there is no evidence that the known allergenic protein has in fact been transferred. A scientist would likely judge the risk in this case to be negligible, but a person with a lethal allergy to peanuts may have a legitimate interest in avoiding the product.

This last justification for mandatory labels on food products is much more controversial than the first two because it departs from the generally accepted principle that a label should communicate only firmly established health or nutritional information. Otherwise, it is often argued, the label does not provide guidance to consumers, but leaves them speculating about the significance of the information and filled with unanswered questions.

Conclusions on Mandatory Labelling

In assessing the justifications for labelling, the Panel has focused primarily on whether mandatory labelling on the basis of health and environmental risk is a policy that could be justified on the basis of a scientific assessment of these risks. We were concerned particularly with the question of whether, from a scientific point of view, there was sufficient reason to require mandatory labelling for GM foods, while not requiring it for novel and exotic foods produced by more traditional non-GM processes. The Panel also attempted as much as possible to distinguish the socio-political justifications from the health and safety considerations and to limit its consideration to the latter. The issue of whether a general mandatory labelling of GM products would be an effective instrument for managing the health and environmental risks uniquely associated with food biotechnology generated a great deal of controversy among the Panel members. In the end, however, the Panel concluded that there was not at this time sufficient scientific justification for a general mandatory labelling requirement. However, the Panel concluded that many of the concerns identified in this Report do call for a strongly supported voluntary labelling system for GM foods.

The Panel wishes to emphasize, however, that these conclusions are premised upon the assumption that the other recommendations of this Report concerning the conditions for the effective assessment and management of the risks of GM organisms are fully implemented by the regulatory agencies. If proper assessment and long-term monitoring procedures are carried out, and the appropriate safety standards enforced, then any significant health and environmental risks of GM organisms should be identifiable, and the products can be either disapproved or approved on the condition of explicit labels warning of the risk (e.g. allergens or nutritional deficiencies).

The Panel also wishes to emphasize that the issue of uncertain environmental impacts from GM organisms crosses over the somewhat fuzzy line between clearly established risk concerns, which are the Panel’s sole mandate, and the broader socio-political concerns, which are commonly advanced in favour of mandatory labelling. Our conclusion with respect to mandatory labelling on the basis of risk and safety concerns should not be read as prejudicing in any way the debate about labelling on these broader grounds.

If the testing procedures we recommend elsewhere in this Report disclose a new allergen, health risk or nutritional variation, labelling would, of course, be required. This approach would be consistent with the present regulatory approach. It is important to note, however, that while we believe that labelling should be reserved for specific health risks and nutritional variations, identifying which risks justify a label may not be easy (e.g. would the existence of a possible new allergen justify a label or should regulatory approval be withheld entirely?). Though such issues will require ongoing consideration by the relevant regulatory agencies, they do not alter the Panel’s general recommendation that a general mandatory labelling scheme is not advisable.

One of the most persuasive considerations for many of the Panel members was that, given our current knowledge about the risks associated with GM foods compared with similar non-GM food products, we see little scientific reason for treating the two differently with respect to labelling requirements. There may be uncertain and currently unpredictable health and environmental risks associated with the long-term production and consumption of GM products. Indeed, other chapters of this Report have identified areas of such potential risks. However, there are also uncertainties and unknowns about the long-term health implications of many non-GM food products. To mandate labelling for potential health risks in GM products alone would promote an inconsistency with no firm scientific justification.

Voluntary Labelling

The preceding considerations have led the Panel to conclude that there are not currently sufficient reasons to adopt a system of general mandatory labelling of GM foods. They do not lead necessarily to the same conclusion about voluntary labelling. Many of the concerns voiced in favour of mandatory labelling can be addressed, at least in part, by voluntary labels. This is true, not only of the social, ethical and political concerns, but also of some of the risk-related concerns, especially those related to uncertainties and even fears about unsubstantiated risks associated with GM foods.

Elsewhere in this report the Expert Panel has identified what it considers to be the most significant risks to human, animal and environmental health posed by current and future food biotechnology products. Chapter 4 (Part 1) identified certain difficulties involved in using traditional toxicological models to identify and assess the health risks associated with GM food products, especially GM foods in their entirety. Chapter 4 (Part 2) also identified the difficulties related specifically to the identification and assessment of potential allergens in novel foods, and concluded that there are currently available no testing protocols that can reliably overcome all these difficulties. It can be expected that new allergic reactions will develop in populations as a result of exposure to new proteins introduced into these foods, and it will not always be possible to predict these reactions. Chapters 5 and 6 have identified potential health and environmental risks posed by GM animals and plants while recognizing that the probabilities of their occurrence and the magnitudes of their harm are difficult to assess (e.g. the risks to aquatic environments of escaped GM fish). Even were these outcomes well established, in many cases there would be widespread disagreement about their acceptability (e.g. loss of habitats or of biodiversity).

The Panel does not believe that these identifiable but relatively uncertain risks are appropriately managed by means of a general mandatory labelling requirement. However, many consumers have strong interests in exercising the power of consumer choice in the market with respect to these environmental and health safety issues. The Panel believes that strong government support for voluntary labels is an effective way of providing consumer input into these issues, and encourages the Canadian regulatory agencies responsible to establish guidelines for the regulation of reliable, informative voluntary labels.

REFERENCES

CFIA Supplement. October 2000. What am I eating: consumers, producers and genetically modified foods. Canadian Living.

Leger and Leger poll conducted in Quebec, 20–23 Apr 2000 by telephone interviews with 1009 respondents.

Gilmore, R. 2000. Agbiotech and world food security — threat or boon? Nat. Biotechnol. 18: 361.

Goldman, K. 2000. Bioengineered food — safety and labelling. Science 290(20): 457.

IFT (Institute of Food Technologists). 2000. Expert report on biotechnology and foods, labeling of rDNA biotechnology-derived foods. Food Technol. 54: 62.

Lutter, R. 1999. Food irradiation — the neglected solution to food-borne illness. Science 286: 2275.

McHughen, A. 2000. A Consumer’s Guide to GM Food: From Green Genes to Red Herrings. Oxford University Press.

McHughen, A. 2000b. Uninformation and the choice paradox. Nat. Biotechnol 18(10): 1018–19.

Miller, H. 1999. A rational approach to labeling biotech-derived foods. Science 284:1471.

Le Monde Diplomatique. 2000 (Sept). At: <http://www.biotech-info.net/ordinary_people.html>

Nightingale, S. 1998. Letter: irradiation of meat approved for pathogen control. JAMA 279: 9.

Nottingham, S. 1999. Eat Your Genes. London: Zed Books Ltd.

OECD (Organisation for Economic Co-operation and Development). 1999. Food Safety and Quality: Trade Considerations. Paris.

Pauli, G. 1999. US Regulatory Requirements for Irradiating Foods. Washington, DC: US Food and Drug Administration, Center for Food Safety and Applied Nutrition. At: <vm.cfsan.fda.gov/~dms/opa-rdtk.html>

Pollara (Pollara Research and Earnscliffe Research and Communications). 2000. Public Opinion Research into Biotechnology Issues. Prepared for the Biotechnology Assistant Deputy Minister Coordinating Committee, Government of Canada.

Slovic, P. 1991. Beyond numbers: a broader perspective on risk perception and risk communication. In D.G. Mayo, R. D. Hollander (eds.), Acceptable Evidence: Science and Values in Risk Management. Oxford: Oxford University Press.

Wilson, B. 26 Oct 2000. MPs vote against GM food labeling. Western Producer.

[admin]

GLOSSARY

abiotic: arising from non-biological sources

adjuvant: a preparation used to stimulate the immune response during antibody induction

agonistic behaviour: competitive behaviour

Agrobacterium tumefaciens: a bacterium used in the process of creating GM plants. In nature, a soil bacterium responsible for the “crown gall” disease in some plants

allele: one of two or more copies of a gene in plants or animals

allergen: a substance, usually a protein, capable of inducing a specific immune hypersensitivity response, often resulting in immunoglobulin E production

allergy: a hypersensitive state involving the immune system as a result of exposure to certain substances, usually foreign proteins. Food allergy (food hypersensitivity) is an abnormal immunologic reaction usually resulting from the ingestion or contact with a food or food component. This term often refers to immunoglobulin E-mediated mechanisms but may include any immune response to a food.

allometry: differential growth of body parts; change of shape or proportion with increase in size

anadromous: fish that return from oceans to fresh water to spawn (e.g. salmon)

anaphylaxis: an acute, severe, sometimes fatal allergic reaction affecting two or more body systems. It results from binding of immunoglobulin E to sensitized immune cells (mast cells and basophils), with release of chemical mediators that cause multiple adverse effects on target organs.

animal commodification: the treatment of animals as commodities rather than as beings with intrinsic worth

animal welfare: most widely used in the sense of encompassing the “Five Freedoms for Animal Welfare”. First formulated by the Farm Animal Welfare Council, a body set up by the UK government, in response to the Agriculture (Miscellaneous Provisions) Act of 1968, to advise on issues relating to farm animal welfare and to develop new standards for agricultural practice. Their five freedoms define the needs of animals which should be met under all circumstances: freedom from hunger and thirst freedom from thermal and physical discomfort freedom from pain, injury and disease freedom from fear and stress freedom to express normal behaviour

antibiotic resistance markers: see selectable marker gene

antibody: a gamma globulin or immunoglobulin produced by the immune system in response to exposure to a specific substance, termed an antigen. Five major immunoglobulin classes exist in humans, IgG, IgM, IgA, IgD and IgE.

antifeedant: plant secondary metabolite that reduces or inhibits feeding by a herbivore. Most plants produce these compounds as a means of defence against natural enemies.

antigen: a substance, usually a high molecular weight protein, polysaccharide or complex, which is capable of inducing specific immune responses, including antibody formation

antinutrient: an undesirable substance in food

Arabidopsis: small plant of the mustard family commonly used to study plant genetics and plant genomics

assortative mating: mating of like phenotypes: resistant with resistant and susceptible with susceptible

atopy: a hereditary tendency to develop allergic diseases which include asthma, allergic rhinitis, food allergy and atopic dermatitis (eczema), in associating with a tendency to oversynthesize IgE antibodies

base pair: two bases that form a “rung of the DNA ladder”. A DNA strand consists of a chain of nucleotides, each of which is made of a molecule of sugar, a molecule of phosphoric acid, and a molecule called a base. The four bases used in DNA (A,T, G and C) are the “letters” that spell out the genetic code (see DNA).

biodiversity: the number and types of organisms in a region or environment. Includes both species diversity and genetic diversity within species.

biological invasion: the introduction of an organism into a new environment or geographical region followed by rapid multiplication and spread

biotechnology: a set of biological techniques developed through basic research and now applied to research and product development. In particular, the use of recombinant DNA techniques.

biotic: from biological sources

broodstock: the group of males and females from which fish are bred for aquaculture

Bt, Bacillus thuringiensis: a soil bacterium that produces a toxin that is deadly to some insects. Many strains exist, each with great specificity as to the type of insects it can affect.

Canadian Nutrient File: a compilation of nutrient values for foods available in Canada, produced by Health Canada

carrying capacity: the maximum number of organisms of a given species that can be supported in a given area or habitat

catecholamines: neurotransmitters in mammals (e.g. adrenaline)

cellularity: characterizes the physical and chemical properties of cells found within a specific tissue

cellulolytic: the capacity to digest cellulose

chemoautotrophic: an organism capable of deriving its metabolic energy from mineral sources

chimera: an organism containing two or more genetically distinct cell or tissue types

chromatography: a technique for separating complex mixtures of chemicals or proteins into their various constituents chromosome one of the threadlike “packages” of genes and other DNA in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes.

clone: descendants produced vegetatively or by parthenogenesis (development of an ovum without fertilization) from a single plant, or asexually or by parthenogenesis from a single animal. More generally, organisms derived by division from a single cell.

confined field trial field trial: carried out with specific restrictions on location, plot size, etc.

conformational epitopes: epitopes whose form derives from specific transient folding patterns in a protein

congeneric: belonging to the same genus

conspecific: belonging to the same species

cross-compatible: the ability of two related organisms to exchange genes through sexual reproduction. Also referred to as interfertility.

cry: designation of a gene encoding insecticidal crystal proteins in the soil bacterium Bacillus thuringiensis

delta-endotoxins: Bt insecticidal proteins

developmental asynchrony: a pattern of development within sub-populations that allows different sub-populations to reach sexual maturity at different times

DNA (deoxyribonucleic acid): the molecule that encodes genetic information. DNA is a double-stranded molecule held together by weak bonds between base pairs of nucleotides.

DNA sequence: the specific order of bases in a DNA molecule, whether in a fragment of DNA, a gene, a chromosome, or an entire genome

dormancy: a delay in the germination of viable seeds because of unfavourable environmental conditions

eclosion: the emergence of an insect larva from the egg or an adult from the pupal case

ecological amplitude: the range of environmental conditions in which an organism can survive and reproduce

ectoparasitoid: a parasitic insect with larval stages found on the external surface of its insect host

endoparasitoid: a parasitic insect in which larval development occurs within the body cavity of its insect host

entomo-fauna: insect species

epiphytic: one organism living within or upon another without causing harm

epistatic: a dependence relationship between genes; the product of one gene is unable to carry out its function because of the absence of another gene in the same organism

epitopes: separate antigenic areas within a given protein

erucic acid: 13 cis-docosadecenoic acid; a fatty acid having 22 carbons and one double bond and common to traditional rapeseed oil. Canola oil contains less than 2% erucic acid.

Escherichia coli (E. coli): a bacterium found in the intestine of animals and humans used extensively in genetic engineering. Some strains can cause disease; the majority are harmless.

Exotic: non-native; refers to an organism that has been introduced into an area

expression (as in gene expression): generation of a mRNA copy of a gene encoded in an organism’s DNA

fibroblasts: irregularly shaped, branching cells distributed throughout vertebrate connective tissue

field trial: tests of the ability of new crop variety to perform under normal cultivation conditions

fitness: the genetic contribution of an individual to the next generation. The fundamental measure of evolutionary success.

flow cytometry: a technique for rapid automatic separation of suspensions of living cells into defined sub-populations

gamete: the products of meiosis; each gamete carries a single copy of the genetic information of the organism (i.e. a single set of alleles)

GE: genetically engineered (see GM)

gene: the fundamental physical and functional unit of heredity. A gene is a specific stretch of DNA located in a particular position on a particular chromosome that encodes a specific functional product (i.e. a protein or RNA molecule).

gene construct: a sequence of genes made by joining several genes together using recombinant DNA technology

gene flow: the movement of genes from one population to another

gene gun: a device for propelling DNA molecules into living cells

gene knockout strategy: an approach used to determine the function of a specific gene by inactivating (knocking out) that gene in the intact organism and studying the consequences of this modification

gene product: the biochemical material, either RNA or protein, resulting from expression of a gene

gene stacking: simultaneous presence of more than one transgene in an organism, usually a GM organism

genetic drift: the random change in the frequency of alleles in populations due to the small numbers of organisms involved

genome: the total DNA sequence of all the chromosomes in an organism, and thus the total genetic information of that organism

genomics: the study of genomes

genotype: the hereditary constitution of an organism

germplasm: a general term for the available pool of different genomes in a species

gill irrigation: the passing of water over gill filaments, the primary site of oxygen transfer from water to the blood in fish

glucosinolates: secondary metabolites found in plants of the mustard family (e.g. canola); their breakdown products can have goitrogenic properties in mammals

glycoalkaloids: toxic secondary metabolites found in the potato family

glycolysis: energy-yielding metabolic reactions by which sugars are converted to acids

GM: genetically modified; in this context, an organism into whose genome has been deliberately inserted one or more pieces of new DNA

GMOs: genetically modified organisms (see GM)

heat-labile: easily destroyed by heat

heterozygous: having two different alleles at a given locus of a chromosome pair

homology: structural similarity due to descent from a common ancestor or form

hybrid: offspring from a cross between genetically dissimilar individuals, often used to describe the progeny produced by matings between members of different species

immunoglobulin (Ig): see antibody

immunoglobulin E (Ig E): an antibody produced by an allergen which has specific structural and biological properties, in particular, ability to bind and activate mast cells and basophils, causing the release of chemical mediators resulting in clinical symptoms of allergy

in utero: within the uterus

in vitro: outside the living body; in a laboratory or test tube

in vivo: within the living body

insulin-like growth factor I: a peptide believed to be primarily secreted by the liver. It has growth-regulating, insulin-like and mitogenic activities. This growth factor has a major, but not absolute, dependence on somatotropin.

intellectual property (IP): the legal rights associated inventions, artistic expressions and other products of the imagination (e.g. patent, copyright and trade-mark law)

introgression: movement of a new gene into a population

irradiation: a process involving use of low levels of radiation to reduce the presence of pathogens during the preparation of food products

leptokurtic: a statistical description of a population whose values are more heavily concentrated about the mean than in a normal distribution

lipogenesis: the conversion of carbohydrates and organic acids to fat

mass spectrometry: a sensitive physical technique for measuring the exact mass of a molecule and its fragments

mating system: the mode of transmission of genes from one generation to the next through sexual reproduction. Used in plants to refer to the amounts of self- and cross-fertilization.

meiosis: divisions of a nucleus preceding the formation of reproductive cells that contain one of each pair of chromosomes found in the parent cell

methanogenesis: the process of creating methane gas during metabolism

mitosis: the process of chromosome division and separation that takes place in a dividing cell, producing daughter cells of equivalent chromosomal composition to the parent cell

monophagous (oligophagous): herbivores that feed on one or a small number of different closely related host plants

muscle ultrastructure: the structure of muscle tissue at the molecular level

mutagenesis: the process of changing the DNA base sequence at a specific site

mycorrhizae: a group of fungi that grow in close association with plant roots

nutrient: a substance required for health

ontogenetic delay: a delay in the course of growth and development to maturity

ontogeny: the course of growth and development of an individual to maturity

opercular region: the part of a fish in the head region, containing and protecting the gills, the tissue used in respiration in fish

operons: gene clusters under common control in bacteria

organoleptic: the taste and aroma properties of a food or chemical

outbreeding depression: a fitness reduction in hybrids produced by matings between individuals from two genetically distinct populations

outcrossing: mating between different individuals or genotypes

patent: a limited term monopoly, usually 20 years, granted to inventors of new, useful and non-obvious ideas with industrial application

phage: bacteriophage; a virus specifically attacking bacteria

phenotype: the sum total of observable structural and functional properties of an organism

plasmids: non-chromosomal pieces of DNA that code for a sub-set of cellular functions. Usually found in bacteria and fungi.

pleiotropic response: multiple changes to an organism’s phenotype associated with a single change at the genetic level

pollination: the transfer of pollen between anthers (male sex organs) and stigmas (female sex organs) in seed plants

polyphagous: herbivores that feed on a wide variety of host plants from many different families

POnMTGH1 gene construct: a construct derived from sockeye salmon that consists of the metallothionein-B promoter fused to the full-length type-1 growth hormone gene

precautionary principle: a regulatory mechanism for managing environmental and health risk arising from incomplete scientific knowledge of a proposed activity’s or technology’s impact

prechondrocytes: precursors to cartilage cells

preweaning: prior to weaning, the time a young mammal stops nursing

prion: normal cell protein present on nerve cell membranes. It is found in most mammals, but its normal function is unclear. A mutated form of prion known as PrPsc is a disease-causing agent.

proteinase inhibitors: another class of proteins capable of inhibiting insect feeding

proteome: the complete complement of proteins made by a given species in all its tissues and stages

proximate analysis: chemical analysis of the main constituents of food

rate-limiting enzyme: an enzyme whose activity controls the overall flux through a linear sequence of reactions

recombinant DNA (rDNA): DNA molecules created by splicing together two or more different pieces of DNA

reporter gene: a gene whose gene product is easily detected

restriction enzymes: DNA-cutting enzymes that recognize and bind to specific short sections of DNA sequence

rhizobacteria: bacteria found closely associated with plant roots

rhizosphere: the soil zone immediately surrounding a plant root system

salmonids: members of the fish family Salmonidae, including salmon, trouts and chars

secondary metabolite: a chemical produced by a plant that does not appear to have a direct role in its energy metabolism or growth; often restricted to particular species, tissues or developmental stages

secondary pests: those species within an ecosystem that are normally kept in check by natural enemies, but which, following certain agronomic practices (e.g. application of pesticides against a primary pest), reach densities that cause economic losses

seed bank: the population of dormant seeds below the soil surface

seed shattering: the spontaneous dispersal of mature seed from a plant following ripening

selectable marker gene: a gene whose product protects the cell containing it from a selection pressure such as a toxic chemical (e.g. antibiotic)

selfing: mating by a single hermaphrodite individual. Occurs commonly in plants.

single nucleotide polymorphism (SNP): single-base variations in the genetic code between different individuals of the same species. SNPs occur at random throughout the genome. Researchers believe that knowing the locations of these closely spaced DNA landmarks will ease both the sequencing of the genome and the discovery of genes involved in major diseases.

smoltification: the combination of physiological, behavioural and morphological changes that salmonid fish experience when they migrate from fresh water rivers into the ocean

somaclonal variation: altered phenotype generated in plant tissues by extended growth in vitro; possibly a form of mutation

somatic cell nuclear transfer: the transfer of cell nuclei between cells in the body not involved in reproduction

stochastic processes: random processes

sympatry: organisms that occur in the same geographical region or area

syrphids: any fly of the family Syrphidae in the Diptera, typically having a colouration that mimics some bees and wasps

totipotency: the ability to regenerate a fully differentiated organism from a single somatic cell

transcription: the synthesis of RNA (ribonucleic acid) molecules concerned in translating the structure of DNA into the structure of protein molecules

transfection: the transfer into another cell of genetic material isolated from a cell or virus

transgene: a gene from one organism inserted into the genome of another

transposons:short stretches of DNA with the capacity to move between different points within a genome

triploidy: three copies of the genome in each cell rather than the normal two copies found in most plants and animals

vector: any organism or DNA construct that enables movement or transmission of another organism or gene

volunteer plant: crop plants that persist for a few seasons without deliberate cultivation

weed: a plant that in any specified geographical region grows mainly in habitats markedly disturbed by human activities. Within the context of agriculture, weeds are generally unwanted plants that infest crops and reduce yields.

wide cross: a sexual cross between distantly related species that normally would not breed

[admin]

ACRONYMS AND ABBREVIATIONS

ALARA: As Low As Reasonably Achievable

ALARP: As Low As Reasonably Practicable

APHIS: Animal and Plant Health Inspection Service of the United States Department of Agriculture

BSE: bovine spongiform encephalopathy (mad cow disease) — a neurological disorder thought to be linked to the presence of mutant prions

BST: bovine somatotropin

Bt: Bacillus thuringiensis — a soil bacterium that produces a toxin that is deadly to some insects. Many strains exist, each with great specificity as to the type of insects it can affect.

CBAC: Canadian Biotechnology Advisory Committee

CCFL: Codex Committee on Food Labelling

CEPA: Canadian Environmental Protection Act

CFIA: Canadian Food Inspection Agency

DFO: Department of Fisheries and Oceans

DNA: deoxyribonucleic acid — the molecule that encodes genetic information. DNA is a double-stranded molecule held together by weak bonds between base pairs of nucleotides.

FAO: United Nations Food and Agriculture Organization

GC: gas chromatography

GE: genetically engineered (see GM)

GH: growth hormone

GM: genetically modified; in this context, an organism into whose genome has been deliberately inserted one or more pieces of new DNA

GMOs: genetically modified organisms (see GM)

HPLC: high performance liquid chromatography

ICES: International Council for the Exploration of the Sea

ICH: International Conference on Harmonization

IFT: Institute of Food Technologists

kb: Kilobases

LMOs: Living Modified Organisms

MTD: Maximum Tolerated Dose

NASCO: North Atlantic Salmon Conservation Organization

NBAC: National Bioethics Advisory Council (United States)

NBAC: National Biotechnology Advisory Committee (Canada)

NOAEL: No Observable Adverse Effect Level

OECD: Organisation for Economic Co-operation and Development

OMNR: Ontario Ministry of Natural Resources

PCPA: Pest Control Products Act

PCR: polymerase chain reaction

PMRA: Pest Management Regulatory Agency

PST: porcine somatotropin

rDNA: recombinant DNA

TSE transmissible spongiform encephalopathy — despite distinctive individual features, a number of diseases of animals (scrapie, chronic wasting disease, transmissible mink encephalopathy), and humans (Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome, bovine spongiform encephalopathy, kuru), are considered to be transmissible spongiform encephalopathies

US NRC: US National Research Council

USDA: US Department of Agriculture

USFDA: US Food and Drug Administration

WHO: World Health Organization

WTO: World Trade Organization

[admin]

EXPERT PANEL ON THE FUTURE OF FOOD BIOTECHNOLOGY

Spencer C.H. Barrett, Ph.D., FRSC, Professor, Botany, University of Toronto

Joyce L. Beare-Rogers, CM, Ph.D., FRSC, Ottawa, Ontario

Conrad G. Brunk, Ph.D., Academic Dean and Professor, Philosophy, Conrad Grebel College,

University of Waterloo. Panel Co-Chair

Timothy A. Caulfield, LL.M., Associate Professor, Faculty of Law and Faculty of Medicine &

Dentistry, University of Alberta

Brian E. Ellis, Ph.D., Associate Director, Biotechnology Laboratory, Professor, Faculty of

Agricultural Sciences and the Biotechnology Laboratory, University of British Columbia.

Panel Co-Chair

Marc G. Fortin, Ph.D., Associate Professor and Chair, Department of Plant Science, McGill

University

Antony J. Ham Pong, M.B., F.R.C.P.(C) Paediatrics, Consultant in Allergy and Clinical

Immunology, Ottawa

Jeffrey A. Hutchings, Ph.D., Associate Professor, Biology, Dalhousie University

John J. Kennelly, Ph.D., Professor and Chair, Department of Agricultural, Food and Nutritional

Science, University of Alberta

Jeremy N. McNeil, Ph.D., FRSC, Professor, Biology, Université Laval

Leonard Ritter, Ph.D., Executive Director, Canadian Network of Toxicology Centres and

Professor and Associate Chair, Department of Environmental Biology, University of

Guelph

Karin M. Wittenberg, Ph.D., Professor and Head, Department of Animal Science, University of

Manitoba

R. Campbell Wyndham, Ph.D., Professor and Chair, Department of Biology, Carleton University

Rickey Yoshio Yada, Ph.D., Professor and Assistant Vice President Research, Agri-Food

Programs, University of Guelph

The opinions expressed in this report are those of the authors and do not necessarily represent

those of the Royal Society of Canada or the opinion or policy of Health Canada, the Canadian

Food Inspection Agency and Environment Canada.

MEMBERS OF THE EXPERT PANEL

Spencer C. H. Barrett, Ph.D., FRSC, Professor of Botany, University of Toronto: Dr. Barrett holds a doctorate in Botany from the University of California, Berkeley (1977) and was elected a Fellow of the Royal Society of Canada in 1998. His general research interests include plant evolutionary biology, evolutionary ecology and genetics, conservation biology, and plants and human affairs. His specific research has focused on such topics as plant reproduction, mating systems, biology of invading plants, and colonization genetics. He is the author of over 180 scientific publications and is co-editor of Floral Biology: Studies on Floral Evolution in Animal-pollinated Plants (1996).

Joyce L. Beare-Rogers, CM, Ph.D., FRSC, Ottawa, Ontario: Dr. Beare-Rogers received her doctorate in Lipid Biochemistry from Carleton University and joined the federal government’s Food and Drug Directorate (now the Health Products and Food Branch) in 1956, where she worked until her retirement in 1992. Dr. Beare-Rogers is an internationally recognized authority in the areas of nutrition, lipids, fatty acids and dietary oils and was the first Canadian, and the first woman, to hold the office of President of the American Oil Chemists’ Society. She was also President of the Canadian Society for Nutritional Sciences and is a Fellow of the Royal Society of Canada (elected 1989) and the American Institute of Nutrition.

Conrad G. Brunk, Ph.D., Academic Dean and Professor of Philosophy, Conrad Grebel College, University of Waterloo (Panel Co-Chair): Dr. Brunk was awarded a doctorate in Philosophy from Northwestern University in 1974 and has held a faculty position at the University of Waterloo since 1976. His areas of specialization include applied and professional ethics, including environmental and bio-medical ethics, and conflict resolution. In addition to scholarly publications, including the book Value Assumptions in Risk Assessment (1991), he is well known for his reports on risk management frameworks for animal health and food trade. He served as Chair of the Royal Society of Canada’s expert panel on the future of Health Canada’s non-human primate colony in 1996.

Timothy Allen Caulfield, LL.M., Associate Professor, Faculty of Law and Faculty of Medicine and Dentistry, University of Alberta: Mr. Caulfield received his LL.M. degree from Dalhousie University (1993) and has been Research Director of the Health Law Institute at the University of Alberta since 1993. He is the co-editor of Legal Rights and Human Genetic Material (1996), Canadian Health Law and Policy (1999), and The Commercialization of Genetic Research: Ethical, Legal and Policy Issues (1999), and the author of numerous publications in scholarly journals, including “Regulating the Genetic Revolution” (1999).

Brian E. Ellis, Ph.D., Associate Director, Biotechnology Laboratory, Professor, Faculty of Agricultural Sciences and the Biotechnology Laboratory, University of British Columbia (Panel Co-Chair): Dr. Ellis received his doctorate in Plant Biochemistry at the University of British Columbia in 1969 and was Head of UBC’s Department of Plant Science from 1989 to 1999); his main interests are in the area of plant metabolism, especially lignin biosynthesis. His current projects include biochemistry of metabolic enzymes, signalling mechanisms whereby plants sense and respond to environmental changes, oxidative stress, and the genetic engineering of crop and forest plants. He teaches sustainable agriculture and professional communication as well as plant breeding and plant–microbe interactions.

Marc G. Fortin, Ph.D., Associate Professor and Chair, Department of Plant Science, McGill University: Dr. Fortin received his doctorate in Plant Molecular Biology from McGill University in 1987 and did post-doctoral work at the University of Chicago and the University of California at Davis. He has been at McGill as faculty member since 1990. His research focuses on applying molecular genetics approachs to better understand interactions between plants and microbes and was one of the initiators of the use of DNA markers for plant improvement. He has spearheaded the organization of two large inter-university research networks focusing on understanding plant productivity, and is an advisor to several provincial and national organizations dedicated to research in plant science.

Antony J. Ham Pong, M.B., F.R.C.P.(C) Paediatrics, Consultant in Allergy and Clinical Immunology, Ottawa, Ontario: Dr. Ham Pong, who has specialist training in Immunology and Allergy and in Paediatrics, has a clinical practice, is a lecturer in Paediatrics and an instructor for the Allergy/ Immunology course at the University of Ottawa. He is a medical advisor to the Anaphylaxis Network of Canada, co-author of Anaphylaxis: A Handbook for Schools (1996), a frequent radio and TV commentator and guest lecturer on allergy issues. He has served on several task forces on Food Allergies and Anaphylaxis for Health Canada and other organizations. His professional publications include the recent co-authored study, Common Allergenic Foods and their Labelling in Canada — A Review (1999).

Jeffrey A. Hutchings, Ph.D., Associate Professor of Biology, Dalhousie University: Dr. Hutchings holds a doctorate in Evolutionary Ecology from Memorial University of Newfoundland (1991). Following research fellowships at Edinburgh University and the Department of Fisheries and Oceans (St. John’s, Newfoundland), Dr. Hutchings has focused his work on the ecology, reproductive behaviour, genetics and population biology of marine and freshwater fishes. Among his 60 scientific publications, approximately onehalf address environmental and genetic aspects of fish life histories, notably those of Atlantic salmon and other salmonids, and one third pertain to the collapse and recovery of Atlantic cod. An Associate Editor of Canadian Journal of Fisheries and Aquatic Sciences and Transactions of the American Fisheries Society, he has recently been appointed to the Committee on the Status of Endangered Wildlife in Canada (COSEWIC).

John J. Kennelly, PhD., Professor and Chair, Department of Agricultural, Food and Nutritional Science, University of Alberta: Dr. Kennelly holds a doctorate in Animal Nutrition from the University of Alberta (1980) and has been a Professor at the University of Alberta since 1987. He is a member of the Board of Directors of the National Institute of Nutrition and he has served as a member of the Alberta Science and Research Authority Biotech Task Force. In previous professional service, Dr. Kennelly was a member of the NSERC Animal Biology Grant Selection Committee for three years and Chair for one. He has also served as a member of the Editorial Board of Animal Science and was Chair of the American Dairy Science Association of Milk Synthesis Committee. Dr. Kennelly leads a research group at the University of Alberta that focuses on his primary scientific interest in nutrition and lactation physiology. Key areas of study are the nutritional and genetic factors that influence the biological efficiency of milk synthesis and its quality as a human food. Publications include over 120 refereed scientific papers, book chapters, conference proceedings as well as numerous extension articles.

Jeremy N. McNeil, Ph.D., FRSC, Professor of Biology, Université Laval: Dr. McNeil received his Ph.D. in Entomology and Ecology at North Carolina State University in 1972 and since then has been a professor in the Biology Department at Université Laval. His research is in chemical and behavioural ecology, looking for ecologically and socially acceptable alternatives to conventional pesticides. He is the author of over 130 scientific publications and serves on a variety of national and international scientific committees. He is also active in the public awareness of science, speaking to more than 2000 children annually. He was elected to the Royal Society of Canada in 1999.

Leonard Ritter, Ph.D., Executive Director, Canadian Network of Toxicology Centres and Professor and Associate Chair, Department of Environmental Biology, University of Guelph: Dr. Ritter holds a doctorate in Biochemistry from Queen’s University (1977) and has been a professor at the University of Guelph since 1993. He is the founding Executive Director of the Canadian Network of Toxicology Centres, based at the university, which involves the coordination of a national, multi-disciplinary toxicology research program. From 1977 to 1993, he worked in various positions at the Health Protection Branch of Health Canada, with responsibilities for the regulation of pesticides and veterinary drugs. He has publications, technical reports or responsibilities on international bodies in the areas of pesticides residues in foods, pesticides exposure and cancer, persistent organic pollutants, food additives, endocrine modulating substances, and the use of hormones in food production.

Karin M. Wittenberg, Ph.D., Professor and Head, Department of Animal Science, University of Manitoba: Dr. Wittenberg has a doctorate in Ruminant Nutrition from the University of Manitoba (1985), where she is now a professor and currently serves as Head of the Department of Animal Science and the Director of the Ruminant Research Unit. She was an invited member (1995–99) of the Committee on Animal Nutrition of the US National Research Council, including its Biotechnology Advisory Council on Microbial Products as Livestock Feed, and for 10 years a member of the Expert Committee on Animal Nutrition of the Canadian Agricultural Services Coordinating Committee. Her research is in the areas of forage utilization, harvest and post-harvest practices, microbial processes in forage, and the use of forage additives; among her publications are a co-authored book, The Role of Chromium in Animal Nutrition, and a review article on “the role of additives in hay production.”

R. Campbell Wyndham, Ph.D., Professor and Chair, Department of Biology, Carleton University: Dr. Wyndham received his doctorate in Biology from the University of Calgary in 1982 and has been a member of both the Institute of Biochemistry and the Institute of Biology at Carleton since 1987. He specializes in studies of microbial ecology, including the ecology and genetics of pollutant-degrading bacteria (particularly in wastewater), and also is increasingly active in applying molecular techniques to understanding how genetically modified microorganisms behave in agricultural ecosystems. In the course of studying the ecological risks of biotechnology, his laboratory is developing rapid and simple soil microcosm and DNA-detection protocols to assess gene transfer frequencies. For the past 10 years, he has contributed expert advice to federal departments on the new substances notification regulations for products of biotechnology under the Canadian Environmental Protection Act.

Rickey Yoshio Yada, Ph.D., Professor and Assistant Vice President Research, Agri-Food Programs, University of Guelph: Dr. Yada was awarded a doctorate from the Department of Food Science at the University of British Columbia in 1984. He has been a faculty member at Guelph since that time, has served as Chair of the Department of Food Science, and currently is the Assistant Vice President Research, Agri-Food Programs. His primary research focus is on structure–function relations of food-related proteins, and he has specialized in the study of potatoes. He has been a member or chair of numerous NSERC research awards panels and committees and is currently one of the Life Science Group Chairs for NSERC, and a member of the Committee on Research Grants. He was Editor-in-Chief of Food Research International Journal from 1992 to 1998 and now is the North American Editor for Trends in Food Science and Technology. He is the author of over 100 refereed journal publications and the co-editor of two major books in his field, Functional Properties of Food Components (1998) and Protein Structure–Function Relationships in Food (1994)