Why We Get Diseases Other Primates Don't

New research might explain why HIV kills only humans and why the clinical test of TGN1412 almost killed six Brits.

Last March the German biotech company TeGenero began testing the drug TGN1412 on human volunteers. The result was one of the most disastrous clinical trials in history. Although TGN1412 is harmless to other primates at high doses, it sent the immune systems of six people into near-deadly overdrive, causing widespread inflammation and multiple-organ failure.

Two months later hematologist Ajit Varki of the University of California at San Diego published a paper offering a plausible explanation for why things went so wrong. The drug hit humans so much harder, he says, because of a difference in the surface molecules of our white blood cells. Varki studies siglecs, small groups of receptors that thickly stud the immune T cells of monkeys and apes but are few and far between in humans. Siglecs act as brakes, stopping the immune system from overreacting. Because human T cells don't have as many of these brakes, our cells are a hundred times more aggressive than those of chimps when faced with drugs like TGN1412, which work by triggering the immune system.

Why the difference? Sometime after humans branched from apes, "we may have faced some terrible pathogen," Varki speculates. "By removing these brakes we may have done better then." An overreactive immune system helps fend off infections, but it could also explain why we suffer from immune-system diseases like bronchial asthma, chronic hepatitis, and type I diabetes, which don't affect chimps. Overactive T cells are also a factor in AIDS, points out Varki, which may help explain why HIV, which evolved in chimps, kills only humans.

Kemo D.7