Crying wolf over bioterrorism

‘Mother Nature is the most dangerous terrorist,” says Michael Kurilla, the nation’s unofficial biodefense czar. “The microbial world is almost unlimited in its [terrorist] potential.”

But despite the emergence of such new diseases as SARS and the H5N1 avian flu, it isn’t Mother Nature only that worries Kurilla, the director of the Office of Biodefense Research Affairs of the National Institute of Allergy and Infectious Diseases. He’s also concerned about the threat from synthetic biology -- the possibility that rogue scientists and bioterrorists could make diseases in the laboratory to be used for terrorism. As he puts it, “The threat and the reality of synthetic biology is becoming greater and greater every day.”

A recent report in Science magazine seems to add another arrow to the quiver of those who worry that synthetic biology could become a source of terrorist weapons. A group of scientists, among them J. Craig Venter, whose team decoded the human genome in 2000, has succeeded in synthesizing a bacterial genome entirely from scratch.

Venter’s feat, however, doesn’t mean that terrorists will be making new germs to kill us. And it shouldn’t mean that the government should spend billions of dollars trying to counter a chimerical threat by developing an equally chimerical antidote.

Synthesizing a bacterium from an existing genome changes nothing fundamental in our understanding of synthetic biology. Virologist Eckhard Wimmer synthesized poliovirus in 2002, and Venter’s team made a bacteria-eating virus in 2003. But Venter’s latest experiment was the first to synthesize so large a piece of DNA. He hasn’t gotten his germ to “boot up” yet -- it still has to be put into a living cell and show that it can grow and multiply. Even so, scientists skeptical about the significance of his achievement think Venter will get his synthetic germ up and running in a matter of months.

Venter’s work makes the creation of murderous new life forms seem more believable. Indeed, the fear of dangerous synthetic germs has prompted the enormous, cumbersome apparatus that is the U.S. biodefense program to lurch in a new direction. If we don’t know what pathogens are coming, the reasoning goes, we had better develop new ways of countering them -- not one at a time but all of them.

After the anthrax letter attacks of 2001, which began a week after 9/11 and killed five people, the biodefense establishment’s immediate response was to focus on the greatest and likeliest of bioterror threats -- the unholy trinity of anthrax, smallpox and plague. In 2004, billions of dollars were set aside for Project Bioshield, which was jointly run by the departments of Homeland Security and Health and Human Services. The program aimed to produce new, safer vaccines and treatments for anthrax and smallpox, in particular.

Almost four years later, Project Bioshield has little to show for all the billions of dollars showered on it. The old “one-bug-one-drug” strategy -- designed to develop vaccines and therapies for anthrax, smallpox and plague separately -- has been abandoned in favor of “broad spectrum technology” -- drugs and methods that will, at least in theory, kill many types of germs.

Rutgers microbiologist Richard Ebright believes that the broader approach is better. As the effectiveness of the antibiotics we already have wanes, it makes sense to search for new classes of these drugs, he believes. The same goes for antivirals. Very few effective ones exist, and viral strains can develop resistance to them too, as some influenza strains have already done with Tamiflu, the newest licensed drug for treating the flu.

But new antibiotics and antivirals represent only a small part of the National Institute of Allergy and Infectious Diseases’ current biodefense program, according to Ebright. The institute is assigning higher priority to radical new approaches. Chief among them is the modulation, or enhancement, of “innate immunity.”

Simply put, there are two components to human immunity: innate, or general, immunity and acquired, or specific, immunity. Innate immunity involves killer cells and chemicals the body launches to fight invading germs. While the germs are held at bay, so to speak, the body develops specific antibodies to mop up the infection. In theory, enhancing innate immunity means creating ways to intensify or strengthen these immune responses so the body can fend off all infections, whether newly evolved or artificial, as soon as they appear.

This sounds good. If you could treat any new disease before the germ is even identified, then artificial bioweapons, or such naturally emerging germs as SARS, would cease to be terrorist specters.

But things are never that simple. Innate immunity is an exquisitely fine-tuned system, honed by millions of years of natural selection.

“It’s not like a stereo system where you can just turn the volume up or down,” says evolutionary biologist Paul W. Ewald of the University of Louisville. He points out that ratcheting up innate immunity might turn the body against itself, producing such autoimmune diseases as lupus or multiple sclerosis. Besides, if innate immunity could really wipe out all infections, why hasn’t it already done so? Why did we evolve the second system of acquired, or specific, immunity at all if innate immunity could completely protect us from disease?

There’s lots of research into innate-immunity enhancement but precious little data supporting it. The scientist most prominently associated with the idea is Ken Alibek, a bioweapons designer who defected from the Soviet Union in 1992 and for years peddled an immunity-boosting nostrum on his commercial website. Harry Whelan, professor of neurology and pediatrics at the Medical College of Wisconsin and lead author of a 2005 article backing this approach in the Journal of Allergy and Clinical Immunology, cites Alibek as one of the “experts” consulted for the article. But though Whelan and his coauthors reviewed a host of research projects testing how various chemical compounds boosted innate immune activity, they reported no data on how well these compounds worked in preventing disease and death.

Charles Hackett of the National Institute of Allergy and Infectious Diseases offers some evidence that limited stimulation of innate immunity can provide some advantages. He points to various vaccine adjuvants, or boosters, that prompt innate immunity to turn on acquired immunity more quickly. But that, Hackett acknowledges, isn’t the same thing as enhancing general innate immunity. “Innate immunity is an area that’s evolved over millenniums and is very clever,” he told me. “If you want to [enhance] it, you really have to understand it better than we understand it now.”

Artificial germs remain an illusion. Venter, like scientists before him, has not made a new germ. He used a genome map to re-create an old one. Similarly, despite all the interest in enhanced innate immunity, no one has been able to show that the approach works. The wreckage of Project Bioshield shows that the one-bug-one-drug approach is a failure. But by banking on the possibility of boosting innate immunity, the U.S. biodefense leviathan could well be, once again, staggering in the wrong direction.

Wendy Orent is the author of “Plague: The Mysterious Past and Terrifying Future of the World’s Most Dangerous Disease.”