TWN Info Service on Health Issues No. 6

At WHA, countries express concern over smallpox research

By Edward Hammond and Lim Li Ching
Geneva, 20 May 2005

Concern over the recommendations of a WHO scientific committee to allow research involving genetic engineering of the smallpox virus was expressed by many countries at a meeting of the World Health Assembly (WHA) on Thursday and Friday.

The countries were worried about the possible risks posed by more dangerous forms of the variola (smallpox) virus and by possible laboratory accidents or accidental release of the virus into the environment.

At the end of the discussion, the head of WHO's division on Communicable Diseases, Dr Asamoa-Baah said the Secretariat took special note of the "concerns and caution" raised by many countries. He added that with regard to the recommendations of the scientific committee, the WHO especially welcomed the countries' views that the committee be asked to revisit and review their recommendations.

The Chairman of Committee A, in which the discussion took place, then noted the Secretariat reports and closed discussion on the agenda item.

It was not immediately clear whether there would be further action by the WHA on the issue or how the WHO Secretariat will follow up on it.

The agenda item, "destruction of variola virus stocks", had been 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 WHO's advisory committee on variola virus research 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 small pox 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 such research (referring to 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 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 to allow transfer of the virus DNA to other laboratories.

Seven countries made interventions on Thursday, and sixteen more spoke on Friday.

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 utilize 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 strongly defended its own antiviral research plans.

Apparently smarting from repeated references by other countries to lab accidents, the US characterized 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 to 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.

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 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 Variola Advisory Committee (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 that the WHO Director General had already expressed concern over. 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 recommendations. It called for an independent body to oversee research. It asked that a report on the reconsideration of the recommendations be submitted to the WHA through the 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 that the existing smallpox virus. It supported the Director General's concern regarding the committee's recommendations 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 are 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 in 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 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 we should set a date 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 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 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 members states. The UK said we need 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 for the WHA to be kept informed.

Thailand reminded the WHA of its previous resolutions calling for 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, Dr Asamoa-Baah said the Secretariat took note of the Russian, Australian and US interventions. It also took special note of the "concerns and caution" articulated by a large number of countries (which he named). He added that the Secretariat especially welcomed the views, that with regards to the committee's recommendations, that we ask the committee to "revisit and review their recommendations."