Since I was interested in the immune system, I was saying, “Is there any way that we can suppress the immune system enough to suppress the disease but not enough to make a person susceptible to the secondary infections you get when you knock out someone’s immune system?”  So, for example, the drugs that were used for cancer — cyclophosphamide, a variety of other drugs — when given to people who have cancer, you want to completely kill all the cells.  The problem is those people are susceptible then to a lot of things like infections and bleeding because platelets go low.  So when I came to the NIH, I had a mentor named Sheldon Wolf, who was an amazing person in that he gave me, at a very young age, a group of patients to work with him and figure out how we can study them.

And it happened that, in the National Cancer Institute — which was two floors away from us in the old building — where I would go up there all the time as the infectious diseases consult because they were getting immunosuppressed and they were getting infections. And when you look at the drugs that they were being treated with, they were being treated with massive doses of these cytotoxic drugs.  So we got the idea that, if we could somehow give a cancer drug at a low enough dose but monitor the immune function and the white cell function of the people enough to kind of titrate the dose, could you turn the disease off without any of the secondary complications?  And we did.  We took a disease that was 98 percent fatal, and we had 93 percent remission rates in that.  And while I did that, I used it as a model to dissect out how the immune system is regulated, what can be turned off, what interacts with that.