College of American Pathologists
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A call to bare arms vs. smallpox

May 2003
Seth L. Haber, MD

This may be a good time for physicians, nurses, and other health care workers who do not want to be vaccinated against smallpox to examine and prioritize their personal and professional obligations to the immunity of the herd.

With a disease that spreads as easily and rapidly as smallpox, our safety (individual, community, national, and international) is a function of our own immunity and that of everyone else—the herd. We are only as safe as our neighbors. That is why health care workers, in my view, should set an example by stepping forward now to be vaccinated and why other groups should do so as they become eligible.

Let’s go back about 40 years. Smallpox vaccination was generally required and universal; you couldn’t enter public school without it. School nurses lined up the children, each child was vaccinated, the inoculation site was casually covered with gauze, and the children were sent on their way. The risk of complications or death from the vaccination did not constitute an excuse not to be vaccinated.

Even those of us who can find the vaccination scar are no longer immune. It lasts only a decade or two, and we haven’t vaccinated for some 30 years in this country. D.A. Henderson’s success 25 years ago in eliminating variola ended vaccination and made us all susceptible, and thereby qualifies smallpox as a doomsday bioweapon.

Smallpox has been used previously in biological warfare: Scab material was spread on the blankets that conquerors of the new world gave to the native Indians, and, in other periods, the bodies of those who died of smallpox were catapulted over the walls of towns under siege.

We have been warned that vaccination, under the currently proposed program, will produce 50 life-threatening complications and one or two deaths per million people, based on data extrapolated from other countries. But the new lower-dose vaccinations may lessen those rates. Whatever the herd rate, complications will be much higher in patients who are immunocompromised and lower in those previously vaccinated.

How communicable is smallpox? The natural strain is second only to influenza and measles in the ease, rapidity, and surety of its spread. Infection takes only one inhaled particle and generally can be spread to 10 to 20 people in the 10 to 14 days before it can be diagnosed. Mortality from natural strains is generally up to 50 percent, but it approaches 100 percent in some virulent forms. Smallpox has killed more people than any other epidemic disease.

I specify “natural strains” because the Soviet Union’s bioweaponeers are reported to have modified the DNA of natural strains to increase the virus’ infectivity and virulence. They have also genetically engineered recombinant smallpox chimeras, with viruses causing Venezuelan equine encephalitis, as well as Marburg, Ebola, and other hemorrhagic fevers. Ebolapox could produce “blackpox,” which should be 100 percent fatal. They may also have developed strains against which vaccination with natural strains of vaccinia is ineffective.

Physicians, nurses, technologists, and other health care workers who have declined vaccination justify their positions with one or more of the following arguments:

  • The morbidity and mortality from the vaccination are unacceptable.
  • There may be secondary spread of vaccinia to immunocompromised persons.
  • There may be secondary spread of vaccinia to family members.
  • President Bush was using the program to spread fear, thereby deceptively mobilizing the country for war with Iraq.
  • Bioterrorists lack the capacity to smuggle and release smallpox in our country.
  • I’ll never catch smallpox, if I’m careful.
  • We’ll have plenty of time for post-event vaccination.
  • It’s really chemical and nuclear attack that we have to fear.
  • The program’s costs are significant and would probably come out of other worthy health programs.

The magnitude and significance of the first three points are largely unknown. It’s difficult to compare unsupported mortality and morbidity extrapolations with the unknown probability of a bioterrorist attack.

Regarding unacceptable morbidity and mortality: At what probability of occurrence does who decide that it is worth risking some 300 deaths (at one per million) to prevent about 120 million possible deaths (at 40 percent mortality)? Like it or not, how to respond to that ratio of about 1:400,000 is the heart of the problem—all else is persiflage. Whether anyone will listen to that decisionmaker, and whether those who listen will have time to act, are also important factors.

How was it determined that holding the entire population hostage to the needs of the immunocompromised is a higher morality? Is it more ethical to risk the lives of the vast majority in favor of the needs of a relative few, the length and quality of whose lives may be diminished by their primary diseases? We must, of course, provide for their medical needs, including isolation, but the quality of their lives is not enhanced by subjecting the majority to the other edge of the sword.

The possibility of spread to family members is debatable and might be as much a benefit as it is a hazard—similar to, for example, the secondary spread of live polio vaccine, chickenpox (varicella) parties to protect against future herpes zoster, and German measles (rubella) parties to help immunize against measles (rubeola).

That President Bush may have been intentionally spreading fear is political dogma, discussion of which will generate far more heat than light.

Regarding bioterrorists’ capacity to release smallpox: Effecting a cataclysmic spread of smallpox is low tech, certainly less than that which is required to commandeer three huge jets and fly two of them into the “sweet spots” of New York’s twin towers. In the 1990s, Russian bioweaponeers learned to grow smallpox virus in large (>630 liters) pharmaceutical tanks, enabling them to produce tons of it in dozens of facilities. When the USSR broke up, the biological warfare programs closed down. Hundreds of then-unemployed scientists took their knowledge of the methods and techniques used by the Russian programs to new jobs in Iraq, Korea, and other countries that are enemies of the U.S. The scientists as they left Russia could easily have carried master seed strains of viruses in one of their jacket pockets, if not a potentially end-of-civilization supply in innocuous-looking bottles.

The Russian scientists were able to produce liquid smallpox by the gallons, subsequently stored in lyophilized, powder, and liquid forms. Twenty tons of bioweaponized liquid smallpox were stored on Russian military bases, ready to be loaded onto warheads. The dry powders are the most powerful bioweapons, with particles less than five micra in diameter, designed to lodge in the lungs. The powder is frighteningly self-dispersing, and the liquids are easily aerosolized. Most of the hundreds of tons of infectious smallpox material is unaccounted for—it simply disappeared. It can be smuggled into this country more easily than out of Russia, probably in the same innocuous, concealable containers.

Regarding our personal immunity: Despite Herculean efforts by health officers and public health departments to mobilize, organize, and educate first-line physicians, most clinicians have no idea what even classical smallpox looks, feels, or smells like, and it would be a long time before we would diagnose it. Henderson, who has seen more cases than anyone and who literally wrote the book, says smallpox takes forms even he can’t diagnose. Does smallpox belong in the differential diagnosis of every case
of cough, sore throat, chills and fever, or exanthema? Even if you diagnose the first case you see, by then everyone in your office, clinic, or emergency room, including you, your colleagues, and assistants, will have been exposed.

In the 10 days to two weeks after exposure, before smallpox can be diagnosed, each person can infect 10 to 20 others. That’s the first wave. Subsequent waves, on a two-week cycle, increase by a factor of about 20. Henderson said about 100 million doses of vaccine would be needed to stop an epidemic in the U.S. if it began with only 100 cases.

If only 10,000 people are infected in a large city during a bioterrorist fly-over, those victims will have infected 100,000 to 200,000 others by the time it is diagnosed. That’s the second wave, and it will surely involve other cities
by then. Thus, we will probably be well into the third wave, of 1 million to 4 million, all over the world before we can even begin a program of vaccination. Of course, we’ll be diagnosing it in unvaccinated health care providers by then.

Why not vaccinate post-event? Bioterrorists can spread smallpox by releasing the agent while flying over major American cities in small rented planes. Or they can release a small container of powder into the air intake system of a major international airport. It doesn’t even have to be on U.S. soil. Essentially everybody in the airport would be infected and become an innocent but undetectable smuggler. If the bioterrorists said nothing, the infected persons would each fly off to their respective destinations, innocently infecting 10 to 20 others in the next 10 to 14 days, in foci throughout the world. Clearly, too many cases and too widespread to be contained by Henderson’s ring of vaccination. Remember, a single person infected with smallpox used to be a global medical emergency. Imagine the riots if the terrorists made a post-event announcement. Who would exercise what authority to command who to close O’Hare Airport?

When a case of smallpox popped up in Yugoslavia in 1972, containing it took the resources and commitment of its authoritarian government. It mobilized the army, exercised full emergency powers, and closed off the country, so that the World Health Organization could administer 18 million doses in 10 days, before the waves of cases stopped. It took a military crackdown and vaccination for every citizen.

Contrast that with our commitment to individual rights, personal freedom, and confidentiality, our desire to debate everything, our demand for at least a court hearing, and the refusal of some hospitals, as well as unconvinced physicians and other health care workers, to participate. Oh yes, we’ll have plenty of time.

With the downsizing of the pools of people who would have constituted emergency response teams, the surge capacity begins to approach zero. How, then, would we vaccinate 250 million Americans in 10 days? And just who is “we”? Where are the frozen ampoules of vaccinia, and how will they be distributed to the vaccination centers? If one death and 50 serious complications per million people vaccinated is worrisome, consider the morbidity and mortality that could result from panicked mobs rioting to be vaccinated. How long will the exhausted members of those first response teams, who are vital to the program, be willing and able to play their designated roles? And how will we protect the immunocompromised?

How should or will we respond to other nations claiming entitlement to a humanitarian share of our supplies of vaccine? Would our neighbors, like Canada and Mexico, launch a first strike in our border states to get at supplies for their nationals?

Although chemical and nuclear weapons of mass destruction are horrendous, they affect only the area in which they are released. Biological weapons, on the other hand, are communicable and self-perpetuating. They are the gift that keeps on giving. The valid fear of other weapons of mass destruction does not justify refusing to prepare for those we can.

Finally, concern about the program’s cost is valid. It will probably be even greater than the highest estimates and will come largely out of other health programs. Yes, it’s a zero sum game. It’s a matter of priorities, who sets them, and whether you agree.

In my view, all health care workers who would be exposed early while caring for patients should be vaccinated while they can. They should give thanks to the U.S. government for initiating the program, thanks to the pharmaceutical companies for being able to produce the vaccine, thanks that they are among the first to qualify for it, and thanks to any and all if I am totally wrong.

Dr. Haber is emeritus chief of the Department of Pathology, Kaiser Permanente Medical Center, Santa Clara, Calif., and clinical professor of pathology at Stanford University School of Medicine. Dr. Haber offers as additional reading three articles from The New Yorker that he says “will ruin your day and interfere with your sleep until you repress them.” Written by Richard Preston, they are as follows: “The Bioweaponeers,” March 9, 1998,; “The Demon in the Freezer,” July 12, 1999,

“Gluttons for punishment,” he adds, might enjoy these books: Preston’s The Demon in the Freezer: A True Story, Random House; Biohazard:The Chilling True Story of the Largest Covert Biological Weapons Program in the World, by Ken Alibek (who directed the Russian bioweapons division before defecting to the U.S.), Dell Publishing; and The Coming Plague, by Laurie Garrett, Penguin Books.