A graduate student tested a molecule and watched a tumor melt away

As a graduate student, Max Krummel, an immunologist who now studies how immune cells behave in tissue, picked up a syringe filled with an antibody he had made in the lab and injected it into a mouse that carried a tumor.

He was not trying to cure cancer. He was trying to answer a much smaller question about a molecule that sat on the surface of T cells, the white blood cells that patrol the body and decide what to attack. In lab dishes, blocking that molecule had made T cells more active, as if he had released a brake. He had some tumors stored in the lab, so he and his colleagues set up the animal test to see if the same thing would happen inside a living body.

What happened next, Krummel said, "was the start of cancer immunotherapy." The tumors melted. Krummel calls that mouse test the first immunotherapy experiment, and his graduate mentor at Berkeley, James Allison, later won the Nobel Prize for the research that led to it. Krummel jokes that he at least got to attend the ceremony and enjoy the after parties.

Krummel says the result came from pure curiosity. At the time, other scientists asked why anyone would go into immunology at all, and his thesis project began simply as, let us see what this molecule does. He knew from AIDS and other diseases that T cells were important, but no one in the lab was talking about shrinking tumors.

Once they saw the effect, new questions opened up. Krummel recalls the thinking as, if the immune system could be dialed up by blocking that brake, what would that mean for vaccination, what would it mean for a disease like multiple sclerosis, in which the immune system attacks the brain and nerves, and what might it mean for cancer. Vaccination might get better, multiple sclerosis might get worse, and cancer might be affected.

Over time, the wider work on cancer immunotherapy changed how scientists thought about the immune system, Krummel says. Instead of a simple guard that attacks foreign germs and leaves the self alone, it looked like a tunable dial. The treatment raised the point at which a T cell would fire, allowing cells that had been letting a tumor slip by to go after it and kill it.

That tuning mattered for tumors because, as Krummel put it, a tumor is "not exactly self" but "also not foreign," adding, "It was once you. It's a cell that's kind of evolved."

Krummel says his career has lasted as long as the field that mouse helped create, a field that, as he put it, is "curing people with cancer, which really wasn't done before."