WHILE one team has genetically engineered deadly new forms of mousepox and cowpox (see left), another wants to breed a new strain of smallpox that infects monkeys.
The researchers say the work will allow new vaccines and treatments to be developed. But critics, including DA Henderson, who led the smallpox eradication campaign, argue that this is unnecessary. Next week, the scientific committee that oversees all smallpox research will meet behind closed doors at the World Health Organization in Geneva to decide whether to approve the work.
Normally smallpox infects only humans. But last year Peter Jahrling of the US Army Medical Research Institute for Infectious Diseases (USAMRIID) at Fort Detrick, Maryland, infected cynomolgus macaque monkeys (New 杏吧原创, 26 January 2002, p 12).
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This meant that for the first time since smallpox was eradicated in the 1970s researchers could realistically test new treatments and vaccines, and study the disease using methods that did not exist in the 1970s. This helped persuade the WHO to suspend orders to destroy the two official stocks 鈥� although the US and Russia might have retained their stocks whatever the WHO had decided.
Last December, however, the WHO committee described the macaque system as 鈥渘ot ideal鈥�, because the monkeys became sick only after receiving 100 million times the amount of virus needed to infect humans, and all died quickly of an illness unlike most human smallpox. But Jahrling told a conference in Geneva last week he can now produce an illness with a tenth that amount of virus.
Like the human disease, it produces pustules and kills a third of the monkeys, although it still lacks an incubation phase. Jahrling has shown that the infection leads to a massive release of a protein called interferon-gamma, which stimulates an inflammatory response. It might be possible to develop treatments that block this extreme response, he says.
Meanwhile John Huggins, also at USAMRIID, has shown that the antiviral agent cidofovir cures monkeys of the disease, when given a day after the lower dose of virus. The US has stockpiled cidofovir in case of a bioterrorist attack involving smallpox, but it could previously be tested only on human cells grown in a dish.
Jahrling suspects that the monkeys have to be given large amounts of virus because only one genetic variant infects macaques. So he wants to 鈥減assage鈥� smallpox virus through the macaques to select a species-specific variant, a standard virological procedure.
鈥淏ut that would be creating a new monkey disease,鈥� he says. The WHO committee may be reluctant to allow such a step, despite its support for the animal studies. It will also be under pressure from Henderson to ban the work completely. Though not a member of the WHO committee, Henderson still wields enormous influence and has long maintained that there is no point keeping smallpox virus around just to test new drugs and vaccines. 鈥淲e have the existing vaccine, which can be used after exposure to treat infection as well as preventing it.鈥�
The existing vaccine, which consist of a live virus called vaccinia, does pose risks for people with weakened immune systems, Henderson admits. But he thinks the answer is not a new vaccine but better ways of treating adverse effects caused by vaccinia. And he also thinks the risks of vaccinia may have been overstated. Ten HIV-positive people in the US military were inadvertently vaccinated during the recent immunisation programme, he says, but none suffered any ill effects.