By Fred Pearce
New Scientist (UK)
Published June 17, 2002
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For environmentalists, the work was proof of the dangers of genetic modification. Transgenes had spread to traditional maize varieties grown in Mexico. Then the journal Nature disowned the research paper, prompting claims that it had given in to a campaign orchestrated by the biotech industry. But why were the authors' strongest critics their own colleagues? Here, we reveal the extraordinary goings-on behind the headlines.
The saga began in September 2001. The Mexican environment ministry announced that DNA from genetically modified maize had been found in native varieties grown on small farms.
The results were, not surprisingly seized upon by campaigners opposed to GM crops. And in November, they were given more ammunition when the findings were published in the prestigious journal Nature. Then, this April, things took a confusing turn. In an unprecedented move, Nature declared that it regretted publishing the paper, and ran two letters that claimed the research was fatally flawed.
The turnaround has generated even more coverage than the original finding. It is the first time Nature has ever disowned a paper in defiance of its authors and referees. Some suspect foul play, claiming that representatives of the biotechnology industry orchestrated a campaign of letters and petitions criticising the original paper. But the paper's critics at the University of California, Berkeley where the key protagonists in this saga have all worked, may not have needed any outside encouragement.
The paper's authors -- graduate student David Quist, an environmental scientist, and his professor, Mexican plant biologist Ignacio Chapela, were already hate figures on the Berkeley campus. In 1998, they had campaigned unsuccessfully to prevent the university striking an extraordinary alliance with the Swiss biotech company Novartis. The deal, signed amid student protests and piethrowing, gave Novartis the rights to cherrypick the best plant research for development in exchange for up to $50 million. But while the protesters see it as compromising academic freedom, many in the Department of Plant and Microbial Biology owe their jobs to the deal with what's now called Syngenta.
Two years later, on the night of 11 October 2000, environmental activists destroyed GM maize being grown at Berkeley by students of Mike Freeling, who is a member of the department. The group told a local paper that they had tested the maize to make sure it was genetically modified.
The angry researchers feared an inside job, and initially pointed the finger at Quist. "Just prior to the vandalism, Quist had requested primers from some of the corn geneticists in my department that might be used to identify transgenics in the field," Steven Lindow, a senior professor in the department, told New Scientist. His colleagues "became concerned, and became even more suspicious after the vandalism", he says.
A fortnight after the crops were destroyed, Lindow spoke to Quist's professor, Chapela, about the allegations. Today Lindow says he quickly accepted that Quist was innocent. But Quist says that the allegation festers on, and "has led to irrevocable damage to my academic credibility".
At the time of the field trashing, Quist was in the Mexican state of Oaxaca, collecting samples of maize from farmers' gelds. When the research based on these samples hit the headlines a year later, it was potentially far more damaging to the careers of biotechnologists at Berkeley than heavy boots in a field at midnight.
Quist and Chapela first used PCR, the standard DNA amplification technique, to detect the DNA sequences engineered into Bt maize grown in the US. "This is a standard method of detection used by regulatory agencies in Europe and elsewhere," says Quist. It can generate false positives, he agrees. But the pair say that results from their controls show "beyond reasonable doubt" that the sequences are present in a few samples of the native strains from remote regions in Mexico.
The pair then used a related technique called inverse PCR to discover the precise position of the transgenic sequences. This seemed to show that the added DNA had fragmented and scattered throughout the maize genome -- the finding that triggered an outcry among scientists.
The authors are still fuelling the dispute. "It suggests that transgenic DNA can move around the genome with a range of unpredictable effects, from disruption of normal functions to modification of expressed products that become toxic agents to the generation of new strains of bacteria and viruses," Quist told New Scientist this month.
The two critical letters published by Nature in April attacked this second finding. And Quist and Chapela conceded that there were flaws, when, in a letter that Nature published at the same time, they said: "We acknowledge that our critics' assertion of the misidentifying of sequences . . . is valid."
New genetics & hazards of genetic modification
The rationale and impetus for genetic engineering and genetic modification was the "central dogma" of molecular biology that assumed DNA carries all the instructions for making an organism. This is contrary to the reality of the fluid and responsive genome that already has come to light since the early 1980s. Instead of linear causal chains leading from DNA to RNA to protein and downstream biological functions, complex feed-forward and feed-back cycles interconnect organism and environment at all levels, marking and changing RNA and DNA down the generations. In order to survive, the organism needs to engage in natural genetic modification in real time, an exquisitely precise molecular dance of life with RNA and DNA responding to and participating fully in "downstream" biological functions. That is why organisms and ecosystems are particularly vulnerable to the crude, artificial genetically modified RNA and DNA created by human genetic engineers. It is also why genetic modification can probably never be safe.
1. Genetic modification done by human genetic engineers is anything but precise; it is uncontrollable and unpredictable, introducing many collateral damage to the host genome as well as new transcripts, proteins and metabolites that could be harmful.
2. GM feed with very different transgenes have been shown to be harmful to a wide range of species, by farmers in the field and independent scientists working in the lab, indicating that genetic modification itself is unsafe.
3. Genetic modification done by human genetic engineers is different from natural genetic modification done by organisms themselves for the following reasons: it relies on making unnatural GM constructs designed to cross species barriers and jump into genomes; it combines and transfers genes between species that would never have exchanged genes in nature; GM constructs tend to be unstable and hence more prone to further horizontal gene transfer after it has integrated into the genome.
4. Horizontal gene transfer and recombination is a major route for creating new viruses and bacteria that cause diseases and spreading drug and antibiotic resistance. Transgenic DNA is especially dangerous because the GM constructs are already combinations of sequences from diverse bacteria and viruses that cause diseases, and contain antibiotic resistance marker genes.
5. There is experimental evidence that transgenes are much more likely to spread and to transfer horizontally.
6. The instability of the GM construct is reflected in the instability of transgenic varieties due to both transgene silencing and the loss of transgenes, for which abundant evidence exists. Transgenic instability makes a mockery of "event-specific" characterization and risk assessment, because any change in transgene expression, or worse, rearrangement or movement of the transgenic DNA insert(s) would create another transgenic plant different from the one that was characterized and risk assessed. And it matters little how thoroughly the original characterization and risk assessment may have been done. Unstable transgenic lines are illegal, they should not be growing commercially, and they are not eligible for patent protection.
7. There is abundant evidence for horizontal transfer of transgenic DNA from plant to bacteria in the lab and it is well known that transgenic DNA can persist in debris and residue in the soil long after the crops have been cultivated. At least 87 species (2 % of all known species) of bacteria can take up foreign DNA and integrate it into their genome; the frequency of that happening being greatly increased when a short homologous anchor sequence is present.
8. The frequency at which transgenic DNA transfers horizontal has been routinely underestimated because the overwhelming majority of natural bacteria cannot be cultured. Using direct detection methods without the need to culture, substantial gene transfers were observed on the surface of intact leaves as well as on rotting damaged leaves.
9. In the only monitoring experiment carried out with appropriate molecular probes so far, China has detected the spread of a GM antibiotic resistance gene to bacteria in all of its major rivers; suggesting that horizontal gene transfer has contributed to the recent rise in antibiotic resistance in animals and humans in the country.
10. GM DNA has been found to survive digestion in the gut of mice, the rumen of sheep and duodenum of cattle and to enter the blood stream.
11. In the only feeding trial carried out on humans, the complete 2,266 bp of the epsps transgene in Roundup Ready soybean flour was recovered from the colostomy bag in 6 out of 7 ileostomy subjects. In 3 out of 7 subjects, bacteria cultured from the contents of the colostomy bag were positive for the GM soya transgene, showing that horizontal transfer of the transgene had occurred; but no bacteria were positive for any natural soybean genes.
12. The gastrointestinal tract of mammals is a hotspot for horizontal gene transfer between bacteria, transfer beginning in the mouth.
13. Evidence is emerging that genomes of higher plants and animals may be even softer targets for horizontal gene transfer than genomes of bacteria.
14. The CaMV 35S promoter, most widely used in commercial GM crops, is known to have a fragmentation hotspot, which makes it prone to horizontal gene transfer; in addition. it is promiscuously active in bacteria, fungi, as well as human cells. Recent evidence also suggests that the promoter may enhance multiplication of disease-associated viruses including HIV and cytomegalovirus through the induction of proteins required for transcription of the viruses. It also overlaps with a viral gene that interferes with gene silencing, an essential function in plants and animals that protects them against viruses.
15. The Agrobacterium vector, most widely used for creating GM plants is now known to transfer genes also to fungi and human cells, and to share genetic signals for gene transfer with common bacteria in the environment. In addition, the Agrobacterium bacteria as well as its gene transfer vector tend to remain in the GM crops created, thereby constituting a ready route for horizontal gene transfer to all organisms interacting with the GM crops, or come into contact with the soil on which GM crops are growing or have been grown.
16. In 2008, Agrobacterium was linked to the outbreak of Morgellons disease. The Centers for Disease Control in the US launched an investigation, which concluded in 2012, with the finding: "no common underlying medical condition or infection source was identified". But they had failed to investigate the involvement of Agrobacterium.
17. New GM crops that produce double-stranded RNA (dsRNA) for specific gene-silencing are hazardous because many off-target effects in the RNA interference process are now known, and cannot be controlled. Furthermore, small dsRNA in food plants were found to survive digestion in the human gut and to enter the bloodstream where they are transported to different tissues and cells to silence genes.
18. Evidence accumulated over the past 50 years have revealed nucleic acids (both DNA and RNA) circulating in the bloodstream of humans and other animals that are actively secreted by cells for intercommunication. The nucleic acids are taken up by target cells to silence genes in the case of double-stranded microRNA (miRNA), and may be integrated into the cells' genome, in the case of DNA. The profile of the circulating nucleic acids change according to states of health and disease. Cancer cells use the system to spread cancer around the body. This nucleic acid intercom leaves the body very vulnerable to genetically modified nucleic acids that can take over the system to do considerable harm.
-- Ban GMOs Now: Especially in the Light of the New Genetics, by Dr Mae-Wan Ho and Dr Eva Sirinathsinghji
In less fraught circumstances, a partial retraction of the original paper might have been enough to satisfy both sides. But Nature demanded the authors retract the whole paper, and they refused. So the journal ran its own unprecedented disavowal, in the same issue as the critical letters. This asserted that "in the light of diverse advice received . . . the evidence available is not sufficient to justify the publication of the original paper".
Quist and Chapela point out that, whatever technical failings might have emerged after publication, their paper had been approved by three anonymous referees. It must have had some merit. And when it and the letters of complaint were submitted to three more referees, two of them specifically noted that none of the comments disproved the conclusion that transgenic corn is growing in Mexico.
"The main finding is not controversial or really being challenged, " says Quist. "Neither of the two letters published in Nature, purportedly showing fatal flaws in our paper, ever questioned our main discovery." Nature has not responded directly to New Scientist's questions about why it would not accept the authors' partial retraction. "Nature has never said that the paper's conclusions are wrong," is all editor Philip Campbell will say. "We have said that they are not convincing on the basis of the evidence that we have published." He denies that a campaign against Quist and Chapela influenced his decision to demand a retraction of their paper -- and to disown it when they refused.
But a campaign there certainly was. Demands that the paper be retracted appeared on Internet biotech forums the day it was published, and continued with mounting vehemence. Yet two of the first, most persistent and apparently scientifically qualified complainants on the Net, "Mary Murphy" and "Andura Smetacek", appear not to be real people. A British anti-GM campaigner, Jonathan Matthews of the Norfolk Genetic Information Network, claims to have tracked their electronic personas to the offices and computer equipment of the Bivings Group in Washington DC, a PR company that has Monsanto as one of its clients. Bivings initially denied everything but has since admitted that one of the emails came from a Bivings' employee or client.
But what has raised most eyebrows is the identity of the scientists whose two letters attacking the paper appeared in Nature. "The antagonists signing the letters are all connected directly with [Berkeley's] local political scandal," says Chapela.
One was co-written by Freeling and Nick Kaplinsky who is also a senior figure at the same department at Berkeley. The other was by Matthew Metz, a former Berkeley microbiologist who was a vocal supporter of the Novartis alliance, and Johannes Futterer, a young Swiss researcher whose boss, Wilhelm Gruissem, was at Berkeley four years ago and was widely regarded as "the man who brought Novartis to Berkeley".
Quist and Chapela believe the animosities created by the furore over the deal, and inflamed by the crop trashing, must be an element in the row over their paper. Kaplinsky denies this. "This issue is strictly about science. Quist and Chapela published bad science and should have done the honourable thing -- retract their paper and apologise."
June 22, 2012
What I did not do was what some experts advise when hit with a DIRA, which is to issue apologies on Twitter. Marc Randazza suggested this, but I just blew it off. Seriously, why would I apologize for doing things I do all the time, and will very likely keep doing for the rest of my employed life? Basically my entire employment is threatening companies and people, except when I’m protecting them from threats, which, however, I do by means of counterthreats. So if Inman gets a pass because he’s an asshole, I’m fucked. In response to my perseverance in inflicting legal punishment upon those who have besmirched the memory of my mother, Tech Crunch and Popehat are posting that “Carreon is still digging,” and really clever jokes about China begin to pop up. Displays of true wit in this crowd are extremely rare. The business of rapeutationing is serious. After all, we’re trying to destroy somebody here. So clichés are more appropriate to this type of work, true humor has no place here, and all these posters have, in my view, declared that they do not hold their mothers, or anyone’s mother, in special regard. They are, to quote The Three Amigos, the “sons of a motherless goat.” Hehe.
Why not go out and address the mob? The opportunity to comment and reply in online forums is entirely illusory once you have been tagged as a douchebag, and thousands of trolls are roaming around online, just aching with a desire to declare that they went mano-a-mano with Charles Carreon and handed him his ass. These trolls are networked, and will collect like cops around a crime-in-progress with endless amounts of verbal ammo to dispatch. I watched a good friend of mine who tried to say good things about me on his own blog eight months after the initial rapeutation kickoff in June 2012. These networked trolls obviously have Google alerts on “Charles Carreon,” so they can immediately attack or add fuel to any fire where the fires of the neverending DIRA are still burning. They discovered that my friend was engaging in douchebaggery by trying to help me out with a little good press, truthfully posting that I had been helping him a lot with his business, and that I was the kind of lawyer who was helpful when times are tough. Like Scientologists descending upon a suppressive who’s been newly-marked as “fair game,” the Charles Carreon rapeutationists simply added my friend to their list of people to fuck and set his reputation on fire at a thread in Tech Crunch. Some of his competitors showed up to declare him a disgrace to his profession for even working with Charles Carreon. When my friend started posting at Tech Crunch to answer the abuse, his bold sallies were quickly repulsed with loads of invective that would have sunk a garbage ferry. He quickly retreated, punched silly by a gang of rapeutationists who had finally got a chance to release that blast of hateful steam I’d been avoiding for the better part of the prior year. I’d sooner try and wrestle a zombie for a fresh brain than engage those TechCrunchers on their terrain. You don’t have to read Sun Tzu to know that.
-- The Real Diary of Charles Carreon, by Charles Carreon
But Kaplinsky doesn't stop there. "Since they seem incapable of admitting their mistakes, they are raising non-scientific issues like the Novartis agreement with our department, vendettas, global conspiracies. Anything so they can avoid talking about the fact that they published artefactual data and then misinterpreted it."
Campbell says he wasn't aware of the allegations surrounding the crop trashing incident when he accepted the letters. But he says it would not have influenced his decision to publish. Neither Nature nor Campbell are poodles of the biotech industry. Campbell himself wrote a hostile editorial about the Berkeley-Novartis deal. But Quist still insists that it was political pressure that brought about the journal's actions. Whoever is right, the row reveals an alarming breakdown in scientific discourse. In the aftermath of the affair, Campbell wrote that it must have been Murphy's law that ensured the journal's embarrassing climb-down "was in relation to one of the most hotly debated technologies of our time". Others see it as more than an accident. They fear that the affair has put the system of peer review to the test, and found it wanting.
The spectre of unseen actors manipulating events is particularly worrying. In its disavowal, Nature asked its readers to make up their own minds about the science behind the row. But it failed to alert them to the private rows behind the public letters. Nor did it reveal the identities and affiliations of the five referees who broadly supported the original paper, or the sixth who appears to have persuaded Nature to make a retraction.
Also out of sight are the individuals behind "Mary Murphy" and "Andura Smetacek", not to mention the people who trashed Freeling's field two years ago. Strange what dark shadows are thrown up by the harsh glare of publicity.
While I was writing the last piece, Bivings sent me an email fiercely denying that it had anything to do with the fake correspondents "Mary Murphy" and "Andura Smetacek", who started the smear campaign against the Nature paper. Last week I checked the email's technical properties. They contained the identity tag "bw6.bivwood.com". The message came from the same computer terminal that "Mary Murphy" has used. New research coordinated by the campaigner Jonathan Matthews appears to have unmasked the fake persuaders: "Mary Murphy" is being posted by a Bivings web designer, writing from both the office and his home computer in Hyattsville, Maryland; while "Andura Smetacek" appears to be the company's chief internet marketer.
-- Corporate phantoms: The web of deceit over GM food has now drawn in the PM's speechwriters, by George Monbiot