Policy: Adaptations of avian flu virus are a cause for concern

Journal name:
Nature
Volume:
482,
Pages:
153–154
Date published:
DOI:
doi:10.1038/482153a
Published online

Members of the US National Science Advisory Board for Biosecurity explain its recommendations on the communication of experimental work on H5N1 influenza.

We are in the midst of a revolutionary period in the life sciences. Technological capabilities have dramatically expanded, we have a much improved understanding of the complex biology of selected microorganisms, and we have a much improved ability to manipulate microbial genomes. With this has come unprecedented potential for better control of infectious diseases and significant societal benefit. However, there is also a growing risk that the same science will be deliberately misused and that the consequences could be catastrophic. Efforts to describe or define life-sciences research of particular concern have focused on the possibility that knowledge or products derived from such research, or new technologies, could be directly misapplied with a sufficiently broad scope to affect national or global security. Research that might greatly enhance the harm caused by microbial pathogens has been of special concern1, 2, 3. Until now, these efforts have suffered from a lack of specificity and a paucity of concrete examples of 'dual use research of concern'3. Dual use is defined as research that could be used for good or bad purposes. We are now confronted by a potent, real-world example.

M. CIZEK/AFP/GETTY

Pathogenic H5N1 avian influenza has led to the culling of hundreds of millions of birds. A human-transmissible form could have much worse consequences.

Highly pathogenic avian influenza A/H5N1 infection of humans has been a serious public-health concern since its identification in 1997 in Asia. This virus rarely infects humans, but when it does, it causes severe disease with case fatality rates of 59% (ref. 4). To date, the transmission of influenza A/H5N1 virus from human to human has been rare, and no human pandemic has occurred. If influenza A/H5N1 virus acquired the capacity for human-to-human spread and retained its current virulence, we could face an epidemic of significant proportions. Historically, epidemics or pandemics with high mortalities have been documented when humans interact with new agents for which they have no immunity, such as with Yersinia pestis (plague) in the Middle Ages and the introduction of smallpox and measles into the Americas after the arrival of Europeans.

Recently, several scientific research teams have achieved some success in modifying influenza A/H5N1 viruses such that they are now transmitted efficiently between mammals, in one instance with maintenance of high pathogenicity. This information is very important because, before these experiments were done, it was uncertain whether avian influenza A/H5N1 could ever acquire the capacity for mammal-to-mammal transmission. Now that this information is known, society can take steps globally to prepare for when nature might generate such a virus spontaneously. At the same time, these scientific results also represent a grave concern for global biosecurity, biosafety and public health. Could this knowledge, in the hands of malevolent individuals, organizations or governments, allow construction of a genetically altered influenza virus capable of causing a pandemic with mortality exceeding that of the 'Spanish flu' epidemic of 1918? The research teams that performed this work did so in a well-intended effort to discover evolutionary routes by which avian influenza A/H5N1 viruses might adapt to humans. Such knowledge may be valuable for improving the public-health response to a looming natural threat. And, to their credit and that of the peer reviewers selected by the journals Science and Nature, the journals themselves, as well as the US government, it was recognized before their publication that these experiments had dual use of concern potential.

The US government asked the National Science Advisory Board for Biosecurity (NSABB; go.nature.com/oeryit) to assess the dual-use research implications of two as-yet-unpublished manuscripts on the avian influenza A/H5N1 virus, to consider the risks and benefits of communicating the research results and to provide findings and recommendations regarding the responsible communication of this research. In our deliberations, we first assessed the potential risks and consequences of the misuse of the information to cause harm to the public.

“We found the potential risk of public harm to be of unusually high magnitude.”

Risk assessment of public harm is challenging because it necessitates consideration of the intent and capability of those who wish to do harm, as well as the vulnerability of the public and the status of public-health preparedness for both deliberate and accidental events. We found the potential risk of public harm to be of unusually high magnitude. In formulating our recommendations to the government, scientific journals and to the broader scientific community, we tried to balance the great risks against the benefits that could come from making the details of this research known. Because the NSABB found that there was significant potential for harm in fully publishing these results and that the harm exceeded the benefits of publication, we therefore recommended that the work not be fully communicated in an open forum. The NSABB was unanimous that communication of the results in the two manuscripts it reviewed should be greatly limited in terms of the experimental details and results.

This is an unprecedented recommendation for work in the life sciences and our analysis was conducted with careful consideration both of the potential benefits of publication and of the potential harm that could occur from such a precedent. Our concern is that publishing these experiments in detail would provide information to some person, organization or government that would help them to develop similar mammal-adapted influenza A/H5N1 viruses for harmful purposes. We believe that as scientists and as members of the general public, we have a primary responsibility 'to do no harm' as well as to act prudently and with some humility as we consider the immense power of the life sciences to create microbes with novel and unusually consequential properties. At the same time, we acknowledge that there are clear benefits to be realized for the public good in alerting humanity of this potential threat and in pursuing those aspects of this work that will allow greater preparedness and the potential development of novel strategies leading to future disease control. By recommending that the basic result be communicated without methods or details, we believe that the benefits to society are maximized and the risks minimized. Although scientists pride themselves on the creation of scientific literature that defines careful methodology that would allow other scientists to replicate experiments, we do not believe that widespread dissemination of the methodology in this case is a responsible action.

The life sciences have reached a cross-roads. The direction we choose and the process by which we arrive at this decision must be undertaken as a community and not relegated to small segments of government, the scientific community or society. Physicists faced a similar situation in the 1940s with nuclear weapons research, and it is inevitable that other scientific disciplines will also do so.

Along with our recommendation to restrict communication of these particular scientific results, we discussed the need for a rapid and broad international discussion of dual-use research policy concerning influenza A/H5N1 virus with the goal of developing a consensus on the path forward. There is no doubt that this is a complex endeavour that will require diligent and nuanced consideration. There are many important stakeholders whose opinions need to be heard at this juncture. This must be done quickly and with the full participation of multiple societal components.

We are aware that the continuing circulation of the highly pathogenic avian influenza A/H5N1 virus in Eurasia — where it is constantly found to cause disease in animals of particular regions — constitutes a continuing threat to humankind. A pandemic, or the deliberate release of a transmissible highly pathogenic influenza A/H5N1 virus, would be an unimaginable catastrophe for which the world is currently inadequately prepared. It is urgent to establish how best to facilitate the much-needed research as well as minimize potential dual use.

To facilitate and motivate this process, we also discussed the possibility of the scientific community participating in a self-imposed moratorium on the broad communication of the results of experiments that show greatly enhanced virulence or transmissibility of such potentially dangerous microbes as the influenza A/H5N1 virus. This moratorium would run until consensus is reached on the balance that must be struck between academic freedom and protecting the greater good of humankind from potential danger. With proper diligence and rapid achievement of a consensus on a proper path forward, this could have little detrimental effect on scientific progress but significant effect on diminishing risk.

There are many parallels with the situation in the 1970s and recombinant DNA technologies5, 6, 7. The Asilomar Conference in California in 1975 was a landmark meeting important to the identification, evaluation and mitigation of risks posed by recombinant DNA technologies. In that case, the research community voluntarily imposed a temporary moratorium on the conduct of recombinant DNA research until they could develop guidance for the safe and responsible conduct of such research. We believe that this is another Asilomar-type moment for public-health and infectious-disease research that urgently needs our attention.

References

  1. National Research Council Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology. Biotechnology Research in an Age of Terrorism (National Academies Press, 2004); available at http://go.nature.com/4vl3ye
  2. National Research Council Committee on Advances in Technology and the Prevention of Their Application to Next Generation Biowarfare Threats. Globalization, Biosecurity, and the Future of the Life Sciences (National Academies Press, 2006); available at http://go.nature.com/hktvtc
  3. National Science Advisory Board for Biosecurity. Strategic Plan for Outreach and Education on Dual Use Research Issues (NSABB, 2008); available at http://go.nature.com/nuriw4
  4. World Health Organization. Cumulative Number of Confirmed Human Cases for Avian Influenza A(H5N1) reported to WHO, 2003–2012; available at http://go.nature.com/epb7ts
  5. Singer, M. & Soll, D. Science 181, 1114 (1973).
  6. Berg, P., Baltimore, D., Brenner, S., Roblin, R. O. & Singer, M. F. Proc. Natl Acad. Sci. USA 72, 19811984 (1975).
  7. Singer, M. & Berg, P. Science 193, 186188 (1976).

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Author information

Affiliations

  1. Kenneth I. Berns is a member of the US National Science Advisory Board for Biosecurity.

  2. Arturo Casadevall is a member of the US National Science Advisory Board for Biosecurity.

  3. Murray L. Cohen is a member of the US National Science Advisory Board for Biosecurity.

  4. Susan A. Ehrlich is a member of the US National Science Advisory Board for Biosecurity.

  5. Lynn W. Enquist is a member of the US National Science Advisory Board for Biosecurity.

  6. J. Patrick Fitch is a member of the US National Science Advisory Board for Biosecurity.

  7. David R. Franz is a member of the US National Science Advisory Board for Biosecurity.

  8. Claire M. Fraser-Liggett is a member of the US National Science Advisory Board for Biosecurity.

  9. Christine M. Grant is a member of the US National Science Advisory Board for Biosecurity.

  10. Michael J. Imperiale is a member of the US National Science Advisory Board for Biosecurity.

  11. Joseph Kanabrocki is a member of the US National Science Advisory Board for Biosecurity.

  12. Paul S. Keim is acting chair of the US National Science Advisory Board for Biosecurity.

  13. Stanley M. Lemon is a member of the US National Science Advisory Board for Biosecurity.

  14. Stuart B. Levy is a member of the US National Science Advisory Board for Biosecurity.

  15. John R. Lumpkin is a member of the US National Science Advisory Board for Biosecurity.

  16. Jeffery F. Miller is a member of the US National Science Advisory Board for Biosecurity.

  17. Randall Murch is a member of the US National Science Advisory Board for Biosecurity.

  18. Mark E. Nance is a member of the US National Science Advisory Board for Biosecurity.

  19. Michael T. Osterholm is a member of the US National Science Advisory Board for Biosecurity.

  20. David A. Relman is a member of the US National Science Advisory Board for Biosecurity.

  21. James A. Roth is a member of the US National Science Advisory Board for Biosecurity.

  22. Anne K. Vidaver is a member of the US National Science Advisory Board for Biosecurity.

Author details

Comments

  1. Report this comment #37994

    Harry Milburn said:

    We should bear in mind that this is "another weapon", we already have public information on how to make an atomic bomb. Who decides who has access to what. We are descending into medieval mysticism if we are not careful.

  2. Report this comment #38021

    Ningcheng Shu said:

    We should never forget that the sole perpetrator of the 2001 anthrax attack declared by the federal prosecutor was Bruce Edwards Ivins, a senior biodefense researcher at the United States Army Medical Research Institute of Infectious Disease in Fort Detrick, Maryland. This suggests that more transparent supervision by the general public on close, secretive segments of government would certainly be in the interests of the whole society; a contrary that certain small agency could deny the access to scientific data by the community and have the potential to deprive the public of their awareness is definitely not. In the long run, open access to the scientific data by the scientific community would contribute to quicker development of cure and prophylaxis against pathogen-led disease, thus render any forms of bio-weapon less effective.

  3. Report this comment #38022

    amna ali said:

    This suggests that more transparent supervision by the general public on close, secretive segments of government would certainly be in the interests of the whole society; a contrary that certain small agency could deny the access to scientific data by the community and have the potential to deprive the public of their awareness is definitely not. In the long run, open access to the scientific data by the scientific community would contribute to quicker development of cure and prophylaxis against pathogen-led disease, thus render any forms of bio-weapon less effective.

  4. Report this comment #38072

    Martin Klvana said:

    'Limiting the experimental details and results' = CENSORSHIP. It would set an extremely dangerous precedence . . .
    And 'threat to biosecurity'? Government is the single biggest threat to life on Earth so why should I think that government has any intention to protect me? It's as ridiculous as it can possibly be.

  5. Report this comment #38123

    Willy Billy said:

    This sounds all very reasonable and carefully thought out. However, I would like the author to answer my questions, skeptic that I am. Who do we turn to for confirmation that your "caution" isn't simply the natural proclivity of a bunch of bureaucrats to say no in the not unfamiliar "CYA or cover your ass" (pardon my language) scenario? I too am objective. I can judge that a very very small probability of something bad happening might be acceptably ignored if the consequences are tiny (someone being injured in a minor fashion that can be easily treated), yet might justify the most concerted, expansive, expensive human endeavour ever undertaken if the consequences are catastrophic (the elimination of most or all human life on earth for example). The fact that you seem incapable of making a similarly reasonable assessment of risk makes me question not only your competence, but the competence of the entire NSABB. The risks here to the human race are roughly equal on its face regardless of where the pandemic virus might originate. Yet you presume to judge the risk of origin from terrorism to be greater than the risk from nature itself. On what basis? This reeks of bureaucracy in the CYA scenario. Your job is to assess the former, not the latter, thus the probability for being held accountable for failing in one respect is massive compared to failing in assessment on the other.

    We can then add to this justifiable skepticism fueled by your behaviour, the fact that this work was undertaken not simply as basic research, but as a response to the stupidity in the bureaucracies controlling health policy worldwide that presumed to discount a virulent H5N1 spreading among humans, seemingly, for no other reason than it meant they would have to put down their donut and deal with a very big problem. Granted, in this era of fiscal insanity in government it might be hard to convince faux patriots to spend money on saving humanity from the near certainty of perhaps a hundred million deaths and a decrease in global GDP of perhaps half or more, but that is no justification for simply dismissing the issue.

    To sum up. Your article pays lipservice to the documented crime of obtuse bureaucratic intransigence committed by the various health policy bureaucracies world-wide. Your article pays lipservice to the research that may now have prevented the horrific crisis their misbehaviour might have allowed to descend upon us. Your article gives great credence to the low probability of terrorists creating a pandemic strain, undetected, and succesfully deploying it as a weapon prior to the scientific infrastructure of the entire planet devising an effective response. This while the good guys have a huge head start, on knowledge, technique, infrastructure, huge advantages in resources, and the ability to control access to any necessary component to the puzzle to at least some degree. In addition, it is the terrorist "threat" that justifies the existence of the NSABB.

    My suggestion to you, is that if you want true scientists with objective minds to consider your assessments credible, that you make them just that. If instead, you blatantly discount the credible, while inflating the incredible, all the while sounding like Giuliani running for president flinging the words 9/11 about like he's in a cocaine fed frenzy, you are liable to read a lot more responses like mine. I'm sorry if you choose to believe I'm attacking you personally. That is not the intent. I am attacking your actions. Absent information to the contray, I find them offensive, destructive, un-Scientific, and completely inappropriate, however "well intentioned" they may be.

  6. Report this comment #38249

    Elizabeth Hart said:

    This is a very important issue, discussion on which should not be reserved to ?experts? with possible conflicts of interest. The rest of us have a say in this too.

    In this regard, I have forwarded an Open Letter, from a ?layperson?s? perspective to the National Science Advisory Board for Biosecurity re the political and ethical implications of lethal virus development.

    My letter has been acknowledged by the acting chair of the NSABB, Paul Keim, and Michael Osterholm, a NSABB member. I have been advised my letter will be considered by the Board.

    My open letter raises questions about the legitimacy of the US sponsoring lethal virus development ? does this contravene the Biological Weapons Convention?

    Bearing in mind the questionable effectiveness of flu vaccines, I also suggest it is time to investigate the ?influenza industry?, particularly the relationships between vaccine manufacturers and governments and other public bodies.

    The Open Letter can be addressed via this link: http://bit.ly/AfyAtQ

    Elizabeth Hart

  7. Report this comment #38468

    Goji Tye said:

    H5N1 can go pandemic via 4 ways:

    1 – naturally evolving virus – as we are seeing tamiflu resistance in Indonesia as well as no poultry connections and tests not showing positives. A worrying pattern is emerging there.
    2 – Lab escape – from either a scientist's error or by a nutcase experimenting in his kitchen as the cost of biological experimentation entry rapidly descends and puts high tech capability in amateur hands.
    3 - terror attack – as feared by this committee.
    4 – State sponsored bio attack – Possible by countries like China, Iran, North Korea, etc... China has had a bio weapons program for years. The PRC could use this as a weapon of last resort as their population rebells as their economy crashes and they experience their own "Chinese Spring". It's not hard to put the pieces together and I hope the DOD has done so and actively working to ensure our safety. I fear this the most. The PRC is not our friend.

    Pick your poison on this one. The outcomes are all the same – Crashing of the JIT delivery system as people become very ill or stay home out of fear.

    This is something no one is talking about. When H5N1 goes pandemic, there will be movement restrictions, either self imposed or forced. It is the only vehicle left for the Gov. to stop the spread and control the masses as a vaccine will not be readily available. Remember, H5N1 kills the chicken eggs used to grow it.

    We have all seen the Flu Shot signs at all the big pharmacies in the past year in response to Swine Flu. They are set up now as opposed to 5 years ago. That is a step in the right direction. But it is not enough since Vaccine manufacturers are dependent on supplies from overseas and are vulnerable to disruptions a severe pandemic will cause.

    They are also dependent on WHO to give them strains they can grow. The Swine Flu vaccine seeds WHO distributed were bad which set us back by 2 months. The first vax to arrive, arrived too late for many children who died. If they had been vaccinated in a timely manor, they most likely would never have gotten sick in the first place. WHO also advised Vax manufacturers to continue making seasonal vaccine when they knew a pandemic from a novel virus was beginning. Why?

    When you look at the leadership of WHO (director Margaret Chan, a Chinese National) and how she got there, you may wonder if there is a connection to the late Swine Flu vax distribution, this seemingly off target discussion about terrorism when there are other possibilities, the avoidance of non pharmaceutical intervention discussion and absolutely no mention of movement restrictions.

    It almost seems as if they don't want the public to know what's going to happen to them.

    WHY?

    DOD please take note – there are those of us who fear our enemies may use weaponized H5N1 against us as well as their own rebellious populations in the near future, and have been working tirelessly in the cyberspace of the Flu Boards to influence us NOT to prepare.

  8. Report this comment #38476

    Duff Smith said:

    As an American, I prefer to think that my country's leadership in the implementation of technology has to do with its citizens' ability to handle technology; the individual morality that keeps Americans driving between the lines on the road and not deciding whether to run people over on the basis of whether there's a brick wall in the way.
    That might seem like an oversimplification relative to these biotech questions, but is it really? Is the restriction of information okay because the technology in question is ever so powerful in this case? I've heard the same argument against the second amendment; the founders never imagined the power of contemporary small arms, or whatever. Well you know, our founders probably DIDN'T foresee... all kinds of stuff. But you don't think their adherence to certain principles had anything to do with why America has been the world leader that is has in so many things? Because depending on what we decide, we will either vote to emphasize the need for individual morality or to marginalize it — in an increasingly dangerous world, in the sight of God.
    But then, there's the inappropriate relationships that have developed between certain industries and the agencies that are supposed to regulate them. Putting Michael Taylor in that top FDA spot. Hmmm. You put people in highly entrusted agencies that are supposed to have it all together and you know what Bruce Edwards Ivins did. Gee, who would'a thought?? Could it possibly be that "government people" are pretty much the same stuff as everyone else? Oh yeah, especially lately. What can I say America? Immorality has consequences. In this case, we're not in the position that we should have been in. We've been sliding toward this situation for some time and as God has been watching it all, it's probably already too late to stop the Great Bird Flu Plague or whatever history is going to call it.
    I planted a vegetable garden and it's doing well. How's yours?

  9. Report this comment #38543

    John Bashinski said:

    Well, that's just strikingly content free. Absolutely no actual risk analysis, absolutely no analysis of the effectiveness of the proposed mitigation, not even any identification of the concerns. You could just have written "trust us, we're all scared, something must be done, this is something, so this must be done, please shut up".

    I'm not sure why anybody would listen to this sort of amateurish maundering on a serious issue.

  10. Report this comment #39795

    Sam Sanders said:

    We should bear in mind that this is "another weapon", we already have public information on how to make an atomic bomb. Who decides who has access to what. We are descending into medieval mysticism if we are not careful. 5

  11. Report this comment #41331

    Jack Henderson said:

    The idea of biological warfare is not something to be spoken of lightly. Oxford Student Health offered vaccination to students for swine flu influenza starting in the fall semester 0f 2011 and 17% (129) of students have chosen to get vaccinated with the H1N1 vaccine to date at Student Health. Orlando web design and H1N1 Vaccines are still available at Student Health. It is not too late to get vaccinated as H1N1 continues to circulate in Georgia during the spring 2012 semester. From what I understand avian flu is a whole other matter.

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