NGOs urge WHO to reject genetic engineering of smallpox

NGOs urge WHO to reject genetic engineering of smallpox

An international alliance of non-governmental organisations launched a campaign in April to urge the World Health Organisation (WHO) to reject a proposal that would permit the genetic engineering of smallpox and to instead ensure that all remaining stocks of the virus are destroyed within two years.

Lim Li Ching

THE World Health Organisation (WHO) is justifiably proud of the global effort that eradicated smallpox in 1977.

Yet, the truth is that the job was never finished. The US and Russia still retain stocks of the smallpox virus (Variola major), an easily transmitted disease that is also a potent biological weapons agent.

Smallpox kills one-quarter or more of the people it infects and leaves many who do not die disfigured and blind. The virus is thought to have killed around 300 million people in the 20th century alone. Into the 1960s, it still killed more than two million people every year.

Smallpox was defeated by a public health surveillance and targeted vaccination programme led by the WHO, that began in 1967. The final natural outbreak occurred in Somalia’s Kurtunwaarey District in October 1977.

Despite the progress in beating the disease, the threat of smallpox is rearing its ugly head once again, this time in the form of a proposal to genetically engineer smallpox virus. That proposal would also permit smallpox genes to be inserted into related poxviruses and would allow the unlimited distribution of small segments of smallpox DNA.

Prompted by the US, the proposal has been recommended to the WHO’s World Health Assembly (WHA) through an imbalanced advisory committee dominated by a small number of countries and scientists with interest in pursuing smallpox virus research.

Debate on the proposal will take place when the WHA meets in Geneva from 16 to 25 May.

To destroy or not to destroy?

Smallpox virus stocks had been slated for destruction on 30 June 1999. However, Russia and the US balked at the WHA resolution calling upon them to destroy the virus.

Under pressure, the WHA then agreed to a time-limited ‘temporary retention’ of live smallpox, rescheduling destruction for the end of 2002. However, in May 2002, the WHA again yielded on the smallpox destruction deadline.

At its 2002 meeting, the WHA took an even larger step backwards, agreeing to an indefinite extension of the destruction order, until the US and Russia completed a far-ranging research agenda.

The US now wants to open the Pandora’s Box of genetically engineered smallpox. It first proposed to genetically engineer smallpox and to insert smallpox genes in other poxviruses in December 2001.

After they passed through an opaque committee process, including e-mail negotiations, in January 2005, the WHO Executive Board agreed to forward recommendations that would permit the US experiments, to the May WHA.

However, because of controversy when the recommendations first drew public attention in November 2004, the WHO Director General also announced that he would conduct a study of the issue. He expressed concern on the recommendation to permit expression of smallpox genes in related poxviruses.

Public health, biosafety and bioweapons risks

Edward Hammond, Director of the US office of The Sunshine Project, an international non-governmental organisation specialising in research on biological weapons issues, warns that the proposal ‘poses a large number of public health, biosafety, and biological weapons risks’.

If implemented, the recommendations would pose serious biosafety risks and could open the road to an artificial reconstruction of the virus. With increased smallpox experimentation, the world would stand closer to an accident or deliberate act that would cause a release of the virus.

Many poxviruses are closely related to each other and in their natural state they are frequently not entirely species-specific, that is, they can infect different species. Thus the insertion of smallpox genes in related viruses has the potential to create dangerous new disease-causing viruses (pathogens).

Through genetic engineering or targeted mutations, laboratories that receive pieces of the smallpox genome may be able to create smallpox or a novel virus with its characteristics without ever receiving an actual sample of the smallpox virus Variola major.

Genetic engineering can cause unintended effects, and more often than not the results of a specific genetic intervention are not entirely predictable. In such cases, there is a potential danger of inadvertently constructing highly lethal pathogens.

Lab accidents a reality

Moreover, human error and equipment failures can lead to accidents, as evidenced by a recent string of lab-acquired infections and environmental releases of SARS, Ebola, tularemia, and other dangerous diseases. The last reported human cases of smallpox were laboratory-acquired.

The recent discovery that a deadly strain of pandemic flu virus had been accidentally sent to 3,747 labs around the world (see box) underlines the risk of disease from laboratory accidents.

The smallpox virus stocks are currently contained in only two labs in Russia and the US, and tightly limited access to the smallpox virus reduces the chances of its use as a weapon. There is no evidence that any country other than Russia and the US has maintained stocks of the virus.

If the WHA approves the recommendations of the advisory committee, it will increase the threat posed by smallpox itself, by adding significantly to the risk of smallpox virus being released. In addition, governments will also send the signal that it is internationally acceptable to genetically engineer other dangerous human (and animal) pathogens, including experiments in which new and more lethal forms may result – or even be intended.

An international alliance of non-governmental organisations is thus urgently requesting that governments reject the recommendations and instead:

* Prohibit the genetic engineering of smallpox, the insertion of smallpox genes in other poxviruses, and any further distribution of smallpox genetic material for non-diagnostic purposes;
* Set a firm and irrevocable date, within two years, for the destruction of all remaining stocks of smallpox virus (including viral chimeras, or hybrids with other poxviruses);
* In the interim before destruction, ensure that the WHO Advisory Committee on Variola Virus Research and its advisers are regionally balanced and that the Committee and its subsidiary groups conduct their oversight activities in a fully transparent and accountable manner.

The NGOs, led by Third World Network and The Sunshine Project, have set up a website,, where organisations and individuals can send letters to the WHO Director General. The website also provides links to national health ministries, so that government representatives can be urged to safeguard the public from smallpox experiments when the WHA meets in May.


Box 1

Flu fear

ON 12 April, thousands of scientists around the world were scrambling to destroy vials of a pandemic flu virus inadvertently sent to 3,747 labs in 18 countries as part of routine testing kits.

The virus that caused the 1957 ‘Asian flu’ pandemic, H2N2, was accidentally released by a laboratory in the US, and sent all over the world in test kits. The WHO called for immediate destruction of the samples. This urgency was sparked by a fear that the samples could spark a global flu epidemic.

The 1957 pandemic strain started in China before spreading worldwide, killing between 1 and 4 million people, and is not included in the current flu vaccines. Persons born after 1968 are expected to have no or limited immunity to H2N2, as H2 type flu was at the time replaced by another hybrid virus. Any escape of the virus in the test kits could thus be lethal to large populations.

The flu testing kits were sent to the labs between October 2004 and February 2005 by the College of American Pathologists (CAP), a professional body which helps laboratories to improve their accuracy, by sending them unidentified samples of various germs to identify.

The CAP kits – prepared by private contractor Meridian Bioscience in Cincinnati, US – were supposed to contain a particular strain of influenza A – the viral family that causes most flu worldwide. But instead of choosing a strain from the hundreds of recently circulating influenza A viruses, the firm chose from its stockpile the deadly 1957 H2N2 strain.

According to the WHO, almost 99% of the labs that received the test kits are in the US. Fourteen are in Canada and 61 samples went to labs in 16 other countries: Bermuda; Belgium; Brazil; Chile; France; Germany; Hong Kong; Israel; Italy; Japan; Lebanon; Mexico; Republic of Korea; Saudi Arabia; Singapore and Taiwan.

On 26 March, National Microbial Laboratory Canada detected the 1957 pandemic strain in a sample not connected with the test kit. The lab eventually traced the virus to the test kit. Worryingly, this means that the virus had already escaped within the lab.

Test kits for flu are not handled at a high level of biological containment as it is assumed they do not carry unusually dangerous viruses. But the escape in the Winnipeg lab is worrying, as the lab contains facilities with the highest level of containment and its staff is expected to maintain high levels of lab hygiene. The most probable means of escape into the outside world would be if a lab worker catches the Asian flu, then passes it on.

The WHO said that no H2N2 flu outbreak has been reported since the first batch of testing kits was sent to laboratories in October 2004. Nevertheless, the incident raises unsettling questions about lab-handling of flu viruses and other pathogens.


Box 2

Scientists express concern

The following is the text of a letter from John P. (Jack) Woodall, PhD on behalf of the Scientists Working Group on Biological and Chemical Weapons, Center for Arms Control and Non-Proliferation, Washington DC, to Dr Lee Jong-wook, Director-General of the WHO, underscoring the urgent need to destroy all remaining stocks of the smallpox virus.

Dear Dr Lee,

Smallpox: to be or not to be?

I write as a virologist who has worked in the field for more than 40 years, a former staff member of CDC for 13 years and of WHO for a similar period, and the leader of the WHO delegation to the 3rd Review Conference of the Biological Weapons Convention. The question of whether smallpox virus should be exterminated transcends considerations of what we might eventually learn about virulence and disease from further study of the virus, and enters the realm of humanity’s responsibility to future generations.

However great the theoretical interest of studying smallpox virus with the latest molecular techniques, the risk of an escape is unacceptably high. Recent laboratory accidents have shown that however secure the laboratory facilities, laboratory workers have become infected with SARS virus and tularemia bacteria, and in fact the last recorded outbreak of smallpox began with a laboratory infection in England. It is true that undeclared smallpox strains may exist in several laboratories around the world, but that is not a reason to keep the declared stocks in the USA and Russia. This is like saying that because your neighbour might conceivably be storing inflammable liquids in his garage, you are going to do the same just in case you might need them in future, oblivious to the risk to your own children and property.

It is important to remember that the highly effective smallpox vaccine is not made using smallpox virus, but a related virus called vaccinia. As long as reserves of this vaccine are maintained, there will be a first line of defence to contain an accidental or deliberate laboratory escape. If smallpox does reappear in the future, it would be well that neither the USA nor Russia could be blamed for maintaining stocks of the virus and thus endangering the health of future generations. The scourge of smallpox was one of the ‘slings and arrows of outrageous fortune’, and we should grasp the opportunity to end it, not like Shakespeare’s Prince of Denmark by contemplating suicide, but by exterminating it once and for all. There should be no ethical imperative that the human race must risk its own decimation in order to allow another form of life to survive. Surely humankind was given self-awareness in order to help ensure its own survival, not to play Russian roulette with it.

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