The Fight Over

COMMENT PHILANTHROPY Charities should VACCINES More collaboration EXHIBITION The scientific OBITUARY Paul Doty, pay their fair share of would spur biomedical legacy of Robert Scott’s chemist and arms-control research costs p.260 research innovation p.261 ill-fated expedition p.264 advocate p.266

We don’t know the worldwide opinion until a group of experts from all parts of the globe is formed. An issue this big should not be decided by one country, but by all of us. JOHN STEINBRUNER A system for OXFORD SCIENTIFIC/PHOTOLIBRARY/GETTY SCIENTIFIC/PHOTOLIBRARY/GETTY OXFORD redacted papers Director, Center for International and Security Studies at Maryland, University of Maryland, College Park

If the two papers (submitted to Nature and Science) describing a transmissible form of the H5N1 virus are the first to be published with key details missing, they probably won’t be the last. We need to establish both a short- term and a long-term solution for how the scientific community should handle such a publication. Who decides who should have access to the full details? Who monitors the community so that the details don’t get The fight over flu passed around outside the group of experts cleared to receive them? A proposal to restrict the planned publication of I believe that the entire process must be research on a potentially deadly avian influenza virus is regulated by a global health body, ideally the World Health Organization (WHO). causing a furore. Ten experts suggest ways to proceed. Already, a WHO committee oversees all research involving the smallpox virus. A National Science Advisory Board for Bio similar, more developed system could work security (NSABB) to remove key details for H5N1 and other deadly pathogens. RON FOUCHIER & from the methods and results sections of An international group of experts would AB OSTERHAUS published papers, including our own, sub approve research involving those agents, mitted to Science (see Nature 481, 9–10; decide who will have access to the details Globalize the 2012). But we do question whether it is of papers that come out of that work, and appropriate to have one country dominate hold those vetted individuals accountable discussion a discussion that has an impact on scientists for what they do with the information. For and public-health officials worldwide. This instance, such a system might allow permit Erasmus MC, Rotterdam, discussion should include the perspective of ted experts to view papers only electroni the Netherlands people in regions where H5N1 has infected cally, so nothing is on paper. A database humans. Will the NSABB also advise on could record the privileged few people who So far, most of the human deaths from the which international researchers and officials have seen the full paper, and what they do deadly H5N1 strain of bird flu have occurred have the right to see the full papers, to help with the information. In all likelihood, legal in Asia and the Middle East. Many labs world implement urgently needed surveillance and safeguards would be needed to protect the wide — including ours — are trying to under other intervention strategies? rights of people who receive the sensitive stand what makes the virus so virulent, and It is not clear whether an international information. Such a process would not offer how to stop it. H5N1 research is thus a global discussion would lead to different recom complete protection against misuse, but it issue, yet the entire research community seems mendations. There is no global equivalent would show the scientific community that to be following the advice of one country. of the NSABB, but many European experts the committee is watching what they do. We are not questioning the unprecedented that we have seen quoted in the press believe Because dangerous pathogens are a global recommendations last month from the US that the research should be published in full. issue, any procedure would need buy-in

from all countries, who would have to give the committee binding jurisdiction over research involving extremely dangerous agents. This will take some time. In the short term, the WHO or some other global health organization should immediately establish an ad hoc committee to review who should receive access to the full H5N1 papers, and ensure that the details do not circulate widely. Most importantly, these discussions should not be controlled by officials focused on national security. H5N1 is primarily a matter of public health. If there is a threat of bioterrorism, let it be judged by a global health organization, which can set rules that do not deprive scientists of information that could save millions of people in the case of N. SHRESTHA/EPA/CORBIS a natural pandemic. If national-security South Asian countries such as Nepal are among the most likely to be hit by avian flu epidemics. organizations become involved, they will vet scientists on the basis of citizenship, and army’s Unit 731 infected civilians and prison will be inclined to discriminate against those ers of war in Manchuria, China, with Yersinia countries in which terrorists have found ref pestis, the bacterium behind the Black Death, LYNN KLOTZ & uge. But some of those countries are among which was first identified in plague patients ED SYLVESTER the few that have experienced human deaths in Hong Kong in 1894. When the unit found from H5N1, and are most likely to witness that the bacteria caused severe organ dam Worry about the origins of a natural pandemic. It is cru age when serially inoculated into prisoners cial that scientists and other experts are of war, the unit began spreading plague-con lab infections judged on their qualifications, not on their taminated fleas in China, causing outbreaks. nationality. If the world is to accept the pro Censoring scientific data for publication Center for Arms Control and cess, national-security officials cannot be will not stop rogue individuals or nations Non-Proliferation, Washington DC; allowed to dominate the discussion. from developing a deadly and highly trans Walter Cronkite School of Journalism missible form of H5N1, but it would at least at Arizona State University buy some time to find and stockpile the KWOK-YUNG YUEN appropriate antivirals, immunomodulators Asian bird flu is just one of the extremely and vaccines to protect against most variants dangerous pathogens researched in labo The Hong Kong of H5N1. Even if the publications omit the ratories throughout the world. Along with methods for making such a deadly virus, the two labs that created a potentially con perspective the genomic signatures associated with air tagious form of H5N1, at least 40 others borne transmissibility should be known to worldwide investigate deadly, highly con Chair of Infectious Disease, the directors of all public-health laboratories tagious pathogens not currently present in Department of Microbiology, in the WHO surveillance network, after they human populations, such as the SARS virus University of Hong Kong sign an agreement of confidentiality. and the recently resurrected 1918 pandemic flu virus. Public-health experts worry about As a scientist working in Hong Kong — the natural pandemics, and governments worry site of the first human epidemic of infection D. A. HENDERSON about the risk that these pathogens pose by the highly fatal H5N1 virus — I appreci to national security — but the probability ate the public-health significance of knowing The ultimate of accidental release is likely to be much which mutations confer airborne transmis higher. sibility in an animal model. The new, much- biological threat We have analysed the likelihood of debated research provides this information. escape from 42 labs, using 1% as the esti Finding similar genomic signatures in animal Center for Biosecurity, University mated probability of an escape from a single or human viruses collected from the WHO of Pittsburgh Medical Center, lab in a single year. This approximates the Global Influenza Surveillance Network may Pennsylvania historical probability, obtained by divid alert public-health workers to an impending ing the documented number of escapes of epidemic of unthinkable magnitude or sever The H5N1 influenza strain poses a poten these pathogens (3, each involving the SARS ity. But I also appreciate the possibility that tial biological hazard far more serious than virus) by our estimate of the total number such mutants could cause a global disaster any we have ever known. It is a virus that is of lab-years of research on these pathogens if accidentally or deliberately produced and capable of killing half its victims, a propor since 2003 (more than 300 lab years). Lab released into animal and human populations. tion greater than that for any other epidemic infections can easily spread: in 2004, after Consequently, I support the recommenda disease. Were that coupled with the trans the only natural SARS outbreak in humans tion from the NSABB to remove key details missibility of a pandemic flu virus, it would was contained, two graduate students lab- from the papers describing this work. have characteristics of an ultimate biologi infected with SARS in Beijing infected seven Biological warfare is familiar to people cal weapon unknown even in science fiction others, causing one death. living in this part of the world. During the (see Nature 480, 421–422; 2011). We should Our analysis shows that the probability of Sino-Japanese War in the 1930s and 1940s, not publish a blueprint for constructing such an escape from at least one of 42 labs in a scientists and physicians of the Japanese an organism. single year is 34%; within less than 4 years,

258 | NATURE | VOL 481 | 19 JANUARY 2012 © 2012 Macmillan Publishers Limited. All rights reserved COMMENT the chance of escape reaches 80%. If more and to investigate how they adapt and cause labs begin studying the (potentially) human disease. The work could provide better sur DAVID L. HEYMANN contagious form of H5N1, that interval will veillance tools to detect viruses that are in decrease even further. the process of adapting to humans. Scien We will always In comparison, the average time between tists must be able to continue to work with the three natural influenza pandemics in these viruses safely and appropriately, in need vaccines the last century was about 30 years (1918, multiple teams utilizing the talents of many 1957 and 1968). We are creating a risk that researchers, and under the numerous layers Head, Centre on Global Health is much greater than that posed by nature. of protection and oversight that safeguard Security, Chatham House, London Laboratories need stronger precautions, such scientists and the public. as mandatory quarantine of lab staff work Of course, scientists will have to continu The creation in vitro of highly transmissible ing on live dangerous pathogens until they ously re-examine and discuss the balance forms of H5N1 is a fresh reminder of how can be certified clear of infection. Regulators between the benefits of conducting and the endgame in infectious-disease control should not be sitting idly by, while the threat publishing pathogen research, and the risk has changed. of a man-made pandemic looms. of misuse of such knowledge. We should For years, scientists and officials have continue the dialogue as we continue the believed that the ultimate application of dis research. ease control was eradication. In a world free from a particular pathogen, the disease no JEFFERY K. TAUBENBERGER longer occurs, and the expense — and small risk — of vaccination is avoided. As a result, Study how viruses RICHARD H. EBRIGHT there would be no need to develop and swap hosts maintain vaccine stockpiles. This idea began Mitigate the to change in 2002, when the poliovirus was Chief, Viral Pathogenesis and Evolution risks of release synthesized de novo. The change has been Section, Laboratory of Infectious profound — the endgame must now take Diseases, US National Institute of Department of Chemistry and into consideration the possibility that con Allergy and Infectious Diseases Chemical Biology, Rutgers solidation and safe storage, or destruction, University, Piscataway, New Jersey of remaining polioviruses is not sufficient to How influenza viruses adapt to humans and eliminate the risk that it will be reintroduced. cause disease has been a significant inter Engineered derivatives of highly patho With the possibility of synthesizing a virus, est of my laboratory, including sequencing genic avian influenza virus capable of it is likely that we will always need to have the genome of the 1918 H1N1 influenza, aerosol transmission in non-rodent mam vaccines readily available. the virus that caused the worst pandemic mals pose potential threats to human health But some say that maintaining samples on record. This work has led to research on and to food production. The major concern of deadly pathogens is a necessary precau how influenza viruses switch hosts and cause is accidental release, for example through tion. Take the discussions about the samples severe disease, and is serving as a basis for new infection of a lab worker who then infects of smallpox virus (Variola), maintained at vaccines and therapies. As a result of these others. Deliberate release by a disturbed or two WHO-sanctioned laboratories since the studies, scientists and public-health officials disgruntled lab worker, bioterrorism and virus’s eradication. Some now argue that we are better prepared to prevent or mitigate a biowarfare are also concerns. need these samples to study the virus, and to similar future pandemic. Studies examining The following steps should be taken imme develop new vaccines and therapies in case adaptation and transmission of avian H5N1 diately. To address accidental release, assign of a bioterrorist attack. Indeed, the WHO influenza virus are similarly important. the viruses as pathogens that require the high Advisory Group of Independent Experts that For reasons not yet clear, some influenza est biosafety level (‘level 4’, not ‘level 3+’ as has reviews the smallpox research programme viruses adapted to poultry can acquire sets been the case to date). To address deliberate noted this year that DNA sequencing, clon of mutations that kill almost every bird that release, assign the viruses as pathogens that ing and gene synthesis could now allow they infect, but rarely infect humans. Since require the highest level of biosecurity (‘Tier de novo synthesis of the entire Variola virus 1997, H5N1 viruses have devastated poul 1’, like smallpox virus and anthrax bacterium, genome and creation of a live virus, using try flocks in southeast Asia and other parts under the revised US select-agent rule that publicly available sequence information, at of the world, and also caused disease in a enters into force this year). a cost of about US$200,000 or less. limited number of the presumably tens of To minimize risks from future research, It is tempting to argue that, for the sake of thousands of humans who have had direct additional steps should be taken. We need public health, research that constructs highly contact with infected birds. Although human to implement a system of mandatory prior pathogenic forms of viruses, such as H5N1, infections are uncommon, the high fatality review of research directed at increasing a should be squashed. But even if we elimi rate in those people infected by H5N1 — pathogen’s virulence, transmissibility or abil nated H5N1 and destroyed all lab samples, more than 50% — raises serious concerns. ity to evade countermeasures. We also need we would still need to consider keeping and A growing body of evidence suggests to re-evaluate, and preferably terminate, bio producing a vaccine, because the virus could that influenza host-switching processes are defence expenditures on research directed potentially be recreated. And stopping this complex, and may be unique to each virus. at creating and assessing new biothreats, as type of research would open a dangerous door. Changes in the 1918 H1N1 virus crucial opposed to addressing existing biothreats. Although adding and deleting genes can cre for adapting to humans, for example, were Creating and assessing new threats rarely ate super-strains that put the entire world at not found in the 2009 increases security. Doing so in biology — risk, such research also helps to develop pub pandemic H1N1 virus. NATURE.COM where the number of potential threats is lic-health tools such as vaccines and diagnos It is essential to con See Nature’s web nearly infinite, and where the asymmetry tic tests. Preventing this research would also tinue research into this focus on the 1918 between the ease of creating threats and prevent us from using all possible scientific with H5N1 and other influenza pandemic: the difficulty of addressing threats is nearly options to prepare for naturally occurring — emerging pathogens, go.nature.com/9rcpjv absolute — is especially counterproductive. or deliberately caused — outbreaks. ■