Countering the smallpox threat: a sensible strategy

In the days following the terrorist attacks that brought down the World Trade Center and demolished part of the Pentagon, I received a series of e-mails from my sister asking what I thought she could do to protect herself and her family. Should she stock up on water? On food? What about buying a gas mask? I told her I doubted that any of those things would really help. At first blush the notion of suburban moms buying gas masks seemed a little silly. But a lot of people were buying gas masks at that point, and mostly they were not silly people, and the impulse they were acting on was not silly. What they wanted was to do something: to exert at least a little control over a new and frightening situation. That is just the sort of impulse that the fight against terrorism needs to put to use. One way to use it is against the threat of smallpox.

Experts have agreed that smallpox terrorism is potentially the Big One. Maybe not bigger in terms of lives lost than, say, a nuclear warhead detonating over Manhattan, but certainly right up there, and probably more socially destabilizing. Unlike chemical agents and some other biological agents, such as anthrax (as we've lately seen) and botulism, smallpox spreads virulently from person to person. The disease is fatal 30 percent of the time and leaves its survivors disfigured and sometimes blind. Symptoms take a week or two to appear. In an urbanized country full of planes, trains, and automobiles, smallpox could easily spread to any number of cities and states before health officials realized what was going on.

Routine smallpox vaccination ended in the early 1970s, because a worldwide campaign had succeeded in eradicating the disease. The virus survived only in laboratories in the United States and the Soviet Union. After the Soviet Union collapsed, credible reports surfaced alleging that the Soviets had produced smallpox in large quantities, for biological warfare. Bio-terrorism experts began to worry that the Russians might have let the virus slip into the wrong hands. Still, most people believed that smallpox's very virulence made it an unlikely weapon of terror. After September 11 a lot of those people changed their minds.

I was vaccinated for smallpox years ago, in childhood; so were many other Americans who are now over thirty. But it's unclear how much good this would do if smallpox were unleashed today. "One of the problems with smallpox vaccine is that immunity doesn't last very long," Peter J. Hotez, a senior fellow at the Sabin Vaccine Institute, in Washington, D.C., told me when I asked if I would be safe. "It can last as few as three to five years." And younger people, of course, weren't vaccinated. America today would be a tinderbox for smallpox: something like 90 percent of the population is thought to be susceptible.

To its credit, the Clinton Administration took the threat seriously. Realizing that existing stocks (about 12 million to 15 million doses of twenty-year-old vaccine) were too thin to cope with a serious crisis, in September of last year the government ordered up a new smallpox vaccine, with the first 40 million doses to be delivered in 2004 and more to come thereafter. This October, as anthrax scares transformed the threat of bio-terrorism into reality, the Bush Administration announced that it would seek to increase the smallpox-vaccine inventory to 300 million doses, possibly by next year.

With the new vaccine will come a new and difficult question: Who should be vaccinated? My first thought was "Everyone." Or at least—as Homeland Security Chief Tom Ridge has suggested—we should resume routine vaccination of children. But this sort of uniform approach has a significant drawback. The smallpox vaccine is not perfectly safe. During the eradication campaign, according to Tara O'Toole, of the Johns Hopkins School of Public Health, about one in 300,000 people died from side effects of the vaccine or suffered irreversible brain damage. At that rate, if all 280 million Americans were to be vaccinated, nearly a thousand people would die or be gravely injured.

For that reason the government instead built its plans around a containment strategy. Vaccine would be stockpiled for use in case of an outbreak. If smallpox were spotted, authorities would declare a health emergency and rush to vaccinate (or quarantine) everyone likely to have crossed the virus's path. (Fortunately, the vaccine is effective even when given a few days after exposure, so in principle post-outbreak vaccination could stop the spread.) There is certainly something to be said for the containment strategy, but it is not without worrisome risks. It relies on health workers, public officials, and the public itself to react quickly, calmly, and efficiently. Virtually everyone who was exposed would need to be promptly vaccinated or quarantined. That would be easier said than done, because the early symptoms of smallpox look like flu. Moreover, once word of a smallpox outbreak hit the street, panic, chaos, flight, and human error would inevitably give the virus chances to spread. Even if a containment plan ran like clockwork, some people—those caught at the onset—would die who might have lived had they previously been vaccinated.

While I was pondering these problems, I came across a news article from October of 2000, in which a biologist named Paul W. Ewald, of Amherst College, suggested something so obvious that no one else seemed to have considered it. He proposed making the smallpox vaccine available to the public, the way many other vaccines are today. Individuals could then decide, after being apprised of the risks and with medical advice, whether or not to get themselves and their children inoculated.

Regular readers of this magazine may recall from an article in the February, 1999, issue—"A New Germ Theory," by Judith Hooper—that Ewald has specialized in thinking about how doctors can use evolutionary pressures to make pathogens more benign, and how terrorists might contrive to make pathogens deadlier. That led him to think about smallpox. I called Ewald recently and asked him to expand on the idea of voluntary vaccination.

"I think the key thing that's been missed in this analysis," he told me, "is that the more any given vaccine is used, the less bang the terrorist is going to get." Even if only a minority of the public chose vaccination, those people's immunity would not only protect them in the event of an attack but would also slow transmission to others. That could buy precious time. Moreover, if, say, 30 million people were vaccinated, there would be 30 million fewer to vaccinate in a crisis. Indeed, Ewald said, "If you have thirty million people vaccinated, the terrorists might just decide, Let's not bother." The terrorists might, of course, try something else—but pretty much anything would be better than smallpox.

"Another problem," Ewald said, "is that if you wait until the crisis is at hand, you lose a chance to have careful analysis on a patient-by-patient basis of the risks posed by vaccinating. It might just be that you're cranking out vaccinations as fast as possible." There is a deeper point here as well. People are as different in their tolerance for risk as they are in their tolerance for vaccines. To weigh the minuscule but real risk of a smallpox attack against the minuscule but real risk of complications from a vaccine is to weigh imponderables. No public-health expert is any more qualified to make this call than is the person who will have to live with the consequences.

It isn't surprising that it was a biologist who suggested letting individual people and doctors, rather than public-health authorities, decide who would be vaccinated. Biologists tend to see a world of variegated individuals, whereas the public-health establishment tends to view the public as a "population" and to think in terms of centralized, one-size-fits-all measures based on expert knowledge. A national anti-terror campaign will certainly need its share of unitary, top-down strategies on the public-health and national-defense models; but if it is to be sustainable and successful it will need to treat the public first and foremost as a resource to be enlisted, not merely as a population to be instructed. As we know from United Airlines Flight 93, engaging the intelligence and moral judgment of ordinary people can make all the difference. Why not apply that lesson to the greatest terrorist threat of all?

>For that reason the government instead built its plans around a containment strategy. Vaccine would be stockpiled for use in case of an outbreak. If smallpox were spotted, authorities would declare a health emergency and rush to vaccinate (or quarantine) everyone likely to have crossed the virus's path. (Fortunately, the vaccine is effective even when given a few days after exposure, so in principle post-outbreak vaccination could stop the spread.) There is certainly something to be said for the containment strategy...

How many people would not have AIDS today if a "containment strategy" had been used at the start of that outbreak? Why is there "...certainly something to be said for the containment strategy" regarding smallpox, but not AIDS?

Mark W.

The risk of a terrorist bio-attack using smallpox is an unknown quantity. Is there a large chance of it happening? A small chance? I feel confident in saying this: "There is at least some chance of such an event taking place."

The risk of serious side-effects of the vaccine are given at 1:300,000. That's pretty close to zero.

The odds of an attack are unknown, but conceivably way higher than 1:300,000.

I'll take my chances with the vaccine. Where do I go to get one? Who do I write my check out to?

For the record, I'd be willing to pay $100 for this shot. I'm sure it would be cheaper and I expect it to be cheaper. But my point is, if $100 was the going rate for an FDA-approved vaccine, I'd do it, for me and my wife.

How many others are there like me out there? I'll bet the number is larger than 1 in 300,000 Americans. Much larger. Maybe not willing to pay $100 (probably because they haven't taken the time to look at the photos of this disease), but willing to pay something.

Where are the entrepreneurs when we need them?

There's never a good pharmicist around when you need one!

"Indeed, Ewald said, "If you have thirty million people vaccinated, the terrorists might just decide, Let's not bother.""

This is utter B.S. Can you imagine Osama thinking this? Gee, we'll only kill five, not ten million.

The alleged threat of a relatively small amount of death or injuries from small pox is akin to Bush's latest admonitions "preparing us" for military casualties. Well, it's a war ain't it? I'm beginning to wonder whether there is a lot of truth in these "paper tiger" allegations.

What I read between the lines in this article is there is some interest, 99% sure relating to someone's pocketbook, not to immunize everyone. If it's the government, and fears of "big government" paying for the safety of the people, I recall the Constitution saying "provide for the common defense..."

>>But my point is, if $100 was the going rate for an FDA-approved vaccine, I'd do it, for me and my wife<<

Under current FDA policies, adopted in the 1990s, there will never be an "FDA approved" smallpox vaccine.

My advice? :

Take it anyway.

>Could it be that we know how smallpox is transmitted and how contagious it is to everyone while the probability of contracting AIDS if you are outside of the obvious risk categories is essentially nil?

1) Nobody knew that when the outbreak started -- in Africa AIDS apparently hits heterosexuals as well as gays. 2) A containment strategy would have protected _everyone_, even the people that you would be willing to just write off. 3) In a population of nearly 300,000,000 people, "essential nil" is not the same as zero. If a _traditional_ protection method for dealing with a disease can do better, why put up with ANY needless deaths?

Politics makes strange bedfellows. (Punny.)

Mark W.

1) Nobody knew that when the outbreak started -- in Africa AIDS apparently hits heterosexuals as well as gays.

Wrongo, the pattern of the spread was obvious at the initial detection - that's why they called it GRIDS - Gay Related Immune Deficiency Syndrome. Many facts are available on Africa; Africa is not the Western world; the proliferation of AIDS corresponds to malnutrition,ignorance, and the lack of western medical treatment; they get UN funding based on AIDS diagnoses.

But note that there is no definitive clinical definition of AIDS even in the USA. Check the CDC web site - the official diagnosis of AIDS is based on inferential analysis of other present disease(s), probable past HIV infection, and lifestyle. And that definition came from political activism not science.

2) A containment strategy would have protected _everyone_, even the people that you would be willing to just write off.

But "everyone" wasn't at risk. I would have loved to watch the liberal news broadcasts on a hypothetical Reagan-imposed public health policy of "round up the gays and heroin addicts and put them in camps". Even now, the idea makes me laugh.

3) In a population of nearly 300,000,000 people, "essential nil" is not the same as zero.

I agree. Too many such infections were either preventable (gay and hard drug lifestyle choices) or too expensive to avoid (hemophiliacs and blood-product users).

If a _traditional_ protection method for dealing with a disease can do better, why put up with ANY needless deaths?

See above. Even the government can't kidnap thousands of otherwise rational thinking people and put them in concentration camps just for their own good (even to cure them).

Johns Hopkins School of Public Health, about one in 300,000 people died from side effects of the vaccine or suffered irreversible brain damage. At that rate, if all 280 million Americans were to be vaccinated, nearly a thousand people would die or be gravely injured.

These statistics were compiled decades ago. While the new vaccine will be somewhat safer due to the use of bioreactors rather than cattle to grow the virus, there are all sorts of antiviral drugs available now to control adverse reactions that were not available in the 1960s. It may be possible to greatly reduce serious and fatal side effects.

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