No WHA approval for expanding smallpox virus research
A proposal by a WHO advisory committee which reflects the desire of the US and Russia to preserve stocks of the smallpox virus in their laboratories for further research, including genetic engineering, was not approved by the World Health Assembly.
Edward Hammond & Lim Li Ching
AT the 58th World Health Assembly (WHA), which was held from 16-25 May, the leadership of the World Health Organisation (WHO) was requested by member states to reconsider proposals to expand risky smallpox research, including genetic engineering of the smallpox virus, and to reassess the process by which such research recommendations are produced.
The WHA discussed, but did not approve, experiments to genetically engineer smallpox (variola) virus and other proposals that would dramatically expand experiments with live smallpox virus. Rather, it ‘noted’ a report containing the proposals, after the WHO Secretariat ‘especially welcomed’ and took ‘special note’ of the serious cautions and criticisms made by member governments.
However, the WHO Secretariat issued a press release implying that the WHA approved most of the recommendations, and NGOs are concerned that the research, which includes genetic engineering, will proceed. NGOs are thus calling on WHO to resolve the issues that governments have raised and which it has committed to address.
Most of the countries speaking about smallpox research expressed serious concerns. These included calls for ongoing research to be terminated, for greater transparency, for a new destruction date for remaining virus stocks, and for strengthened WHO oversight mechanisms that are more independent and scientifically and regionally balanced.
Concern over the recommendations of a WHO advisory committee, the Advisory Committee on Variola Virus Research (or ‘VAC’, for Variola Advisory Committee), was expressed by many countries during the debate on 19 and 20 May. The countries were worried about the possible risks posed by more dangerous forms of the smallpox virus and by possible laboratory accidents or accidental release of the virus into the environment.
Controversial proposals
The agenda item, ‘destruction of variola virus stocks’, was one of the WHA’s most controversial issues. Contrary to the title of the agenda item, the WHA was actually considering a set of recommendations from the VAC that would dramatically expand research on live smallpox virus, rather than destroy the last remaining stocks of the virus, as previous sessions of the WHA had agreed to do.
Many scientists and NGOs had voiced opposition to the committee’s five recommendations, involving the genetic engineering of the smallpox virus to express a green fluorescent market protein; the expression of the smallpox virus genes in other orthopoxviruses; the simultaneous handling of the smallpox virus and other orthopoxviruses; the in vitro synthesis of variola virus DNA and mutagenesis of orthopoxvirus DNA; and the distribution of the virus DNA to other laboratories.
In a report for the WHA, the WHO Secretariat said the recommendations had been reviewed by the Director-General, who expressed that the proposal to allow expression of smallpox virus genes in other orthopoxviruses ‘could have broader implications, including certain biosafety and biosecurity concerns’.He recommended that this issue be reconsidered by the committee.
Due to WHO-coordinated actions, the smallpox disease has been eliminated. However, the WHA has allowed small stocks of the smallpox virus to be held in two laboratories (in the US and Russia) for research purposes, but had resolved that they be eventually eliminated.
The destruction of the virus has been postponed several times, and instead the programme of research has expanded.The present recommendations are the first to involve genetic engineering, and would dramatically expand the distribution of the virus DNA to other laboratories.
As expected, the two countries that hold the virus stocks (Russia and the US) spoke in favour of prolonging the period of research and supported the committee’s recommendations.
Russia endorsed the recommendations for more research and also in particular asked for the right to continue to utilise live smallpox virus in research on diagnostics, an area of research that WHO has concluded no longer requires live virus.
The US stated that it ‘agrees entirely with Russia’, which had earlier called for even more live virus research than the recommendations presented by the VAC. Noting the possibility of undeclared smallpox stocks, the US said that its research is not finished and that setting a date for destruction would be ‘arbitrary’ and ‘not at all warranted’. In response to a statement by Canada, the US defended its own antiviral research plans.
Apparently smarting from repeated references by other countries to lab accidents, the US characterised the chances of an accident as ‘incredibly small’ and claimed that existing smallpox stocks are held at ‘the absolute highest standards of biosafety and biosecurity’.
It is, however, unclear to what standards the US referred because there are no international lab biosafety or biosecurity standards, nor does the US have domestic lab biosafety standards. Backing Russia, the US said that it believed further sequencing of the Russian smallpox stocks is necessary for developing diagnostics.
Australia expressed support for the controversial recommendations, including the genetic engineering of smallpox and wider distribution of smallpox DNA. On the issue of Russia’s desire to continue to use live smallpox virus to develop diagnostics, Australia’s answer was ambiguous.
It said that diagnostic tests could be validated with smallpox scabs from monkeys, a position that implicitly endorses US work injecting monkeys with large amounts of smallpox virus, research that is particularly dangerous. Australia did, however, share the WHO Director-General’s concern that smallpox genes should not be inserted into related poxviruses.
Concerns
In contrast to the strong support for the committee’s recommendations by these three countries, many other countries expressed concerns ranging from caution to expressions of anxiety and suggestions that the research on smallpox be stopped.
In a detailed intervention, China underscored the public health risks of the virus escaping from the lab and called for strengthening WHO oversight of smallpox virus research. It noted that existing vaccines and control strategies could respond to emergencies and that the benefits of destroying remaining virus stocks are greater than those of continued research with the live virus. China called for the WHA to set a deadline for the destruction of remaining virus stocks.
Iran took the floor reiterating China’s observation that existing vaccines can be used in the event of a smallpox outbreak. Recalling recent laboratory accidents involving tularemia (in the US) and SARS (in Taiwan, Singapore, and China), Iran argued that the risks posed by escape of smallpox virus were too high to justify continued research on the eradicated disease and strongly endorsed destruction of the remaining virus stocks.
Japan urged rapid conclusion of ongoing research, and called for transparency. Japan said that the results should be ‘the property of all nations and human beings’.
South Africa reminded delegates of the WHA’s previous commitment to destroy the remaining live virus stocks, held in two labs, one in the US and the other in Russia. Taking a strong stance, South Africa called for research on the live virus to be stopped. It proposed the establishment of a ‘task team’, with better balance and broader representation than the VAC. The ‘task team’ would evaluate the status of work with live smallpox virus and its oversight.
South Africa called for a review of all the VAC recommendations, including the genetic engineering of smallpox and the wider distribution of smallpox DNA, as well as that to permit expression of smallpox genes in related poxviruses, an item over which the WHO Director-General had already expressed concern. Another report should be submitted to the WHA on the issue.
The Netherlands said that in relation to the plans for research involving genetic engineering of the virus, it was concerned about the potential dangers. It was not satisfied that adequate protections to take care of safety concerns are in place. It questioned the need to genetically engineer smallpox. The Netherlands supported the Director-General’s call for a reconsideration of the committee’s recommendation on expression of smallpox virus genes in other orthopoxviruses.It called for an independent body to oversee research and asked that a report on the reconsideration of the recommendations be submitted to the WHA through WHO’s Executive Board.
Canada reminded delegates that any research on smallpox should remain geared to precise results and be time-limited. Canada insisted that any live virus research ‘must be essential for public health’. In this respect, Canada expressed concerns that US research on antivirals (linked to the proposal to genetically engineer smallpox) would be lengthy and costly, asking, ‘Is this really essential for public health?’
Like many other delegations, Canada was concerned about the risks of laboratory accidents.It also raised concern that genetic engineering experiments could result in a virus that is more dangerous than the existing smallpox virus. It supported the Director-General’s concern regarding the committee’s recommendation and asked that the matter be referred to the next WHA meeting.Canada called for prompt destruction of the virus once there is no public health reason to maintain it, and expressed support for China’s request that WHO follow up on the issue of fixing a new date for the destruction of smallpox virus stocks.
The Pacific island nation of Tonga weighed in with a lengthy intervention. Referring to the committee’s proposal to distribute the smallpox DNA to other laboratories, it said there were many brilliant and responsible scientists all over the world but there were a few who may be different and there was a possibility that some scientists can use pieces of DNA material to reconstruct the smallpox virus and this could possibly fall into the hands of terrorists. Could the committee say that it is not possible? Tonga was thus very worried about the possibility.
Tonga also said that it is not convinced that the prohibition on the synthesis of smallpox DNA, mentioned in the Secretariat report, was strong enough. Concerned about the proposed widespread distribution of smallpox DNA, Tonga observed that ‘too many hands on smallpox virus and the dangerous DNA materials relating to it will enhance the possibility of bioterrorism’.
Tonga concluded that there should be a process to make it a crime against humanity for any person or laboratory to hold on to the smallpox virus excepting for the two laboratories. It called for the existing ‘official’ stocks of the smallpox virus in the two labs to be targeted for destruction sooner rather than later.
Cuba said a number of countries feared the possibility of lab accidents or bioterrorism, and thus wanted to maintain reserves of the vaccine. It said there should be a final date set for the destruction of the smallpox virus. There was a risk of genetic mutation of the virus, for which there is no effective vaccine.
Egypt briefly stated that it supports the research recommended by the advisory committee.
Saudi Arabia noted that sufficient sequencing and diagnostics research has been conducted and that smallpox virus should no longer be retained for these purposes. Saudi Arabia said that all research and manipulation using live virus should end, and that a date should be set for destruction of the virus, as previously mandated by the WHA.
Pakistan said it could agree to the retention of virus stocks for a limited period. It, however, expressed concern about lab accidents and called for the virus repositories to be open to full inspection and for a comprehensive system of oversight and for research results to be published.
The UK supported ongoing research for the development of vaccines and antivirals, adding that such research should be outcome-oriented and time-limited. However, the UK ‘strongly’ shared the WHO Director-General’s biosafety and biosecurity concerns about the committee’s proposals, and said it has implications for member states. The UK said it needs to be assured that all research is under WHO control and that live smallpox virus should not be proliferated.
Zimbabwe supported South Africa’s call for a more representative ‘task team’ to reassess live smallpox virus work and its oversight and that developing countries be added onto the team. It supported greater research transparency and called for the WHA to be kept informed.
Thailand reminded the WHA of its previous resolutions calling for the destruction of remaining stocks. Thailand expressed reservations about the ill-defined limits of permissible research in the Secretariat’s report. It was also concerned about the proposed wider distribution of smallpox DNA and said that such distribution should be decided by WHO on a case-by-case basis.
Some other countries (including France, Germany and India) spoke up on a related issue (the proposal to maintain reserve stocks of smallpox vaccine) but did not refer to the issue of the recommendations for expanded smallpox research.
Responding on behalf of the WHO Secretariat, WHO Assistant Director-General of Communicable Diseases Dr Anarfi Asamoa-Baah tooknote of the Russian, Australian and US interventions.He also took special note of the ‘concerns and caution’articulated by a large number of countries, which he named. He added that with regard to the recommendations of the advisory committee, WHO especially welcomed the countries’ views that the committee be asked to revisit and review its recommendations.
Reform of oversight process
According to the NGOs Sunshine Project and Third World Network, WHO’s leadership has been thus given a mandate to radically restructure its oversight of smallpox in the interim before destruction of the remaining stocks. This includes the terms of reference, membership, and procedures of the VAC. Once restructured, the VAC then needs to reconsider past recommendations and seek approval from the WHA before any research that goes beyond the existing limits (established in 1994) is allowed.
Governments had essentially requested that WHO smallpox oversight be transformed into a stronger and more independent process that separates research proponents from those who perform reviews, that is regionally balanced, and that incorporates heretofore neglected perspectives of public health, biosafety, and preparedness for deliberate outbreaks of disease. NGOs say that major world regions are underrepresented or entirely unrepresented on WHO’s current committee. WHO should heed the calls from governments and NGOs for this problem to be addressed.
Third World Network and the Sunshine Project are requesting that WHO take the following steps in response to the concerns and objections raised about smallpox virus research at the WHA:
1. Launch a transparent and balanced process to overhaul the VAC, including its terms of reference, membership, and procedures, aimed at:
a. preventing research proponents from reviewing their own proposals,
b. incorporating neglected areas of expertise, such as public health and biosafety,
c. achieving regional balance among members and advisers,
d. instituting a separate, and transparent, laboratory safety review procedure,
e. reforming committee modalities to create greater transparency, including that of subcommittees, and to create more frequent, high-quality reporting to the WHA.
2. Once the VAC has been so restructured, it should reassess its prior recommendations, forwarding revised ones to the WHA for its consideration and (dis)approval.
3. In keeping with prior WHA resolutions and as requested by member states, WHO should prepare a resolution to fix a new destruction date for all remaining stocks of smallpox virus.
4. Prepare a WHO Secretariat study for the next WHA on options for how possession of live smallpox virus may be deemed a crime against humanity following the destruction of remaining stocks.
Edward Hammond is Director of the US Office of the Sunshine Project, an international non-profit organisation working to strengthen the global consensus against biological warfare. Lim Li Ching is a researcher with the Third World Network.