Arthur Allen

During the Vietnam War, in response to the more than 100,000 cases of malaria recorded among American troops, the United States invested significant funds for development of antimalarial drugs. In the decades since then, however, malaria research has been a disheartening, underfunded field — despite the fact that the parasite is the No. 1 killer of children in Africa, claiming more than 1 million victims a year, and causes illness in 400 million people annually worldwide.

Once the U.S. military managed to control the disease among its troops, the failure of a United Nations-backed global antimalarial campaign around the same time — stymied by stubborn mosquitoes and parasites and a lack of resources — caused a decline in Western interest in the disease. U.S. and European governments spent less than $50 million annually on malaria research while drug-resistant strains of malaria proliferated in Africa.

Poverty and disorganization have frustrated African efforts to control malaria’s spread with low-tech means — such as spreading oil on stagnant ponds where mosquitoes breed and distributing window screens and bed nets. And until recently, few pharmaceutical companies had shown much interest in what may be the most promising solution — a vaccine.

As it happens, though, Rabinovich may be a harbinger of a change in that picture. She was a prominent public health official at the National Institute of Allergy and Infectious Diseases before being named in December 1999 to head the private malaria initiative, part of a $1 billion philanthropic investment by the Gates Foundation for development of vaccines for the Third World. Her group plans to create partnerships with universities and private companies that commit to creating a malaria vaccine.

The Gates Foundation’s spending on malaria follows upon big investments over the past few years by the National Institutes of Health, the World Health Organization and Britain’s Wellcome Fund, with total spending from all sources totaling $100 million or more. What’s more, the World Bank has pledged up to $500 million in interest-free loans to African countries for malaria prevention and control. And the lame-duck Congress could add to its appropriations a $1 billion tax credit program — pushed by the Clinton administration and based on a proposal by Harvard professors Jeffrey Sachs and Michael Kremer — to encourage spending on malaria research by the pharmaceutical industry.

Money has begun flowing into this fight for two reasons. Public health officials are worried about drug-resistant strains of the parasite that are on the rise around the world, and they are encouraged by the emergence of several promising antimalarial vaccines, which need big cash infusions to move forward.

But when both houses of Congress approved a $50 million U.S. Agency for International Development program to combat malaria on Oct. 26, another factor was at play: the self-interested inclination to do something about malaria before global climate change brings a “third-world disease” to our doorstep.

“As we know from our experience with the West Nile virus,” said Rep. Barbara Lee, D-Calif., during floor debate on the bill, “if we do not act quickly to break the back of a disease abroad, the inevitable result is outbreaks of the disease here in the United States.”

Global climate change does seem to be bringing more mosquito-borne diseases to this country. Scientists speculate that an errant mosquito that somehow traveled to the United States in the belly of a plane may have caused New York’s 1999 outbreak of the occasionally deadly West Nile virus. By this fall the germ — which spreads from mammals and birds to mosquitoes and back again — had established itself all along the East Coast, prompting spraying campaigns in places as far south as the Washington suburbs. Scientists believe that the West Nile virus is here to stay, and will probably spread across the entire country within a few years.

Dengue fever, a dangerous mosquito-borne viral disease that causes joint pain and sometimes death, has dramatically increased along the U.S. side of the Mexican border in the past few years, according to research presented at a conference in Houston in November. As in the case of West Nile, dengue-carrying mosquitoes may be hitching rides across the border in tractor-trailers brought north by increased trade, with warmer temperatures allowing the virus to gain a foothold.

Malaria thrives in hot temperatures, which enable the plasmodium parasite that causes the disease to mature more quickly in the bodies of the mosquitoes that carry it. Paul Epstein, a Harvard Medical School tropical disease specialist, has presented computer models suggesting that malaria, endemic in areas of the world where 45 percent of the population lives, could affect 60 percent of the world’s population by 2100 if warming trends continue.

In the 19th century, wealthy Washingtonians sent their children to cooler climes in the summer and British diplomats living in the city got hardship pay for their posting in the federal district’s malarial sump. But many malaria experts are skeptical that the disease could become endemic in America again. Lifestyle changes and aggressive anti-mosquito campaigns were what rid Europe and North America of the disease, they point out, not the fact that the regions were cold.

“Yes, malaria could return to these regions,” says Jo Lines, a malaria researcher in Britain, “but only if we go back to living together in unglazed houses with our animals.”

Still, the return of endemic malaria in the United States is not out of the question. “If warming brought in populations of mosquitoes that are more efficient vectors than the ones we have now, it could happen,” says Ripley Ballou, who led malaria vaccine research at the Walter Reed Army Institute of Research for 17 years.

In the 1930s, Anopheles gambiae mosquitoes, deadly efficient malaria carriers, were brought from Africa to Brazil by accident and caused major outbreaks before aggressive spraying campaigns subdued the invaders. The Anopheles strains of mosquitoes in this country aren’t nearly as effective as Anopheles gambiae at transmitting the disease — which may be why the United States, despite frequent cases of imported malaria such as Rabinovich’s, hasn’t experienced large outbreaks.

“We don’t have gambiae in North America, but if they moved in because of global warming, even a small population of [these] infected mosquitoes could cause a lot more disease,” Ballou says.

Still, researchers like Ballou, who retired from the military last year and now consults part time for Rabinovich’s initiative, view the threat of malaria in the United States as a narrow basis for attracting funding for their work. “If we start seeing more cases of malaria in New York City and along the population centers around the country — which is certainly possible — there will certainly be more resources put on this,” says Ballou. “But I don’t see that as a very good way of moving the emphasis along.”

Rabinovich agrees. Seeking increased funding based on fear would be a short-lived effort, she says, because she doubts malaria will become a chronic U.S. problem. “I’m hoping for more of a perspective that we’re a global community and this is an infectious disease affecting the world, and the U.S. should have a role,” she says. “That’s more sustainable.”

Whatever motivates funding for malaria research, there are some encouraging signs in a field with vexing difficulties. It has been tough to develop a malaria vaccine because the parasite that causes the worst symptoms, Plasmodium falciparum, has evolved a remarkable capacity to thrive in our bodies. Falciparum, the dominant strain in Africa, lives out four life stages in humans, and it tends to colonize cells in a way that protects it from a person’s immune system.

Last year, for the first time, an experimental malaria vaccine successfully protected a large group of people. The trial of 306 adults was conducted in Gambia by researchers from Walter Reed; Smith Kline Beecham Biologicals (SB Bio), a Belgian subsidiary of the pharmaceutical giant; and the British Medical Research Council. The vaccinated group had 71 percent fewer episodes of malaria than the controls — although the protection lasted only two months.

Rabinovich, whose initiative is likely to help fund further trials of this and related vaccines, was accompanying SB Bio officials on a visit to the Gambian villages that took part in the trial when she got her nasty bite.

The Gambia vaccine, known as RTS,S, marshals an immune response against malarial sporozoites, the spindly forms of the parasite that the mosquito injects into the body and that quickly swim through the bloodstream to lodge in the liver. Scientists at Walter Reed are working to incorporate another component into the vaccine so it can attack the next stage in the parasite’s life cycle — the seedlike merozoites, which propagate from the mature sporozoite and burst out of the liver into the bloodstream by the tens of thousands, colonizing and destroying an infected person’s red blood cells.

One particularly awful aspect of malaria is that for reasons that aren’t entirely understood, humans don’t develop immunity to the disease after getting it once. “What really hits you,” says Rabinovich (who during an interview in her office is wearing a sweat suit against recurring malarial chills despite Washington’s October heat), “is that, OK, I’ve been through this. I’ve seen the millions of antigens multiplying in my blood, and yet the next time I go back to Africa I could get just as sick.”

No malaria vaccine is likely to be as effective as, say, the measles vaccine. But in the Third World, where the parasite’s resistance to common, inexpensive antimalarial drugs is growing and expensive drugs just aren’t an option, a vaccine may be the best hope, as in the case of AIDS.

It would be easy to blame the drug industry for failing to develop a malaria vaccine until now. But malaria researchers make it clear that some major technical hurdles had to be crossed before sinking big bucks into a vaccine made sense.

In the United States, the only sustained, well-funded malarial vaccine work in the past few decades has been done by the military, at Walter Reed or at the Naval Medical Research Center in nearby Silver Spring, Md.

Key breakthroughs began in 1979, when scientists discovered that the sporozoite proteins could be targeted with a vaccine. From about 1986 to 1995, Walter Reed and the Navy tested nearly two dozen vaccine formulations. They all flopped.

Usually, the drill went like this: Scientists developed a new vaccine; scientists tested the vaccine on animals for safety; then the lead scientist and lab partners rolled up their sleeves, got a shot and exposed themselves to malarial mosquitoes.

Next, everyone came down with malaria.

While recovering from the disease — whose symptoms can easily be controlled if treated quickly enough — the scientists often learned that the company working with them on the vaccine had decided to end the partnership.

“The term ‘rolling up your sleeves’ has a particular connotation when it comes to malaria research,” says Ballou. He got a malarial bite in 1987 while testing a failed, early-generation vaccine. Gray Heppner, now head of immunology at Walter Reed, got malaria in 1993 while testing an updated version. “That vaccine was safe, well-tolerated and completely without effect,” Heppner says with a laugh. “There were 17 of us — controls [who also exposed themselves to mosquito bites] and vaccinees — and we all got malaria.”

Companies typically worked with Walter Reed to the point of testing a vaccine on a few people. “If it didn’t show results, they bailed,” says Heppner. “Things were tough. An awful lot of people said it’s not possible to make a malaria vaccine.”

To this day, SB Bio is the only division of a major pharmaceutical company that has shown a long-term commitment to working on a malaria vaccine. A side benefit for SB Bio has been that its malaria research enabled it to test vaccine technologies with applications for other, more salable vaccines.

The military’s malaria vaccine research has trundled along for years as “a flea on the back of military R&D,” says Ballou. Funding for the labs was hurt some by downsizing of the military and, Ballou adds, “we didn’t have a deployment where we had a lot of people getting malaria, to the point where some general hollers, ‘Where’s my vaccine!’” Most of the malaria drugs on the market, Ballou points out, were developed as a result of a huge drug-screening program the military funded in response to the devastating effects of malaria on U.S. troops in Vietnam.

The hope now is that private initiatives like the Gates fund — with federal support — can sink enough money into partnerships with researchers to lower the financial risk for the pharmaceutical companies that ultimately will have to manufacture the vaccine.

Rabinovich and other experts say that an effective, widely available vaccine is probably still at least 10 years off. In the meantime, they continue to risk their health in the hopes of saving babies. Rabinovich sometimes wears a pin with three children on it — the number of African children who die each minute of malaria.

One night during her visit to Gambia, Rabinovich attended a celebration of the vaccine trial. Villagers performed humorous skits about the painful shots and the misery of malaria. “As dusk came down we were passing bug spray back and forth and surreptitiously rubbing it on ourselves, because you could tell what was around,” she says.

For the scientists lathering themselves with protective bug juice, it was sobering to watch the children, who had no protection at all. “The village kids,” Rabinovich recalls, “were all just running around.”

We spoke with Holland last week, ahead of the Oscar nominations, in Washington, D.C., where “In Darkness” was screened at the U.S. Holocaust Museum.

Many of us approach the Holocaust with a mixture of horror and wonder, it’s so inexplicable. Do you keep returning to it in film because it’s unsolvable, or because you’re trying to understand something about it?

About the Holocaust, no. About human nature, yes. In these borderline experiences of humanity you see suddenly how fragile and how strong and how miserable human nature is. Sometimes you have little sparks of greatness — but you can’t really count on them.

Your father was a Jew in the Warsaw ghetto, your mother a gentile who helped Jews as a girl. It’s a personal story for you, but you weren’t there. Do you view the Holocaust in a different way than, say, an American of your age?

I have quite a particular connection to the Holocaust; maybe it’s a mystical thing. When I hear the stories of the Holocaust, it very rarely seems new to me — it’s as if I dreamed it already. With this script, it was as if I had dreamed it already before I read about it. [Polish filmmaker Andrzej] Wajda, my friend and mentor, lived through the Holocaust as a Polish partisan. His view of the war experience is very different from the Jewish perspective. And some Jews have been very unhappy with the vision in his wartime films (“Kanal,” “Korczak,” “Samson”). His films were accurate but they were from the perspective of young Polish underground fighters.

My perspective is closer to the perspective of the Jewish survivor in some way. When I show survivors my movies or talk about their experiences, the communication is very easy. They accept my vision and I understand very well what they went through. My mother was Polish, helping Jews as a young girl. I have those two things in myself, which sometimes is very uncomfortable but at the same time gives me a more objective view. And I don’t feel any guilt.

Why did you insist that “In Darkness” be in the original languages? Does the cacophony of different languages –  where the Jews are divided among those speaking Yiddish and German, the Poles speak dialect – telling you something about a vanished world?

Right. Especially I wanted the use of Yiddish and Balak (the working-class dialect of the city of Lwow, now Lviv) to reflect that diversity. Some of the characters – Socha and his partner Szczepek, and Socha’s wife and daughter – speak Lwow dialect.

What’s different about that dialect, to a Polish ear? And how hard is it to find people who still use it?

It has many differences from the classical Polish in terms of the accent and vocabulary. It was spoken by the lower classes, sort of what Cockney, or northern dialect is to English; it became the language of comedies and songs and cabaret before the war. There was a famous 1930s Lwow radio program by two guys, Szczepko and Tonko – a Jew and a Pole — they also did several movies.

Balak has different connotations to a Polish speaker. It tells you something about class, about time and place. It has some Ukrainian in it, some Czech and German and Hungarian and Yiddish. This was Galicia, once part of the Austro-Hungarian empire, and the influences were very mixed. The language only exists today in these recordings and movies. No one speaks it anymore; it died with the generation that grew up in the war. After World War II, the Polish people left Lwow [Stalin expelled them] and it became part of the Soviet Ukraine. Today Polish people don’t understand Balak, even half of it. I had to subtitle the dialogues in Polish.

We found one person who was a really good coach, a specialist in this dialect. He made recordings for the actors, and they watched the old movies. They had to do their homework, and with the Yiddish as well. Many of the Jewish characters speak German — many Lwow Jews of this generation attended university in Lwow or Vienna or Berlin, and the upper class spoke correct literary German. And the mixture of Ukrainian and Polish was a kind of lingua franca in Lwow.

It was a pleasure to try to re-create this environment. For Americans it doesn’t make so much difference, but for Polish audiences this has been one of the great attractions of the film. People say it’s fantastic to hear all of those languages again. The richness of these languages that reminds them of how it was.

Does the city of Lwow mean anything special to you?

I come from central Poland, from Warsaw. But Lwow for many people in Poland is like the lost Arcadia. Their attachment to the city was very strong. Even in the second and third generation if someone is from Lwow he feels he’s from this special place that was taken away from us. It has this nostalgic and mythological quality. When I read the story I thought it would be great to try to create a taste of Lwow, even without showing the city — to show its spirit. We wanted to film in Lviv, but it was more expensive than Poland, and besides we had to spend our money in the places that gave us subsidies. I planned to go there for two or three days at the end, but we ran out of money.

There’s a scene where Socha, the hero, says to Mr. Chiger, “Here you are bargaining for your life. Always a Jew.” Someone might call that anti-Semitic. But Jews in places like Lwow were traders, hagglers, so in a sense, it’s a completely natural statement.

Stereotypes are always based on realities. Polish peasants learned the expression, “Give a Jew your finger, he’ll take your entire hand.” If you ask the same peasant if he hated Jews, he’d say, “No, not at all.” But of course it’s very dangerous, because in situations like this it had consequences. The Germans used those stereotypes to reinforce the feeling that Jews were not human. Stereotypes are dangerous. But that is how they existed.

The Jews in the film regard the Poles as a constant danger. And they despise Socha, the “dumb Polak.” The mistrust was reciprocal. It wasn’t something that would have spread to genocide. Of course there were pogroms against Polish Jews before the wars. But it’s same thing in the former Yugoslavia; people live together for centuries, nothing major is wrong. Suddenly one little match and everything is on fire.

At the end, Socha shouts, “Look, my Jews!” This is embarrassing and yet he’s right, in a sense.

It’s a little pathetic but poignant. The audience is laughing and at the same time crying.

The film has done very well in Poland. What do Poles of our generation or younger take from a film like this compared to Americans?

They’ve been surprisingly responsive. They take its human dimension very strongly. I think the depictions are easier to accept than to show all the Jews as angelic and the Poles as petty criminals and murderers, or as heroes, any kind of stereotypical presentation. We tried to make the film as subjective as possible. And young people love it for this reason. Audiences feel they can identify with it, with the people on both sides.

Are there any characters in “The Wire” who remind you of Polish characters you’ve worked with?

No, but I love all the characters. Bunk and McNulty, Omar of course. .. I liked Snoop, this girl. She was real – a real criminal who’d spent years in prison. It was some kind of redemption for her to be in the series. But she recently was arrested again.

I’m amazed you can go between these two worlds. Did you feel like a stranger when you were filming “The Wire“?

No, not after a while. The world of fiction is my natural world. It can be Victorian England, it can be Baltimore of today , it can be the Second World War. Of course, some settings are closer to my interest and sensitivities, and sometimes the real, you know, stories are more exciting than fantasy. I never wanted to do fantasy or science fiction. I went to New Orleans and shot “‘Treme” and after a few days I felt so close to that story. It’s very rewarding; it makes your life richer.

Nature, in all its whimsy, has thrown us a big, fat, ugly curve — a virus with a harmless background that suddenly turned lethal.

In Hong Kong this week, hundreds of contaminated people were rounded up and bused to quarantine camps. In Singapore, schools were closed and nurses were posted at the airport to ferret out sickly-looking arrivals. In Toronto, two hospitals stopped their admissions to avoid spreading the disease. And in San Jose, Calif, an American Airlines flight from Tokyo was held on the ground until five crew members and passengers reporting SARS symptoms could be removed to a hospital and everyone else on the plane could be briefed about how to monitor themselves for signs of the illness. Those hospitalized were later declared disease-free. But clearly the newly identified disease is raising the public’s anxiety level.

One virologist, who wished to remain anonymous, described the potential, in a worst-case scenario, for “total panic.”

Researchers scrambling to identify the cause of SARS believe it may result from the genetic mixture of two strains of a previously innocuous organism called the coronavirus, or possibly of a coronavirus and another bug. This chance recombination might have occurred inside a mouse, a chicken or a pig before the virus jumped to humans.

Human coronavirus infections — responsible for about a quarter of all common colds — are usually so mild that no one has ever tried to make a vaccine to prevent them or a drug to treat them. That’s no one’s fault, considering the seemingly limited threat posed by the infections, but it puts the world at a disadvantage. While intensive care can keep most SARS patients alive, there are no drugs designed to combat the infection.

“In terms of antivirals and vaccines, we are way behind,” says Ken McIntosh, a Harvard microbiologist who helped discover coronaviruses back in 1965. Like other virologists, he is not necessarily surprised by the evidence that this virus family has given birth to a killer; coronaviruses mutate easily, and are notoriously free and easy with their genetic material.

“I always thought something like this would happen. It was just a matter of time,” says Pierre Talbot, a coronavirus expert and chief of the Armand-Frappier Institute, a public health research center at University of Quebec.

But hypotheticals do not translate into research grants, and Talbot’s lab is one of only a handful in the world working with coronavirus. “It’s not HIV,” he says. “It’s not a very popular field.”

“No one thought [coronaviruses] were very important,” adds Stan Perlman, a virologist at the University of Iowa.

Until now, of course.

So far, SARS has infected more than 1,800 people in 13 countries, killing 62 of them, in the past few months. Most of the infections have hit middle-aged to elderly people, though in one reported case, the virus was identified in a 1-year-old child adopted from China and brought to Massachusetts. The initial symptoms — fever, chills, dry cough — are like common upper respiratory ailments, but this bug is capable of overwhelming the immune system. About 10 percent of SARS infections lead to severe breathlessness, oxygen depletion and organ failure, and about a third of the severe cases die — particularly old patients and those with existing medical problems.

Up to now, SARS has had a fatality rate of about 3.5 percent. If that sounds mild compared, say, to the virus that causes AIDS, consider this: The pandemic flu of 1918 killed “only” about 2.5 percent of those whom it infected. That amounted to 50 million people worldwide.

SARS is not the first scary microbe to emerge in the era of globalization, but it could be the one most likely to spread. Ebola killed its hosts too quickly to get out of Africa. Hantavirus and Nipah, which hopped from mice and bats, respectively, were plenty deadly, but did not spread person to person. Only mosquitoes (and blood transfusions, it turns out) transmit West Nile. The difference with SARS is that you can get it from someone coughing in your elevator.

Public health officials are still a bit uncertain as to just how contagious SARS is. Most cases seem to spread to close relatives or healthcare workers heavily exposed to virus-containing droplets from coughing and bodily fluids. But there have been a few breakout cases — spread on hotel floors, airplanes and apartment buildings, for example — that don’t fit the pattern.

There appears to be a subset of “superinfectors” whose coughs produce aerosolized viral balloons that can float in the air for hours. Using the example of one Hong Kong apartment complex where more than 200 people were infected with the disease, World Health Organization officials speculated — without offering any evidence — that the virus occasionally spread through sewage.

The appearance of a highly contagious coronavirus would not surprise Pierre Talbot. In research conducted at a neonatal clinic in Brittany, Talbot found traces of one human coronavirus on aluminum table tops and sterile latex gloves up to three hours after patients left a room. “It survives in the environment quite easily,” he says. “People are going to have to be very prudent with this virus.”

Added Larry Anderson, who is running the CDC lab investigation of SARS, “This is the first new virus infection associated with such serious disease which is transmitted, we suspect, by respiratory droplets. I think it will be difficult to control the spread of SARS.”

Even though SARS, a virus thought to have been brewed in nature’s cauldron on a farm in southern China, has the potential to create global panic, it is possible that the epidemic could burn out in a month and never seriously threaten us again. Viruses sometimes pass through a few hosts, mutate and lose their juice, notes Kathryn Holmes, a coronavirus expert at the University of Colorado. “If it’s new to the human population,” she says, “it’s impossible to predict.”

Up to now, U.S. authorities have been effective and probably fortunate in controlling the spread of SARS. Except for a handful of close relatives and health workers, the 69 known suspected SARS patients here were all sickened in Asia. By keeping them off the streets, U.S. officials have prevented community outbreaks so far. The same is largely true of Vietnam and Singapore.

But that is not the case in Hong Kong, where officials have dusted off a colonial-era law to place as many as 1,000 people in two vacation camps requisitioned for quarantine. About 240 residents of the Amoy Gardens Apartment were being moved to the camps Tuesday night. Their 33-story building was sealed off to keep them from spreading the infection, which has killed 16 people in Hong Kong, but hundreds managed to flee the building when they heard about the impending quarantine. The handling of the Amoy outbreak, and the rapid spread of the disease in Hong Kong, has led to criticism of that government’s handling of the epidemic.

In Canada, with over 100 suspected cases, the fear is palpable. “This is a big deal,” says Donald Low, chief of microbiology at Toronto’s Mount Sinai Hospital. “It’s not just an Ontario problem, but a Canadian problem, a North American problem.”

Meanwhile, the World Health Organization says Chinese officials haven’t allowed its investigators into Guangdong province to find clues about the disease’s origin or determine whether the epidemic is still burning there. WHO officials believe it is. Nonetheless, scientists expect to have the genetic sequence of the coronavirus in a week or so, which may help them to find drugs to treat it, and may enable them to figure out where it came from.

In the past, virulent new flu strains have arisen in Southern China. It seems to be particularly good at breeding new viruses, possibly because peasants there live close to their animals, and many shoppers choose their poultry from the cage to pluck and kill it themselves. Bedding down with swine and handling live fowl are both good ways to expose oneself to species-jumping viruses.

But just as viruses can become more lethal by jumping from host to host, they can also lose their power over time. For example, bad flu bugs rarely last more than one season.

Three decades ago, during the war in Southeast Asia, a physician named Richard Wenzel surveyed antibodies in the blood of Marine recruits training at Camp Lejeune, in North Carolina, to determine what types of germs were passed around the densely populated barracks.

In 1971, Wenzel found, more than half the recruits showed evidence of coronavirus infection. The 1970 and 1972 recruits, however, had hardly any coronavirus. For Wenzel, this suggests that perhaps “an epidemic one year doesn’t mean it’s going to be an annual event.”

But that may be wishful thinking.

With a different war being fought, this time in a country reported to have biological weapons, President Bush has asked the nation’s doctors to vaccinate up to 10 million people against smallpox, a viral disease that was eradicated 25 years ago but which “evildoers,” it is hypothesized, may possess.

Many have refused to answer the call, and this week 10 states suspended the smallpox shot because of safety concerns about it. Wenzel, now chief of internal medicine at the Medical College of Virginia Hospital in Richmond, has been among the smallpox program’s most outspoken critics.

The SARS threat, which could end up requiring considerable vigilance and resources, bears out what many state and local health officials said about the smallpox vaccine program: that it was a waste of their precious time and energy.

“I’m more worried about smallpox vaccine than I am about smallpox currently,” says Wenzel. Meanwhile, his hospital is treating its first possible SARS patient.

“That’s real,” he says. “That’s here.”

Over the past five years, more than 1,000 volunteers have come to an unheated backcountry cabin north of West Yellowstone to participate in a remarkable campaign of environmental activism. They have come to the coldest spot in the lower 48 states from places as far-flung as New Zealand and Israel and Germany to witness, and at times obstruct, the Montana Department of Livestock in its roundup and slaughter of buffalo that wander out of Yellowstone National Park.

There are reasons for the roundup. About 40 percent of the bison in Yellowstone carry antibodies to brucellosis, a bacterial disease that weakens cattle and sometimes causes them to have spontaneous abortions. In the 68th year of a brucellosis eradication campaign, the U.S. Department of Agriculture is on the verge of eliminating the disease from cows and other domesticated animals. But the bacteria live on in the wild, particularly in Yellowstone. European beef cattle originally spread the disease to elk and bison. Now, these animals threaten to return the microbial favor.

During the summer, about 2,000 head of cattle graze on the private and Forest Service lands around Yellowstone where buffalo like to wander. Morbidly afraid that their cows will be contaminated by the bison, the state Department of Livestock is spending $1.4 million this year to haze wandering buffalo back into the park, using trucks, snowmobiles, helicopters and firecrackers. When hazing fails, the livestock agents capture the buffalo and test them for brucellosis — those with positive serology are slaughtered, their meat donated to Indians in Bozeman.

Protests against the roundup began in earnest following the bitterly cold winter of 1996-97. Montana slaughtered 1,083 bison that had migrated from the Yellowstone plateau onto less snowy lands outside the park. Another 800 — out of a total herd of perhaps 3,500 — died of starvation.

Mike Mease, a self-described “undercover journalist” who had produced CopWatch-like documentaries for Indian tribes and environmental activists, was so incensed by the slaughter that he and Rosalie Little Thunder, a Dakota activist, set up the Buffalo Field Campaign to try to stop it. The following year, Mease and his volunteers started filming every step of the operation.

“I learned a quick lesson: I could be out there with a video camera and they would not kill the herd,” says Mease, 40, who is your basic blue-eyed, shaggy-haired, Christ-lookalike Army brat. “They didn’t want it documented. Because this had been a pretty swept-under-the-rug operation.”

Mease argues that the eradication campaign is pointless. Brucellosis is essentially a form of ungulate venereal disease, spread through the reproductive tract or aborted fetuses. There haven’t been any confirmed cases of bison-to-cattle transmission, he says. And the antibody tests performed on the bison, he argues, result in false positives and unnecessary killing.

But scientists dispute Mease’s analysis of the brucellosis threat, even if they don’t necessarily support the slaughter.

“Our work has shown that the bison are truly infected and we’ve shown that the organism is the same one that can infect cattle,” says Thomas J. Roffe, the wildlife veterinarian in charge of the U.S. Geological Survey’s brucellosis research program, based in Bozeman. “Of course, until you see a cow walk up to a bison abortion, lick it and then abort herself, you’re never going to have proof that it occurs.”

The buffalo campaign, offbeat as it is, has the support of many people living in the area west of the park. Increasingly, these are not cattle ranchers but transplanted suburbanites in expensive new housing developments. Mease’s minions offer a free removal service for bison that trample gardens or wreck fences. With the property issue taken care of, many of the transplants actually enjoy having these charismatic megafauna in their midst.

There is no danger that the anti-brucellosis campaign will drive bison to extinction; the Yellowstone herd has already grown back near its 1996 level. Buffalo conservation is in fashion, actually, throughout the West, where the population of bison (the American variety of the buffalo) has increased at a 14 percent annual rate in the past decade.

Still, there is something symbolically appalling about killing buffalo. Perhaps it is the manner in which the animals dumbly accept a bullet to the brain. Or, more likely, the dithering thump of a 2,000-pound beast hitting the ground faintly echoes the 19th century slaughter of 60 million of the beasts, an essential element of the drive to deracinate the Indians and repopulate the Plains with cattle-raising Protestants. Bison bison, hump-shouldered survivor of those campaigns, is the iconic trapezium of the American West. His brown eyes are beady, suspicious and unvanquished. The horns and dark wooly mane are so familiar they could almost be costumes.

“They represent wildness,” says Summer Nelson, a veteran activist in the Buffalo Field Campaign. “They are connected with so much — with the history of public lands, the native wildlife and people and our lack of respect for the land.”

The campaigners wax misty about the animals, often describing them in human terms. Mease tells a story about a male buffalo, nicknamed Houdini because of his ability to escape capture, who one day led 13 other bulls around the livestock agents. “Later that day,” says Mease, “11 of the bulls walked to within 20 feet of us, stopped and nodded and thanked us for letting them know that the DOL was in town.”

The bison understand that Mease is helping them?

“Oh, without a doubt. Every single day they’re out of the park we’re with them,” he says. “We’ve been known to shepherd them to safe areas.”

When federal and state officials try to influence the animals’ movement — sometimes by flying helicopters low and slow behind them — it is called hazing. When Mease and his merry band do it, they call it shepherding.

In a larger sense, both activities — the culling of infected animals, and the protection of the animals by radical environmentalists — are forms of wildlife management, the somewhat oxymoronic activity that is as old as Yellowstone — which became the first national park in 1872.

As the largest national park in the continental U.S., Yellowstone can be a very wild place. It has thousands of virtually unvisited acres, and an intact ecosystem with large mammals at the top of the food chain. But, historically at least, much of this food chain has been managed by humans in one way or another.

Elk, grizzly bears and wolves, once hunted nearly to extinction, were reintroduced to the park by rangers and now thrive there. The “wild” bison are descendants of the 23 wild stragglers and 21 imports that were herded together in the park’s Lamar Valley starting in 1907 — in response to one of President Theodore Roosevelt’s pangs of guilt about the dismemberment of the West.

History would seem to undermine absolutist philosophies of nature in Yellowstone. Yet something about the place invites absolutes, even demands them — the grandeur of the mountains, the vast meadows and waterfalls and incredible, almost surrealistic geysers, the psychedelic blue hot pots. To quote Edward Abbey, patron saint of the Green paganism, “An increasingly pagan and hedonistic people (thank God!), we are learning finally that the forests and mountains and desert canyons are holier than our churches.”

One week this winter, 35 people were living in the cabin or in one of four teepees set up around it on a pine-forested hillside above Hebgen Lake. Three stunning mountain ranges surround the lake, with Yellowstone on a plateau to the west. There is plenty of room for sleeping bags in the loft above the main room of the cabin and Seeds for Peace, a nonprofit catering group, does all the (vegetarian) cooking. At night there’s a big communal meeting for people to bitch and posture and plan the next day’s activities.

For an environmentalist looking for action, this is something of a dream gig. Yellowstone, with its furry and sacred icons, is the perfect animistic shrine — definitely a better work environment than a Superfund site in New Jersey.

Each day, at least a couple of two-member patrols cover each of three checkpoints to watch for bison on the move, or Montana Department of Livestock agents on the move against the bison. They travel by car and cross-country skis. Every patrol carries an FM radio for communication and a video camera to record whatever happens.

A lot of times, nothing much happens at all. Other times, the buffalo resist the loving embrace of the field campaign. “In 1999 we had round-the-clock patrols to keep the buffalo from leaving the park,” recalled Dan Brister, 32, who spends his winters in the cabin and lives the rest of the year in Missoula, where he’s a graduate student in environmental studies at the University of Montana. “It was very hard to do because the animals were hungry and you felt like you were starving them to death. But if they left they’d just head into the trap for the hay, and get slaughtered. Sometimes we’d give them a little shove.”

The “little shove” meant walking to within 50 yards of the bison and clapping, usually enough to cause a retreat. Sometimes, though, the animals wouldn’t budge. “When the buffalo’s tail goes up in the air it means they are going to charge or discharge. So if they don’t poop it shows they are pretty agitated and it’s probably a good idea to get out of their way,” says Brister.

Other dangers lurk as well. In 1999, Brister, Mease and two other activists were arrested when they tried to keep livestock agents from capturing two buffalo. The buffalo, trapped on a road between the activists and the agents, bolted up 12-foot-high snow berms on either side.

Brister was charged with negligent endangerment for “trying to cause death or serious injury to a state official by hazing a buffalo at him.” The group’s video footage absolved him of the charge, which was dropped.

Mease believes that the Yellowstone bison have “pure genetic links” to the Indian days. But this eugenic romanticism is based, like most of Yellowstone lore and the rest of our beliefs about nature, on a human construct.

“What is unique about YNP bison? You tell me,” says Roffe. “If you go to the National Bison Range [a federal preserve in Moiese, Mont.], you can’t tell the difference between those animals and the Yellowstone bison. But every year they round them up, give them blood tests and cull them. They are handled differently from the Yellowstone herd. Does that make them less valuable? There’s nothing about wildlife management that isn’t colored by our own perspectives.”

The perspective of the Buffalo Field Campaign is colored by environmental concerns, but also by youthful enthusiasm and romance. Unlike the more ephemeral or relentlessly frustrating battles in the defense of nature, this one is a ground war with discernible, if debatable, results.

“It’s a lot better now than it was when they were shooting every buffalo that came out of the park,” says Brister. Better for Brister, definitely. Better for the buffalo? As a symbol, certainly. For the animals themselves? We may never know.

That’s deep stuff for a panel charged with telling Bush how to think. The stuff got even deeper Friday, when the government unveiled the man selected to serve at Kass’ side as executive director of the President’s Council on Bioethics.

Kass is no ayatollah — he’s generally considered to be an open-minded academic — but his newly appointed right hand, Dean Clancy, can come off like a mini-mullah. The 37-year-old Republican, a senior staffer for Republican Majority Leader Dick Armey since 1993, is passionately opposed to abortion, public schools, federal taxes and Democrats. As a Georgetown student in the 1980s, he once made an impression by tearing up his libertarian roommates’ porno films with his bare hands.

Prior to working for Armey, Clancy was a speechwriter for Dan Quayle and Jack Kemp. His writing tends to reflect a fanatical verve. In a 1998 letter to a right-wing magazine called the Journal of American Citizenship Policy Review, for example, Clancy attacked Steve Forbes’ tax reform plans as namby-pamby, raged against Teddy Roosevelt and called for the repeal of the 16th and 17th amendments, which establish federal taxes and the directly elected Senate.

The federal tax, Clancy fulminated, “bribes the states with their own citizens’ money, shackles them with intolerable mandates, forbids them from curbing such crimes as abortion and pornography and now threatens to nationalize health care.”

“The moral regeneration of America,” he added, “will require, ultimately, more significant reforms.”

The other 17 commission members have yet to be announced, but the appointment of Clancy as agenda-setter suggests that the new council will make a radical departure from the bioethics committees of previous administrations.

Clancy replaces Eric Meslin, a hardworking, exceedingly polite Canadian scholar who now heads the Indiana University Center for Bioethics. Meslin oversaw the publication of six thick reports as executive director of Clinton’s National Bioethics Advisory Commission, which met 48 times before disbanding in June. In addition to the issues of cloning and stem cells, NBAC considered the ethics of international clinical trials and experiments on the mentally ill.

Cultural conservatives charged that the NBAC during the Clinton administration was stacked with abortion rights supporters predisposed to accept the destruction of embryos for research. This was true, though NBAC did invite ideologically disparate guests to testify. Clancy’s appointment hints at a new ideological fixing for the council.

With Clancy, “They didn’t pick someone noted for thoughtful analytic views, they didn’t get someone hooked up in the scholarly community. Instead they’ve gone for a politico,” said Sean Tipton, a spokesman for the American Society for Reproductive Medicine.

Tipton has good reason to be worried; the charter for the Presidential Council includes long overdue scrutiny of the field of reproductive medicine. There’s plenty for Kass and like-minded committee members to feel repugnance about. Most of the science behind the creation of clones and embryonic stem cells derives from unregulated experiments by fertility doctors to help their patients get babies.

But some of Kass’ bioethics colleagues say Kass’ heavy reliance on “wisdom of repugnance” (others call it the ‘yuck factor’) — has not always worked for him, especially in the area of reproductive technology. In the early 1970s, as a bioethics professor at Georgetown University, Kass was an outspoken opponent of the emerging in-vitro fertilization, which he saw as immoral experimentation on the children that were its products.

Kass’ essays on the subject, laced with warnings of scientific hubris and quotations from Orwell and Huxley, were ignored by a child-hungry world. With mass multiple births, selective abortions and donor egg sales, there is plenty to feel yucky about in the fertility industry Kass railed against; but it has not produced the mutilated children he warned about. (In a recent interview, Kass said he was OK with IVF for married couples, as long as it didn’t weaken families.)

“In a sense Kass is a bit of a technological pessimist,” says Leroy Walters, a leading bioethicist at Georgetown.

Kass certainly isn’t alone in his pessimism or his objection to the manipulation of natural processes. A news conference held this week to denounce the Massachusetts biotech company that is trying to clone a human embryo included everyone from right-to-life Sen. Sam Brownback, R-Kan., to the president of Friends of the Earth.

In fact, Kass is something of a pioneer in his objections to technology muddying the waters of pure science. Consider this quote — vintage Kass — from his 1985 essay collection, “Toward a More Natural Science”:

“We have paid some high prices for the technological conquest of nature, but none perhaps so high as the intellectual and spiritual costs of seeing nature as mere material for our manipulation, exploitation and transformation.”

He continues, “We are already witnessing the erosion of our idea of man as something splendid or divine, as a creature with freedom and dignity. And clearly, if we come to see ourselves as meat, then meat we shall become.”

Eloquent as he has been on the topic, Kass does not do much for pragmatic bioethicists, many of whom believe that his approach is potentially dangerous.

“The problem with repugnance and fear-and-trembling ethics is, they are good starting points but bad ending points,” says Art Caplan, head of the Center for Bioethics at the University of Pennsylvania. “If intuition is the last word, then African-Americans are at the back of the bus, women and people who have no property aren’t voting and we still have slaves.”

These critics allow that there is certainly a place in the debate for Kass’ eloquent defense of intuition, but bioethicists who’ve done time on the commissions predict he’ll have to come to grips with pragmatic objectives. This may be difficult, however, given that Kass has written that pragmatism “is like a warm bath that heats up so imperceptibly that you don’t know when to scream.”

The other challenge facing Kass has little to do with his philosophy and more to do with bureaucracy. Government committees like the panel he is in the process of selecting must by law meet in public. For a committee ensconced in the discussion of bioethics this can be a huge annoyance: Panelists have to address a wide range of public audiences as plainly as possible, while at the same time examining and debating complex issues of science and philosophy.

“Part of the challenge of doing bioethics in public is, you don’t have the luxury of sitting quietly in a room and working through some of these problems by yourselves,” says Meslin. “When you have 18 members in public thinking through an urgent policy problem it requires creative thinking and spectacular leadership — but it also requires a reorienting of what one thinks bioethics is.”

Kass goes into this maelstrom with many supporters, regardless of their diverging views. Bioethicist colleagues are particularly admiring of his insistence that the President’s Council not be required to show consensus on difficult ethical issues, which would allow members to issue divergent opinions.

The disadvantage of this seeming advantage is that it could banish the council to obscurity for a lack of sound-bites. “In Washington,” says Caplan, “if they want long deliberation they’ll read a book. They want a quick quote, get it on one page, let’s go.” On the other hand, the council won’t be required to dumb down complex arguments. Assuming some liberal pragmatists are appointed, they’ll be able to express themselves alongside the conservatives.

“Leon is a teacher,” says Ruth Faden, a bioethicist who holds appointments at both Johns Hopkins and Georgetown. “In a sense he’s holding a national class. We need to get the science clarified so that it isn’t so complex that people throw up their hands, but not so simplified that people have misleading understandings.”

If pragmatic bioethicists are appointed to the panel, they are certain to clash with colleagues who will want to factor concepts of divine law and virtue into the discussion. But these considerations, sure to find a place at Kass’ table, fly in the face of pragmatic considerations — principles of self-determination, nonmaleficence, beneficence and justice used by secular bioethicists in reaching ethical decisions.

The question is, of course, just how many secular types will be invited? It’s always possible that Bush hard-liners unleashed Clancy as a way of scaring off unwanted intellectuals.

“I don’t know how the political leanings of the chair and executive director will affect willingness to serve,” says Alta Charo, a medical ethics and law professor at the University of Wisconsin, who delicately points out that “Clancy, in particular, is quite far-reaching in his political positions.”

Whatever the case, there will be plenty to chew over. Bush’s August announcement on stem cells, which limited researchers to experiments with cell lines that had already been established, is likely to sour soon.

Scientists already have denounced the decision, saying that existing stem cell lines may not prove useful enough. Meanwhile, hard-line opponents of stem cell research also are disgruntled, insisting that in making an announcement, Bush opened a Pandora’s box.

It is the contents of this box, which include the current hot topic of human cloning, that Kass and his commission will intellectually riffle before a confused and often angry audience. The outcome of the public ordeal won’t be known for a long time, but the appointment of Clancy may be a hint as to the tenor and content of the argument.

“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.