Executing a killer
THE international scientific community is contemplating the passage of a sentence of death: variola, the lethal smallpox virus, may become the first life form to be officially exterminated following a conscious decision of the community. If the World Health Assembly comprising representatives of all United Nations members gives the green signal in its meeting (to be held in Geneva Switzerland) in May this year the virus will be Wiped out from the earth; the last two stocks of variola kept in us and Russian laboratories will be put into autoclaves (vessels used for high-pressure sterilisation with steam) on June 301999and incinerated.
The successful eradication of smallpox - the only naturally occurring disease afflicting humans to have been wiped out so far - was the result of a 10-year-longus $313 billion World Health Organization (WHO) campaign that began in the late 1960s.Till 30 years ago smallpox was endemic in 31nationsstriking 10-15 million people annually killing nearly two million and scarring and blinding millions of its survivors for life. The last known natural case of smallpox was detected in Somalia in October 1977.
Soon after the WHO declared the -world free of smallpox in1980it was decided to reduce and restrict the virus stocks to the two WHO collaborating centres with maximum security the Centers for Disease Prevention and Control Atlanta Georgia USA and the Russian State Research Centre of Virology and Biotechnology Koltsovo, Novosibirsk regioninthe Russian federation.
The final act - the extermination - now requires a voteof the full membership of the WHO which has granted a three-year interim period for reaching a broader consensus in the medical and scientific communities on the issue. This is because even after a decade of debate scientists are still in two minds over this unprecedented move. The resolution to kill variola was taken by the WHO executive boardon January 251996 in Geneva. A WHO committee had recommended extermination way back in 1986arguing that the risk of the killer disease spreading from the laboratories accidentally or by an act of terrorism was greater than the risk of losing the virus altogether. The board decision seeks the destruction of variola'S DNA clones as well. Says the board's resolution: "The remaining stocks of variola virus including all whitepox viruses viral genomic DNA sequences clinical specimens and other material containing the infectious variola virus (must) be destroyed."
The date for the sentence in 1990 had been fixed as December 30,1993But the virus received two leases of life as the WHO hoped for a broader consensus. Not leaving anything to chance the WHO executive board had recommended that 5000vials of smallpox vaccine should be kept ready and that the smallpox vaccine seed Virus (vaccinia virus strain Listerelstree) should be maintained. Provision for continuing further studies was kept as well. The sequence information of the genome of several variola virus strains and the cloned DNA (deoxyribonucleic acid) fragments of variola allow scientific questions about the properties of the viral genes and proteins to be solved, the WHO board noted.
To kill or not to kill
Response to the move in the Indian scientific community has been varied. Although WHO scientists assure that "there is nothing to worry about" many are not convinced. Says P MB hargava former director of the Centre for Cellular and Molecular Biology Hyderabad: "We should not destroy a life-form. If there is a comeback of the disease we may not be able to find a solution using the genetic information about the virus." Some scientists oppose the move on pragmatic grounds. Says A C Banerjee, smallpox expert with the National Institute of Immunology New Delhi. We cannot study a disease process by studying the genetic sequence of the virus or smallpox genes cloned into plasmids, for we have yet to understand how viruses cause disease at the biochemical and molecular levels.
There are others who support the WHO recommendation. Kalyan Banerjee, director of the National Institute of, VirologyPuheis a s 'taunch advocate of the elimination move. Says Banerjee The smallpox virus has to be destroyed; and there should be strict control in handling of the viral clone. Virologist and deputy director of the National Institute of Cholera and Enteric Diseases Calcutta,Shekhair Chakraborty, points out, "The stock of any agent like the variola virus always threatens humankind considering the current global situation. Chakraborty at the same time, stresses that "the DNA of varibla which is not infectious, should be preserved for future research."
The questions which the extermination move engendersare complicated as several scientific technical and ethical issues are involved. Debated threadbare during the IXth International Congress of Virology in Glasgow, Scotland in1993, supporters of the move put forward the following arguments:
• To prevent accidental release
• To prevent terrorists from acquiring the virus for carryingon biological warfare
• To eliminate forever this scourge of humanity
As a large proportion of the global population lacks immunity from smallpox, an accidental release could become fatal scientists point out. Three smallpox deaths resulted from accidental laboratory infection in the 1970s in UK. In fact the WHO's 1981 decision to restrict the viral stock was prompted by an escape of variola from a British laboratory. In 1978aphotographer in the University of Birmingham and her mother were infected with smallpox virus from a secure laboratory room in the vicinity of her workplace. This incident raised a hornet's nest; the Global Commission for the Certification of Smallpox Eradication recommended that all remaining smallpox viral stocks be destroyed or transferred to four specified sites.
Scientists have also raised their concern about growing political uncertainties possibly leading to unscrupulous elements gaining control over the stocks. Says Brian W J Mahy, director viral diseases division at the National Center for Infectious Diseases, Atlanta US in Science magazine (Vol262No 5137): "Recent political uncertainty in several parts of the world including the former Soviet Union and its satellite countries has re-emphasised this danger. Destruction of the remaining smallpox virus would eliminate this potential weapon consistent with the aims of the International Biological and Toxic Weapons Convention of 1972."
What buttresses Mahy's point is that even a decade after complete eradication vaccination continued for military personnel in a few nations. The existence of viral stocks in Russia and the US was thought to represent a potential military hazard from any terrorist group that would succeed in gaining access to the virus. Scientists pointed out that under such circumstances maintaining the viral stocks had become a burden on the nations that kept them.
With the development of DNA components and cloning techniques during the 1970sdifferent viruses similar to variola were found to have characteristic patterns that could be used to distinguish smallpox from other potential human infections such as monkeypox and cowpox. Mahy argues that the latest developments in genetic engineering have made the viral stocks redundant. Already DNA fragments have been cloned in bacterial plasmids to resolve any future diagnostic problem involving suspected smallpox infection. This method is a safer bet, scientists argue. The cloned' DNAS could be used potentially to create a smallpox like virus by recombination with vaccinia or monkeypox viruses. This is why in 1990theWHO requested registration of all clones of smallpox virus DNA and restricted their use and distribution. Says Mahy: "Even though smallpox virus DNA might be synthesised in future on the basis of published sequence it would not be infectious."
Besides the already forwarded arguments a question of ethics too is involved. What is controversial is whether human beings can play God and whether they have- the right to put to sleep a 'living' species. Says Bhargava, "You should not. For you never know what will emerge tomorrow, and how an organism can be of use.
Despite the doubts raised by various quarters, several major scientific Organisation's and institutions particularly in the us have reached a consensus. By 1993the American Type Culture Collection the American Society for Microbiology and the International Union of Microbiological Societies had all agreed that all remaining stocks of variola should be destroyed.
The section of scientists which opposes the extermination move is pushing for conservation of the virus for future research purposes. This section knocks down the three basic premises of the 'pro-extermination'-group. At the Glasgowconferencethose who preferred conservation of the virus asked for a 10-year grace period for variola. Leading smallpox researcher Wolfgang K Joklik of Duke UniversityMedicalCentreDurhamusand four other international scientists wrote in Science: "The danger of accidental smallpox virus release from the two isolation laboratories is surely minimal. As -for the use of smallpox virus as a military or terrorist weapon this is also a most unlikely scenario because the smallpox virus can be readily controlled by public healthmeasures."
Joklik also claimed. quoting from the UK government's enquiry report on the Birmingham incident that the accidental leak was caused by improper handling of the virus in the laboratory. ''The third argument says Joklik, relates to the emotional sociological and political desirability of eliminating this frightening scourge of humanity." He points out that destruction of the two stocks would provide only an "illusory increment" to safety for there are three more sources which could spread the disease:
• Cadavers of smallpox patients preserved in permafrost (they may contain smallpox virus)
• Specimens which contain thesmallpox virus (collected during the eradication) still existing in various labs
• Monkeypox virus that causes a disease in humans which resembles smallpox (monkeypox transmits slowly; 404monkeypox virus caseswith33deathswere reported between 1970-1986mostly inZaire; but recorded cases of successive human-to-human transmission were limited to 4)
Re-emergence nightmares
The WHO executive board'sJanuary resolution has included under its purview all the samples and specimens containing the virus. If the extermination becomes a reality then the onlyspecimens that might get leftbehind will be the unidentified or unrecognised ones which had The hand of death? been collected in the course ofthe smallpox eradication campaign. What lends significance to the 'pro-conservation' group's arguments is the possibility of a smallpox re-emergenceor that of a mutation of a poxvirus just like the human immunodeficiency virus which originated in monkeys according to one theory monkeypox virus for instance could evolve into a new threat. "Monkeypox virus could evolve to fill the biological niche once occupied by the smallpox virus says Joklik. In fact, Maharashtra's Beed district has recently reported the detection of buffalo pox - belonging to the same group - in five children.
In such a scenario, retaining the smallpox virus isolates and studying in detail their molecular pathogenesis makes good sense. Says A C Banerjee, It (the smallpox virus) should be kept in maximum containment (technically called P4) facilities." Banerjee explains that the disease -causing' mechanism of a virus is an extremely complex process that involves not only the interaction of viral components but also especially in the case of poxviruses in general and smallpox virus in particular proteins that mimic or interfere with host immune and regulatory functions. "In the case of are-emergence scientists would need the entire virus to study its disease-causing mechanism Banerjee points out.
The WHO board recommendation, with the accompanying debate regarding its pros and cons, opens up an unprecedented chance for scientists to be the 'destroyers' of a life form. Also, it raises questions about the claims of genetic engineering: can a life form be destroyed and then assembled again as and when the need arises? As the date for the World Health Assembly meeting draws close, more scientists are expected to join this debate on the fate of variola.
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