When a representative of the Nobel Foundation could not reach Dr. Ralph M. Steinman by telephone Monday to deliver the thrilling news that he had been awarded a Nobel Prize in Medicine for his breakthrough work in immunology, he sent him an email about the honor.
But Steinman would never see the message nor learn of the prize. He died of pancreatic cancer on Friday, three days before the phone call from the Nobel committee. He had been battling the deadly disease for four years, using a treatment he devised to try to prolong his life, essentially turning his body into an extension of his research.
But Nobel Prizes cannot be awarded posthumously. And so the Nobel committee, which had believed Steinman to be alive, faced a quandary.
On Monday morning, one of Steinman’s daughters, Alexis, saw the email from the Nobel Foundation and contacted Rockefeller University, where her father had worked. The president of the university, Marc Tessier-Lavigne, immediately called the chairman of the Nobel Prize committee to inform him.
Then, the committee, at the Karolinska Institute in Stockholm, scrambled to figure out what to do. As heartless as it might seem, would the prize for Steinman have to be revoked?
“This is a unique situation — Steinman died hours before the decision was made,” Göran K. Hansson, secretary of the Nobel committee for physiology and medicine, told Swedish Radio News after the situation came to light. “News of his death was not made public. We had no idea, nor did they know at his place of work.”
The foundation’s nine-member board of directors met Monday afternoon and consulted lawyers concerning the interpretation of the statutes of the Nobel Foundation issued in 1974. The statutes hold that the Nobel Prize is not to be given posthumously. But if a person who is announced as a prize winner dies before receiving it at the Nobel ceremonies on Dec. 10 — the anniversary of the death of Alfred Nobel, the Swedish industrialist who endowed the prizes — the award remains valid.
Because Steinman’s award was made in good faith on the assumption that he was alive at the time of his election, he should receive it, the directors decided.
The drama seemed to overshadow the fact that Steinman was awarded one-half of the prize, and two other immunologists shared the other half. They were Dr. Bruce A. Beutler of the University of Texas Southwestern Medical Center in Dallas and the Scripps Research Institute in San Diego, and Dr. Jules A. Hoffmann of France. All three scientists were honored for discoveries of essential steps in the immune system’s response to infection.
But it was Steinman who actually used his discoveries in the laboratory to try to save his own life. His career-long quest had been to develop a vaccine against cancer for humans, having shown 20 years ago that such a treatment could be effective in mice.
Four and a half years ago, after he was found to be jaundiced from a spreading pancreatic cancer, he began tailoring an experimental vaccine against his own tumor. The idea was to use the principles learned in the experiments on mice and in the laboratory to produce immune cells derived from his dendritic cells, a class of cells that he discovered in 1973.
After a piece of Steinman’s cancer was removed, a colleague, Dr. Michel Nussenzweig, grew it in the laboratory to produce enough material to send to at least 20 researchers at Rockefeller University and at least five other laboratories around the world. Steinman organized the work among the researchers who developed the experimental vaccine.
Steinman received standard chemotherapy for his cancer as well as the experimental vaccine, which other doctors at Rockefeller University injected under his skin, Nussenzweig said Monday in a telephone interview. Rockefeller University’s institutional review board approved the experiment.
“Ralph believed strongly that it would work,” Nussenzweig said. “Obviously, it did not work or he would be here now, but possibly it prolonged his life.” The research, he added, will continue.
Pancreatic cancer is among the most aggressive malignancies, in part because it arises in a gland deep in the abdomen that is hard for doctors to feel with their hands and because usually it produces symptoms only after it has become advanced. About 20 percent of patients with pancreatic cancer survive one year after detection and four percent after five years, according to the American Cancer Society.
Nussenzweig and other doctors said it was impossible to determine whether Steinman would have survived as long without his self-tailored experimental treatment.
At the time of his death Steinman was working to develop a general method for making a vaccine that would not need to be tailored to each patient and that could be used against cancer and certain infections. Other vaccines based on dendritic cells are being tested in patients, researchers said.
Provenge, a vaccine against advanced prostate cancer, was based on Steinman’s work with dendritic cells. It was approved by the Food and Drug Administration last year and is sold by the Dendreon Corp. of Seattle. (Nussenzweig said that neither he nor Steinman had any connection to Dendreon, financial or otherwise.)
Scientists who knew Steinman and his work said the Nobel committee made the right decision.
“All I can say is that the work deserved the prize,” said Susumu Tonegawa of the Massachusetts Institute of Technology, who himself won the prize in 1987 for his work on immunology.
Honored along with Steinman were Hoffman, who was born in Luxembourg, and Beutler, an American. In 1996, Hoffmann discovered the cell receptors in laboratory fruit flies that are activated by pathogenic bacteria or fungi. Two years later, Beutler identified the cell receptors in mice that respond to a substance in the coat of bacteria and that can trigger septic shock if overstimulated. These receptors turned out to be made by the same family of genes as those in the fruit fly, known as Toll-like receptor genes.
Hansson, of the Nobel committee, said Nobel Prizes have been awarded posthumously twice before: in 1931 for literature to the poet Erik Axel Karlfeldt, and, 30 years later, to Dag Hammarskjold for peace.
“The situation was a little different then because the committee was aware that the recipients were dead,” Hansson told Swedish radio. “The practice now is not to award the prize to someone who is deceased.”
The Nobel committee was not able to make contact with any of the three winners before the announcement was made, Hansson said, adding that the committee normally makes personal contact with the winners before going public with the news.
Annika Pontikis, a spokeswoman for the Nobel Foundation, said she did not know whether the board had discussed how to check whether future recipients were alive at the time of their election.