October 20, 2010
Dr. Georges Mathé, Transplant Pioneer, Dies at 88
By DOUGLAS MARTIN

In the morning of the atomic age, there was optimism that the nuclear genie could heal as well as kill. By the mid-1950s, researchers had cured mice of leukemia by destroying diseased bone marrow with near-lethal doses of radiation, then rescuing them by transplanting healthy marrow.

But experiments on humans were stymied by fears that radiation exposure sufficient to kill the cancer might also kill the patient. Then came the news that six physicists had become ill from radiation exposure during a 1958 nuclear reactor accident in Yugoslavia.

One physicist died from especially heavy exposure, and one was relatively unaffected. Dr. Georges Mathé, who died in France on Friday at 88, used the remaining four as guinea pigs in a radical experiment.

He gave them life-threatening doses of radiation, then injected bone marrow collected from donors to replace the damaged marrow. Bone marrow is spongy tissue found inside bones that contains stem cells that produce the body’s blood cells. For the first time, a human marrow transplant seemed to take, and the physicists survived. It was called the first successful bone marrow transplant not performed on identical twins.

In 1963, four years after treating the physicists, Dr. Mathé shook the medical world by announcing that he had cured a patient of leukemia by means of a bone-marrow transplant. In this case, there was no doubt that he had performed the feat of obliterating the patient’s stem cells and replacing them with a donor’s: the patient’s blood type had changed to that of the donor, the first time this had happened.

Most important, he demonstrated that stem cells injected in a patient not only heal radiation damage but also fight cancer. The reason is that the donor’s cells rule the body of the patient — whose own cells have been devastated — and attack the cancer as a foreign invader. The donor cells, however, can also attack the patient’s healthy ones, and vice versa. Preventing these attacks has been a principal concern of transplant science.

The leukemia patient died after 20 months, apparently of encephalitis. Judgments vary on whether the patient’s survival was long enough for Dr. Mathé to declare success.

But Dr. Brian Bolwell, chief of hematology at the Cleveland Clinic, said in an interview that Dr. Mathé had proved an important principle: “You can cure an incurable leukemia patient.”

In the process, Dr. Bolwell said, Dr. Mathé developed both a technique and an important term, “adoptive immunotherapy,” to describe how a person’s own immune system can be used to combat cancer and other diseases.

“It was quite a leap of scientific genius,” Dr. Joseph H. Antin, chief of stem cell transplantation at the Dana-Farber Cancer Institute in Boston, said in an interview. “He’s one of the original innovators. Much of what we have accomplished can be linked back in a fairly direct way to the work that he did in the 1950s and ’60s.”

Dr. Mathé’s death, in Villejuif, outside Paris, was announced by President Nicolas Sarkozy’s office.

Dr. Mathé worked at a time when original research on bone marrow transplants was percolating. A leader was Dr. E. Donnall Thomas, an American who in 1956 performed the first bone marrow transplant on a leukemia patient using marrow from an identical twin. (For years, such twin transplants were the only ones that worked.) In 1969, Dr. Thomas led the team that performed the first transplant between people matched by molecular analysis.

Dr. A. John Barrett, president of the American Society for Blood and Marrow Transplantation, believes, like Dr. Antin, that Dr. Mathé should have shared the Nobel Prize in Physiology or Medicine with Dr. Thomas, who received the award in 1990.

“It’s always dangerous to say who was first,” Dr. Barrett said of Dr. Mathé in an interview, “but he was a leader, he was an inspiration, he was certainly ahead of his time.”

Dr. Barrett said Dr. Mathé’s insights helped lay the foundation for today’s sophisticated versions of immunotherapy that direct specific molecules to specific molecular targets. Transplants of stem cells have given way in many cases to removing stem cells from the patient or a donor, modifying them in a test tube, then putting them in the patient to fight cancer.

Georges Mathé was born on July 9, 1922, in Nièvre, France, earned his medical degree from the University of Paris and fought with the Resistance against the Nazis in World War II. He was arrested and sent to a Polish concentration camp in a cattle car, but the war ended shortly after he arrived.

In 1951 he worked for a year at the Sloan-Kettering Institute in Manhattan, where, he said, he became skeptical of overreliance on chemotherapy. He became chief of hematology at Institut Gustave Roussy in Villejuif in 1961 and in 1964 founded the Institute of Cancer and Immunogenetics in Paris, where he was director.

He was also founder and president of the European Organization for Research and Treatment of Cancer, president of the European Society for Medical Oncology and a fellow of the Royal Society of Medicine and the New York Academy of Sciences.

Dr. Mathé is survived by a wife and daughter, Agence France-Presse, the French news agency, said.

Early in his career, Dr. Mathé contracted hepatitis B and spent two years in a hospital bed. The memory motivated him to visit his patients at the end of each day in the lab. In a 1974 interview with New Scientist, he explained, “Experiencing suffering is necessary to be a complete doctor.”