Race and Medicine

[Alex Linder]

Soon after Watson and Crick published the blueprint for the double helix in 1953, George Hitchings and Gertrude Elion at Burroughs Wellcome began designing drugs systematically around the biochemistry presented by their intended targets. This logical approach foreshadowed the future of medicine and (in a weirdly circuitous way) the reinvention of the FDA almost three decades later. Scientists caught on much sooner, and “structure-based” drug design advanced rapidly as biochemists acquired the tools needed to read, configure, and build the molecules that choreograph life.

Drug designers take diseases apart. Iressa, for instance, targets a single receptor that proliferates in the most common form of lung cancer. The FDA licensed the drug in 2003, after clinical trials yielded good results. Follow-up trials involving almost 2,000 patients suggested, however, that the drug wasn’t working after all. Further analysis then revealed that Iressa had indeed worked—but only on receptors found in 300 patients of Asian ancestry. Similar variations apparently explain significant differences in the efficacy of drugs used to treat many other cancers. White Americans have less tolerance for some antidepressants, antipsychotics, and heart-disease drugs, while blacks respond poorly to certain drugs for high blood pressure and hepatitis. Eleven variations in just one gene affect responses to common antidepressants.

Drug designers take the rest of the patient apart, too. Tolerance for many drugs often hinges on how well patients metabolize and expel them, which seems to depend on a couple of thousand variants in a couple of hundred different genes. What were once inexplicable “side effects” are now predictable interactions between the drug’s chemistry and healthy parts of the patient’s. That lets medicine keep the drug and vote the too-delicate patient off the island.

Designers are also finding out when to leave well enough alone. A gene variant discovered in early 2008 apparently protects about 40 percent of African-Americans from heart disease as well as certain drugs do, by tinkering in much the same way with adrenaline’s effect on heart cells. Adriamycin has been routinely used against late-stage breast cancers, even though it can cause serious heart problems and spawn other cancers. A test that profiles 21 genes now identifies patients who will do as well on milder drugs, and others who can skip chemo altogether.

http://www.city-journal.org/2008/18_...diversity.html