Monday, October 3, 2011

RIP, Ralph Marvin Steinman (1943-2011), Nobel Laureate

It was just last week when I wrote about a paper featuring Dendritic Cells, the surveillance sentries of the mammalian immune system. It was remiss of me, and unconscionably so (hindsight, as they say, is 20-20), not to mention the name of Ralph Steinman, who - in conjunction with Zanvil Cohn (in whose lab he was a post-doctoral fellow at that time) - discovered, and coined the term, 'dendritic cell'. Steinman passed away on September 30, 2011, at the age of 68, three days before his name was announced for the 2011 Nobel Prize in Physiology and Medicine in recognition of his life's work on Dendritic Cells.

Nobel Prize Press Conference at Rockefeller University regarding the death of Nobel laureate Steinman. Image courtesy: Jeanne Garbarino, via Twitter.

Born in Montreal, Quebec, Ralph Steinman got his Bachelor of Science from McGill University, and his MD from Harvard Medical School. While working at the Rockefeller University with Zanvil Cohn (1926-1993), he identified a novel immune cell type present in peripheral lymphoid organs (spleen, lymph node, Peyer's patch). The cells were relatively rare in the lymphoid organs (1-1.6% of the total nucleated cells in spleen; smaller numbers in Peyer's patches and lymph nodes; none in bone marrow, thymus, liver, or peritoneal cavity), but possessed distinct morphological features with branched projections (or dendrites) - leading to the coinage of the term 'dendritic cell' - that separated them from other adherent nucleated cell populations in mouse lymphoid tissues, such as lymphocytes, granulocytes, and mononuclear phagocytes. The 1973 study, published in the Journal of Experimental Medicine (JEM), found that these mitochondria-rich cells were motile, continuously extending, retracting and reorienting the dendritic processes, but did not appear to engage in active endocytosis.

Two companion papers under Steinman's first-authorship, published next year in JEM, elaborated in vitro and in vivo the functional characteristics of these cells. These papers noted that they are functionally distinct from large lymphocytes and pro-monocytes, as well as from other types of reticular cells in lymphoid organs. They also don't differentiate into macrophages and appeared not to retain antigens or immune complexes on their cell surface. However, in vivo they were postulated to play a role in modulating immunologic memory. As a result of subsequent work on DCs (both his own and that of others), we now know that plasmacytoid and myeloid DCs take up antigens from their surroundings by endocytosis, and are efficient antigen-presenting cells, presenting the antigens to CD4+ T-cells in lymph nodes and acting as a bridge between innate and adaptive immunity. For a nice summary of Ralph Steinman's work and how it shaped DC research, read Alla Katsnelson's 2006 article in JEM on the discovery of DCs.

A recipient of many key awards in his lifetime for his work on dendritic cells (notably, the Albert Lasker Award for Basic Medical Research - considered by many to be the rehearsal for Nobel - in 2007), Steinman was elected to the US National Academy of Sciences in 2001, and elected a member of the Institute of Medicine the next year. In 2011, the Nobel Prize Committee announced on October 3 that this year's prize in Physiology and Medicine is to be divided between Steinman, for "his discovery of the dendritic cell and its role in adaptive immunity" and the duo of Bruce Beutler and Jules A. Hoffmann for "their discoveries concerning the activation of innate immunity". Unfortunately, Nobel rules prohibit posthumous awarding of the prize; the Nobel Committee was unaware of his death when it made its decision. Currently, the Nobel Prize jury is discussing whether he would be allowed to keep his prize.

UPDATE: The Montreal Gazette is reporting that "The Nobel Prize for medicine awarded to Canadian-born research Ralph Steinman and two other scientists will stand, despite Steinman's death Friday from pancreatic cancer, the Nobel Foundation has confirmed." However, I haven't yet found independent confirmation of that.

UPDATE 2: As indicated by Austin in the comments, it has now been confirmed that Ralph Steinman remains as one of the recipients of the Nobel Prize this year. A Press Release from the Nobel Foundation indicates:

...the decision to award the Nobel Prize to Ralph Steinman was made in good faith, based on the assumption that the Nobel Laureate was alive. This was true – though not at the time of the decision – only a day or so previously. The Nobel Foundation thus believes that what has occurred is more reminiscent of the example in the statutes concerning a person who has been named as a Nobel Laureate and has died before the actual Nobel Prize Award Ceremony. The decision made by the Nobel Assembly at Karolinska Institutet thus remains unchanged.

Further Reading:

  1. RM Steinman, and ZA Cohn. 1973. J Exp Med. 137:1142-1162.
  2. RM Steinman, and ZA Cohn. 1974. J Exp Med. 139:380-397.
  3. RM Steinman, DS Lustig, ZA Cohn. 1974. J Exp Med. 139:1431-45.
  4. A Katsnelson. 2006. J Exp Med. 203:1622.
  5. "The 2011 Nobel Prize in Physiology or Medicine - Press Release". 3 Oct 2011

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