By LAWRENCE K. ALTMAN and NICHOLAS WADE
Published: October 3, 2011
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 e-mail about the honor.
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| Stan Honda/Agence France-Presse — Getty Images The family of the late Dr. Ralph M. Steinman, pictured on the screen, on Monday after he was announced as a Nobel Prize winner. |
However, Nobel Prizes cannot be awarded posthumously. And so the Nobel committee, which had believed Dr. Steinman to be alive, faced a quandary.
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| Carlos Barria/Reuters Dr Jules A. Hoffmann, above, and Dr Bruce A. Beutler, both immunologists, shared this year's Nobel Prize in Medicine with Dr. Ralph M. Steinman, who died of pancreatic cancer on Friday before learning of their selection. |
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 Dr. Steinman have to be revoked?
“This is a unique situation — Steinman died hours before the decision was made,” Goran 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.”
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| Mike Groll/Associated Press Dr. Bruce A. Beutler |
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 Dr. 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 Dr. Steinman was awarded one-half of the prize, and that 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 Dr. 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 Dr. 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. Dr. Steinman organized the work among the researchers who developed the experimental vaccine.
Dr. Steinman received standard chemotherapy for his cancer as well as the experimental vaccine, which other doctors at Rockefeller University injected under his skin, Dr. Nussenzweig said Monday in a telephone interview. Rockefeller University’s institutional review board approved the experiment.
“Ralph believed strongly that it would work,” Dr. 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 4 percent after five years, according to the American Cancer Society.
Dr. Nussenzweig and other doctors said it was impossible to determine whether Dr. Steinman would have survived as long without his self-tailored experimental treatment.
At the time of his death, Dr. 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 Dr. Steinman’s work with dendritic cells. It was approved by the Food and Drug Administration last year and is sold by the Dendreon Corporation of Seattle. (Dr. Nussenzweig said that neither he nor Dr. Steinman had any connection to Dendreon, financial or otherwise.)
Scientists who knew Dr. Steinman and his work said the Nobel committee had 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 Dr. Steinman were Dr. Hoffmann, who was born in Luxembourg, and Dr. Beutler, an American. In 1996, Dr. Hoffmann discovered the cell receptors in laboratory fruit flies that are activated by pathogenic bacteria or fungi. Two years later, Dr. Beutler identified the cell receptors in mice that respond to a substance in the coat of bacteria and that can set off septic shock if overstimulated. These receptors turned to be made by the same family of genes as those in the fruit fly, known as Toll-like receptor genes.
Mr. Hansson of the Nobel committee said Nobel Prizes had 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,” Mr. 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, Mr. 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.
A version of this article appeared in print on October 4, 2011, on page A1 of the New York edition with the headline: Death Doesn’t Rob Recipient Of Nobel Prize.
http://www.nytimes.com/2011/10/04/science/04nobel.html?_r=1&ref=science
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The excerpt below is taken from:
http://www.rockefeller.edu/research/faculty/labheads/RalphSteinman/
Heads of Laboratories
Ralph M. Steinman, M.D.
Senior Physician
Henry G. Kunkel Professor
Laboratory of Cellular Physiology and Immunology
Ralph.Steinman@rockefeller.edu
Dendritic cells, which were originally codiscovered by Dr. Steinman with Zanvil A. Cohn at Rockefeller, are pivotal to the adaptive and innate branches of the immune system. Dr. Steinman’s research focused on the mechanisms employed by dendritic cells to regulate lymphocyte function in tolerance and immunity, as well as the use of dendritic cells to understand the development of immune-based diseases and the design of new therapies and vaccines.
The immune system contains a system of dendritic cells, which captures, processes and presents antigens and provides additional controls on the development of antigen-specific immunity and tolerance. Because of these functions, dendritic cells (DCs) are providing an important means to monitor and manipulate immune function in several disease states.
Dr. Steinman was the recipient of the 2011 Nobel Prize in Physiology or Medicine, the A.H. Heineken Prize for Medicine in 2010, the Albany Medical Center Prize in Medicine and Biomedical Research in 2009 and the Albert Lasker Basic Medical Research Award in 2007. He received the Debrecen Prize in Molecular Medicine in 2006, the New York City Mayor’s Award for Excellence in Science and Technology in 2004, the Novartis Prize in Immunology in 2004 and the Gairdner Foundation International Award in 2003. He was a member of the National Academy of Sciences and the Institute of Medicine.
For more, see http://www.rockefeller.edu/research/faculty/labheads/RalphSteinman/
