On Tuesday evening, October 22, the phone rang. It was a federal official I have known for years. "The U.S. government can't sit on this much longer," he told me. His normally calm voice was cracking. "Three people down in Florida have a rash; 30 are in quarantine. The CDC is all over it." He would not say the word we both were thinking: smallpox. "I can't stay on the phone; turn on the news," he said.
I thought it was the end of the world. By the end of next year, the U.S.government probably will have grown enough cell-culture smallpox vaccine toimmunize everyone in the country. In four or five years, testing of new antiviraldrugs presumably will have progressed, giving us a good idea of whetherpost-infection treatment of smallpox will actually work. But right now? What canwe do right now? Not a lot.
The Florida rashes were a false alarm. By the next morning, four doctors haddiagnosed shingles in the afflicted patients, who with their contacts werereleased from quarantine. Smallpox had slipped back again from appallingcertainty to specter--a "low-risk, high-consequence threat," as experts like toput it.
But that has new meaning nowadays. A few months ago, the CDC wouldn't havedreamed of slapping three people with shingles into quarantine together withtheir friends and relations. How serious is the smallpox threat? There is nounambiguous answer. What we know is this:
Smallpox, unlike the ubiquitous anthrax, would be hard for terrorists toobtain, but not impossible. Since 1980, when the disease was declared eradicated,the only legal stocks of the smallpox virus have been held in two repositories,the Centers for Disease Control in Atlanta, Georgia, and the Vector ResearchCenter in Koltsovo, Siberia. But American intelligence reports indicate that thevirus is also in the hands of the North Korean bioweapons program, as well as thesecret Russian military laboratory at Sergiyev Posad. And that's just forstarters. Most experts believe that the Iraqis also possess the virus--not leastbecause Iraqi soldiers captured during the Gulf War showed evidence of havingbeen recently vaccinated for smallpox, and this was 10 years after the diseasewas supposed to have disappeared from the earth. Though with less certainty, theexperts also suspect Iran, China, India, Syria, and Israel of having illicitstocks of the virus. In the circumstances, we cannot be confident that stocks ofsmallpox could not fall into terrorist hands.
The common claim is that a smallpox attack, if it were to happen, would killabout one infected person in three. But it is actually quite difficult tocalculate the damage a smallpox outbreak would cause--especially if the diseasewere seeded in many locations at once, the most dangerous scenario.
In part this is because smallpox strains--even variola major, the formresponsible for most infections throughout human history--vary quite a lot intheir virulence. Experts say that variola-major strains from Africa typicallykilled about 10 percent of those infected, while the much hotter strains fromIndia and Bangladesh, where crowded circumstances permitted the easy passage ofextremely lethal strains from one person to another, killed up to half of thoseinfected. Furthermore, some people, regardless of the strain involved, just getmuch sicker than others do. Pregnant women, for instance, and persons withcompromised immunity are more likely than others are to develop hemorrhagicsmallpox, a severe and almost always fatal form of the disease. According to KenAlibek, former first deputy director of the Soviet bioweapons program, Russianscientists weaponized India-67, an extremely lethal smallpox strain, years ago.But the truth is that we have no idea what strain a bioterrorist might use.
Several factors suggest that the death rate from a smallpox attack in theUnited States could be much lower than is usually projected. For instance, theAmerican public, and indeed the rest of the world, while certainly lacking totalimmunity, is far from a virgin-soil population. When smallpox swept throughNative American communities after European settlers brought the disease with themto the New World, 75-90 percent of those exposed to the disease apparently diedof it. This was because Native Americans lacked any genetic history of exposureto the disease. But Asians, Europeans, and Africans have lived with smallpox formore than 3,000 years. Over that much time, genetic resistance to so fatal adisease must have evolved. Even Native Americans, given the intensity of theirexposure to the disease after its introduction, undoubtedly have some resistancenow: They didn't all die of it, and those who lived must have passed some measureof inherent resistance on to their descendants.
In addition, the better people's general level of immunity, the better they'reable to fight off even a serious infectious disease. (According to virologistAlexis Shelokov, who was part of a 1992 investigational team that studied thenotorious 1979 outbreak of inhalational anthrax in the Russian city ofSverdlovsk, the range of victims was extremely skewed: Of the 68 people who died,the overwhelming majority were heavy smokers over 40, probably with damagedlungs, and in generally poor health.) It is thus quite possible that smallpoxwould not cause the damage in America that it once did--and might again--in, say,Calcutta or Bangladesh.
Finally, anyone who was vaccinated against smallpox before routinevaccinations were stopped in 1972 probably has a certain amount of residualimmunity, and the literature suggests that this protection may be considerable.In one study of 680 infections in Canada between 1950 and 1971, 52 percent ofunvaccinated people died, compared with 1.4 percent of those vaccinated 10 yearsor less before exposure and 11 percent of those vaccinated 20 years or morebefore exposure.
That's the good news. The bad news is that the world is much more crowded thanit was back when our models of smallpox infection were constructed. This meansthat the disease could now spread more easily (which would also make it possiblefor more virulent strains to persist). We have, moreover, much better means oftransportation now, which could result in infection rapidly spreading to allparts of the globe. And in the United States, there are many more severely"immunocompromised" people (despite the overall general health of the Americanpopulation) than there ever have been before, because of AIDS and because ofanticancer therapy. The experts believe that immunocompromised individuals,besides being more vulnerable themselves, may shed more virus than infectedpeople with normal immune systems do.
If smallpox were to return now, it would come back to a world cruciallydifferent from what it was a generation ago. In one respect, though, the world isthe same: Grave or slight, the threat of smallpox again exists in it.
The surest way to deal with that threat is to take it completely off thetable by reimmunizing the world's population against smallpox. There then wouldbe no point in unleashing the virus anywhere as a biological weapon. Widespreadimmunization is not, however, the Bush administration's policy.
This may be in part because the government doesn't have the vaccine. Over theyears that we've known of the existence of illicit stocks of the smallpox virus,it's never been official U.S. policy to produce more vaccine. Consequently, wenow have only some 15.4 million doses, which is not even enough to control onemajor outbreak if it were to happen, say, along the eastern seaboard of theUnited States.
Experiments are now under way to test diluted vaccine. In theory, our existingstocks of vaccine could be stretched in this way to cover 75 million people. Butthe only way to tell if diluted vaccine will work in practice is to try it out:If the vaccine produces a significant pock on the skin after inoculation, it mostlikely will provide effective immunity against smallpox. Meanwhile, a newcell-culture vaccine (as opposed to the old vaccine, which was produced byscraping the bellies of infected calves) is now being developed. But even in themost optimistic scenarios, it will be a year before there's enough smallpoxvaccine for everyone in the country--and this assumes that the new vaccine willactually work as well as the old one did.
Smallpox vaccine is not without its dangers. Immunocompromised individualscan develop progressive vaccinia, an often fatal condition in which the vacciniasores spread over the body. AIDS isn't the only disease that produces such severereactions. After vaccination, even the uncomplicated skin disease eczema canproduce a severe, sometimes fatal condition called eczema vaccinatum. During themass vaccination of between five million and six million New Yorkers in 1947, 28people developed this condition just from exposure to someone who was vaccinated.Furthermore, people who touch their vaccinia pocks and then rub their eyes candevelop serious and even blinding eye infections.
Given these risks, many experts believe that mass vaccination of the public isjust too dangerous. Lance Gordon, a vaccinologist who developed a vaccine nowroutinely given to prevent bacterial meningitis in children, thinks that thegovernment's best strategy is to stockpile enough vaccine to provide for everyonein the nation--but not to use it unless the disease actually strikes. "It's aquestion of risk/benefit," he says. "The risk of adverse reactions with vacciniais too great if we don't have smallpox. By keeping it stockpiled ... we have thebenefit without the risk." This is the administration's position as well. Wewould first try to contain an epidemic by isolating the patients and vaccinatingonly those who've been in contact with them, the strategy called "ringvaccination." Eventually, the entire nation might need to be immunized, but onlyif an outbreak were spiraling out of control. Ring vaccination, developed byWilliam Foege, now of Emory University's Rollins School of Public Health, workedbrilliantly in the past. But this painstaking and labor-intensive method wasdesigned for a natural outbreak and might not work at all in a bioterroristattack, especially if terrorists launched many simultaneous releases across thecountry.
Stockpiling vaccines is considered the conservative strategy. But it may notbe the fairest or the wisest one. "If we have a vaccine which is given to themajority of the population, an epidemic would not get out of control," saysKonstantin Chumakov, a former Russian scientist who is now a vaccinologist withthe U.S. Food and Drug Administration's Center for Biologics Evaluation andResearch. Some of the most thoughtful people in the field agree.
If we choose to stockpile and not immunize, says Paul Ewald, a specialist inthe evolution of infectious disease and author of the recent Plague Time, we are accepting the deaths of the first people who become infected in a bioterrorist attack. "People are canaries in the mines here. Are you going to plan to sacrifice these people, without giving them a chance to protect themselves?" Meanwhile, terrorists will not be deterred. They could simply adjust their strategy to cause maximum damage--panic, terror, death--in the period before the disease was recognized and a vaccination campaign begun.
Furthermore, in the event of a smallpox attack, you'd probably have no choiceabout being vaccinated unless you were seriously ill with an immune disorder. Thedecision would be made for you, out of necessity, given the rush of events. Itwould be far better, Ewald thinks, to allow people to make that choice forthemselves to the extent possible, particularly since massive voluntaryimmunizations in advance of any crisis could well be sufficient to prevent one.
If you could choose whether to be immunized, you'd have a number of factors toweigh, such as your general health, your HIV status, your age, your anxiety overthe smallpox threat. You might decide that the risks are too great and you'drather not be vaccinated. Or you could decide that although you are HIV-negativenow, your personal behavior might someday expose you to AIDS and it would be farbetter to be immunized now than later on, when a smallpox vaccination could killyou. Women who plan to become pregnant might make a similar choice to bevaccinated now rather than put themselves and their babies at risk later. Andmany Americans might choose vaccination just because they understood that gettinga smallpox shot could reduce the chances of a smallpox attack on the nation.
Whether the U.S. strategy is to immunize or tostockpile, however, producingthe necessary vaccine will take time--and time is what we may not have. For thisreason alone, the administration ought to be looking into the most obviousalternative: getting help from the Russians. Recently, Russian Minister of HealthYuri Shevchenko offered the United States that assistance: "The Ministry isready, in case of an emergency, to provide medical assistance and vaccines toAmerica... . Besides vaccines, Russia has technology, a collection of strains,and much experience to offer." Shevchenko seems to have been speakingspecifically of anthrax, but American officials I've spoken with--all of whominsist on anonymity--suggest that the offer extends beyond anthrax to the wholerange of potential biological weapons. Russian scientists at Vector claim to havedeveloped an oral vaccine against smallpox, according to one American official;another says that the Russians are in the process of developing a multipurposevaccine for smallpox and hepatitis B. At the very least, the Russian Ministry ofHealth certainly has large supplies of vaccinia virus, the traditional smallpoxvaccine--a useful resource, should we need it.
Some U.S. biodefense experts argue that collaboration with the Russians couldhave other benefits as well, including helping to transform wary former enemiesinto allies. Although both sides have their "dinosaurs," as one officialacerbically puts it, we can learn a lot about biodefense from Russian scientistsand there's much we might prevent by working together. "If Russians [were to]throw their support to the Taliban," says the FDA's Chumakov, "it would be theend of the world."
At this writing, the Bush administration is not saying what it might bediscussing with the Russians--if, indeed, it's discussing any of this. Theofficial U.S. policy is to press forward with the stockpiling of our own vaccineand hope that there's no attack in the meantime. It's a policy that we ought tobe debating.
