Man Made H5N1 - Super Version

[sharon sanders]

Re: Man Made H5N1 - Super Version

The NSABB Recommendations: Rationale, Impact, and Implications

1. Paul S. Keim

+ Author Affiliations

1. <address>National Science Advisory Board for Biosecurity, Office of Biotechnology Activities, National Institutes of Health, Bethesda, Maryland, USA; Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA; and the Translational Genomics Research Institute, Phoenix, Arizona, USA </address>

1. Address correspondence to paul.keim@nau.edu.

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ABSTRACT

The National Science Advisory Board for Biosecurity (NSABB) has recommended that two scientific papers concerning the laboratory adaptation of avian H5N1 influenza virus to mammal-to-mammal respiratory transmission restrict their content to prevent others from replicating their work. After hearing from experts in the field of influenza research and public health, the benefits of the research were deemed less important than the potential negative consequences. The evaluation followed established NSABB procedures and prior policy recommendations for identifying dual use research of concern (DURC). This recommendation was received by the United States Government, endorsed and forwarded to the research teams and scientific journals involved with the publications.

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Commentary

In October 2011, the U.S. National Science Advisory Board for Biosecurity (NSABB) was asked to review two papers for their potential as dual-use research of concern (DURC). These papers contained results on the adaptation of the highly pathogenic avian influenza A/H5N1 virus to mammalian hosts such that it could be transmitted via respiratory droplets from animal to animal. We found that this work had great potential for harm or misuse and “recommended that the general conclusions highlighting the novel outcome be published, but that the manuscripts not include the methodological and other details that could enable replication of the experiments by those who would seek to do harm” (NIH Press Release, http://www.nih.gov/news/health/dec2011/od-20.htm). The recommendation “not to publish scientific results” was highly unusual and the first such recommendation by the NSABB membership. We are primarily a group of actively practicing basic research scientists, and we have consistently advocated for open publication practices. As per our advisory nature to the U.S. Government, these recommendations were not binding and could have been ignored. However, after careful consideration, the U.S. Government accepted the recommendations and relayed them to researchers and the scientific journals.
There was agreement by NSABB voting members for these recommendations, though the rationale of individual members as they arrived at the same conclusions varied. We had to judge the beneficial attributes of these research results against their potential to cause harm. Over the last 7 years, NSABB has studied the issues associated with dual-use research, including risk/benefit assessments, and developed principles and tools to guide the deliberative process. Much of this has been formalized in a series of reports and recommendations that are available at a public website (http://oba.od.nih.gov/biosecurity/biosecurity.html). Despite this experience and carefully crafted guidance, there are points in the deliberations where uncertainties and even contradictory information necessitate subjective decisions. When do the negative consequences of research results outweigh the beneficial ones? Is there a clear and bright line to be crossed or is this a more nebulous and fuzzy region of “yes” or “no” for this research? I will present only my personal rationale and how I came to the strong conclusion that this work had the potential to be very dangerous and that its communication should be restricted at this time.
I heard from members of the influenza research community and reviewed the World Health Organization (WHO) data indicating that this avian virus had a very high mortality rate in humans. While the influenza A/H5N1 virus rarely infects humans, when it does it causes catastrophic disease. We are all aware of the rapid global spread of human-adapted influenza both on a yearly basis and during less common pandemics. The documented devastation of the 1918 influenza pandemic, even with its lower mortality rate, was a testament to the powerful potential of influenza. The thought of combining the high human mortality of influenza A/H5N1 with a highly transmissible human-adapted phenotype was sobering. A pandemic by such a pathogen could reasonably be concluded to cause such devastation that it should be prevented at all costs.
I carefully considered how restricting the information would compromise scientific research progress and even how it would hinder public health efforts to prevent such a horrific pandemic. I know from firsthand experience that the free flow of information is part of the best and most productive research endeavors and that any restrictions burden the progress. The conclusion that this virus could be adapted to mammal-to-mammal respiratory transmission was, in my mind, the foremost beneficial part of the research. With this firm conclusion in hand, policy makers, granting agencies, public health officials, and vaccine and drug developers should have both the motivation and a compelling argument to move forward to improve our influenza-fighting infrastructure. The details of the research, on the other hand, would add little to this short-term effort and could enable someone to replicate the work in a short period of time. The short-term negative consequences of restricting experimental details seemed small in contrast to the large consequences of facilitating the replication of these experiments by someone with nefarious intent. Current public health surveillance and public health responses would be enhanced little by these details. This comes not only from my own professional experience in globally tracking dangerous pathogens but also from personally watching the 2009 H1N1 influenza pandemic spread globally. It was impossible to contain, and I believe that the same would be true for an H5N1 influenza pandemic. We were lucky in that the H1N1 virus has low virulence, but the best current data suggest that this would not be the case for the H5N1 virus. Publishing a detailed experimental protocol on how to produce a highly transmissible H5N1 virus in a highly regarded scientific journal is a very bad idea.
Since our recommendations were announced in mid-December, there has been considerable response from scientists, policy makers, funding agencies, and global health organizations. There have been criticisms that we were censoring and compromising academic freedom. There have been criticisms that restriction of the publications was insufficient and that even performing such experiments should be restricted. The debate has touched upon both biosafety and biosecurity aspects, with some calling for the destruction of the virus or for moving all such research to the highest safety level, biosafety level 4 (BSL-4). The NSABB has not yet offered specific recommendations concerning these statements, and my personal opinions are relatively unimportant. What is gratifying and essential is that the debate is occurring; it is occurring on an international stage, and it is occurring rapidly.
In the midst of NSABB deliberations and formulation of our recommendations, the need for a global debate to develop policy has always been in our discussions. Why should the NSABB be telling the world what to do? Why has not the world already had these discussions and debates? How could the NSABB stimulate the process such that global leaders in science, policy, and public health engage in a broad-based conversation on these issues? The specific NSABB recommendations seem to have been accepted and are being implemented by two research groups and two scientific journals; more importantly, the research issue of adapting an avian virus to mammals, potentially humans, is a topic that is being widely discussed. The influenza research community is voluntarily suggesting a moratorium on this type of research. The WHO has agreed to participate and facilitate in policy development. And the U.S. Government is working on guidelines for the distribution of restricted information.
Research and public policy will be developed from this global engagement process, a process that should increase the public’s confidence in the scientific endeavor, in scientists’ ethical behavior, and in the transparency that a free research environment embraces. The NSABB recommendations have been effective in both their primary and secondary goals. They are the right recommendations for this time and this problem.

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Notes

The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM.

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Footnotes

• Citation Keim PS. 2012. The NSABB recommendations: rationale, impact, and implications. mBio 3(1):e00021-12. doi:10.1128/mBio.00021-12

• Copyright &#169; 2012 Keim

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

http://mbio.asm.org/content/3/1/e00021-12.full

[sharon sanders]

Re: Man Made H5N1 - Super Version

The H5N1 Manuscript Redaction Controversy

1. Arturo Casadevall and
2. Thomas Shenk

1. Address correspondence to Arturo Casadevall, casadeva@aecom.yu.edu.

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Editorial

Scientists are an argumentative bunch, and science is no stranger to controversy. Since the beginning of the scientific revolution, science has witnessed and engaged in great controversies, including heliocentrism, the theory of evolution, the N-ray affair, and most recently the debate over climate warming. Prior controversies were settled with additional scientific study, which provided convincing data for one faction or the other. Today scientists are engaged in a new type of controversy involving the benefits, debits, appropriateness, and wisdom of redacting experimental data from scientific manuscripts on the grounds that the information could be used for nefarious purposes. This controversy was triggered when a government advisory committee known as the National Science Advisory Board for Biosecurity (NSABB) examined two manuscripts describing genetic changes that enabled bird flu virus (H5N1) to become transmissible in mammals. The NSABB then advised the U.S. Department of Health and Human Services that the main conclusions of the study should be published but that much of the methodology and experimental data that would allow repetition of the experiments and/or the de novo synthesis of mammalian-transmissible H5N1 virus should be redacted (for the press statement, see http://www.nih.gov/news/health/dec2011/od-20.htm).
Unlike other contentious areas of human endeavor, such as religion, philosophy, and politics, science has historically been lucky in that it has always had an accepted mechanism for conflict resolution in the form of carrying out additional experimental work. However, the current H5N1 manuscript redaction controversy cannot be settled by additional experimentation, at least not in real time, because many of the issues involved in favoring or opposing redaction consist of differences in beliefs, principles, and judgment calls. The discussion is further constrained by ignorance and/or uncertainty on major scientific and medical questions regarding the relative value of, and danger posed by, the information to be redacted. For example, precise answers to such questions as to whether infectivity in ferrets translates to humans, the case/fatality ratios of H5N1 infection in humans, and the relative value of mutational information to public health agencies and terrorists are not yet available, and many of the arguments for or against publication are largely a matter of opinion, judgment, and conjecture. It is all but certain that the well-tried tools of experimental science will, in the future, provide additional information that informs the wisdom of the decisions taken today. However, that information is not at hand to affect the current actions, debate, and controversy. Hence, scientists find themselves in somewhat unfamiliar territory as both sides try to convince their colleagues, and the public, of the wisdom of their positions by mixing hard science with nonscientific forms of argumentation, including belief-based arguments, positions of principle, and the art of politics and political persuasion.
In an attempt to inform the ongoing discussion, mBio has commissioned three views on the H5N1 redaction controversy, written by Keim, Racaniello, and Webster (1, 2, 3). Our goal in publishing these views is to provide a venue for differences of opinion that will inform the debate. We note that the overwhelming majority of, if not all, participants in this controversy are well-informed and well-meaning individuals who hope to help and protect both society and science by espousing and promoting their views. We believe that a healthy debate will lead to the best decisions and help avoid great mistakes. We are also fully aware that some aspects of the ongoing debate have echoes in past philosophical debates, since the issues in question are in essence questions of value, belief, judgment, and principle. Consequently, we urge comity, respect, civility, self-examination, consideration, kindness, and generosity as we all navigate through this uncharted territory. In that spirit, we encourage our readership to contribute to the debate by using the commenting feature at the end of the ?full text? versions of the online articles.

Arturo Casadevall
Editor-in-Chief, mBio

Thomas Shenk
Chair, Publications Board
American Society for Microbiology


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Footnotes

• Dr. Casadevall serves on the NSABB, and the views expressed in this Editorial do not represent official policy or those of the NSABB. In addition, the views expressed in this Editorial do not necessarily reflect the views of the journal or of ASM.
• Citation Casadevall A, Shenk T. 2012. The H5N1 manuscript redaction controversy. mBio 3(1):e00022-12. doi:10.1128/mBio.00022-12.

• Copyright ? 2012 Casadevall and Shenk.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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REFERENCES

1. 1.↵
   1. Keim PS
   
   <cite>. 2012. The NSABB recommendations: rationale, impact, and implications. <abbr class="cit-jnl-abbrev">mBio </abbr> 3(1):e00021-12. </cite>
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   1. Webster RG
   
   <cite>. 2012. Mammalian-transmissible H5N1 influenza: the dilemma of dual-use research. <abbr class="cit-jnl-abbrev">mBio </abbr> 3(1):e00005-12. </cite>
   Abstract/FREE Full Text
   

[sharon sanders]

Re: Man Made H5N1 - Super Version

Science Should Be in the Public Domain

1. Vincent R. Racaniello

+ Author Affiliations

1. <address>Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York, USA</address>

1. Address correspondence to Vincent R. Racaniello, vrr1@columbia.edu.

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ABSTRACT

Variants of avian influenza H5N1 virus that are transmitted by the airborne route among ferrets have been identified. The National Science Advisory Board for Biosecurity has advised against publication of the details of the methods used to obtain these viruses and the amino acid changes that lead to transmission in ferrets. This decision is not based on sound scientific principles and risks setting a precedent that will make it easier to put in place highly restrictive regulations on scientific research and publication.

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Commentary

Two laboratories recently identified variants of an avian influenza H5N1 virus strain that are transmitted by the airborne route among ferrets (1). When these laboratories submitted their work for publication, the National Science Advisory Board for Biosecurity (NSABB) asked the authors to remove critical details from the manuscripts to ensure that they cannot be used by bioterrorists. This decision is wrong, not only because it rests on weak scientific grounds but also because it threatens to transform the landscape of biological research by setting a precedent to restrict research that can benefit, not harm, humanity.
The goal of the experiments was to determine what makes the influenza H5N1 virus transmissible. This virus strain is lethal in birds, humans, and ferrets, but airborne transmission does not readily occur among humans or ferrets. One group found that after 10 serial ferret-to-ferret passages, a virus that could spread by the aerial route among ferrets was obtained. The NSABB asked that details on how the virus was isolated and the amino acid changes leading to transmissibility be redacted from the manuscript.
A major reason why the NSABB does not want this information made public is that the virus is believed to be highly lethal in humans. The chair of the NSABB notes that he “can’t think of another pathogenic organism that is as scary as this one.” The reason for this view is exemplified by a recent statement about H5N1 in the New York Times: “In its natural form, it is known to have infected only about 600 people since its discovery in 1997, but it killed more than half of them” (2). We cannot say with any certainty that the virus has infected only about 600 people. What we do know is that among the 600 seriously ill individuals infected with H5N1 influenza virus who are admitted to the hospital, over half of them die.
The fatality rate of avian H5N1 influenza virus in humans is determined by dividing the number of fatalities by the number of infections. We do not know the last number—but there are hints that it could be quite large. In a recent study of rural Thai villagers, sera from 800 individuals were collected and analyzed for antibodies against several avian influenza viruses, including H5N1, by hemagglutination inhibition and neutralization assays (3). The results indicate that 73 participants (9.1&#37 have antibodies against one of two different H5N1 strains, suggesting that subclinical avian influenza virus infections are frequent in Thailand. If 9% of the rural Asian population has been infected with avian H5N1 influenza virus strains, it would dramatically change our view of the pathogenicity of the virus. Extensive serological studies must be done to determine the extent of human infection with avian H5N1 influenza viruses.
Ferrets are not humans and cannot be used to determine whether any influenza virus is a threat to humanity. Ferrets are a good model for influenza—they display similar flu-like symptoms, immune responses, and pathological alterations, such as elevated temperature, weight loss, and histological changes (4). It would be foolish to conclude that ferret influenza is the same as human influenza in all aspects. Not all influenza virus strains have the same virulence in humans and ferrets. An example is the 2009 pandemic H1N1 virus, which caused severe infections in some ferret studies, but was relatively mild in humans (5). The fact that an H5N1 virus is transmissible among ferrets does not mean that it will be equally transmissible among humans. The experiment to answer this question cannot be done.
Passage of viruses in a different host is one strategy for reducing viral virulence in humans. Many live, attenuated viral vaccines have been produced in this way, including vaccines against yellow fever virus and poliovirus (6, 7). The possibility that passage of the H5N1 virus in ferrets will attenuate its virulence in humans has been ignored.
It is highly unlikely that the sequence of the ferret-adapted H5N1 influenza virus would be used for bioterrorism, as its potential for transmission and lethality in humans is unknown. Bioterrorists do not want to carry out an experiment; they want to instill terror. Assuming that the H5N1 virus passaged in ferrets could start a pandemic, knowing the amino acid changes required for transmission in ferrets does not immediately enable construction of a biological weapon. The virus must be recovered from cloned DNA, which requires finely honed skills in virology. A good virologist would have already thought to serially passage the H5N1 virus in ferrets, which would be faster than reconstructing a virus from the nucleotide sequence.
It seems simplistic to assume that laboratory-modified viruses can cause extensive disease in humans. When humans genetically modify viruses, they generally do not know what the virus needs to replicate efficiently, cause disease, and transmit among humans. Consequently, they are likely to introduce changes that attenuate pathogenesis in humans. In nature there is strong selection for fitness and transmission. To think that we can duplicate the enormous diversity and selection pressures that occur in the wild is a severe case of scientific hubris.
No one can guarantee that the ferret-passaged H5N1 virus would not be lethal and transmissible in humans. However, the same could be said about many laboratory-modified viruses, none of which have attracted the attention of the NSABB or the press. When we created the first animal virus from cloned DNA in 1981 (8), there were no calls to redact the paper or prevent further research, despite the theoretical possibility that this reagent might be used to produce more-virulent polioviruses. It was recognized that cloned viral DNA could be used to make important advances in our understanding of viral replication and pathogenesis.
Perhaps more troubling than the weak scientific basis for the NSABB’s argument is the precedent set by withholding experimental details from a scientific publication. Science has always worked best when information is freely accessible. Unexpected individuals from diverse areas often solve difficult research problems. For decades, scientists have carried out experiments on pathogens, and the results have been published in a way that allows other scientists to repeat the experiments, verify conclusions, and expand on what is known. This cycle of publication, replication, and advancement has lead to most scientific and medical advances of the past century and has saved millions of lives. To suggest that studies of legitimate scientific merit should be published without complete methods and data is to abandon a system that brought us to the modern age of medicine.
The decision by the NSABB to restrict publication of data on H5N1 influenza viruses that are transmissible among ferrets is not rooted in sound scientific principles. Of greater concern is that it risks setting a precedent that will make it easier in the future to put in place highly restrictive regulations on scientific research and publication. Fear has clouded the NSABB’s vision. We cannot allow fear to limit our ability to address medical problems.

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Notes

The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM.

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Footnotes

• Citation Racaniello VR. 2012. Science should be in the public domain. mBio 3(1):e00004-12. doi:10.1128/mBio.00004-12.

• Copyright &#169; 2012 Racaniello.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

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REFERENCES

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http://mbio.asm.org/content/3/1/e00004-12.full

[sharon sanders]

Re: Man Made H5N1 - Super Version

Mammalian-Transmissible H5N1 Influenza: the Dilemma of Dual-Use Research

1. Robert G. Webster

+ Author Affiliations

1. <address>Division of Virology, Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA</address>

1. Address correspondence to robert.webster@stjude.org.

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ABSTRACT

The National Science Advisory Board for Biosecurity (NSABB)’s recommendation to restrict publication of the details of the generation of mammalian-transmissible H5N1 influenza virus is unprecedented. Dual-use considerations indicated that the potential biosecurity risks of a transmissible H5N1 virus with a possible mortality of 50&#37; in humans outweigh the substantial benefits of open and complete scientific exchange in this case, although the benefits include potential early detection strategies for H5N1 viruses with specific genetic markers and control strategies, including development of antivirals and vaccines. It is argued that both the funding agency (the National Institute of Allergy and Infectious Diseases) and the scientists were responding to societal needs and acted entirely responsibly. These studies usher in a new era for life sciences, compelling the research community to confront important decisions: under what conditions should such research be done? How can the principle of full release of information be balanced with the moral imperative to protect the public health?

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Commentary

The majority of biological scientists are surprisingly unaware of dual-use research and the role of the U.S. National Science Advisory Board for Biosecurity (NSABB), although influenza researchers did know that a review board had recommended publication of Jeffrey Taubenberger’s complete sequence of the 1918 Spanish influenza virus (1, 2), despite potential biosecurity risks. Consequently, authors and journals alike were surprised by the NSABB’s recommendation that the full details of the generation of mammalian-transmissible H5N1 influenza virus be withheld. Why the apparent reversal in policy? Why does the risk of publishing the details of H5N1 transmissibility in mammals outweigh the benefits of disseminating important new information of immense human and veterinary public health importance?
The reasons include the greater lethality of H5N1 influenza (>50%) than of Spanish influenza (2.5%) in humans, the availability of highly pathogenic H5N1 viruses in nature, and the nearly universal susceptibility of humans to H5N1 infection. This combination of factors creates an unacceptably high level of risk to humanity should mammalian-transmissible H5N1 virus be accidentally or intentionally released. To cope with this dilemma, the NSABB recommended publication of revised manuscripts that withheld some of the details. A full manuscript would be prepared for distribution to global health officials on a need-to-know basis after further consideration and planning.
Both the Fouchier and Kawaoka groups used the ferret model to demonstrate mammalian transmissibility of highly pathogenic H5N1 virus. While the ferret is considered the best available model of human influenza virus infection and transmission, we do not know whether the ferret fully recapitulates these events in humans. For one thing, H5N1 infection tends to be milder in ferrets than in humans; only a minority of H5N1 strains are lethal in ferrets, whereas lethality greater than 50% has been documented in humans. Thus, while we cannot confidently equate transmissibility and pathogenicity of influenza virus in ferrets and humans, can we afford to disregard data from the best available model?
Concern has been expressed that the agency funding the research (the National Institute of Allergy and Infectious Diseases [NIAID]) and the two groups of scientists conducting the research on H5N1 influenza transmissibility may have acted irresponsibly (3). However, after the 1997 emergence of H5N1 influenza in humans, with its greater than 50% lethality and its potential transmissibility from avians to humans, both the World Health Organization (WHO) (4) and a Blue Ribbon Panel of influenza research advisers to NIAID asserted that further H5N1 research was necessary (5). One of the research recommendations of the 2009 WHO Public Health Research Agenda for Influenza was to “Investigate virus-specific factors associated with zoonotic and pandemic potential (e.g., infectivity, transmissibility, and pathogenicity).” In 2006, the Blue Ribbon Panel on Influenza Research recommended to NIAID that “Learning more about how influenza viruses circulate between animal reservoirs and about the evolutionary pressures that lead to the emergence and spread of new viral subtypes—especially the factors that favor transmission from animals to humans—are urgent research priorities.” Unfortunately, neither the Blue Ribbon Panel nor WHO addressed the question of dual-use research. The focus was on the benefits of knowledge, including the development of better control strategies, such as novel antivirals and vaccines. Now that researchers have generated mammalian-transmissible H5N1 and the U.S. NSABB has raised the dual-use concern, there is a clear and acknowledged need for full discussion of the way forward. WHO has also raised considerable concern about the risk of developing mammalian-transmissible H5N1 viruses.
The two manuscripts formally demonstrating generation of mammalian-transmissible H5N1 influenza virus make major contributions to our knowledge and usher in a new era in the life sciences. The question before the scientific community is how to preserve scientific openness while minimizing risk to the public. Control strategies for influenza and other emerging diseases are not adequately developed; the Fineberg Report on the evaluation of WHO’s response to the 2009 H1N1 pandemic (6) emphasized that “the world is ill prepared to respond to a severe influenza pandemic or to any similarly global, sustained and threatening public health emergency.” The urgent need for general guidance in this matter is reminiscent of the dilemma addressed at the Asilomar conference on recombinant DNA molecules in 1975 (7). One possibility is to involve the national academies of science from all interested countries and WHO in considering the topic of dual-use research and an approach that both promotes research and maintains biosecurity. It has been argued that suppression of information serves no purpose, as the information will inevitably be “leaked.” Although this viewpoint is likely correct, I do not believe we should publish the detailed methods of preparing transmissible H5N1.
Further, we must consider and establish the biosecurity level needed for future work on transmissible H5N1. Because highly pathogenic H5N1 is enzootic in multiple regions of Eurasia, the use of biosecurity level 4 (BSL4) for all H5N1 research would markedly restrict advancement of knowledge needed for vaccine and antiviral research. Enhancing BSL3 biosecurity with electronic surveillance, advanced personal protective equipment (PPE), and prior dual-use assessment of proposed studies is a possibility for further consideration. It is noteworthy that in the United States there were 395 biosecurity breaches involving select agents and 7 laboratory-acquired infections during 2003 to 2009 (8). These incidents, which occurred in both BL3 and BL4 laboratories, highlight the potential risks and the need to fully consider improved biosecurity and the immunization of staff with regularly updated H5N1 vaccines.
The groundbreaking manuscripts by the Fouchier and Kawaoka groups will be of great interest to life scientists and will no doubt increase their familiarity with the concept of dual-use research. These two reports challenge us to take action to ensure that research and open dissemination of knowledge can be safeguarded without compromising biosecurity. Both causes are fundamentally important, but public safety must not be compromised. While bioterrorism is of real concern, nature has the potential to do much greater damage.

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ACKNOWLEDGMENTS

Robert Webster is supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, contract no. HSN266200700005C, and by the American Lebanese Syrian Associated Charities.
I thank Sharon Naron for scientific editing and James Knowles for manuscript preparation.

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Notes

The views expressed in this Commentary do not necessarily reflect the views of the journal or of ASM.

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Footnotes

• Citation Webster RG. 2012. Mammalian-transmissible H5N1 influenza: the dilemma of dual-use research. mBio 3(1):e00005-12. doi:10.1128/mBio.00005-12.

• Copyright &#169; 2012 Webster.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Previous Section

REFERENCES

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   <cite>. 2011. Report of the Review Committee on the Functioning of the International Health Regulations (2005) in relation to Pandemic (H1N1) 2009 (“Fineberg Report”). http://apps.who.int/gb/ebwha/pdf_fil.../A64_10-en.pdf. Accessed 10 January 2012. </cite>
   
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http://mbio.asm.org/content/3/1/e00005-12.full

[sharon sanders]

Re: Man Made H5N1 - Super Version

A Chat with Mike Osterholm

Posted on 2012.02.04 by Alan

I got a call last night from Mike Osterholm, noted epidemiologist and member of the National Science Advisory Board for Biosecurity (NSABB). He wanted to talk about H5N1 flu ? if you don?t know why, scroll down to the previous few posts.

First, I want to thank Mike for calling. We had a good conversation in which I think we came to understand each others? viewpoints a bit better, though we still disagree strongly on some key issues. That means that as I had hoped, the H5N1/censorship debate is finally moving forward. To clarify my own position, and also help those who aren?t in direct touch with NSABB members, here?s a synopsis of what we talked about. Bear in mind that this was not an ?on the record? interview, so I won?t be quoting Mike, but I?m pretty sure he won?t mind me discussing our conversation publicly. If I misstate anything, I hope he posts up in the comments to correct it.

more..

http://alandove.com/content/2012/02/a-chat-with-mike-osterholm/

[sharon sanders]

Re: Man Made H5N1 - Super Version

Flu Fighters
February 3rd, 2012 2:26 AM by Carl Zimmer

snip

Laurie Garrett, an award-winning health reporter who now works at the Council on Foreign Relations, pointed out that the flu is not just something that American scientists study in their labs. It’s a global problem. There’s a huge amount of resentment in poor countries where bird flu is the biggest threat, not just to humans, but to the poultry industry. “Poor people are killing their chickens for you,” Garrett said. “They’re going bankrupt.”

Making matters worse, as Garrett has recently written, is the distrust that has developed in the developing world towards Western medical research and the pharmaceutical industry. Indonesia, where many of the H5N1 deaths have occurred, has been reluctant to share bird flu samples with Western scientists, for fear that they would make huge profits from vaccines developed from them. The World Health Organization has set up an international agreement for the exchange of wild bird flu strains between different countries, but it’s in fragile shape.

So for all the sparks that flew in New York Thursday night, the real fireworks over the flu are yet to come.

[Update 2/3 9 am: Corrected description of Racaniello's experiment. Thanks to Matt Frieman. 2:50 pm Fixed Fouchier's institution name and month of his talk. Thanks to Jon Cohen. 8 pm: Expanded Osterholm's "mainstream of influenzologists" quote after seeing his objection to a similarly truncated version in Christine Gorman's story for Scientific American and reviewing my own recording. It's a valid clarification .]

http://blogs.discovermagazine.com/loom/2012/02/03/flu-fighters/

[sharon sanders]

Re: Man Made H5N1 - Super Version

Schism over H5N1 Avian Flu Research Leaks Out

By Christine Gorman | February 3, 2012


NEW YORK—Sparks flew Thursday night at a New York Academy of Sciences panel discussion about whether or not certain recent research into the H5N1 avian flu virus has created a major biosecurity threat and what, if anything, to do about it.

snip

Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis and a member of the National Science Advisory Board for Biosecurity (NSABB), characterized as “propaganda” a scientific paper published last week by co-panelist Peter Palese, a noted flu researcher at Mt. Sinai School of Medicine in New York City.

snip

Update (8:41 PM, Eastern): Carl Zimmer originally posted the shorter version of Osterholm’s quote as well. Carl has since checked his tape and concluded that in fact Osterholm said, “You do not represent the mainstream of influenzologists when it comes to this issue on influenza.”

http://blogs.scientificamerican.com/observations/2012/02/03/schism-over-h5n1-avian-flu-research-leaks-out/

[gsgs]

Re: Man Made H5N1 - Super Version

it depends on the details of the experiment, which are secret.
How easier is it to redo the experiment, if the secret data were known ?
Fouchier,Kawaoka etc. should know, but from what I read
I don't trust their judgement on this very much.
So for me it's OK to have NSABB involved.
But then, I know nothing about NSABB and their qualification...

[Michael Coston]

Re: Man Made H5N1 - Super Version

I thank you for your well considered comments, JJackson.


As I hope those who read my blog can tell, I'm not firmly entrenched in either camp. I see merit in some of the points being made by both sides, while at the same time remain less than convinced by others.



Personally, I'm not at all convinced that the `terrorist threat' is as great as some would have us believe, but I accept that the risk is not zero.

At the same time, I find precious little comfort in the argument that the virus - if it were to escape from the lab (a greater risk IMHO) - wouldn't be `as deadly' as advertised and could be dealt with with our vaccines and antivirals.


Whether the NSABB is right or wrong on the publication of these papers - and that is something for the international scientific community to assess - they have provided us with an opportunity to stop and confront a number of pressing issues facing life sciences research.


Something that, quite frankly, should have been done years ago.

[JJackson]

Re: Man Made H5N1 - Super Version

I am wholly in agreement with Mike's arguments and applaud his balance. However anyone who has read my earlier posts will realise I have nailed my colours squarely in the 'publish' camp. How do I square this apparent contradiction?

I agree the NSABB did what they were formed to do but my problem stems from my belief that the risk of any 'nefarious' grouping weaponising H5N1 is negligible and that if there were such a group there is more than enough information already available so to do. Everything hinges on that.

If that is true then when you apply the 'do no harm' principle anything that slows down or stops research is doing harm. It has been argued that there is no real value to the research, in practical terms, but I disagree. It is not just that Fouchier's team have shown mammalian droplet transmission can be achieved, with relatively few changes. What is important is that this experiment is repeated many times, with different strains, to find out if there are many ways to achieve this or only one or two. If it appears there is a common requirement then we have the possibility of producing, and stockpiling, a useful pre-pandemic vaccine if there are dozens of viable routes then not. This is genuinely useful information. I do appreciate the many caveats, just because it works for ferrets does not have to hold true for man, nature has a much broader pallet of genes so may find solutions we don't etc.
Once the strains are sequenced they could be destroyed.

I am very much in favour of the wider debate and have significant concerns about lab escapes - which are very much a proven danger. I am also alarmed by some of the genetic engineering of resistance in food crops and the ability to keep it where intended. I am not at all sure the US's preoccupation with WMD's is the correct vehicle for driving this debate or that these experiments are the correct ones to be concerned about.

There has been one useful side effect of this debate which is a number of H5N1 canards, which are often left unchallenged,have been aired.

The CFR calculations in the absence of reliable seroprevalence data has been put front and centre by Prof. Racaniello. Where I disagree with Prof. Racaniello is in this quote

In the unlikely event that the virus somehow escaped and began to infect people, its spread could be controlled by vaccines (candidates are under development) and antivirals (existing neuraminidase inhibitors are active against influenza H5N1).

while I am on his side, not Osterholm's, in the wider argument here I think Osterholm is correct

Michael Osterholm on LiveChat
Michael Osterholm: Andy provides a number of thoughtful ways the detailed information can be potentially used. All of these suggested areas are worthwhile but they have no practical implications for a modern a infleunza vaccine. We are stuck with a largely 1940's technology vaccine antigen and manufacturing platform. All the efforts that Andy details have no practical implications for immediately improving our public health response at this time. If our vaccine technology changes, this might be a different story.

I wish Vincent was right but our current vaccine production system can not produce vaccine quickly enough or in sufficient quantity. There are 7 billion of us now and the antivirals may help a few more than the vaccine but most people would get neither.

Sadly I find myself agreeing with Osterholm again on the WHO pandemic containment plan, or at least the aspect of it that calls for early outbreak identification and containment by use of a Tamiflu blanket. Anyone who has been following the way human cases and clusters get reported in the press, and to WHO under the IHR(2005), will realise this was never likely to work. It would not have worked with H1N1(2009) in Mexico/USA and has next to no chance in the less affluent and more restrictive, news-wise, regions.

It has been suggested that surveillance for a pre-pandemic virus similar to what is described in these studies will lead to early and comprehensive intervention to quash an emerging pandemic. This is simply not practical. Neither the animal or human surveillance capacities of the H5N1 endemic countries are in any position to use this genetic information to identify the emerging pandemic virus and undertake comprehensive programs to eliminate its emergence. The WHO recognized this very point with A(H1N1)pdm09 and its emergence in Mexico.

[sharon sanders]

Re: Man Made H5N1 - Super Version

hat tip Michael Coston -

Friday, February 03, 2012

Pathogens, Publishing, And The Precautionary Principle




# 6118


Over the past few months we?ve been witness to a fascinating, volatile, and sometimes unseemly debate over controversial `dual use? H5N1 research. I?ve tried to present both sides of this issue as fairly as possible, without interjecting my own opinion.

Not because I don?t hold an opinion on this topic (I most certainly do), but because I believe that these issues are far too important this non-scientist to marginalize either side by taking pot shots at them in this blog.

I certainly understand (and share) the deep feelings that many scientists hold regarding the sanctity of independent and unfettered scientific research, and their abhorrence of anything that smacks of government censorship.

And from a practical standpoint, given the backchannel communications in the scientific community, I have considerable doubts as to whether this H5N1 genie can now be coaxed back into its bottle.

But I also know from my years working as a paramedic ?where patient safety and the principle of Primum non nocere ("First, do no harm") reign supreme - why the NSABB would have been hard pressed to come up with any recommendation other than the one they did.

And it boils down to the Precautionary Principle, which is a basic tenant of public policy which says:

When the health of humans and the environment is at stake, you need not wait for scientific certainty of risk before taking protective action.

So basic and widespread is this ideal that its use has become a statutory requirement in many countries.

In 1998, the Wingspread Conference on the Precautionary Principle summarized the policy as:

When an activity raises threats of harm to human health or the environment, precautionary measures should be taken even if some cause and effect relationships are not fully established scientifically.

Essentially, if an action, or a byproduct of some action can reasonably perceived as being potentially harmful to the environment or to public health, the onus of proof of its safety falls to the activity?s proponent.

The NSABB?s role, as defined in their FAQ, is to

` . . . provide advice, guidance, and leadership regarding biosecurity oversight of dual use research to all Federal departments and agencies with an interest in life sciences research.

The NSABB advises on and recommends specific strategies for the efficient and effective oversight of federally conducted or supported dual use biological research, taking into consideration national security concerns and the needs of the research community.?

In other words, it was their job to look at these research projects, and if they found a reasonable concern for public safety, to raise a red flag.

Which is precisely what they did.

The dismissive arguments over the true CFR of the H5N1 virus, or whether transmissibility in ferrets necessarily translates transmissibility in humans, completely misses the point.

Whether you agree or disagree with the committee?s conclusions, the NSABB simply did what they were designed to do as part of a system of checks and balances.

While there is no scientific certainty that any harm would come from the publication of these papers, it can be reasonably argued that - in the wrong hands - this information could potentially lead to a serious, even catastrophic mishap.

And under the Precautionary Principal, the NSABBhad little choice but to raise their concerns, with the onus then falling on those wishing to proceed to prove the safety of doing so.

Although there has been a lot of outrage and posturing on both sides of this issue - it seems clear to me that however flawed - the system has worked this time.


The NSABB committee raised their concerns, and in doing so, has forced a conversation that?s been too long overdue.

How are we to handle this brave new world of life sciences, where new viruses and other life forms can be created in the laboratory?

Who decides what is appropriate, or safe research? Or what should be published, and who should have access to redacted information?

What laboratory protocols and protections are necessary for working the the H5N1 virus?

And under the WHO?s PIP (Pandemic Influenza Preparedness) Framework, adopted last May by the 64th World Health Assembly, who is entitled to receive samples of these new strains of the virus?

Over the past few weeks I?ve been saddened to see some of the world?s best scientists and researchers maligned by the media as crazed present day Dr. Frankensteins ? ready to unleash a killer plague that would wipe out half of humanity for the sake of getting another research grant.

While those urging caution - recommending a review of research protocols and possible redaction of these papers - have been characterized as being tools of an oppressive and paranoid biosecurity industry.

When the simple truth is, both sides are simply doing the job we rightfully expect of them. They may have different mandates, and priorities, but both are valid and important.

If we manage to keep ahead of the H5N1 virus, it will be due in large part to the kind of groundbreaking work being done in the labs of Ron Fouchier, Yoshiro Kawaoka, and others.

But these research projects are not without some risk, and that is why some oversight is necessary.

While the NSABB won?t be the final arbiter of this case (this needs to have an International solution), the only reason we are now having this conversation today is because they took a difficult and unpopular stance.

The hard work lies ahead; forging some sort of workable compromise that will protect important scientific research, and at the same time shield the public from unnecessary and avoidable risks.

I don?t pretend to have the answers. And I fully expect that there is no `perfect? solution to be had.

But I do know that the first step towards reaching any meaningful compromise is for all sides involved to accept as valid the concerns held by the other stakeholders in this debate, instead of simply trying to dismiss them as unfounded or overblown.

And discouragingly, so far I?ve seen precious little of that in the debate so far.

Posted by Michael Coston at <a class="timestamp-link" href="http://afludiary.blogspot.com/2012/02/pathogens-publishing-and-precautionary.html" rel="bookmark" title="permanent link"><abbr class="published" title="2012-02-03T15:39:00-05:00">3:39 PM</abbr>

[mixin]

Re: Man Made H5N1 - Super Version

Pathfinder,

“...To prove these guys wrong, we needed to make a virus that is transmissible.”

So the goal was to produce a transmissible one.

Is it typical for the U.S. to fund research in other countries? Or did they specifically want Dr. Fouchier to do the research?

From your link (good to know we have a vaccine that will work on these strains?):

Can researchers become infected with the virus and then spread it?
The laboratory staff members have been well-trained and take all the required precautions to work safely in the research areas. The staff members have been vaccinated. In the interest of everybody’s safety, no unauthorized persons are admitted to this area and all work is carried out under the supervision of a Biological Safety Officer. In the unlikely event of an incident, antivirals are available to treat staff members. Erasmus MC also has the facilities to accommodate people in an isolation room after possible infection.

[Pathfinder]

Re: Man Made H5N1 - Super Version

I find this whole research issue confusing; I'm not knowledgeable about how research projects are funded.

Surely when these were funded, the expectations were clear.. in that the goal was to do what was finally accomplished. I find it hard to believe that guidelines were not laid out as to what the researchers would do with the information if they were successful.

My Mixin is that many have been taken by surprise by the "unexpected" result of this research, Dr. Fouchier included. I also find it hard to believe that no protocol was implanted before the start of the research in case of "successful results", considering the fact that this experiment was supervised by the CDC and the NIH.


?There are highly respected virologists who thought until a few years ago that H5N1 could never become airborne between mammals,? Dr. Fouchier said. ?I wasn't convinced. To prove these guys wrong, we needed to make a virus that is transmissible.?
...
Looking back on that day in July with Sander Herfst, the member of his team who told him the virus had gone airborne, Dr. Fouchier said, ?We both needed a beer to recover from the shock.?

Then they planned their next step, repeating the experiment to make sure the results were reliable.

There was one major obstacle: they had run out of ferrets. They ordered a new shipment from Scandinavia. So they had to wait several weeks to find out whether their discovery was real. Dr. Herfst took a vacation, timed to end the day the ferrets arrived.

They ran the tests again. Once more, A(H5N1) went airborne."
--------------------

"The Dutch government and the United States Centers for Disease Control and Prevention approved the laboratory, and the National Institutes of Health gave the Erasmus center a seven-year contract for flu research."

"... The research was also commissioned by the American National Institutes of Health (NIH) and therefore also assessed by experts in an international context. Because of the American funding, the researchers not only have to comply with Dutch law and regulations but also with American law and regulations. The facilities and researchers are inspected every three years by inspectors of the ?Centers of Disease Control?(CDC) in Atlanta. A positive recommendation with regard to the safety was once more given by the inspectors during the last inspection in February 2011."

Sources:

http://www.nytimes.com/2011/12/27/science/debate-persists-on-deadly-flu-made-airborne.html?pagewanted=2

http://www.erasmusmc.nl/perskamer/faq-vogelgriep/?lang=en

[Pathfinder]

Re: Man Made H5N1 - Super Version

From Sharon's post:

"The exceptions are those who don't understand the science, and the bioterror community......They are not practicing scientists and they don't appear to understand the underlying science."

The conflict of opinions on this research seems to be, not only between governments and scientists, but also among scientists themselves.

[JJackson]

Re: Man Made H5N1 - Super Version

Prfvvr good luck! I regret you will need it as they have packed the panel with bio-threat industry spokesmen.