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Finding the Talismans That Protect Against Infection

Science  16 Feb 2001:
Vol. 291, Issue 5507, pp. 1183
DOI: 10.1126/science.291.5507.1183

Since 1995, the mini-genomes of dozens of pathogenic microbes have been sequenced, including those that cause tuberculosis, cholera, and ulcers. Many others are almost in the bag, including the much larger genome of Plasmodium, the malaria parasite. That data flood is helping researchers understand how nefarious microorganisms work—and how they might be stopped.

CREDIT: ILLUSTRATION: CAMERON SLAYDEN

The giant human genome promises to help solve another poorly understood problem: why some people get sick and die when they encounter a pathogen, whereas others stay healthy as an ox. Such information could eventually help put more people in the latter category.

Researchers have long known that differences in disease susceptibility are partly genetic, the most famous example being the gene for sickle cell hemoglobin, which offers protection against malaria to those who inherit one copy of it. (Having two copies causes sickle cell anemia.) Several other susceptibility genes have been discovered for various diseases; malaria now tops the list with 14 genes. “We're just beginning to scratch the surface,” says Adrian Hill, a geneticist at the University of Oxford in the United Kingdom.

To identify genes that might confer susceptibility or resistance, researchers try to find genetic differences between large groups of patients and healthy controls. Without the complete genome, they could only look for previously discovered genes. Now, they can theoretically take each and every gene into consideration. Eventually, such work will lead to a better understanding of the molecular interaction between a bug and its host. That, in turn, may reveal new drug or vaccine targets.

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