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 Schaffer something he never expected to hear: “You need a liver transplant.”

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 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 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 per cent of patients on average have died. Within 10 years, 35 to 40 per cent have died.

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

Kidneys in particular may be damaged. “It is not uncommon to end up doing a kidney transplant in patients who previously had a lung or liver or heart transplant,” Humar said.

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.

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.

That turned out to be a difficult task. The immune system is already developed in adults, while in baby mice it is still “learning” what is foreign and what is not.

“You are trying to fool the body’s immune system,” Humar said. “That is not easy to do.”

Most of the scientific research so far has focused on liver and kidney transplant patients for several reasons, said Dr James Markmann, chief of the division of transplant surgery at Massachusetts General Hospital. Those organs can be transplanted from living donors, and so cells from the donor are available to use in an attempt to train the transplant patient’s immune system.

Far more people need kidneys than need any other organ — there are about 19,500 kidney transplants a year, compared with 8,000 transplanted livers. And those transplanted kidneys rarely last a lifetime of battering with immunosuppressive drugs.

“If you are 30 or 40 and get a kidney transplant, that is not the only kidney you will need,” said Dr Joseph Leventhal, who directs the kidney and pancreas transplant programmes at Northwestern University, US.

The more researchers learned about the symphony of white blood cells that control responses to infections and cancers — and transplanted organs — the more they began to see hope for modifying the body’s immune system. Many types of white blood cells work together to create and control immune responses. A number of researchers, including Markmann and his colleague, Dr Eva Guinan of the Dana-Farber Cancer Institute, chose to focus on cells called regulatory T lymphocytes. These are rare white blood cells that help the body identify its own cells. If these regulatory cells are missing or impaired, people can develop diseases in which the body’s immune system attacks its own tissues or organs.

The idea is to isolate regulatory T cells from a patient about to have a liver or kidney transplant. Then scientists attempt to grow them in the lab along with cells from the donor. Then the T cells are infused back to the patient. The process, scientists hope, will teach the immune system to accept the donated organ. “The new T cells signal the rest of the immune system to leave the organ alone,” said Angus Thomson, director of transplant immunology at the University of Pittsburgh Medical Center. Markmann, working with liver transplant patients, and Leventhal, working with kidney transplant patients, are starting studies using regulatory T cells.

At Pittsburgh, the plan is to modify a different immune system cell, called regulatory dendritic cells. Like regulatory T cells, they are rare and enable the rest of the immune system to distinguish self from non-self. One advantage of regulatory dendritic cells is that researchers do not have to isolate them and grow them in sufficient quantities. Instead, scientists can prod a more abundant type of cell — immature white blood cells — to turn into dendritic cells in petri dishes.

When Schaffer was told that he could be the first patient in the group’s clinical trial, he shrugged. “Someone has to be first,” he said. Schaffer is one of eight brothers. Four were older than 55, too old to safely undergo removal of part of their liver. The three younger brothers were in poor health. He moved on to nieces and nephews. Three agreed to donate, and one, Deidre Cannon, 34, who was a good match, went forward with the operation. It took place in September 2017. Afterward, Schaffer was taking 40 pills a day to prevent infections and to tamp down his immune system while his body learned to accept the new organ.

But now he has tapered down to one pill, a low dose of just one of the three anti-rejection drugs he started with. And doctors hope to wean him even from that.