TWN Info Service on Health Issues (Jan12/03)
This article pertains to US sponsored research (undertaken by US and Netherlands labs) which has led to man-made mutated strains of H5N1 that are easily transmitted between mammals, and which are believed to pose a particularly high pandemic potential among humans. Amidst biosafety and national security concerns, the US has censorsed the experiments and is planning to make the results available to a select group of laboratories.
From a public health perspective this approach raises further concerns as well as dilemmas for implementing the WHO's PIP Framework.
The full news report by Edward Hammond is found below.
US-sponsored risky research may affect global flu virus framework
Austin, Texas, United States, 16 Jan (Edward Hammond*) -- The fallout from United States-sponsored experiments with pandemic influenza strains has raised strong biosafety concerns and raised dilemmas for implementing the World Health Organization's Pandemic Influenza Preparedness (PIP) Framework.
This Framework was negotiated over several years and only recently adopted at the 64th World Health Assembly in 2011.
A WHO statement released on 30 December 2011 said that the Organization is "deeply concerned about the potential negative consequences" of the experiments and stressed that addressing the controversies that have been created should not interfere with the PIP Framework (http://www.who.int/mediacentre/news/statements/2011/pip_framework_2011122 9/en/index.html).
The experiments, which have yet to be published, involved two separate teams that took H5N1 "bird flu" influenza strains and deliberately mutated them to make them transmit easily between ferrets. Ferrets are used as a model for humans in influenza research. The research results are thus thought to indicate how to alter a H5N1 strain so that it spreads from person to person, potentially causing a highly lethal global pandemic.
It is feared that a criminal might use the research results to create and deliberately release such an influenza strain, or that a laboratory accident could cause a global catastrophe. As a result of these fears, US officials have imposed a de facto moratorium on publication of the studies and are debating proposals to censor public versions of the papers, while restricting access to the scientific details to laboratories that have a "legitimate" need to know.
The situation raises significant issues for the PIP Framework. It is the WHO System that originally provided the H5N1 strains mutated by both researchers. In mutating them, the US-sponsored researchers have deliberately created new strains with a particularly strong pandemic potential.
The PIP Framework and guiding principles established for WHO-affiliated laboratories emphasize that significant research results with pandemic implications should be reported to the international laboratory system, and that novel potentially pandemic strains should be provided to the WHO System for characterization by its laboratory network.
In this case, however, it appears that the US will not be willing to share its viruses and research results with WHO Member States. This contradicts the position recently taken by the US in the negotiation of the PIP Framework, where the US was a strong advocate of freely sharing potentially pandemic viruses among WHO laboratories. The US even questioned the need for any type of Material Transfer Agreement in order for potentially pandemic viruses to be internationally shared.
There is significant irony in the situation. In 2007, when Indonesia announced that it would cease to share potentially pandemic H5N1 viruses with the WHO System, the country was harshly criticized by senior WHO and US officials, who went so far as to accuse the Indonesian government of being a menace to global public health. After negotiation of the PIP Framework providing for some benefit-sharing, Indonesia has resumed virus sharing.
Now, it is the US which may suspend virus sharing, but while the outward similarities are striking, there are important distinctions between the cases. Indonesia ceased to share H5N1 viruses to protest the lack of benefits it received from the WHO System, which provided viruses to a vaccine industry that failed to serve developing country needs.
Vaccines manufactured from Indonesian viruses were unavailable or unaffordable in developing countries. And when Indonesia ceased to share viruses, the PIP Framework did not exist, so it was not under any international obligation to share influenza isolates.
The current situation with the US, however, is different because the US has agreed to the PIP Framework and, indeed, was a major proponent of open sharing of viruses and characterization data in those negotiations. Also, the US is potentially balking at its sharing commitment for its own security-related reasons. These seem weak and narrowly focused in comparison to Indonesia's more principled stand. WHO's reaction too has been muted in comparison to its striking criticism of Jakarta.
Censorship of the recent experiments and similar ones in the future could impede international pandemic preparedness by effectively creating secret genetic profiles of potentially pandemic viruses. This genetic information might be available to some WHO Member States but not to others, creating two "tiers" in the international laboratory system - one composed of laboratories the US deems "legitimate" and the other composed of the rest.
This may delay, complicate, or create new disparities in pandemic planning and response, delaying access to critical data to some laboratories or countries.
The experiments were both funded by the US government's National Institutes of Health and conducted by laboratories in The Netherlands and Wisconsin, USA. The twin projects nearly advanced to print before US security policymakers learned of them and imposed a de facto moratorium on their publication by requesting that the editors of Science and Nature refrain from putting the methodological details into print.
Experts are divided on whether it was justified to conduct the experiments to begin with. Some scientists, particularly those close to the projects, argue that deliberate creation of more dangerous pandemic strains is justified in order to learn how to combat them. Others counter that defense doesn't justify creating a new disease agent, and that the man-made strains are of limited use because their mutations and behaviour are unlikely to parallel what happens in nature, making the lessons learned not particularly useful.
Critics also point out that this kind of experiment greatly increases the possibility of a man-made influenza pandemic resulting from a laboratory accident. These concerns are particularly high because under current laboratory biosafety guidelines (binding rules do not exist in most countries), the anthropogenic (human-made) pandemic strains are being handled at biosafety level three (BSL-3, or P-3), a relatively common type of laboratory that lacks the highest safeguards against accidental release.
Well over 300 BSL-3 facilities exist in the US alone, many of them newly-constructed as part of its post-2001 biodefense boom. Underscoring the concern, in 2003-4, the SARS virus escaped no less than three times from three separate BSL-3 facilities in Asia.
The sheer number of BSL-3 facilities, in the US and elsewhere, vastly increases the possibilities of an accident if the pandemic experiments are widely reproduced. And it is anticipated that they will be widely reproduced if published.
Experts concerned about biosafety risks are currently lobbying the US government to restrict the viruses to biosafety level four (BSL-4, or P-4) facilities. These laboratories are much less common (there are several dozen globally) and feature maximal safety equipment and procedures. Some influenza scientists, however, mainly citing reasons of personal convenience, prefer that the viruses remain at BSL-3.
The US government is in the midst of a sharp internal debate over the extent to which it should restrict access to these and similar research results. It has also said that it will publish long-delayed "biosecurity" guidance to research laboratories in the coming weeks.
That project, on hold for nearly a decade, was originally conceived to address risks generated by the expansion of research on biological weapons agents in the US after 2001. US officials, however, have traditionally shied away from issuing mandatory biosafety rules for research laboratories, so it is not clear how obligatory the new "guidance" will be.
Some officials and independent observers hope that the new US system will place emphasis on reviewing projects before the fact, so as to weed out unnecessarily risky research and to avoid last minute debacles such as that which occurred with the recent H5N1 experiments (and previously with experiments involving 1918 pandemic influenza). If, however, the guidance is optional and decisions are placed in the hands of the researchers that conduct the experiments, it is unlikely that they will be effective.
Others hope that enhanced domestic oversight will be linked to an international system to review such research.
A 7 January 2012 New York Times editorial condemned the research for its "catastrophic" potential and urged that "In the future, it is imperative that any such experiments be rigorously analysed for potential dangers - preferably through an international review mechanism, but also by governmental funding agencies - before they are undertaken, not after the fact as is happening in this case."
US policymakers are reportedly troubled and in disagreement about the international dimensions of the human-made pandemic strains. Some in Washington DC appear to have realized that the US government is not in a position, at least not credibly, to unilaterally create an international censorship system for dangerous influenza research.
There are also technical legal questions about how censorship could be done in the US without resorting to formal state secrecy, a step which would create still greater domestic and international information access difficulties and pose an even more direct problem for the PIP Framework.
The editors of Science and Nature have agreed to temporarily withhold the publications until the US administration proposes a system for disseminating the censored research details to "legitimate" laboratories.
Neither the US nor the journal editors have offered criteria for determining who has a "legitimate" need for full details. It is also widely acknowledged that no matter what steps are taken to censor these and future research results, that the information will eventually trickle into the broader scientific community.
Whatever results from the back-and-forth currently underway between the US government, scientists, and journal editors, it is likely to have ramifications for the PIP Framework, and could pose a threat by limiting access to information by some laboratories and Member States. It is also clear that if a system is created to review research and research results to avoid disseminating information that could be deliberately abused, that the US will have to turn to international partners in order for it to be effective.
At present, it is very unclear how the US would move internationally to restrict access to influenza research information. WHO is the intergovernmental leader on pandemic preparedness, but it is ill suited for security-tinged discussions, which many Member States feel have a tendency to subvert public health goals to the national interests of security-conscious states. Furthermore, WHO has already made clear that censorship poses problems for the PIP Framework.
By the same token, there is no other intergovernmental organization with WHO's credibility or which is positioned to take on the issue. The World Organization for Animal Health (OIE), based in Paris, does not address issues of human disease. The Food and Agriculture Organization, in Rome, has even more limited purview in the area.
The Biological and Toxin Weapons Convention (BTWC), ostensibly the best topically suited venue after WHO, lacks a Secretariat and is locked in long-term stagnation - unable to agree to substantive discussion on a variety of long unresolved internal issues.
US policymakers may thus opt for some sort of meeting of influenza experts and governments outside of the existing intergovernmental system, although such a meeting is unlikely to produce more than statements of common interest.
WHO Member States will be tracking this issue, however, because of its bearing on the PIP Framework and its important international biosafety dimensions. There is also the possibility that the debate will arrive directly at WHO as scientists and policymakers try to sort through the difficult problems raised by the experiments.
The WHO Executive Board's 130th session will take place in Geneva from 16-23 January and its agenda includes a discussion on the PIP Framework.
Note: At the time of print, WHO Assistant Director-General Keiji Fukuda has been quoted by The Canadian Press (15 January) as stating that WHO will "pull together the discussions" on issues raised by man-made pandemic influenza viruses. Fukuda is further quoted as saying that WHO is the "right organization" to ensure that "technical and scientific and the political and the public health concerns are all brought together".
(* Edward Hammond is a senior policy researcher from the US on issues related to influenza viruses and biodefense.)