The scramble for the smallpox vaccine

Barely 25 years after a public health crusade eradicated the disease, scientists are gearing up to defeat it again. But should everyone get vaccinated?

Published November 12, 2001 10:58PM (EST)

For the first time in 30 years, young Americans are again baring their arms to be pricked with the 3-inch, two-pronged smallpox needle. The needle is dipped in a vial of liquid vaccine and the dose is trapped by capillary action between the tiny prongs, which are then gently pushed, 15 times, into the upper arm.

The new Americans, mostly university students, are taking part in a study this month to determine whether the 15 million existing U.S. vaccine doses can be stretched to make as many as 150 million. It's a gloomy experiment with an outdated vaccine.

"Who would ever have thought in our lifetime we'd be working on this again?" asks Dr. Carol Tacket, who heads the Baltimore wing of the trial at the University of Maryland's Center for Vaccine Development. "The conquest of smallpox was certainly the greatest achievement of public health. And to think that we're revisiting that so soon just gives this undertone of sadness to the whole undertaking."

Dr. Mary Guinan shares that sadness. In 1974, the freshly minted doctor headed off to Uttar Pradesh, India, to fight smallpox. "It was mind-blowing," she recalls. "You'd go to these unbelievable remote places in the mountains near Nepal. It was cold. There were no maps. There were no hotels, just mud huts. Smallpox was where civilization wasn't."

Guinan was part of a historic mission -- the purposeful elimination of a disease, and a truly horrific disease at that. "The amazing thing," says Guinan, now the state medical officer for Nevada, "was that you'd look at the reports every month, and the smallpox cases were going down. Pretty amazing. The idea that by design of man you could eradicate a disease from the world -- my God, was that exciting!"

In 1977 the very last case of smallpox was reported in Somalia, which had been the final wild refuge of the virus. By "design of man," smallpox had been defeated. But now, by design of man, it may return. If it does, it will return to the metropolis, the places young idealists like Guinan, a Brooklyn, N.Y., native, left behind in their crusade. Smallpox will return to where civilization is.

Of course, smallpox isn't back -- not yet, anyway. But we're getting ready for it. An enormous amount of money will be spent to chase this specter. President Bush set aside $509 million three weeks ago. Now, Health and Human Services Secretary Tommy Thompson says it may cost $2 billion to get a new dose of smallpox vaccine for every man, woman and child in America.

But should we vaccinate every American? Clearly, the public is anxious. Sen. Arlen Specter, R-Pa., demanded at a hearing last week to know why all Americans couldn't be "given the opportunity" to vaccinate their children against smallpox. Specter wanted his four grandchildren vaccinated "as soon as possible."

Perhaps the most chilling smallpox news of the last week came from a group of Russian germ-warfare scientists, who at a news conference in Moscow urged a return to worldwide vaccination in order to protect against the virus.

"All you need is a sick fanatic to get to a populated place," said Lev Sandakhchiev, head of Vektor Institute. Of course it was Sandakhchiev and the Vektor Institute who betrayed humanity by turning smallpox into a weapon in the 1980s. Many believe out-of-work scientists have taken that weapon to "rogue" states and possibly terrorists like Osama bin Laden.

Supposedly, only two stocks of smallpox exist -- at Vektor and in Building 15 at the CDC. But "if you only believe that two labs in the world have smallpox virus," says Michael Osterholm, an epidemiologist previously known as the boy who cried wolf of bioterrorism, "you also believe in Santa Claus and the Easter Bunny."

The good news is that the public health activists who battled smallpox are in powerful positions in the U.S. public health system now. They know how horrible smallpox is, but they also know how to whip it -- at least in most conceivable circumstances. D.A. Henderson of Johns Hopkins University, recently named to head Bush's Office of Preparedness, headed the smallpox eradication campaign. (Another scientist, William Foege, was the visionary behind it. Foege later headed the CDC, and most recently he was responsible for the Gates Foundation's $1 billion investment in global vaccine development and distribution.) Another veteran of the subcontinent smallpox campaign, Jeffrey Koplan, is the current CDC director. Another, Walter Orenstein, heads the CDC's immunization program.

And these veterans know that one key lesson from the smallpox era is: Don't vaccinate indiscriminately. Most experts think even a terrorist's smallpox attack could be contained by quarantining the sick and vaccinating those likely to be exposed to the virus. Very few of them are recommending a mass vaccination program -- yet.

The last great smallpox scare in America took place in 1947. A businessman named Eugene Le Bar contracted smallpox in Mexico City, then got on a bus that meandered across the continent toward Maine. On March 1 Le Bar and his wife left the bus in New York and checked into a Midtown hotel when he began to feel ill. The Le Bars strolled along Fifth Avenue shopping, but on March 5 Eugene checked himself into a hospital, where he died five days later with hemorrhaging lungs. It wasn't until March 28, when two other patients at the hospital were diagnosed with smallpox, that the city realized it had an outbreak on its hands.

But there were bigger stories in 1947: the partition of India, starving Germans, Yugoslavia making claims on Austrian territory. Deadly infectious diseases were still commonplace, and the smallpox outbreak didn't make the front page of the New York Times for a week. New Yorkers, fresh from wartime mobilization, calmly lined up and got their shots. In two weeks more than 5 million people were vaccinated. The mayor got vaccinated. President Truman also joined what the newspapers called "the Order of the Itching Arm."

Although the global campaign to eradicate smallpox didn't begin until the 1960s, in most of the U.S. and Europe vaccination had been mandatory for children since at least the early part of the 20th century, so the disease had become more and more unusual here. By the 1930s, most U.S. outbreaks resulted from imported cases -- as in the New York outbreak.

When the outbreak was officially declared over on May 3, smallpox had killed only one person besides Le Bar, while sickening about a dozen. But the smallpox vaccine had killed at least seven people, and caused brain damage to several others. Nobody complained. Those were the costs of defeating a grave enemy.

But in retrospect, 5 million smallpox pricks were probably overkill. And today, the vaccine isn't much safer. Then, as now, it contained vaccinia, a live, essentially man-made virus, which tricks the immune system to defend against smallpox. It's cleaner than the 1947 version, but both consist of vaccinia incubated in calf bellies. This is the same vaccine many of us got as children. But even then 20 people a year died from it; now, the great number of AIDS and cancer chemotherapy patients, whose compromised immune systems make them vulnerable to such a virus, mean it could be deadlier still.

It wasn't many years after the New York epidemic that scientists realized there were ways to combat smallpox, which was no longer an endemic disease in the U.S., without subjecting entire cities to a relatively dangerous vaccine.

In 1966, former CDC head William Foege, then a Lutheran medical missionary, was running out of smallpox vaccine during a campaign in eastern Nigeria when he heard of a case of smallpox in a nearby village. To conserve vaccine, Foege had runners go from village to village, looking for other sick people. This method of intensive surveillance and eradication became the model for global smallpox eradication. In Bangladesh, for example, 10,000 health workers were hired for nine days in 1974 to visit all 15 million households in the country. Any smallpox cases were quarantined, with armed guards, and their contacts carefully tracked and vaccinated.

"Working hard, smart and focused is the way it worked before," says Joel Breman, who worked in the eradication campaign most of the years 1967 to 1980. Breman, a National Institutes of Health scientist, currently is consulting with international agencies on smallpox. "We go with what we know."

It's interesting how many of the public health administrators of today were yesterday's shaggy idealists -- the "shoe-leather epidemiologists" Berton Roueché glorified in a series of articles in the New Yorker in the 1950s through '70s. Some of the smallpox volunteers, such as Donald Francis, now president of Vaxgen, which is testing the world's first major AIDS vaccine, were just trying to beat the draft. Mary Guinan recalls, "I was the only woman physician in my class at Hopkins. I wasn't eligible for the draft, so I knew someone was going to Vietnam because I took the job."

From the Bronx and Los Angeles and Chicago, they set off to the dustiest corners of the world, Pakistan and Somalia, Nigeria and Upper Volta. They worked with Frenchmen and Italians and Russians and, of course, the locals, who had seen smallpox ravage their towns and villages, killing thousands and leaving others so scarred that their lives were ruined.

"A colleague of mine, Kamrul Huda, died on the way to investigate one outbreak," recalled Stan Foster, who headed the eradication efforts in Bangladesh. "He said he worked on the campaign because he knew that young girls, if they got smallpox, would be cast out. I called him on Sunday night and he was on his way to an island. He drowned the next day.

"For me, the lesson of this campaign," says Foster, now a professor at Emory University's Rollins School of Public Health, in Atlanta, "was that every person in the world really does matter. And we'd have a lot fewer problems if we only accepted that."

Today, most of them advise against mass smallpox vaccination, for now. "I think it would not be justified to vaccinate the general public, but that would have to be revisited quickly if there was a terror episode," says Mt. Sinai Hospital's Philip Landrigan, a leading expert on chemical health hazards who did smallpox tours of duty in Nigeria and El Salvador during the 1970s.

"I think how the public will deal with the vaccine's dangers is very much an issue of how it's presented to them. If it's presented rationally by leaders who say, 'We want everyone to understand there's going to be some illness and maybe even death [due to the vaccine] but in the scale of things it's better than thousands of deaths due to smallpox.' I think people will accept that."

The atmosphere of the smallpox-vaccine trials, in Rochester, N.Y., Houston, St. Louis and Baltimore, is a long way from Uttar Pradesh and Bangladesh. But there's an echo of the same idealism. The trials seek volunteers between 18 and 32 -- no longer children, but too young to have been vaccinated before smallpox immunizations stopped in the early 1970s.

Kati Tusinski, a 24-year-old master's candidate in communications at St. Louis University, who got the vaccine last Tuesday, called it "my way of contributing to the critical situation that society's faced with right now. Hopefully my participation will help other people in the future."

When she joined the study, Tusinski agreed to visit the clinic every three to five days to see whether the injection site was turning pustulent the way it should if she gets a "take" -- an immune response showing protection against smallpox. If everything goes well, she'll have a scab before Thanksgiving.

Tacket has tried to recruit Baltimore firemen and police, knowing they feel a strong need to get involved in the nation's defense. Meanwhile, the trial centers have been flooded with hundreds of calls from panicky adults seeking vaccine.

One was a woman who works in the Senate's Hart Building. "She's got her 60 days of Cipro and now she wants to be vaccinated against anthrax and smallpox," said Kathleen Palmer, the chief nurse in the Baltimore study. "But we can't guarantee people in the trial that they'll be protected."

The three arms of the trial include a normal dose, a one-fifth dilution and a one-tenth dilution. Neither the patient nor medical staff will know who got what until the trial is over.

In Carson City, Nev., Mary Guinan also gets calls every day from people who want smallpox vaccine. Back in India, she got immunized probably 100 times. She'd ask the paramedic to prick her with the needle in front of the villagers, to prove to them the stuff was safe. "We were using the Russian vaccine, which was really concentrated," she says. "But I never gave it a second thought."

Guinan shudders at the idea that scientists themselves may be responsible for unleashing smallpox on the world again. If the disease indeed reemerges, some will want to see Lev Sandakhchiev and his colleagues at the Vektor Institute be tried as war criminals.

"It would just be the ultimate crime against humanity, It would be mass murder, just the antithesis of what we do with science," says Guinan.

By Arthur Allen

Arthur Allen writes on health, science and other issues for Salon and Kaiser Health News. He lives in Washington.

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