Scientists Are Teaching the Body to Accept New Organs

It was not the most ominous sign of health trouble, just a nosebleed that would not stop. So in February 2017, Michael Schaffer, who is 60 and lives near Pittsburgh, went first to a local emergency room, then to a hospital where a doctor finally succeeded in cauterizing a tiny cut in his nostril.

Then the doctor told Mr. Schaffer something he never expected to hear: “You need a liver transplant.”

Mr. Schaffer had no idea his liver was failing. He had never heard of the diagnosis: Nash, for nonalcoholic steatohepatitis, a fatty liver disease not linked to alcoholism or infections.

The disease may have no obvious symptoms even as it destroys the organ. That nosebleed was a sign that Mr. Schaffer’s liver was not making proteins needed for blood to clot. He was in serious trouble.

The news was soon followed by another eye-opener: Doctors asked Mr. Schaffer to become the first patient in an experiment that would attempt something that transplant surgeons have dreamed of for more than 65 years.

If it worked, he would receive a donated liver without needing to take powerful drugs to prevent the immune system from rejecting it.

Before the discovery of anti-rejection drugs, organ transplants were simply impossible. The only way to get the body to accept a donated organ is to squelch its immune response. But the drugs are themselves hazardous, increasing the risks of infection, cancer, high cholesterol levels, accelerated heart disease, diabetes and kidney failure.

Within five years of a liver transplant, 25 percent of patients on average have died. Within 10 years, 35 to 40 percent have died.

“Even though the liver may be working, patients may die of a heart attack or stroke or kidney failure,” said Dr. Abhinav Humar, a transplant surgeon at the University of Pittsburgh Medical Center who is leading the study Mr. Schaffer joined. “It may not be entirely due to the anti-rejection meds, but the anti-rejection meds contribute.”

Patients usually know about the drugs’ risks, but the alternative is worse: death for those needing livers, hearts or lungs; or, for kidney patients, a life on dialysis, which brings an even worse life expectancy and quality of life than does a transplanted kidney.

In 1953, Dr. Peter Medawar and his colleagues in Britain did an experiment with a result so stunning that he shared a Nobel Prize for it. He showed that it was possible to “train” the immune systems of mice so that they would not reject tissue transplanted from other mice.

His method was not exactly practical. It involved injecting newborn or fetal mice with white blood cells from unrelated mice. When the mice were adults, researchers placed skin grafts from the unrelated mice onto the backs of those that had received the blood cells.

The mice accepted the grafts as if they were their own skin, suggesting that the immune system can be modified. The study led to a scientific quest to find a way to train the immune systems of adults who needed new organs.

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