The Smallpox Wars

UPDATE: "The White House announced Thursday that President Clinton has decided to retain the US held stores of the smallpox virus...." (4/25/99)

The poet Robert Frost once said the world would end in ice or fire. One or the other will also be the fate of the smallpox virus—and we don't yet know which. Smallpox, driven out of nature but not yet out of history, faces the final judgment of the World Health Organization (WHO), where ice represents not death, but half-life, frozen inertness, and fire comes in the form of autoclaves, to pressure-cook the strains into oblivion. In 1986 the Executive Committee on Orthopox of the WHO unanimously decided to destroy the last strains of smallpox left in the world. Thirteen years later they are still trying to impose that sentence: the date set for destruction is now June 30, 1999.

But what seemed so clear in 1986 has now exploded into confusion as scientists, defense officials, and policymakers in the U.S. government and around the world fiercely dispute whether the final sentence should be carried out. It's a devilish problem. Smallpox destruction wraps together issues of national security and public health: the threat of bioterrorism, the need for new drugs and vaccines to protect against a possible bioterrorist attack—even the prom ise of smallpox for new revelations in the study of the human immune system. It's difficult to overstate the consequences of a large-scale release of the smallpox virus. Since the virus has been eliminated from nature for more than 20 years, most countries, including the United States, have discontinued standard inoculation for the disease. This leaves populations subject to what epidemiologists refer to as "virgin soil epidemics," in which smallpox has had a mortality rate as high as 75 percent. What has changed in the last 13 years is not the virus, but the world itself, which is now more complex and deadlier than we could have imagined then. And with doubts now being raised, the destruction campaign that was once so sane and reasonable has taken on the trappings of a holy war.

Those who question the destruction of the virus are asking questions like these: What if the virus isn't only where it's supposed to be, in the two approved WHO stocks, but has proliferated far beyond the ability of the WHO, or of anyone else, to control? What if the strategy used to exterminate the wild virus will no longer work, because vaccination cannot be used in people infected with the AIDS virus? And should we proceed with destruction if medical research and molecular biology have advanced to such a point that we have far more to gain by studying the smallpox virus than by destroying it?

Unfortunately, reasonable questions like these now run the risk of being drowned out by the counterarguments of destructionists, which too often seem based on faith and desire. And as the evidence for the proliferation of smallpox becomes ever more widely known, the arguments of the destructionists grow ever more shrill.


Weaponizing Smallpox

It's been just over a year since the publication of the first press reports revealing that Soviet researchers had weaponized smallpox. But the U.S. government has known this since the early 1990s, from at least three intelligence reports from 1991 and 1992, which revealed that stocks of smallpox existed in several places in Russia. Furthermore, by 1993, rumors of another ominous development began to surface, this time from a KGB report that suggested that smallpox was also in the hands of North Korean bioweapons researchers.

The first report came in January of 1991, when a commission of British, American, and Soviet scientists, under an agreement permitting joint visits to biological laboratories in all three countries, visited the Bio prep arat laboratories in Novosibirsk, deep in the Siberian forest. The Bioprep arat was the vast, secret web of biowarfare research facilities that stretched across what was then still the Soviet Union. Dr. Frank J. Malinoski of Nabi Corporation, then a medical virologist working at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), was a member of that commission. In discussions with Soviet scientists at Novosibirsk, Malinoski learned and reported to U.S. intelligence that the Russians there "were working with the smallpox virus."

Another former high-ranking intelligence officer, who speaks only on condition of anonymity, shocked the U.S. intelligence community in 1991 when he reported that a Soviet general revealed at a conference in Geneva that the Soviet military ranked smallpox as their number one strategic weapon. The U.S. Department of Defense promptly placed smallpox on the Validated Threat List of dangers facing U.S. soldiers, a designation indicating weapons that constitute a clear and present danger to U.S. troops.

Third, and most disturbing, was the 1992 testimony of a high-ranking Soviet defector, Dr. Kanatjan Alibekov, now known as Ken Alibek, the deputy director of all of Biopreparat. Alibek defected after visiting U.S. research institutions—including the rusting, abandoned Pine Bluff, Arkansas, site of a long-defunct biological warfare facility—on the very same program that had brought Malinoski to Novosibirsk. Alibek revealed to his American handlers the secrets of the Soviet bioweapons trade, including the industrial process developed in Novosibirsk in December 1990 (only one month before Malinoski's visit) and implemented at the military laboratory at Sergiyev Posad, which had a mandate to stockpile "never less than 20 tons" of the smallpox virus. Some in the United States intelligence community doubt certain elements of Alibek's testimony, which has ex panded since the early 1990s. But senior U.S. intelligence officers as well as government scientists with close knowledge of biological weapons research believe that Alibek's testimony regarding smallpox research is genuine, because of the level of technical detail which he was able to produce about the process as well as other confirmatory evidence.

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As for North Korea, the first mention that smallpox stores existed outside of Russia and the Centers for Disease Control (CDC) came from a 1993 KGB report, an account that some U.S. officials do not take seriously. But two independent, well-placed U.S. intelligence officers have recently confirmed this report, using an entirely different, and still classified, source. The recent news that North Korea has been testing long-range missiles seems all the more disturbing in this light. North Korea is the only country about which reliable intelligence for smallpox proliferation exists, but there are suspicions about other countries, and many government experts are particularly troubled by the implications of work done in Iraq with camelpox, a virus which can serve as a stand-in for smallpox.



But by 1993, despite all the U.S. government knew, the movement to destroy smallpox began to gather force. From the outset, one of the most passionate advocates of destruction was Dr. Donald A. Henderson, chief architect of the World Health Organization's drive to eradicate smallpox from the wild. In 1991, Henderson became associate director of the White House's Office of Science and Technology Policy; and in 1993 he became deputy assistant secretary of HHS for health and science. A white-haired and imposing man with a disarming smile, Henderson led an army of dedicated doctors and epidemiologists into desolate places in Africa and Asia to hunt down smallpox and exterminate it. He won, of course, and the virus, which has no host but humanity, was driven from nature.

The eradication of smallpox is perhaps the greatest medical feat of all time; it began with Edward Jenner's vaccination of a little boy 200 years ago and it ended in 1977 with Henderson and his army and the total rout of the deadliest disease in history. Whatever else can be said about Henderson, the success which he and his associates shared in eradicating smallpox can scarcely be overstated. One government scientist who supports retention of the virus notes that in 1960, about five million people a year were still dying of smallpox. Over 30 years that's 150 million people who owe their lives to Henderson and his team. Following on this success, Henderson promised the World Health Organization he would destroy the virus altogether—that, after a suitable time, all remaining stocks would be ceremoniously pressure-cooked out of existence. And despite all he knows—and has known for some time about existing military stockpiles of the virus—it's a promise he intends to keep.

The story of how the United States government got behind the effort to destroy smallpox even after evidence of proliferation had become known, is in part a cautionary tale about the baleful effects of bureaucratic inertia and the unintended consequences of government secrecy. It is not clear, at every point, that those in charge of government policy on smallpox had been made aware of all the information which the various intelligence arms of the federal government had compiled on the topic.

But Henderson himself, the man who has spearheaded the destruction effort, can't claim ignorance. One senior U.S. intelligence analyst who "briefed the government chain of command" about smallpox proliferation beginning in 1993 found Henderson, who had been a science advisor to the White House since 1991, awaiting him at every turn. Once, the same analyst walked into the office of a top government official and found Henderson already there. "We sat around the coffee table chatting, and I gave my report. He tried to counter every single argument I raised." Others agree that Henderson was fully informed on the topic. "Henderson probably has more knowledge on this topic than anyone in the country—he worked with the people at Fort Detrick [the Defense Intelligence Agency]," says microbiologist Harlyn O. Halvorson. (When contacted in early March of 1999 during the preparation of this article, Dr. Henderson told The American Prospect that he had no recollection of being briefed on the issue of smallpox proliferation or illicit smallpox biowarfare research prior to 1996.)

But for a long time the supporters of destruction maintained the pleasant fiction that the only supplies of smallpox on the planet resided under tight security in Moscow and at the CDC. None of the flood of articles which began to be published in 1993 contained any hint that the quietus promised by the WHO's autoclaves would not be permanent and final. Certain members of the Ameri can intelligence community knew the truth about smallpox pro liferation, but they weren't telling anyone—not the press or the public, certainly, but also not the health officials responsible for determining the U.S. position on smallpox destruction. The former analyst responsible for so many briefings of high officials acknowledges that if the scientists at lower levels in the government didn't know about smallpox proliferation, "that's a breakdown in the system." He describes one briefing he held for a group of committed destructionists, including Henderson and Brian Mahy, Chief of Viral and Rickettsial Diseases at the CDC, who, with smallpox frozen in his basement, is also a passionately committed destructionist. The analyst managed to sway everyone in the room but Henderson and Mahy. When they saw the response of the others, he recalls, Henderson and Mahy were "pretty ticked off."

Other scientists were given less information, with predictable results. Harlyn Halvorson and Dr. James Chin, clinical professor of public health at Berkeley, both served in April 1995 on an appointed panel of six civilian advisors to the Departments of Defense and Health and Human Services on smallpox destruction. They were given a "sanitized briefing" by what one observer called "faceless intelligence types." "We had limited information on what was happening," says Halvorson. "They hinted that there were problems [with smallpox proliferation]. It didn't convince me. I had concerns over not seeing raw information. One becomes skeptical after a while. I didn't feel we had been fully briefed—I thought it was another Defense plan to build up their budgets." The entire panel voted to postpone destruction for three years, until June 30, 1999, to allow time for three kinds of studies: testing available antiviral agents; testing standard and new cell-culture vaccines on monkeys infected with massive doses of inhaled monkeypox (another virus which serves as a stand-in for smallpox); and developing tools for rapid diagnosis of the virus. This became the official position of the U.S. government. (Another of the panelists, Dr. Michael Ascher of the California Department of Health Services, insists that the panel never voted to support destruction at all, but merely to reevaluate the entire question in 1999 after the government's studies were completed.)


A Necessary Virus

Henderson has considerable influence in the government, but nowhere more, perhaps, than in the White House, where he has a firm supporter on the National Security Council (NSC), Elisa Harris. Harris is the NSC staffer responsible for biological and chemical warfare issues. "She wants the destruction of smallpox to be her legacy," comments one analyst. Harris herself refuses to discuss the matter. But she astounded several observers last spring when she publicly suggested a workshop be held by the National Academy of Sciences/Institute of Medicine that would assess the scientific importance of maintaining the stocks of smallpox virus—an idea Joshua Lederberg of Rockefeller Univer sity, renowned molecular biologist and outspoken retentionist, had been promoting for some time.

Some suspect that Harris's decision to propose the workshop actually amounted to an effort to keep the debate over smallpox-related research going until the final decision on destruction had already been made. The workshop's timing was critical; in April 1998, the State Department had received a circular letter from the WHO asking the U.S. to reaffirm its position on destruction in 1999. The Executive Board of the World Health Assembly would meet in January of 1999; the entire assembly would meet in May; a U.S. government decision to support destruction or retention was needed, at the latest, in April 1999. The government was deeply split. Harris and Henderson had their supporters, but advocates of retention, bolstered by the flood of attention given to Ken Alibek and his public testimony about smallpox proliferation and by new information on the scientific value of the virus, insisted that the government reconsider its pro-destruction stand.

The proposal for the workshop, written over one weekend in May by Judith Bale of the National Academy of Sciences (NAS), quickly won support and funding from the Departments of Defense and Energy. But it still languished for months, subject to waves of contrary political pressure, while the destruction clock ticked on.

In August of 1998, Health and Human Services officials finally signed off on the workshop, and the academy staff selected a distinguished committee of virologists to hear a panel of experts on all scientific—but not political—aspects of the smallpox question. These included the importance of retaining the stocks for use in testing new antiviral therapies, new vaccines, and also for certain kinds of basic science research. Many scientists, including immunologist Alan P. Zelicoff of Sandia National Laboratories, Joshua Lederberg, and Sergei Schelkunov, a molecular biologist from Novosibirsk, all insist that the smallpox virus is a mine of information on the human immune system, which it subverts in unique ways. But in a conversation last year, Henderson dismissed the whole immunology issue as "hype and smoke."

At the NAS workshop, which was held on November 20, the pressing issue was not immunology but antivirals; Henderson insisted that the government would never fund research on treatments for an extinct disease. This enraged John W. Huggins, a peppery researcher from USAMRIID, who has tested one antiviral drug, cidofovir—developed for an entirely different disease—on live smallpox virus and on monkeys exposed to monkeypox. Both trials suggest cidofovir could be used effectively to treat people infected with smallpox. But Henderson was having none of it, insisting that vaccinia virus, which he and his team used to eradicate smallpox from the wild, can serve instead.

It won't serve instead. You can't give vaccinia virus to anyone with a serious immune disorder like HIV. It kills them. "Antivirals are the Achilles' heel of the destruction effort," says Peter B. Jahrling, a senior virologist at USAMRIID. "Who is going to tell a politically formidable group like ACT UP that they will be excluded from the only available treatment option (ring vaccination) because of their intercurrent HIV? It's political suicide." The mills of government grind slowly: the committee's painstaking report, in which every idea, every sentence, has been subject to intense debate, was due in March of this year. "You've got to have faith in the process," says Zelicoff, confident the committee will reach a rational conclusion.



Meanwhile, Henderson and his supporters battle on. The so-called Ad Hoc Executive Committee on Orthopox of the World Health Assembly, which Henderson chaired this year by acclamation, met in January in Geneva. Observers describe this group as "a good old boys club"—it has no official standing but functions, as its name suggests, in a sort of improvisational advisory capacity. Only nine of those present, considered "participants," were allowed to vote, and all others—"observers"—were dismissed after one day of deliberations. The categories are fluid and unclear; status as a participant appears to be generally justified by past participation in the Executive Committee (and involvement in the global eradication campaign). Furthermore, participants are almost all eminent pox virologists. These restrictions apply to all participants except the Russian scientist V. Zverev, who was included for no discernible reason.

The doors which were opened for Zverev slammed shut for Lev Sandakchiev of Vector Laboratories, who was not involved in the destruction campaign but is certainly, if rather unpalatably, a smallpox expert. Why was Sandakchiev omitted? Observers speculate that the three Russian votes for retention would be one vote too many, and so Sandakchiev, willy-nilly, was classed as an observer and asked to leave. The three Committee members from the U.S., Henderson, Mahy, and Joel Breman of the National Institutes of Health, all voted for destruction.

The final vote was five to four for immediate destruction: one British representative favored destruction; the other Briton and the South African representative wanted to delay and then reconsider destruction in five years; and two Russians, including Svetlana Marrenikova, the highly respected Russian virologist who has official control of the Russian-held WHO reference stocks, wanted to postpone destruction for the indefinite future. The Ad Hoc Committee declared victory and went home.


The Russian Pox

One of the reasons four participants voted against immediate destruction was the Russian announcement of recent research on mutations in the monkeypox virus, observed in a recent outbreak of the disease in central Africa, which point to the possibility that smallpox or a smallpox-like virus could reemerge in the wild. But Lev Sandakchiev, director of the Novosibirsk facility, also made a surprising revelation that raised more troubling questions about how open the Russians have been about their own research. Sandakchiev now insists that Russian scientists never worked with the live smallpox virus until 1997. But this would seem to contradict a letter he sent to a number of American scientists last year, in which he admitted that Novosibirsk had had the live virus since 1994 when, with the WHO's permission, the official reference stocks were moved out of Moscow to the Vector Laboratories at Novosibirsk. It's also despite intelligence reports placing illicit stocks—not the WHO stocks—in Novosibirsk since at least 1991.

Zelicoff, who takes Sandakchiev at his word, has his own experience to relate. He traveled to Novosibirsk in December 1994 on assignment from the Department of Defense, serving as a technical advisor to the International Science and Technology Center. During his four days in the giant complex, he spent considerable time with a distinguished virologist from the Russian Institute of Standardization and Control of Medicinal Immunologic Preparations, one T. A. Bektimirov. "We did some terrible things [in the Soviet days] but no longer," Bektimirov told him (though Bektimirov denied having done any terrible things himself). Once, as they were traveling by bus to Building Six, the alleged research site for smallpox and other dangerous viruses, Bektimirov casually mentioned that Russian researchers in Building Six had the smallpox virus. Zelicoff, exhausted by jet lag, had been drifting "more or less on autopilot," as he put it. But that statement wonderfully concentrated his attention.

Lederberg doesn't immediately dismiss Sandakchiev's claim: "Maybe they used DNA clones [noninfectious strips of genetic information]. That's the way I would do it, to minimize the risk of an outbreak." As for the process developed at Novosibirsk in December 1990, Lederberg remarks, "I can't imagine they would load live virus into a weapon, unless they were prepared to use it that afternoon. All of that research could be done perfectly well with simulants, if we take Alibek's account at face value." But when I asked Ken Alibek about Sandakchiev's remark he laughed. "They say they worked with DNA clones. It's a cover story developed in 1988, '89 to explain work on smallpox to visiting American inspectors. They were vaccinated on, let us say, their bottoms, so that the scars wouldn't show."

"In 1994," Alibek continues, "they received approval to transfer [the WHO reference stocks] from the Ivanov Institute. Svetlana Marrenikova says 1997—she is absolutely right. This is the Russian way—it's a huge country of liars. Sandakchiev has no choice [but to say 1997]—or it's political death for him." Jahrling explains that Marrenikova said in Geneva that the WHO stocks were transferred in 1994 but kept sealed until 1997.

All of this says a great deal about how things work in Russia and about the Russian scientists' determination to keep on with their research. There is some indication that the Russians will not submit to the charade of destruction: at the ad hoc meeting, Marrenikova insisted that the Russian government, not the WHO, actually owns the stocks she holds. This is one step away from refusing to participate in destruction altogether. Alibek goes further. He claims that the Russians, confronted with a World Health Assembly decision to destroy smallpox, will never comply, whether they appear to do so or not. "They will take some ampoules and seal them up," insists Alibek. In sum, the Russians seem intent on supporting the formal retention of smallpox, making the continued possession and study of the virus permitted under international norms. But if the formal decision is made for destruction, Alibek contends, it seems likely they will keep their stocks regardless.

At the Geneva meeting Henderson produced a revelation of his own. He seemed to put forward an explanation for why he continued to support destroying the virus even after he was aware of the evidence of proliferation. He now insists that he never cared much about destruction before 1994 or 1995, when he first learned about smallpox weaponization and proliferation. Henderson hopes, through destruction, to "raise the moral high bar" and inspire anyone growing smallpox as a weapon to destroy their stocks too. He insists that not until we destroy our stocks can the possession of illegal supplies be a crime against humanity. He hopes, by the force of his gigantic will, to force the world to yield to his increasingly irrational demand, a demand that remains the official position of the U.S. government.

The twists in Henderson's logic are difficult to fathom. You would think that learning that the prisoner has escaped his wardens would make plans for his execution a bit more problematic. But Henderson persists, even knowing as he has for years that destroying all the known controlled stocks of smallpox will not eradicate the virus from the face of the earth. Each new challenge—weaponization, proliferation, the limits of vaccinia, the need for new antivirals—seems only to renew his fervor.

But some of those who contributed to Henderson's stand, including Halvorson and James Chin, who voted in 1996 to support destruction, have changed their minds in the face of new information. "If samples are being stored elsewhere we didn't know about, then destruction loses its meaning. . . . I have a feeling that destruction should not go forward," says Halvorson. "I myself do not see how the official stockpiles could threaten humanity," Chin points out. "It's the ones that are not accounted for that would be the major concern."

This is the voice of reason—moderate and spare. Chin does not believe, ultimately, that much would be achieved by destroying smallpox. Most countries don't seem to think it matters. The last time they were polled, most didn't even bother to vote. To others like Zelicoff, Lederberg, and Huggins, however, the destruction of smallpox is a cruel deception and a waste. It represents the destruction of our best means of testing new antiviral drugs against that day—which is not impossible to imagine—when smallpox will again be released among us. It also means squandering a precious scientific resource, one from which we can learn a great deal about the still mysterious processes of immunity.

But holy warriors don't often listen to reason, and the fight for destruction has a momentum and a blinding power of its own. Smallpox has been driven from nature, but its threat to humanity remains. It seems foolish to cast away the best protection we still have against that threat: the smallpox virus itself.

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