Based on this handful of experiments, there seems little proof that engineered bioterror agents can work better than natural pathogens. According to the Molecular Science Institute’s Brent, however, the science of synthetic biology is still in its infancy, and he cites viruses that are used as vaccine vectors and bacteria created to make plastics as examples of synthetic life forms that can survive and multiply.

Yet others don’t consider such examples as having much to do with the prospect of creating disease agents. “Vaccine viruses are great for vectoring, but they are not pathogens,” says Earl Brown of the University of Ottawa, who studies virulence genes in viruses. “Vaccine viruses are attenuated and neutered.” Brown also points out that in his lab, when a gene is added to viruses, it generally weakens them, because the gene isn’t in its normal context. “When you mix and match genes, you tend to lose some replicative and growth function,” says Brown, who doubts that extensively hacked germs will be able to compete with highly evolved, effective natural disease agents. “Natural pathogens that have the ability to be weapons have evolved to deliver their toxins and survive,” says geneticist and biodefense expert Roy Curtiss of Arizona State University. “Changing the venue of these toxins means they may not do any harm.”

Still, because it’s impossible to know for sure what kind of bioterror threat we may face, there’s an obvious appeal to the idea of improving our immune system so that it could shrug off any attack. If you could rev up nonspecific immunity, which releases a torrent of immune chemicals—interferons, interleukins and other cytokines—you could wash out new threats immediately, without waiting for the body to produce antibodies. Yet the immune system, like natural pathogens, has been finely tuned by natural selection, and tinkering with it could have devastating results.

One problem is that heightening innate immunity might itself cause disease. Many pathogens manipulate the human immune system for their benefit, weakening or killing their host by generating an overproduction of innate immune chemicals. In recent research on the 1918 flu virus, recreated in several laboratories, the virus killed mice by generating a toxic storm of cytokines. Several current diseases, too, kill by sparking overreactions of the immune system. For example, a liver disease, primary biliary cirrhosis, can be triggered by repeated bladder infections with gram-negative bacteria. Multiple sclerosis, another autoimmune disease, is also thought to result from the overreaction of the innate immune system to microbial assault.

Then there’s the argument that if augmenting innate immunity were the ticket to fighting new pathogens, natural selection would already have achieved it. Something so fundamental to our existence as the ability to fight off pathogens is likely as enhanced as it could be, and any tweaking could destroy the delicate balance between under- and overreaction of innate immunity. Moreover, if innate immunity were the key to fighting infection, why did we evolve an entire system of humoral immunity, of antibody production?

There are, however, specific instances in which delicate, precise intervention to improve innate immunity may work well. Carolyn Hovde-Bohach of Idaho University has done intriguing research with the plague germ, Yersinia pestis, which has the ability to shut off innate immunity and “convince” a host it isn’t under attack. After inactivating the body’s normal inflammatory response, the cytokine production system, Yersinia pestis uses something called the type 3 protein injection system to stick tiny needles into immune-killer cells and destroy them.

Hovde-Bohach’s work interrupts this deadly message from pathogen to host. Using a nontoxic mimetic of a harmful compound known as lipid A, Hovde-Bohach managed to save 40% of her test mice. When she added gentamicin, a common antibiotic, to her compound, she saved 85%. Without this protection, plague would have killed all the mice. The lipid A mimetic binds to human immune cell receptors of a class known as toll-like receptor 4, stimulating production of the inflammatory compounds Yersinia pestis has evolved to turn off. The strategy works directly around the bacterial tactic that allows Yersinia pestis to silence innate immunity.

Still, Hovde-Bohach’s approach is far from a simple, universal fix. “We aren’t just ratcheting up the innate immune response—and this isn’t going to be a panacea for everything,” she says, noting that the lipid A mimetic did nothing, for example, to save the test mice from tularemia infection.

Dossier

1. Germs: Biological Weapons and America’s Secret War, by Judith Miller, Stephen Engelberg and William Broad (Simon & Schuster, 2001). Its publication, which coincided with September 11, 2001, propelled a book intended for a relatively small audience into an instant international bestseller. The book remains a useful introduction to biological weapons, clearly explaining the threat and its dimensions.

2. Unit 731: Japan’s Secret Biological Warfare in World War II, by Peter Williams and David Wallace (Simon & Schuster, 1989). This responsible and deeply horrifying book describes the largest-scale use of biological weapons in history, in which the Japanese military managed to get weapons to work despite primitive technology.

3. Scourge: The Once and Future Threat of Smallpox, by Jonathan Tucker (Atlantic Monthly Press, 2001). Tucker, an expert in biological and chemical warfare, presents a lucid account of the struggle between those who want to destroy the remaining virus stocks and those who want to preserve them to develop countermeasures against an attack.

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