This past Monday the Nobel Prize in Physiology or Medicine was awarded to a very deserving candidate: Ralph Steinman. Steinman, however, never received the final good news, as he passed away from pancreatic cancer just three days prior to the announcement. He is the first laureate to be awarded a posthumous Nobel Prize, which is against the regulations of the foundation.1 Steinman was awarded the prize for his discovery of dendritic cells, “a kind of sentinel”2 looking for pathogens in the body.
Dendritic cells (DCs) were given their descriptive name due to their physiological appearance, with many finger-like extensions that protrude from the main cell body increasing the surface area of the cell for the intake and output of information from and to other cells in the body. Dendritic cells come in several different types. Some DCs, called “migratory” DCs, roam the periphery of the body searching for foreign substances or dead cells that they can engulf. The internalized substances are then processed in the DC and presented on the cell’s surface, so that a passing B or T cell might recognize the presented pathogen and go find it in the body to fight. “Resident” DCs reside in the lymph nodes of the body, sampling the lymph for pathogens and undergoing the same pathways of processing and presenting pathogens as the migratory DCs.
Steinman first discovered dendritic cells in 1973, and died three days before his work was recognized with the highest of honors: the Nobel Prize. Upon his initial discovery, the scientific community was hesitant to accept Steinman’s finding, as his results did not seem reproducible. Reproducibility is the hallmark of a significant scientific finding, and so it was not until many years later, when dendritic cells were isolated in large quantities, that Steinman’s finding was widely accepted and celebrated. Modernly, dendritic cells are arguably considered to be one of the most significant elements of the immune system. Dendritic cells are antigen-presenting cells (APCs), which gives them the capability to express both endogenous and exogenous antigens, and they also possess the ability to activate B and T cells, which have cytotoxic capabilities.
In addition to their antigen-presenting and activating properties, dendritic cells can “phagocytose” and “degranulate”. Phagocytosis is the process by which these cells engulf a foreign body or a dead self cell and internalize it. The proteins in such a body may be broken down inside the dendritic cell and presented on the cell’s surface for B and T cell recognition. Degranulation is the process by which the DCs release small granules, which may have anaphylatoxins, histamines, and other unfriendly substances as components. Other granulocytes are eosinophils, basophils, and mast cells, which contain many interior granules that can be viewed under a microscope when stained with eosin and hematoxylin.
The discovery of dendritic cells is as significant as the prestigious award indicates. The implications for potential disease treatments are astounding. In fact, dendritic cells have already been implicated as cancer therapy targets in prostate cancer and have been used in a recent vaccine for melanoma.2 In possibly the most remarkable aspect of Steinman’s discovery and story, the researcher himself used his dendritic cells to invent a personal vaccine to help combat his own pancreatic cancer.1 While the success of the self-vaccination cannot be pinpointed, Steinman did outlive the average pancreatic cancer patient by quadruple the infected life expectancy.2
Ralph Steinman’s discovery of dendritic cells made an invaluable contribution to the field of immunology. Although it took many years for the expansive nature of his discovery to be recognized, in his last years of life he was widely commended for his find. He was aware of his consideration for the Nobel Prize, and while he was not informed of his final status as a winner, the designation is one that will serve his legacy well. Steinman was one of three Nobel Prize recipients in Physiology or Medicine this year, and of the three he was the primary winner. He was awarded one half of the prize, and his two companion winners were each awarded one quarter.1 The two other winners, Bruce Beutler and Jules Hoffmann, contributed to the discovery of a receptor found in fruit flies and mice, respectively. This receptor is expressed on Steinman’s dendritic cells and is found to form a catalytically active dimer upon activation. It is clear that Steinman’s legacy will live on in the works of others and that his contribution to health science cannot be underestimated.
Reference: Messina, J., 2011. “Nobel prize-winner Ralph Steinman”. Crain’s New York Business. 9 Oct 2011 http://www.crainsnewyork.com/article/20111009/SUB/310099977
1Everts, S., 2011. “Nobel Prize in Physiology or Medicine”. Chemical & Engineering News. 9 Oct 2011 http://pubs.acs.org/cen/news/89/i41/8941notw8.html
2Messina, J., 2011. “Nobel prize-winner Ralph Steinman”. Crain’s New York Business. 9 Oct 2011 http://www.crainsnewyork.com/article/20111009/SUB/310099977
Steinman image: "Ralph M. Steinman - Biographical". Nobelprize.org. 9 Oct 2011 http://www.nobelprize.org/nobel_prizes/medicine/laureates/2011/steinman.html
DC image: Gitig, D., 2010. “Crohns Disease Treatment Also Helps Protect the Gut from Infection”. Highlight Health. 9 Oct 2011 http://www.highlighthealth.com/research/crohns-disease-treatment-also-helps-protect-the-gut-from-infection/
For more information about this year’s Nobel Prize in Physiology or Medicine, see: http://pubs.acs.org/cen/news/89/i41/8941notw8.html
For more information about dendritic cells, see:
Wieder, E., et al. 2003. “Dendritic Cells: A Basic Review”. International Society of Cell Therapy. 9 Oct 2011 http://www.celltherapysociety.org/files/PDF/Resources/OnLine_Dendritic_Education_Brochure.pdf