by Lynn C. Klotz, The Center for Arms Control and Non-Proliferation, Washington, DC, USA; and Edward J. Sylvester, Science and Medical Journalism, Walter Cronkite School of Journalism and Mass Communication, Arizona State University, Phoenix, AZ, USA
Frontiers in Public Health
August 11, 2014
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In letters to the journals Science and Nature (1, 2), 22 virologists notified the research community of their interest in expanding research to develop strains of the already deadly H7N9 Asian influenza virus that would be transmissible via aerosols among mammals, thus creating potential pandemic pathogens. PPPs are defined as pathogens that are potentially highly contagious, potentially highly deadly, and not currently present in the human population. Mammalian contagious avian flu, the 1918 pandemic flu, and SARS are examples. The letter writers cite their scientific reasons for the need for such research, much the same reasons as given by those working on similar projects for the H5N1 avian flu virus (3, 4). This new proposed research signals wider interest in making dangerous influenza viruses (5, 6) contagious in mammals via respiratory aerosols. At present, there are no international regulations or guidelines in place to decide whether such a research project should proceed.
Now is the time to address the next critical question: what is the likelihood that one of these viruses will escape from a lab and seed the very pandemic the researchers claim they are trying to prevent? As we shall estimate, that probability could be as high as 27%, a risk too dangerous to live with.
First, from the calculations in two in-depth pandemic risk analyses (7–9), there is a substantial probability that a pandemic with over a 100-million fatalities could be seeded from an undetected lab-acquired infection (LAI), if a single infected lab worker spreads infection as he moves about in the community. From the Klotz (2014) analysis, there is about a 1–30% probability, depending on assumptions, that, once infected, the lab worker will seed a pandemic. This large probability spread arises from varying the average number of people infected by an infected person between 1.4 and 3.0 (R0, in standard epidemiology notation), varying the details of commutes to and from work on public transportation, and whether infected acquaintances are quarantined before spreading infection. The Merler (2013) study, based on a computer-generated population grid of size and varying density of the Netherlands, supports our concern over a lab escape not being detected until it is too late: “there is a non-negligible probability (5–15%), strongly dependent on reproduction number and probability of developing clinical symptoms, that the escape event is not detected at all.”
Different methodologies were used in the Klotz (2014) and Merler (2013) risk analyses. Additional analyses are needed using other methodologies, such as the mathematical model employed for SARS (10), which hopefully will lead to some consensus on risk. The Klotz and Merler studies, however, are the first to raise these concerns and point to valid issues about the potential risks from a single LAI.
Given such a dire predicted outcome by the existing studies, the critical question is: what is the probability that a worker acquires an undetected infection in the lab in the first place? To answer this question, we reproduce here one part of the Klotz (2014) analysis: the probability of an escape through an LAI from at least one of the many labs expected to be involved in this research enterprise.
A 2013 Centers for Disease Control report is a significant source of recent data on LAIs (11). The report documents four undetected or unreported LAIs in registered US Select Agent, high-containment BSL-3 labs between 2004 and 2010. An undetected or unreported LAI implies an escape when the infected person leaves the lab. The report identifies an average of 292 registered Select Agent BSL-2, BSL-3, and BSL-4 labs operating over those 7 years, for a total of 292 × 7 = 2,044 lab years. Unfortunately, the study does not break down numbers into BSL-2, BSL-3, and BSL-4 labs or lab years.
Thus, the probability of escape for a single year, p1, can only be calculated as 4 LAIs/2,044 lab years = 0.002 or 0.2% per lab per year. This is clearly an underestimate since BSL-2 and BSL-4 labs contribute to the denominator. (The denominator used here, 2,004, equals the number of BSL-2 plus number of BSL-3 plus number of BSL-4 labs. But the denominator in our calculation should be just the number of BSL-3 labs, so the denominator is overestimated and the percent escape is then underestimated. Although requested, the CDC has not supplied us with the number of BSL-3 labs for us to do the exact calculation.) This basic probability is consistent with that for SARS escapes in Asia through LAIs (12) and with all known escapes from BSL-4 labs in the Soviet Union from LAIs and Great Britain from a mechanical failure (13).
To illustrate potential risk, the probability of no escape from a single lab in a single year is (1 − p1), so
pno=(1− p1)N × Y (1)
is the probability of no escape from N labs in Y years. And
pat least one= 1−(1− p1)N×Y (2)
is the probability of at least one escape from N labs in Y years.
Given the Science and Nature articles listed above (1, 2), it is reasonable to assume that at least 10 labs will undertake this research and that this work would continue for 10 years, so
pat least one= 1−(1−0.002)10×10= 0.18 (3)
or an 18% likelihood of at least one escape from at least one lab for the whole research enterprise, almost 100-times greater than the likelihood for a single lab in a single year.
We noted above that the probability p1 = 0.2% is conservative, estimated from the CDC data alone. The first Department of Homeland Security risk assessment for the planned National Bio- and Agro-Defense Facility in Manhattan, Kansas estimated a significantly higher escape risk, over 70% likelihood for the 50-year life of the facility (14), which works out to be a basic probability of escape, p1 = 2.4% per year. The National Research Council (14) overseeing the risk assessment remarked “The … estimates indicate that the probability of an infection resulting from a laboratory release of FMDv from the NBAF in Manhattan, Kansas approaches 70% over 50 years (see Figure 3-1) with an economic impact of $9–50 billion. The committee finds that the risks and costs could well be significantly higher than that…” While the DHS subsequently lowered the escape risk to 0.11% for the 50-year lifetime (14), the NRC committee (14) was highly critical of the new calculations: “The committee finds that the extremely low probabilities of release are based on overly optimistic and unsupported estimates of human error rates, underestimates of infectious material available for release, and inappropriate treatment of dependencies, uncertainties, and sensitivities in calculating release probabilities.” We have more trust in the NRC committee conclusions, as they have no skin in the game.
With this higher number, which we take as a worst-case scenario, the likelihood of at least one escape from 10 labs in 10 years becomes 91%, almost a certainty. It follows that, if the likelihood of one LAI leading to a pandemic is 30% in the worst-case scenario, the likelihood of an LAI-caused pandemic resulting from this whole research enterprise could be as high as 30 × 91% = 27%, a likelihood that is too dangerous to live with, as we noted. While this represents a worst-case scenario, it is not improbable.
Recent self-reported mistakes at the CDC (15), involving a particularly deadly strain of anthrax removed from BSL-3 containment and H5N1 Asian bird flu released from the CDC laboratories altogether, lend support to our concern that the probability of escape may be much greater than the 0.2% per lab per year from just LAIs. The CDC report spawned a congressional inquiry (16) and led to dozens of newspaper articles with concerns about lack of safety in high-containment laboratories.
Our concern is shared by many virologists and epidemiologists. A recent letter to the President of the European Commission (17) co-signed by 56 scientists from more than a dozen countries warned, “The probabilities of a lab accident that leads to a global spread of an escaped mutated virus are small but finite, while the impact of global spread could be catastrophic.” The European Centre for Disease Prevention and Control (18) weighed-in with its concerns as well, as did the Cambridge Working Group (19). It must be noted that some of the signers of the European Commission letter and the Cambridge Working Group’s consensus statement are the same.
The risk of a man-made pandemic from a lab escape is not hypothetical. Lab escapes of high-consequence pathogens resulting in transmission beyond lab personnel have occurred (20, 21). The historical record reveals lab-originated outbreaks and deaths due to the causative agents of the 1977 pandemic flu, smallpox escapes in Great Britain, Venezuelan equine encephalitis in 1995, SARS outbreaks after the SARS epidemic, and foot and mouth disease in the UK in 2007. Ironically, these labs were working with pathogens to prevent the very outbreaks that they ultimately caused.
Do benefits outweigh risks? Those who support PPP experiments either believe the probability of PPP escape is infinitesimal or the benefits in preventing a pandemic are great enough to justify the risk. In making decisions for what lines of research will lead to new knowledge, experts must rely on intuition honed by years of research in a particular field. In the case of this PPP research, in our opinion it would take extraordinary benefits and significant reduction of risk via extraordinary biosafety measures to correct such a massive overbalance of highly uncertain benefits to too-likely risks (Wain-Hobson, 2013).
Whatever number we are gambling with, it is clearly far too high a risk to human lives. This Asian bird flu virus research to develop strains transmissible via aerosols among mammals, and perhaps some other PPP research as well, should for the present be banned. We must emphasize that we have been considering only a very small subset of pathogen research. Most pathogen research should proceed unimpeded by unnecessary regulations.
Special precautions in BSL-4 laboratories for work with PPPs should be adopted (22). These would include:
• Training a full-time technical staff for work with PPPs. Experiments could be directed by scientists outside the laboratory using modern audio-video technology.
• Requiring the staff to follow up extended work shifts with periods of quarantine before they leave the containment area to assure that no PPP escapes from the containment area through an LAI.
• Restricting these PPP laboratories to remote locations, where an aerosol escape or other containment failure would pose the least risk of infecting an outside community.
We label BSL-4 laboratories with the special precautions, BSL-4+. While PPP experiments would be carried out primarily under BSL-4+ containment, BSL-3 containment with the special precautions might suffice for some work.
Given the global threat, the international community should insist on discussions leading to an international agreement that would require the strictest oversight to conduct this particular research anywhere. To place responsibility with the international community where it belongs and to provide maximum transparency, policy makers should require that international inspectors have access to facilities at any time on short notice.
As it stands, there is no proactive oversight nor regulations for this PPP research, so any and all of the world’s nations can carry out this dangerous work without regard to consequences. But consequences would be shared by all of us. In the meantime, insurance companies who routinely provide insurance for biological research should consider excluding such risky research from coverage.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
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17. Wain-Hobson S. Response to Letter by the European Society for Virology on “Gain-of-Function” Influenza Research. The Foundation for Vaccine Research (2013). Available from: http://www.nature.com/polopoly_fs/7.145 ... letter.pdf
KNAW has invited two scientists who contributed to the debate on gain-of-function by writing a letter to the president of the EU-Commission, Mr Barroso. In his capacity as chairman of the European Society for Virology, professor Giorgio Palù, asked attention for the potential benefits of this kind of research. Professor Simon Wain-Hobson, chairman of the Foundation for Vaccine Research, responded with a letter undersigned by 56 other scientists -- that challenged the arguments in favour. In their opening statements both Dr Palù and Dr Wain Hobson will explain and elaborate their main arguments.
Following their presentations both speakers will –- for the first time -– have a debate with each other. Of course there will be attention for the more scientific aspects of gain-of-function research. However, the political and societal debate was not only –- and probably not even in the first place – on science, but even more on the security aspects. One of the reasons for the debate is the risk of bioterrorism: the creation of a pandemic by terrorists having the knowledge and the biological agents. Since the attack with anthrax letters in the USA life scientists know -– or should know -– that this is a real issue of concern. How to deal with it, as science and as society?...
PRESENTATION SIMON WAIN-HOBSON
His main thesis for this debate is as follows: gain-of-function avian influenza research is frighteningly out of touch. The flu that worries us is that among humans. Influenza viruses are characterized by two kinds of proteins called H (hemagglutinin) and N (neuraminidase) at the surface of the virus that allow it to get into and out of cells. Human pandemics have been provoked by H1N1 (Spanish flu 1918, 1977 and 2009), H2N2 (Asian flu, 1957) and H3N2 viruses (Hong Kong flu, 1968). By contrast the greatest reservoir of influenza viruses is among ducks, birds and chickens and they rarely cross over to humans. Occasionally an epidemic of avian flu spills over to humans and can give rise to hundreds of H7N9 infections in man in a matter of months. Fortunately, these viruses are almost never transmitted from human to human. This is the same as with the rabies virus. Such dead end infections are not new in virology. The question is could these viruses become transmittable between humans and if so how? In modern virological parlance, what mutations are necessary to convert such a virus into a highly transmissible virus between ferrets, the animal of choice in influenza biology. This is the basis of the H5N1 projects of Fouchier and Kawaoka. As is now well known, they succeeded in doing this for the H5N1 virus and it involved a handful of mutations.
It should be emphasized that the conditions in a laboratory differ enormously from those in nature. Influenza virus evolution takes years, while in a laboratory there is a massive acceleration thanks to the selection of mutants by the virologist. To illustrate this, suffice to say that for some reason nature has not yet succeeded in morphing any influenza virus into a major human pathogen other than H1N1, H2N2 and H3N2 in 100 years. Even the resurrection of the Spanish flu HIN1 virus did not help us to predict or prepare for the H1N1 flu pandemic of 2009.
This is one of the major scientific weaknesses in the so-called gain-of-function influenza research. We do not know if the experiments reflect what happens in nature. As an HIV expert he can say this because the lab is not a good template for what happens in the clinic. There are hundreds of possible trajectories and only a few can be tested in laboratory. One can never know which are the “right ones” – that can only be appreciated as being “right” once the pandemic has struck. As for obvious ethical reasons these experiments cannot be done in humans, an important objection to this work is that it is not falsifiable. This constitutes a real issue as science tries to solve problems, not to create them.
He gave two examples of quantum jumps in recent gain-of-function influenza research. An ostrich H7N1 virus was selected to become droplet transmissible between ferrets. It did not lose lethality -- three out of five animals died (Sutton et al., J Virology 88, 6623 (2014)). A 60% lethality rate is much greater than the 2% that characterized Spanish flu. We must realize that until now no case of H7N1 in humans has been reported, so it is no threat to humans. The world is becoming a more dangerous place by making the virus aerosol transmittable. The second example is an unpublished experiment from Dr Kawaoka. He engineered the human 2009 pandemic H1N1 virus to escape neutralization by convalescent sera. By doing this the virus escaped vaccine coverage. It needs no explanation that if there ever were a lab accident the consequences could be enormous because this virus is unquestionably transmissible between humans.
The benefits of this kind of research: Scientists are used to work with the probability of benefits versus risks, just as they are used to handling dangerous agents. One of the arguments in favour of this gain-of-function research is developing vaccines and drugs. GOF research has nothing to offer for making vaccines. Development of vaccines is a very time-consuming and expensive effort. Moreover, each strain of influenza virus would need its own vaccine. And as mentioned above there is a great number of possible strains. And as it cannot be predicted which strain will cause an epidemic, this kind of research does not have much utility. Developing and stockpiling these vaccines would cost an enormous amount of money. As for drugs the choice is binary: we must hope that the next pandemic strain is sensitive to available drugs and use them accordingly. If the strain is resistant, it will take too long for the new drugs to be tested -– by then the pandemic will be over.
Now the risks of gain-of-function research: There is always the risk of an accident. For a virus that the human system has never seen this could lead to millions of deaths. Wain-Hobson does not call this risk, but catastrophic risk. But there are also less catastrophic outcomes, e.g. the equivalent of a seasonal flu outbreak where mortality is less than a million. The economic burden of seasonal flu costs a lot of money (say $71-167 bn/year to US economy alone). What would be special in the event of release of a lab engineered virus is that it is genetically ‘barcoded’. It would be trivial to trace the origin. Massive liability claims would be sought for the unwarranted deaths and economic damage. Liability experts (e.g. from RAND corporation) say that this really could lead to claims of 100 billion dollars and more, an amount that no insurance company would be willing, or able, to pay. Liability of this magnitude would jeopardize the existence of private universities and institutions such as the Institut Pasteur or even Harvard.
Some scientists argue that there is not much guidance on these biosafety issues. Of course there is the Fink report of 2004 (NRC -- National Research Council (2004), Biotechnology Research in an Age of Terrorism. Washington DC: National Academies of Science). And there is the InterAcademy Panel 2007 Statement on Biosecurity. This statement has been signed by 76 Academies of Sciences, such as KNAW, Royal Society, Leopoldina and the US NAS. Basically this statement says that scientists have an obligation to do no harm (the Hippocratic oath). It also says that individual good conscience of scientists does not imply that one can ignore the possibility of misuse. However, many scientists do so. Scientists are responsible for the knowledge they produce and publish. The statement also refers to the necessity of oversight over the research. This certainly is relevant for funders but also journal editors should adhere to these principles in making their decisions on the publication of dual use research. Amazingly hardly anyone knows about this document. It is good to have such a statement, but it is important that people know about it! So, maybe there is not so much a lack of guidance, but a lack of good communication of that guidance. For the moment scientists effectively transfer their biosafety and biosecurity problems to journal editors who have to handle them at “5 minutes before midnight”.
From his point of view we should freeze on gain-of-function research, because not doing so means waiting for an accident. With this breathing space virologists can look for more coordination and cooperation in taking safety and security measures, because they are very divergent now. Very important –- and Giorgio Palù and Simon Wain-Hobson agree on this -– is having more debates with more stakeholders getting in; lawyers, defence experts, insurance companies, etc. We need more risk–benefit analysis, although with the disagreement among virologists, it seems hard to get an agreement on the benefits. For the moment learned societies, governments and funders do little to advance this field. They fund and support this research without taking care of risk or liability.
Wain-Hobson finishes with this statement: On 22 March 2012, Russian president-elect Vladimir Poutin [Putin] promised to develop new weapons based on advanced technologies, including genetics (Raymond Zilinskas, The Soviet biological warfare program and its uncertain legacy, Microbe v9, p151, 2014). Although the Soviet Union was one of the initiators and first signatories and depository state of the Biological and Toxin Weapons Convention, there are clear signals that they went on with research and development of biological weapons until 1990. It has never been verified, because that was not possible for political reasons. So, how do we understand this recent statement from Poutin [Putin]? Bluff or a serious warning?
Virology is hopelessly misguided in pursuing gain-of-function research. It will not lead help us predict or prevent influenza. Although virology has made great advances, it is a dream that is still years away. Indeed flu viruses may always be one step ahead of us precisely because they evolve to escape immunity to them. As long as that is the case debate is needed, among virologists, but also with experts from other fields.
-- Gain-Of-Function Research: Report of a Debate between Prof. Giorgio Palù and Prof. Simon Wain-Hobson, 25 June 2014, Trippenhuis, Amsterdam, by Koos van der Bruggen
18. Circulating Avian Influenza Viruses Closely Related to the 1918 Virus Have Pandemic Potential. European Centre for Disease Prevention and Control. (2014). Available from: http://ecdc.europa.eu/en/activities/sci ... d72&ID=765
Circulating Avian Influenza viruses closely related to the 1918 virus Have pandemic potential
by European Centre for Disease Prevention and Control
July 16, 2014
A recent article by Watanabe et al. in the Cell Host & Microbe journal describes an attempt to assess the risk of emergence of pandemic influenza viruses closely related to the 1918 influenza virus.
Reverse genetics methods were used to generate an avian influenza virus closely related to the 1918 influenza virus, based on sequence information reported from various avian influenza viruses. Further experiments were done to demonstrate what mutations are required for this virus to become easily transmissible between mammals. Effectiveness of the current influenza vaccine and the antiviral drug oseltamivir against the 1918-like influenza virus was also assessed.
It was experimentally demonstrated that a 1918-like avian influenza virus with a limited number of additional mutations exhibits relatively high pathogenicity in mammals, although lower than the original 1918 influenza virus strain that was also recreated with reverse genetics technology in the laboratory. In the transmissibility studies, only some constellations of the virus genes allowed transmissibility between ferrets, suggesting roles for RNA replication complex, HA and NA in virus transmission.
To further assess the risk of the emergence of such avian influenza viruses that could infect humans, the team examined the prevalence of avian influenza viruses that are similar to the 1918 influenza virus, and looked for avian influenza viruses possessing human-type amino acid residues.
The study thus demonstrated the continued circulation of such avian influenza viruses that possess 1918 virus-like proteins and viruses that may acquire 1918 virus-like properties. This would suggest that a potential exists for a 1918-like pandemic virus to emerge from the avian virus gene pool.
ECDC comment
The study by Watanabe et al. is the latest in a series of genetic engineering experiments where research groups have created influenza viruses of pandemic potential. The new study discussed here further confirms the power of recombinant technology to create pathogenic viruses that are not currently circulating in nature. From the public health perspective, this poses a risk both for the laboratory personnel working with these viruses, even in very secure biosafety conditions, and to the general public in case of a laboratory escape. Recent incidents remind us that laboratory accidents and laboratory escapes can happen with dangerous pathogens, even if the highest security standards are applied [1,2,3]. The developments in technology should not and cannot be stopped and research laboratories should have the freedom to apply the latest technologies for science purposes as long as this is done with full adherence to good ethical and biosafety practices. However, the decision to fund this type of gain of pathogenic function studies in influenza viruses and other human pathogens has stirred scientific controversy about the mechanisms currently in place to ensure sound assessment of risk and benefits by independent reviewers [4].
The public health perspective to the critical review of funding such dual-use research of concern including studies aiming at the creation of potential pandemic pathogens has been so far limited. Very often the research groups justify their research agenda with pandemic preparedness and better understanding of the avian influenza viruses without further specifying how exactly the results may improve the preparedness plans. It is important to ask what this type of result adds to the field of pandemic influenza preparedness and how the prediction of efficacy of influenza vaccines or antivirals against influenza viruses is improved based on these results. Furthermore, it is pertinent to ask for justification of the methods, and if any of those could be replaced by safer experiments. It is of utmost importance that the biosafety practices and controls in the laboratories undertaking such research are kept to a high standard. A forum for public health discussion around dual-use research of concern topics is not yet available at European level. ECDC advocates for open discussion about studies where potential pandemic threats are created. The research community should in all their work apply the medical ethical principle of “first do no harm”.
19. Cambridge Working Group Consensus Statement on the Creation of Potential Pandemic Pathogens (PPPs). Available from: http://www.cambridgeworkinggroup.org/
Cambridge Working Group Consensus Statement on the Creation of Potential Pandemic Pathogens (PPPs)
by cambridgeworkinggroup.org
July 14, 2014
Recent incidents involving smallpox, anthrax and bird flu in some of the top US laboratories remind us of the fallibility of even the most secure laboratories, reinforcing the urgent need for a thorough reassessment of biosafety. Such incidents have been accelerating and have been occurring on average over twice a week with regulated pathogens in academic and government labs across the country. An accidental infection with any pathogen is concerning. But accident risks with newly created “potential pandemic pathogens” raise grave new concerns. Laboratory creation of highly transmissible, novel strains of dangerous viruses, especially but not limited to influenza, poses substantially increased risks. An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control. Historically, new strains of influenza, once they establish transmission in the human population, have infected a quarter or more of the world’s population within two years.
For any experiment, the expected net benefits should outweigh the risks. Experiments involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches. A modern version of the Asilomar process, which engaged scientists in proposing rules to manage research on recombinant DNA, could be a starting point to identify the best approaches to achieve the global public health goals of defeating pandemic disease and assuring the highest level of safety. Whenever possible, safer approaches should be pursued in preference to any approach that risks an accidental pandemic.
Original Signatories & Founding Members:
(Founding Members met in Cambridge on July 14 and crafted the statement)
Amir Attaran, University of Ottawa
Barry Bloom, Harvard School of Public Health
Arturo Casadevall, Albert Einstein College of Medicine
Richard Ebright, Rutgers University
Nicholas G. Evans, University of Pennsylvania
David Fisman, University of Toronto Dalla Lana School of Public Health
Alison Galvani, Yale School of Public Health
Peter Hale, Foundation for Vaccine Research
Edward Hammond, Third World Network
Michael Imperiale, University of Michigan
Thomas Inglesby, UPMC Center for Health Security
Marc Lipsitch, Harvard School of Public Health
Michael Osterholm, University of Minnesota/CIDRAP
David Relman, Stanford University
Richard Roberts (Nobel Laureate '93), New England Biolabs
Marcel Salathé, Pennsylvania State University
Lone Simonsen, George Washington University
Silja Vöneky, University of Freiburg Institute of Public Law, Deutscher Ethikrat
Charter Members:
(Charter Members of the Cambridge Working Group endorse the statement)
Porter W. Anderson Jr (Lasker laureate '96), Harvard Medical School & University of Rochester
Roy Anderson, Imperial College London, UK
Rustom Antia, Emory University
Ann Arvin, Stanford University School of Medicine
Birgitta Åsjö, University of Bergen, Norway
John Bartlett, Johns Hopkins University School of Medicine
Patrick Berche, Necker-Enfants Malades Medical School, Paris, France
Paul Berg (Nobel laureate '80), Stanford University
Pamela Björkman, California Institute of Technology, Pasadena
Steven Black, Center for Global Health, Cincinnati Children's Hospital
Jesse D. Bloom, Fred Hutchinson Cancer Research Center
Sebastian Bonhoeffer, ETH Zürich, Switzerland
Michel Brahic, Department of Genetics, Stanford University School of Medicine
Christian Bréchot, Institut Pasteur, Paris
Sydney Brenner (Nobel laureate '02)
Roger Brent, Fred Hutchinson Cancer Research Center
John S. Brownstein, Harvard Medical School
Donald S. Burke, University of Pittsburgh
Dennis Burton , Scripps Research Institute, La Jolla
Donald Coen, Harvard Medical School
Vittorio Colizzi, University of Rome Tor Vergata, Italy
Larry Corey, Fred Hutchinson Cancer Research Center
Roel Coutinho, University Medical Center Utrecht, The Netherlands
Pascale Cossart, Institut Pasteur, France
Clyde S. Crumpacker, Beth Israel Deaconess Medical Center
Malcolm Dando, University of Bradford, UK
Norman Daniels, Harvard School of Public Health
Patrice Debré, Hôpital Pitié Salpetrière, Paris
Jonathan A. Eisen, University of California, Davis
Santiago Elena, CSIC, Spain
Max Essex (Lasker laureate '86), Harvard School of Public Health
Stanley Falkow (Lasker laureate '08), Stanford University School of Medicine
Michael Farzan, Scripps Research Institute, Miami
Marcus W. Feldman, Stanford University
Neil M. Ferguson, Imperial College, UK
Adam Finn, University of Bristol, UK
Christophe Fraser, Imperial College, UK
Julio Frenk, Harvard School of Public Health
José Gatell, Hospital Clínic, University of Barcelona, Spain
Gabriela Gomes, Instituto Gulbenkian de Ciencia, Portugal
Eric P. Goosby, University of California San Francisco
Nathalie Grandvaux, Université de Montréal, Canada
Warner C. Greene, Gladstone Institute of Virology and Immunology, University of California San Francisco
Jeanne Guillemin, MIT
Willem Hanekom, Bill & Melinda Gates Foundation, and University of Cape Town, South Africa
Elisa D. Harris, Center for International and Security Studies at Maryland
Eric Harvill, Pennsylvania State University
Daniel L. Hartl, Harvard University
Donald A. Henderson (Presidential Medal of Freedom '02), University of Pittsburgh
Martin S. Hirsch, Harvard Medical School
Richard Jackson, University of Cambridge
Laura H. Kahn, Princeton University
Phyllis Kanki, Harvard School of Public Health
Lynn Klotz, Center for Arms Control & Non-Proliferation
Keith Klugman, Bill & Melinda Gates Foundation
Roberto Kolter, Harvard Medical School
Mathilde Krim, Founding Chairman, amfAR, The Foundation for AIDS Research
Leonid Kruglyak, UCLA
Richard E. Lenski, Michigan State University
Matti Lehtinen, University of Tampere, Finland
Bruce R. Levin, Emory University
Gunnar Lindahl, Lund University, Sweden
W. Ian Lipkin, Columbia University
Ian M. Mackay, University of Queensland, Australia
Adel A. Mahmoud, Princeton University
Rick Malley, Boston Children's Hospital
Howard Markel, University of Michigan
Robert M. May (former president Royal Society), University of Oxford, UK
Mike McCune, University of California, San Francisco
Kenneth McIntosh, Boston Children’s Hospital
Andrew McMichael, University of Oxford
Andreas Meyerhans, ICREA & Universitat Pompeu Fabra, Barcelona, Spain
Julio S. G. Montaner, University of British Columbia
Jonathan D. Moreno, University of Pennsylvania
Richard Moxon, Oxford University, UK
Neal Nathanson, Microbiology, University of Pennsylvania
Kathryn Nixdorff, Darmstadt University of Technology, Germany
Kate O'Brien, Johns Hopkins Bloomberg School of Public Health
Paul Offit, The Children's Hospital of Philadelphia
Gérard Orth, Institut Pasteur, France
Eli Perencevich, University of Iowa
Joshua B. Plotkin, University of Pennsylvania
Stanley Plotkin, University of Pennsylvania
Peter Piot, London School of Hygiene & Tropical Medicine, UK
Mark Poznansky, Harvard Medical School, Massachusetts General Hospital
Andrew Rambaut, University of Edinburgh, UK
Johannes Rath, University of Vienna, Austria
Andrew Read, Pennsylvania State University
Gili Regev-Yochay, Sheba Medical Center, Israel
Félix Rey, Institut Pasteur, Paris, France
Douglas D. Richman, University of California San Diego
Steven L. Salzberg, Johns Hopkins School of Medicine
Philippe Sansonetti, Institut Pasteur, Paris
Mathuram Santosham, Johns Hopkins University
Mauro Schechter, Projeto Praca Onze, Universidade Federal do Rio de Janeiro, Brazil
Olivier Schwartz, Institut Pasteur, Paris, France
Jeffrey Shaman, Columbia University
Kai Simons, Max Planck Institute of Molecular Cell Biology & Genetics, Dresden, Germany
Stephen C. Stearns, Yale University
Tomoko Steen, Georgetown University Medical School
John Steinbruner, University of Maryland
Bruce Stillman, Cold Spring Harbor Laboratory
Klaus Stöhr, Novartis Vaccines and Diagnostics
Amalio Telenti, University of Lausanne, Switzerland
Paul Turner, Yale University
Robert D. Truog, Harvard Medical School
Ross Upshur, University of Toronto, Canada
Paul Volberding, AIDS Research Institute, University of California San Francisco
Mark Wainberg, McGill University, Montreal, Canada
Simon Wain-Hobson, Institut Pasteur, France
James D. Watson (Nobel laureate '62)
David Weiner, University of Pennsylvania
Robin Weiss, University College London, UK
Hans Wigzell, Karolinska Institutet, Stockholm, Sweden
Daniel Wikler, Harvard University
Claus O. Wilke, The University of Texas at Austin
Rüdiger Wolfrum, Max Planck Institute, Germany
Priscilla Yang, Harvard Medical School
Moshe Yaniv, Institut Pasteur, France
Patrick Yeni, Hôpital Bichat and University of Paris 7 Paris, France
Jerome A. Zack, David Geffen School of Medicine, University of California Los Angeles
Charter Members who signed the statement online:
Andrew Noymer, University of California, Irvine
Maimuna S. Majumder, MIT
Christopher McCabe, University of Alberta, Canada
Mike McCormick, Labwatch
Nicole E Basta, Princeton University
Steven Riley, Imperial College London
Ben Ashby, University of Exeter
Gautam I Menon, The Institute of Mathematical Sciences, Chennai, INDIA
Ted Cohen, Harvard School of Public Health
Toby Ord, Oxford University
Sean O hEigeartaigh, University of Oxford
Daniel Dewey, University of Oxford
Joann Mead, @JoannJMead
Christian Althaus, Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland
Marius Gilbert, Université Libre de Bruxelles
Joshua S. Weitz, Georgia Institute of Technology
Charles N Haas, Drexel University
R. Taylor Raborn, Indiana University
Amy Greer, University of Guelph
Brett Edwards, University of Bath
Antoni Trilla, Hospital Clinic - Univ. of Barcelona
David S. Fedson, Sergy Haut, France
Hortense Gerardo, Lasell College
Joseph Baglieri, Barrister & Solicitor
Dawn Kubly, Fort Healthcare
Charles R. Stack, University of Illinois at Chicago School of Public Health
Lisa Murillo, Los Alamos National Laboratory
Anders Sandberg, Oxford University
Evan Skowronski, TMG Biosciences
Kathleen Gilbert, California Institute of Technology
Mukilan D Suresh, SRM University, School of Bioengineering (student)
Roberto Anitori, Clark College, WA, USA
Andrew Leifer, Princeton University
Pankaj Mehta, Boston University
Megan Murray, Harvard Medical School
Eric S. Starbuck, Department of Health & Nutrition, Save the Children USA
Carl T. Bergstrom, Department of Biology, University of Washington
Nicola Low, University of Bern, Switzerland
Sünje J. Pamp, Technical University of Denmark
Andrew Snyder-Beattie, University of Oxford
Viktor Müller, Eötvös Loránd University and the Hungarian Academy of Sciences, Budapest
Tami Lieberman, Harvard Medical School
Alan Barbour, University of California Irvine
Sven Bergstrom, Umea University, Sweden
Sophia Roosth, Assistant Professor of the History of Science, Harvard University
Sibel Ascioglu, Hacettpe University, Dept. of Infectious Diseases, Turkey
Janet D. Stemwedel, San José State University
Fernando Baquero, Department of Microbiology, Ramón y Cajal Institute for Health Research (IRYCIS) Madrid, Spain
Carlos S. Moreno, Emory University
Sarah Otto, University of British Columbia
Richard Levins, Harvard School of Public Health
Andrew Tatem, University of Southampton
Benjamin Kerr, University of Washington
A. David Paltiel, Yale School of Public Health / Yale School of Management
Rochelle Walensky, Massachusetts General Hospital
John W. Jackson, Brigham and Women's Hospital
Julie Parsonnet, Infectious Diseases, Stanford University School of Medicine
John McGowan, Emory University Rollins School of Public Health
John Quackenbush, Dana-Farber Cancer Institute and Harvard School of Public Health
Rafael Canton, Servicio de Microbiologia. Hospital Universitario Ramón y Cajal. Madrid. Spain
Jane Kim, Harvard School of Public Health
Thomas F O'Brien, Brigham and Women's Hospital, Boston, MA
Simon Levin, Princeton University
James Lloyd-Smith, UCLA
Andrew Yates, University of Glasgow
Richard C. Larson, Massachusetts Institute of Technology
Victor DeGruttola, Harvard University
Melinda M. Pettigrew, Yale School of Public Health
Marc D. Natter, Harvard Medical School
Ramanan Laxminarayan, Center for Disease Dynamics, Economics & Policy, New Delhi
Cynthia Schuck-Paim, Origem Scientifica
Emma McBryde, University of Melbourne & Victorian Infectious Diseases Service, Doherty Institute
Robin Bush, University of California, Irvine
Pieter Trapman, Stockholm University
Lumi Viljakainen, University of Oulu
Isabelle Magnoli, Université catholique de Louvain
Jeremy Van Cleve, Duke University
Francisco Dionisio, University of Lisbon
Daniel Wilson, University of Oxford
Amy Hurford, Memorial University of Newfoundland
Sergios-Orestis Kolokotronis, Fordham University
Pedro Silva, University of Lisbon, Portugal
Oscar E. Gaggiotti, University of St Andrews, UK
Richard Edwards, University of New South Wales
Emilia Vynnycky, London School of Hygiene & Tropical Medicine, UK
Martin Kulldorff, Harvard Medical School
Erik F. Y. Hom, University of Mississippi
John Mekalanos, Harvard Medical School
Stephen W. Schaeffer, Pennsylvania State University
Christina Davy, Trent University, Peterborough, Ontario, Canada
Clark Freifeld, Boston Children's Hospital
David A Harmin, Harvard Medical School
Anne D. Yoder, Duke University
Nicholas G Reich, University of Massachusetts - Amherst
Gerald Learn, University of Pennsylvania
Pleuni Pennings, San Francisco State University
Zachary A Szpiech, University of California, San Francisco
Stan Finkelstein, MIT/Harvard Medical School
Paul Avillach, Harvard Medical School
Alain-jacques Valleron, Inserm. Paris, France
Ellen L. Simms, University of California, Berkeley
Anahi Espindola, University of Idaho
Claudio Jose Struchiner, Oswaldo Cruz Foundation, Brazil
Jan Medlock, Oregon State University
Maarten Vonhof, Western Michigan University
Heather Douglas, University of Waterloo
Michael Höhle, Department of Mathematics, Stockholm University
Joy Scaria, Cornell University
Preben Aavitsland, Epidemi, Kristiansand
Fernando Gonzalez-Candelas, University of Valencia, Spain
Dr. Sameeh Ghazal, King Fahad Medical City
William J. Etges, University of Arkansas
Sadia Shakoor, Aga Khan University
Angela Hancock, Max F. Perutz Labs, University of Vienna
Michael Merson, Duke University
Donald R. Olson, New York City Department of Health and Mental Hygiene
Robert Gordon White, Carleton University
Paul Schmid-Hempel, ETH Zurich
Matt Keeling, University of Warwick
Victoria Shaffer, Infection Preventionist; CHWC, Bryan, Ohio
Matthew J. Brown, University of Texas at Dallas
Joel L. Sachs, University of California - Riverside
Jacques Dubochet, University of Lausanne (retired)
François-Xavier Weill, Institut Pasteur, Paris, France
Rodrigo Angerami, State University of Campinas/UNICAMP
Omar Cornejo, Washington State University
Wladimir J. Alonso, Origem Scientific Consultancy
Jacob-S. Seeler, Institut Pasteur, Paris
Sarah Cobey, University of Chicago
Joshua Metlay, Massachusetts General Hospital/Harvard Medical School
Barbara E. Giles, Umea University, Sweden
Brigitte Autran, University Pierre et Marie Curie, Paris
Nicholas S Kelley, University of Minnesota
Jean-Michel Guillon, University of Paris Sud, France
Jon Zelner, Princeton University, Dept. of Ecology and Evolutionary Biology
William C. Miller, UNC - Chapel Hill
Katia Koelle, Duke University
Thomas W. Jeffries, University of Wisconsin - Madison
Harry Greenberg, Stanford University
Romain Gallet, INRA - Montpellier (France)
Allan Hance, INSERM, Paris, France
Simon Fellous, INRA - CBGP, France
Tatyana Novossiolova, University of Bradford
Patricia Baldacci, Institut Pasteur
Godwin Wilson, Hamad Medical Corporation, Qatar
Ralf Koebnik, Institut de Recherche pour le Développement
Elaine Nsoesie, Boston Children's Hospital, Harvard Medical School
Nicolas Voirin, Hospices Civils de Lyon
Mariet Feltkamp, Leiden University Medical Center
Conor Browne, Queen's University Belfast
Quentin Sattentau, University of Oxford
Michael Costa, Abt Associates
Jonathan A. Cooper, Fred Hutchinson Cancer Resarch Center
Andrew Lakoff, University of Southern California
Peter V. Markov, Institut Pasteur
Doug Cyr
bracha rager, faculty of health sciences, ben gurion univ. Israel
Mark Eisler, University of Bristol
Miles Davenport, UNSW Australia
David Bofinger, Grand Canyon Univerity - Graduate Student -Psychology
Daniel Leifer, UC Davis School of Medicine
Benjamin de Bivort, Harvard University
James Lyons-Weiler, PhD, Ebola Rapid Assay Development Consortium
Camillo Di Cicco, University of Rome
Roberto Bruzzone, HKU-Pasteur Research Pole
Anders Huitfeldt, Harvard T.H. Chan School of Public Health
Viktoriya Krakovna, Harvard University PhD student, Future of Life Institute cofounder
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Emma Kowal, Harvard University
Ales Flidr, Harvard College
Max Kesin, Professional
Dr. Roman V. Yampolskiy, University of Louisville
Robert J. Taylor, Sage Analytica, Bethesda Maryland
Niel Bowerman, Future of Humanity Institute, University of Oxford
Nancy Connell, Rutgers New Jersey Medical School
Kathleen Burns, Sciencecorps
Louis Kang, Harvard University/MIT
Thomas Choate, Air
Aaron Supple, Beth Israel Deaconess Medical Center
Dominic Hall, Cambridge University, Stem Cell Institute
Niran Adeyanju, Obafemi Awolowo University, Nigeria.
Joseph (Jo) Walker, US CDC (signing in personal capacity)
Jeremy Ferranti, Researcher
Bonnie Page
NICOULAUD GHISLAINE
Alexandra Richter, DPFA-Regenbogen-Schulen
David Hartsuch, MD MS CPA, Emergency Resource
Jimmy Joseph Moise, Le P'ti Club inc.
20. Furmanski M. Lab Escapes and “Self-fulfilling prophecy” Epidemics. Center for Arms Control and Nonproliferation (2014). Available from: http://armscontrolcenter.org/Escaped_Vi ... -17-14.pdf
21. Furmanski M. Threatened pandemics and lab escapes: self-fulfilling prophecies. Bull Atom Sci (2014). Available from: http://thebulletin.org/threatened-pande ... hecies7016
22. Klotz LC, Sylvester EJ. The unacceptable risks of a man-made pandemic. Bull Atom Sci (2012). Available from: http://thebulletin.org/unacceptable-ris ... e-pandemic