An important man in medicine died today, and most people don’t recognize his name.
Stephen Crohn, dubbed The Man Who Can’t Catch AIDS in 1996 by The Independent, committed suicide at age 66. He became well known to science in 1982, when his boyfriend Jerry Green became one of the first patients to die of AIDS. What puzzled scientists was Crohn’s resistance to AIDS despite taking no precautions. Dr. Bill Paxton, working with Dr. David Ho from the Diamond AIDS Research Center in New York, took notice, and began to study HIV by examining Crohn’s cells, which proved to be immune to the virus. They discovered that Crohn’s CD4 cells, which are the targets of HIV, appear to have one defective receptor called CCR5 on their surface that makes it impossible for the virus to enter the cell. (They do still have Fusin, another protein coreceptor on CD4 cells, but that alone is not enough for HIV to latch onto CD4 cells). The name of this genetic mutation is Delta 32, and a homozygous mutation is found in < 1% of the population. Having this defective receptor doesn’t affect the person negatively, and it makes him immune to HIV infection.
As Crohn puts it in a “Nova” documentary on PBS:
“It’s like a key — the virus comes with this. It’s looking for a two-holed keyhole. I don’t have one of the holes. Period. It’s never going to attach to me.”
I did a quick literature search on the topic and came across quite a few papers published in the late 1990s in Nature and Cell describing the findings of this research. One titled “Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection” published in 1996 describes Crohn and one other individual with the same Delta 32 mutation. Both of their mutations produced severely shortened CCR5 receptor proteins that were undetectable on CD4 cell surfaces. Both patients also had parents who had one copy of the mutation, meaning that this is not a spontaneous mutation but rather, an inherited one. The paper also suggested that heterozygotes for the CCR5 mutation were perhaps somewhat protected as well, with their receptors being less able to allow HIV into the cells.
The reason why this story fascinates me is the idea of learning from patients’ bodies and letting clinical knowledge guide bench research. There is a big push for translational research now at major medical centers, emphasizing the “bench to bedside” flow that research should take. But this story highlights how you can go from bedside to bench. The knowledge that Crohn and others like him contributed to HIV and AIDS led to the development of negative modulators of the CCR5 receptor like Maraviroc. His sister Amy Santaga said, “My brother saw all his friends around him dying, and he didn’t die … He went through a tremendous amount of survivor guilt about that and said to himself, ‘There’s got to be a reason.’ ” By living and being willing to participate in research, he contributed to great science that will impact thousands of people around the world.
It saddens me that Crohn took his life today. I can only speculate about the motives – guilt, frustration, even loneliness or fear? We may never know. But we should all thank him today, and spare a moment of silence for the man who couldn’t catch AIDS.