Oct. 18 —  Smallpox vaccinations in the United States were discontinued nearly 30 years ago, and the last known case anywhere in the world was in 1977. So why are federal health officials suddenly asking for $500 million to buy 300 million doses of the smallpox vaccine?

AS EARLY as January 1999, a World Health Organization committee warned that smallpox now poses “the most serious bioterrorist threat to the civilian population.” But the recent cases of anthrax exposure, including one death, have made the chances of an attack more worrisome. While the United States has antibiotics to treat anthrax, a potentially lethal bacteria, the smallpox virus is much harder to treat—its fatality rate is nearly 1 in 3 cases. That makes vaccination the most effective weapon against the disease. Secretary of Health and Human Services Tommy Thompson has promised that enough doses will be ready to vaccinate every American by “sometime next year.” Will that be soon enough?
        Jonathan Tucker, director of the Chemical & Biological Weapons Nonproliferation Program at California’s Monterey Institute for International Studies, and author of the book “Scourge: The Once and Future Threat of Smallpox,” spoke with NEWSWEEK’s Jennifer Barrett about the threat of smallpox and the possibility of reinstating nationwide vaccinations against the virus. Tucker recently fractured his jaw, but was able to conduct the interview with NEWSWEEK via e-mail.
       
       NEWSWEEK: On Wednesday, Secretary of Health and Human Services Tommy Thompson announced that he had asked lawmakers for $509 million to contract four pharmaceutical companies to produce as much as 300 million doses by the end of 2002, enough to protect every American from smallpox. Is that a realistic monetary figure and timeline? What’s involved in building up the vaccine supply?
       Jonathan B. Tucker: Secretary Thompson’s proposal to acquire 300 million doses of smallpox vaccine by the end of next year is an enormously ambitious proposal. The old smallpox vaccine was produced by inoculating the vaccine virus (vaccinia) into the scarified skin of living calves and harvesting the virus-rich pus. This method resulted in a vaccine that, while effective, was often contaminated with bacteria and other viruses. As a result, the old production method no longer meets the quality-control

       standards of the Food and Drug Administration (FDA). Instead, the vaccine virus will be grown in living animal cells suspended in a nutrient medium in a stainless-steel tank known as a bioreactor. Developing the new production process, scaling it up, and ensuring that the new vaccine is safe and effective, will all take time. Even if all 300 million doses can be produced by the end of 2002, a task that will pose major technical challenges, the new vaccine will not have been approved by the FDA. Thus, it could only be administered in an emergency situation as an Investigational New Drug, requiring informed consent. Finally, whether or not Congress is prepared to appropriate more than $500 million to acquire smallpox vaccine remains to be seen.
       
       What prompted you to write “Scourge”?
       As a specialist on biological weapons, I found the story of smallpox particularly dramatic and compelling, reflecting both the positive and negative sides of human nature. For thousands of years, smallpox killed hundreds of millions of people and repeatedly changed the course of world history. It was also the first—and thus far, only—infectious disease to be eradicated by means of a global vaccination campaign that was coordinated by the World Health Organization during the late 1960s and early 1970s. Yet at the same time Soviet epidemiologists were participating in this noble effort, the Soviet military was secretly turning the smallpox

       virus into a strategic weapon. The fact that the smallpox eradication campaign—one of the greatest achievements of 20th-century medicine—had been betrayed did not become known to Western governments until the defection in 1992 of a senior Soviet bioweapons scientist. His revelations led to growing concern in the West that other countries with bioweapons programs, such as Iraq and North Korea, might have followed the Soviets’ lead and turned smallpox into a weapon.
       
       How much of a threat is smallpox as a biological warfare agent?

“Smallpox virus (scientific name variola major) would be a “good” biological warfare agent because it is unusually robust, can be disseminated through the air as an inhalable aerosol to infect people over a large area, and—unlike anthrax—is contagious from one person to another. ”
— JONATHAN TUCKER
director, Chemical & Biological Weapons Nonproliferation Program

       Smallpox virus (scientific name variola major) would be a “good” biological warfare agent because it is unusually robust, can be disseminated through the air as an inhalable aerosol to infect people over a large area, and—unlike anthrax—is contagious from one person to another. Even if a relatively small group of people were infected in an initial attack, they could spread the disease widely. As a result, release of the virus could trigger an expanding epidemic unless transmission was halted by means of an aggressive vaccination campaign. The drawback of smallpox as a biological weapon is that it could not be “targeted”—unless contained, the disease would continue to spread and might eventually boomerang against the attacking country.
       
       You say the deliberate use of smallpox as a military/terrorist weapon is the most likely source of recurrence. Why?
       Because the smallpox virus only infected people and did not have a wild-animal host, it was possible to eradicate the disease by using vaccination to interrupt the chains of human-to-human transmission. A number of scenarios have been suggested for a possible resurgence of smallpox. First, there is a finite risk that the smallpox virus could escape from the two maximum-containment laboratories in the United States and Russia where internationally sanctioned research with the virus is taking place. Second, it is possible that global warming could cause the frozen corpses of smallpox victims in the Arctic who were buried in the permafrost to rise to the surface and infect someone who came into contact with them. Third, a related virus called monkeypox, which causes sporadic outbreaks of human disease in jungle regions of central and western Africa, might mutate to become more virulent and contagious in humans. Most experts downplay these risks, however, and contend that the most likely source of a recurrence of smallpox would be the deliberate release of the virus as a military or terrorist weapon.
       
       How hard would it be for someone to obtain and to release the smallpox virus?
       Acquiring, producing, and delivering the smallpox virus would pose a series of challenging technical hurdles for terrorists, making an attack with the virus unlikely—although potentially catastrophic were it to occur. First, because the smallpox virus no longer exists in nature, terrorists would have to acquire it from a state with undeclared laboratory stocks of the virus, or perhaps from former Soviet bioweapons scientists who had smuggled out samples of the virus. Second, the terrorists would have to grow the virus in eggs or animal cells, which is technically challenging. Third, they would have to find some means of disseminating the virus as a fine, inhalable mist of microscopic particles or droplets (called an aerosol), which would require specialized technology and know-how. For a low-tech attack, suicide terrorists might consider infecting themselves and spreading the disease, but they would have only a few days to do so before the facial rash became obvious. Moreover, even terrorists prepared for instant martyrdom in an explosion might hesitate before willingly suffering a slow, painful, and hideous death from a disease like smallpox.
       
       Where might one find smallpox virus stocks?
       Only two laboratories in the world have been authorized by the World Health Organization (WHO) to retain samples of the smallpox virus. The first is at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta, and the second at a Russian laboratory known as “Vector,” in the town of Koltsovo near Novosibirsk. These two repositories are currently conducting research with live smallpox virus under close oversight by the WHO, with the aim of characterizing multiple strains of the virus, screening a wide variety of antiviral drugs for possible efficacy in treating smallpox, and developing an animal model of the disease. It is rumored, however, that undeclared stocks of smallpox virus may exist in a number of countries, including Russia, North Korea, and Iraq. The evidence in the public domain is circumstantial, such as the fact that Iraq and North Korea continue to vaccinate troops against smallpox. Iraqi officials also admitted to U.N. weapons inspectors that they had conducted military research on a closely related virus called camelpox, which could have been used as a “surrogate” to develop production and dissemination techniques for smallpox virus.
       
       If someone gained access to the stocks, how much would he or she need to create a major outbreak?
       Because smallpox is contagious, even a relatively small release that infected a few dozen individuals could spread considerably by the time the first cases were diagnosed. Since smallpox has a two-week incubation period before the first symptoms appear, the exposed individuals might disperse widely. The worst-case scenario would involve a release of smallpox in an airport, so that infected people would travel to cities around the country and trigger multiple outbreaks.
       
       What makes smallpox so dangerous? How does it compare to anthrax and other forms of bioterrorism?
       Smallpox, which has a mortality rate of about 30 percent, is less lethal than inhalational anthrax, which kills roughly 90 percent of its victims [if untreated]. But whereas anthrax is not contagious and is treatable with antibiotics at an early stage, smallpox spreads readily from person to person, and no drug treatment is available. Thus, anthrax would only affect those individuals who were directly exposed to the bacteria, but a release of smallpox could trigger a major epidemic that, if not aggressively contained by vaccination, could spread uncontrollably.
       
       How can we protect ourselves from a smallpox outbreak?
       Given the lack of a drug therapy for smallpox, the best approach for reducing our vulnerability to smallpox is to expand the available supply of the vaccine. Most Americans alive today are susceptible to smallpox infection, either because they were never vaccinated or because their immunity has worn off. Since a single vaccination provided protection for only about 10 years, people who were vaccinated once in childhood have little residual immunity. Those who received at least one “booster,” or revaccination, probably have a greater level of immunity today, but not necessarily enough to protect them fully.

       Thus, in the event of a smallpox outbreak, it would be necessary to vaccinate all those at immediate risk of exposure. At present, the United States retains somewhere between 7.5 million and 15 million doses of smallpox vaccine, far from enough to manage even a medium-size epidemic. Responding to this situation, the U.S. government is moving to expand the national supply of the smallpox vaccine by taking a two-pronged approach. First, as a stop-gap measure, the National Institutes of Health have commissioned studies of the feasibility of diluting the existing vaccine 5- or even 10-fold, which could expand the available supply to some 75 million doses. Second, the government is accelerating the acquisition of a large additional supply of vaccine.
       
       In your opinion, why hasn’t our government taken the threat more seriously before now?
       Before the recent anthrax attacks, bioterrorism was largely seen as a theoretical threat. Only one major incident in the United States had been previously reported: a scheme by the Oregon-based Rajneeshee cult in 1984 to affect the outcome of a local election by contaminating local restaurant salad bars with salmonella (food-poisoning) bacteria. That incident made more than 750 people sick, but did not result in any deaths. Although the Clinton administration began to take concrete measures to address the threat of bioterrorism, these programs were poorly coordinated, and Congress declined to fund a number of proposed initiatives. Since Sept. 11, the once hypothetical threat has become a reality, resulting in a dramatic change of attitude on the part of policymakers, the Congress and the public.
       
       Why did we not reinstate nationwide (or worldwide) vaccinations earlier, particularly if the government was aware of the danger of an intentional smallpox outbreak?
       Vaccination of American children against smallpox was mandatory before school entry until 1972, when the U.S. government determined that the risk that cases of the disease would be imported into the country—the last U.S. case was in 1949—was lower than the risk of serious complications associated with the vaccine. (The smallpox vaccine is based on a live virus called vaccinia, which is closely related to the smallpox virus and protects against it, but normally does not cause disease itself.)
        In people with eczema or an impaired immune system, however, the vaccine virus can proliferate out of control, causing serious complications such as encephalitis or even death. Rare complications were also reported in otherwise healthy people, and it was impossible to predict in advance who would be stricken. When Americans were routinely vaccinated against smallpox, roughly one in every million recipients suffered death or permanent brain damage. The risk of complications would probably be significantly higher today because of the greater incidence of immunosuppression associated with HIV/AIDS infection, cancer chemotherapy, and organ transplantation.
        Given this situation, it would make sense to begin vaccinating the general population against smallpox only if the risk of terrorist use of the disease was assessed to be higher than the risk of complications from the vaccine. That is not currently the case. One advantage of the smallpox vaccine is that it works extremely rapidly and can either prevent or reduce the severity of the disease even if administered up to five days after infection. Thus, in the event one or more cases of smallpox were diagnosed, the vaccine could be administered in a targeted manner to all those who had come in contact with the first wave of cases, thereby containing the outbreak and preventing further spread.
       
       What measures should the government take to protect us from other bioterrorist threats? What would that require in terms of money, manpower and time?
       In addition to stockpiling antibiotics and vaccines, the best approach to reducing the nation’s vulnerability to bioterrorism is to fill a number of serious gaps in our public-health system. These gaps include: (1) training primary-care providers to recognize unusual infections such as anthrax and smallpox, which they would normally never encounter in their medical practice, and telling them where to report suspicious cases of infectious disease; (2) increasing the staffing and resources of city, county and state public-health departments, so that they can respond to doctors’ reports on a 24/7 basis; (3) increasing the number of diagnostic laboratories with the ability to diagnose bioterrorist threat agents, and (4) helping hospitals to develop contingency plans for handling the massive influx of patients that might result from a bioterrorist attack, particularly with a contagious agent.
        Local, state and federal public-health agencies will also need to be networked together with computers and Internet links so that the system functions as an integrated whole, and resources (such as vaccines, drugs, manpower and expertise) can be brought to bear promptly where they are needed. The advantage of strengthening the U.S. public-health system is that such measures are “dual-use.” Even if a major bioterrorist attack never materializes, we will be better prepared to respond to a serious outbreak of a natural-emerging infection, such as the recent outbreak of West Nile virus in New York City. In the worst-case scenario, we might have to deal with a serious natural epidemic akin to Spanish influenza, which killed more than 20 million people worldwide in 1918-19.

       
       
       © 2001 Newsweek, Inc.