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Bioterror? Nature beat us to it

September 03, 2006|Wendy Orent | WENDY ORENT is the author of "Plague: The Mysterious Past and Terrifying Future of the World's Most Dangerous Disease."

IN THIS AGE OF terrorist plots, the Department of Homeland Security's decision to build a super-secret institute to study possible bioterrorist agents seems natural. But the proposed institute at Ft. Detrick, Md., which was the site of a U.S. biowarfare program that was shut down in 1969, is worrisome. Ft. Detrick has been the home of the Army Medical Research Institute of Infectious Diseases, an open biodefense facility, for decades. But according to news accounts, the new $128-million facility, to be known as the National Biodefense Analysis and Countermeasures Center, will be "black": Nobody working outside the agency, including politicians, will have a clue about what goes on inside.

Although there is no reason to believe that the U.S. will develop offensive bioweapons at the center, there's another question: How useful will it be?

One of its divisions is supposed to analyze "materials recovered from a biological weapons attack," according to its website. But in its other division, the Biological Threat Characterization Center, scientists will seek to create germ agents that they think terrorists might use against us -- and to come up with drugs and vaccines to protect us from them.

In this age of "synthetic genomics," the argument goes, we face a new world of horror. According to biodefense expert Steven Block of Stanford University, "Nature is constantly creating new pathogens, testing out new agents. It seems rather inevitable that if someone is bent on destruction, it should become possible to synthesize entire genes and make chimeras you can mix and match."

That's a lot to expect from strips of genetic information cobbled together in a laboratory.

Despite all the advances in synthetic genomics, making a new germ is harder than it looks. Pathogens don't just happen. They evolve in a particular host, in a particular context.

A germ has to be able to infect, replicate and exploit enough human tissues to kill, never mind spreading from host to host. Re-creating a small, existing virus, as virologist Eckard Wimmer of the State University of New York at Stony Brook showed in 2002 with poliovirus, is possible and easier today. But Wimmer had the polio blueprint in hand. He re-created an agent that had already been through the mill of natural selection.

Scientists in the former Soviet Union's biological weapons program learned that even if you're working with a natural pathogen, it's hard to get the results you want. According to Igor V. Domaradskij, one of the principal designers of the Soviet program, altering a pathogen is easy but maintaining its deadliness isn't. Even the simplest genetic engineering -- adding genes for antibiotic resistance to bacteria -- is difficult without sacrificing the germ's virulence. These problems can be solved, but it's difficult because you're working with living things.

Still, in 2001, a group of Australian scientists inadvertently made a virus deadlier. They added a mammal gene to a mousepox virus to make the virus produce a chemical called interleukin-4. These scientists discovered that their altered mousepox killed even vaccinated mice. Mousepox is related to smallpox, the most virulent of the highly contagious human diseases. Putting interleukin-4 in smallpox might produce a vaccine-resistant smallpox strain. A terrorist release of such a strain would be a catastrophe.

Or would it? Follow-up experiments performed by Marc Buller of St. Louis University showed, in research he has not yet published, that this strain doesn't spread well because the mice die too quickly. "You'd give them an injection in the foot, and they died," Buller said. Even in experiments in which the mice lived longer, the disease still didn't spread as well as naturally occurring mousepox.

In other words, if interleukin-4 had the same immune-suppressing effect in smallpox as it does in mousepox, a lot of people could be killed. But the disease would end there. You'd essentially have what Buller calls a "one-cycle kill."

This result isn't surprising. For all germs, transmissibility and virulence exist in a delicate balance. If a germ kills the host too quickly, it won't spread. Block admits this but contends that new virulent germs "don't have to work at all well. They don't have to be successful in the wild, they just have to kill a lot of people."

But why would a rogue scientist bother to create a new pathogen if all he wanted was to kill a lot of people? There are guns and bombs and chemicals. There is a proven bioweapons agent -- anthrax, as we saw in 2001, perhaps the most durable, and one of the most lethal, of all germs.

Two other deadly agents, plague and smallpox, not only kill, but spread. These three are the "best" threats nature has to offer. There's a handful of second-stringers: tularemia, botulinum toxin, viral hemorrhagic fevers like Ebola and Marburg, perhaps cholera or polio -- if we're ever foolish enough to let our immunity wane.

Why waste hundreds of millions of dollars pursuing the fantasy of an engineered disease when deadly agents honed by natural selection are on hand?

The National Biodefense Analysis and Countermeasures Center is a potential boondoggle -- and a dangerous one. Its work, even if done by our best scientists, isn't likely to produce any genuinely threatening new germ -- and thus no new means of defense. The likelihood that rogue scientists elsewhere could do better is vanishingly small.

But if we keep our enemies wondering what the new biodefense center is up to, they may be disposed to try themselves. Secrecy can only make an arms race more likely -- a race in which both sides are running after chimeras, where there's plenty to lose in time and talent and money, and little or nothing to be won.

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