Last week, the Bush administration did a radical about-face and said that anyone who fears a biowar attack by Iraq or al-Qaida and wants the smallpox vaccine should have access to it. (Current plans call for mass vaccination to start in 2004, unless there's a smallpox attack.) As Bush reversed himself, public health officials around the country muttered, sotto voce, "Ohmigod." The vaccine might be the most successful medicine ever made, having eradicated smallpox from the globe. But even when taken as directed, the vaccine can injure and kill.

The smallpox vaccine usually does its magic without serious incident, leaving only a small scar as a reminder of the inoculation. But the smallpox vaccine has more ill side effects than any vaccine now on the market. For every 1 million people vaccinated, 15 or so will develop life-threatening problems such as inflammation of the brain, and at least one will die. After taking the vaccine, some will go blind, and people with skin problems such as eczema can break out in horrific lesions. And most of the 30 million to 50 million Americans with compromised immune systems (chemotherapy patients, HIV cases, transplant recipients taking immuno-suppressive drugs) shouldn't take the vaccine and are at some risk if exposed to those who do. [Clarification, Oct. 11: The 30 million to 50 million figure includes the people with skin problems.]

You'd think that in the 21^st century, a safer alternative to the existing vaccine should exist. And you'd be right. There is one. So why can't we have it?

The existing smallpox vaccine (which contains a virus called vaccinia) has only modestly improved since 1796, when country doctor Edward Jenner injected goop taken from a dairy maid's cowpox pustule into a boy and proved it could protect humans from the disease. Originally, doctors harvested pus from the sores of the vaccinated and used it to vaccinate others. In 1864, researchers started mass-producing the vaccine on the skin of living calves, and since the 1890s scientists have labored to make a safer medicine. The disease last erupted domestically in 1949, and the United States, weighing risk against benefit, discontinued its routine use of the smallpox vaccine in 1972.

Nearly every effort to build a vaccine with fewer side effects has produced a less effective product. The one that moved furthest along before smallpox vaccination came to a halt now has moved to center stage. Developed by German researchers in the '70s, the vaccine contains a virus called Modified Vaccinia Ankara. Unlike the classic smallpox vaccines, MVA does not copy itself in humans and causes no serious side effects, even when given to the immuno-compromised. More than 100,000 Germans took the vaccine in the '70s, and early tests showed that it stimulated immune responses against smallpox. But MVA shipped after the war was won. It never had a chance to demonstrate its ability to thwart smallpox in the real world because the old vaccine erased the smallpox virus from the human population by 1977.

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Researchers think MVA may well lead to safer protection against smallpox if used alone or, more likely, before a subsequent inoculation with the traditional vaccine. This "priming" dose of MVA both boosts the impact of the subsequent dose of the old-fashioned vaccine and minimizes the chance that it will run riot in the body.

The U.K./U.S biotech company Acambis hopes to win a contract from the federal government's National Institute of Allergy and Infectious Diseases to develop and test MVA in both humans and animals. If initial studies prove positive, NIAID plans to fund production of 30 million MVA doses. Another company bidding for the NIAID contract, Bavarian Nordic, already produces MVA in bulk and has tested it in 87 humans.

"We see a strong immune response," says company CEO Peter Wulff, who also says they could scale up production to deliver tens of million of doses by late 2004. But the company has yet to publish results, and Wulff says he cannot discuss the preliminary data further.

Bavarian Nordic recently supplied the German army with 1 million doses of MVA, which Wulff says the company thinks they are using to prime soldiers before vaccinating them with the old vaccine. "That approach has a lot of merit," says Wulff. If MVA performs well in a series of planned test-tube, animal, and human experiments, Wulff would advocate using it alone.

In parallel to the NIAID effort, Peter Jahrling of the U.S. Army's main biodefense lab plans to work with NIAID smallpox vaccine guru Bernard Moss to conduct a critical monkey experiment with MVA. Moss suspects they should have results by June—which may beat the time frame for NIAID to award its contract—and if the vaccine works, the data likely will dramatically elevate MVA's standing.

Even if 1) the MVA tests succeed; 2) the drug manufacturers show they can produce enough MVA; and 3) MVA wins Food and Drug Administration approval (the agency relaxed standards for biodefense meds in May), no one will know for certain whether it will stop smallpox until someone unleashes the plague on the planet.

All medicines demand that we measure their risks against benefits and make educated guesses about using them. Officially, the only smallpox in the world is stored under tight security in two Russian and American laboratories. The Bush administration's nightmare—the risk—is that Saddam has weaponized smallpox he bought from the Russians or that he's re-engineered smallpox from camelpox.

If the United States goes to war with Iraq soon, the risk/benefit equation will change dramatically, and it may make more sense to risk the injuries associated with the old-fashioned vaccine than to leave a vulnerable population exposed to a smallpox attack. Meanwhile, we should evaluate MVA's potential with the utmost urgency and even consider ordering millions of doses of MVA before it wins FDA approval. The March of Dimes did just that in 1954 with poliovirus vaccine, gambling that it would prove worthy the following year—and accepting that, if it did not, the vaccine would wind up in the trash. The March of Dimes turned out to have won the bet, sparing thousands of children in 1955 who otherwise certainly would have wound up crippled or even dead. And that is a priceless benefit worthy of a great financial risk.

Related in Slate

Even if somebody drops the smallpox bomb on the United States, we're not all toast, Jon Cohen reported last year. On the anthrax front, Cohen reported about the viable anthrax vaccine, the one we're not making available to the public.

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Jon Cohen, the author of Shots in the Dark, writes for Science magazine. You can e-mail him at joncohen45@hotmail.com.
 

Illustration by Robert Neubecker.