Non-governmental organizations around the world are urging the World Health Organization to block a dangerous proposal that would allow the smallpox virus to be genetically engineered, and to ensure that remaining stocks of the virus are destroyed within two years. Lim Li Ching
Smallpox kills one quarter or more of the people infected and leaves many others 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 2 million people every year.
Smallpox was eradicated by the WHO-led public health surveillance and targeted vaccination programme that began in 1967. The final natural outbreak occurred in Somalias Kurtunwaarey District in October 1977. However, the US and Russia still hold onto stocks of the infectious smallpox virus (Variola major); and this has long been a source of contention, as the virus is also a likely biological weapon that could be deployed in a terrorist attack.
Alarm was raised recently by a US-led proposal to genetically engineer the virus, and also to allow small segments of smallpox DNA to be freely distributed and the smallpox genes to be inserted into related poxviruses.
The proposal has been recommended to the World Health Assembly (WHA) through an imbalanced advisory committee dominated by a small number of countries and scientists with interest in smallpox virus research. The proposal will be debated at the meeting of the WHA in Geneva, Switzerland, 16-25 May 2005.
The WHA had previously called for the smallpox virus stocks to be destroyed by 30 June 1999; but neither Russia nor the US had complied. Under pressure, the WHA had then agreed to a time-limited "temporary retention" of the live virus, rescheduling destruction for the end of 2002. In May 2002, however, the WHA again gave way on the destruction deadline and 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 first proposed to genetically engineer smallpox in December 2001 via a WHO advisory committee.
After an opaque committee process including e-mail negotiations in January 2005, the WHO Executive Board agreed to forward recommendations to the WHA that would permit the US experiments.
But because of controversy aroused when the recommendations were first made public in November 2004, the WHO Director General also announced that he would conduct a study of the issue.
Edward Hammond, Director of the US office of The Sunshine Project, an international watchdog on biological weapons issues, warns that the proposal "poses a large number of public health, biosafety, and biological weapons risks."
It could open the gate to the artificial reconstruction of the virus, and leave the world vulnerable to accidental or deliberate releases of the virus.
As many poxviruses are closely-related to one another, and in their natural state frequently not entirely species-specific, the insertion of smallpox genes in other poxviruses has the potential to create dangerous new 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 Variola major.
Genetic engineering can cause unintended effects, and more often than not, the results are not predictable. In such cases, there is a potential danger of inadvertently constructing highly lethal pathogens.
Moreover, human error and equipment failures can lead to accidents, as shown by a recent spate of lab-acquired infections and environmental releases of SARS, Ebola, tularemia, and other dangerous diseases. The last reported cases of smallpox in humans were laboratory-acquired.
The recent panic over a deadly strain of pandemic flu virus that had been accidentally sent to 3 747 labs around the world (see Box) underlines the risk of disease from laboratory accidents.
Killer flu virus accidentally released by US lab
On 12 April 2005, 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.
The virus that caused the 1957 Asian flu pandemic, H2N2, was accidentally released by a lab in the US and sent all over the world as part of a test kit. The WHO urged immediate destruction of the samples, fearing that the samples could spark a global flu epidemic.
The 1957 pandemic strain started in China before spreading worldwide and killing between 1 and 4 million people. It is not included in the current flu vaccines. Persons born after 1968 are expected to have little or no immunity to H2N2, as another hybrid virus had replaced the H2 type virus by then. So an escape of the virus in the test kits could be lethal for them.
The College of American Pathologists (CAP) had sent the flu-testing kits to the labs between October 2004 and February 2005. The CAP is a professional body that helps laboratories to improve their accuracy by sending them samples of various germs to identify.
The CAP kits were prepared by private contractor Meridian Bioscience in Cincinnati, US, and 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 2005, 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. 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. 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 test kits was sent to laboratories in October 2004. Nevertheless, the incident raises unsettling questions about lab-handling of flu viruses and other pathogens.
If the WHA approves the recommendations, it will not only increase the threat of smallpox through accidental or deliberate release, it will also be setting a precedent for other dangerous human (and animal) pathogens to be genetically engineered.
An alliance of NGOs* are urging governments to reject the recommendations and instead to:
*The NGOs, including Third World Network and The Sunshine Project, have set up a website, www.smallpoxbiosafety.org, where organizations and individuals can send letters to the WHO Director General. The website also provides links to national health ministries, so that people can contact their government representatives.
Article first published 02/05/05
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