TWN Info Service on Health Issues (January 07/05)

24 January 2007

WHO Board urged to act on worrying smallpox research trends

Disturbing indications that the US is expanding or intending to expand research with smallpox virus outside of WHO control and that WHO may be back-pedalling on some of its previous decisions, have led NGOs to call for a strong resolution on smallpox on the part of the Who Executive Board which meets this week in Geneva.

The following story is reproduced with the permission of South-North Development Monitor (SUNS) #6174, 23 January 2007.

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Health: WHO Board urged to act on worrying smallpox research trends

By Lim Li Ching*, Kuala Lumpur, 22 January 2007

The WHO Executive Board, meeting this week in Geneva, has been urged by NGOs to produce a strong resolution on smallpox (variola), including fixing a new date for the destruction of existing stocks, banning genetic engineering experiments, and strengthening WHO control over variola research.

This is in light of increasing indications that the United States is expanding or intending to expand research with the smallpox virus and with variola genes, including the synthesis and use of variola virus genes outside of WHO-authorized repositories.

There are three worrying trends that should lead to strong action by the WHO Board, say two NGOs following the smallpox issue, the US-based Sunshine Project and the Malaysia-based Third World Network:

-- A laboratory linked to the US government and whose work includes designing weapons of mass destruction for the US army has initiated experiments with variola virus genes engineered into other organisms, using smallpox genes that are not from a WHO-authorized repository, but synthesized by a company.

-- A US government biosecurity committee has proposed that domestic US legal restrictions on possession of variola virus be repealed, which would effectively allow possession of the virus.

-- The WHO advisory committee overseeing the remaining stocks of smallpox virus and research using it seems to be backpedaling on some of its previous decisions. Prompted by disagreement over if and how the WHO should control synthesized variola genes, it is also reviewing the rules restricting the distribution of smallpox DNA and the type of research allowed. Critics fear that, given the committee's previous attempt to weaken these rules, this could be a dangerous move.

The WHO Executive Board is meeting on 22-30 January in Geneva and will consider a draft resolution on smallpox, which was deferred from the Fifty-ninth World Health Assembly (WHA) in May 2006. Then, the WHA was unable to agree on the text of a resolution on destruction of variola virus stocks, which are held in WHO-authorized repositories in the US and Russia.

Many developing countries, led by Africa, had sought a resolution to establish a new destruction date (June 2010) for the virus, a prohibition on genetic engineering, annual substantive WHA review of virus research, and strengthened WHO oversight.

Despite lengthy discussions, agreement was not reached at the WHA. The US refused to consider fixing a new destruction date, and developing-country offers of a compromise were also rejected. The issue was then passed on to this week's Executive Board meeting to resolve.

While smallpox was generally eradicated in 1977, the US and Russia still retain the virus. These remaining stocks were slated for destruction in 1999, but the two countries balked at the WHA resolution calling on them to destroy the virus.

Since then, the destruction date has been again postponed from 2002, and after that there has been an indefinite extension of the destruction order, until the US and Russia complete an ambitious research agenda on smallpox, limited to public health purposes.

Moreover, the WHO's decision to leave oversight of smallpox research in the hands of a largely unbalanced advisory committee, known as the Advisory Committee on Variola Virus Research, has contributed to the problem.

The need for a strong resolution on smallpox has never been greater, say NGO critics. Since the WHA in 2006, two events have come to light that have heightened concerns that WHO control over variola virus is deteriorating.

Firstly, Sandia National Laboratories, part of the US Department of Energy, has initiated experiments with variola virus genes engineered into other organisms.

Sandia did not obtain the smallpox genes from a WHO-authorized repository. Instead, they were synthesized by a company and then used by Sandia in at least four experiments.

As Sandia's mission includes the design and testing of Weapons of Mass Destruction for the US armed forces, it is unclear if and how the research with variola virus genes was construed to be within the public health bounds established by the relevant WHA Resolutions.

Secondly, a US government biosecurity committee has proposed that domestic US legal restrictions on possession of variola virus be repealed. The de facto effect of this recommendation would be to legalize possession of variola virus.

Although holding an exact copy of the entire virus in replication-competent form would remain subject to regulation, possession of large amounts of smallpox DNA and construction and manipulation of viruses almost genetically identical to smallpox (i.e. essentially composed of variola genes) would not be subject to legal controls or even reporting to the government. Such viruses could pose an international public health threat.

These developments strongly suggest that an expansion of US research with variola virus is underway, particularly with variola genes and genetic engineering. They strengthen the argument of those who want the WHO to fix a destruction date for the virus, ban genetic engineering experiments, and strengthening WHO control over variola research.

Meanwhile, the WHO Advisory Committee on Variola Virus Research may be backpedaling on some of its previous decisions.

At its seventh meeting in 2005, the Committee concluded that there is no justification for continued retention of variola virus for the purposes of sequencing, as the full sequence of dozens of strains has already been obtained, or for developing vaccines, as in addition to older, effective vaccines, new vaccines are in advanced development, which do not require variola virus for testing or production.

It had also concluded that sufficient rapid and accurate diagnostics have been developed, with the majority of members in broad agreement that no additional research involving the use of variola virus is required for this purpose.

However, following its eighth meeting in November 2006, the Committee appears to be reconsidering these decisions.

The Committee meeting also revisited the question of modifying the rules concerning possession and use of variola virus and its genes. These rules touch on both genetic engineering and issues raised by synthetic biology.

The rules were put forward in 1994 by the WHO Ad Hoc Committee on Orthopoxvirus Infections. They ban genetic engineering of variola, the insertion of variola genes in other orthopoxviruses, and require that variola DNA only be provided to non-repository labs with WHO approval and even then in tightly limited quantities.

For years, the US has sought to weaken those rules. In 2004, it almost succeeded when the Committee recommended modification of the 1994 rules to permit dangerous experiments involving insertion of smallpox genes into related poxviruses and genetic engineering of smallpox itself. Many countries raised concern about these recommendations at the WHA in 2005 and the recommendation to permit insertion of smallpox genes into related poxviruses was subsequently withdrawn by the Committee.

Yet, at the Committee meeting in 2006, the US again expressed its desire to genetically engineer smallpox genes into other orthopoxviruses. This proposal was rejected by the Committee.

But the same rules that prohibit such smallpox genetic engineering also govern possession of smallpox genes by non-repository labs. After abandoning its previous attempt to weaken the 1994 rules, in 2006 the Committee has started a new process that may modify them.

This time, the effort has been reportedly prompted by synthetic biology, specifically, disagreement over if and how the WHO should control synthesized variola genes. Obviously, the importance of the protections at the WHO-authorized repositories will become very limited if synthesis of variola genes is permitted elsewhere.

The current rules state that the repositories cannot distribute smallpox DNA without WHO approval and that recipients of such DNA cannot send it to others. These provisions are appropriate and should remain.

In light of research using synthetic variola genes, as exemplified by the Sandia research, NGOs such as the Third World Network and The Sunshine Project are asking the Executive Board to include in the draft resolution a request for an analysis and study on the synthesis of variola genes, particularly outside of the WHO-authorized repositories, with a view to developing a further resolution that addresses the novel risks posed by synthetic biology. (Details and further information are in www.smallpoxbiosafety.org).

They are also recommending that the draft resolution fix a new date for destruction of the stocks, ban genetic engineering experiments and those involving distribution of variola DNA for non-diagnostic purposes, as well as withdraw the temporary authorization for the retention of variola virus for DNA sequencing, diagnostics and vaccines purposes.

Other recommendations include a request for a detailed report of all completed, current and planned research at the two repositories, reform of the Advisory Committee on Variola Virus Research, ensuring that approved research proposals, research outcomes and their benefits are made available to all Member States, and clarifying the legal status of the virus strains held at the two repositories with respect to their ownership.

(* With inputs from Edward Hammond.)