Nobel winner dies three days before prize announcementBMJ 2011; 343 doi: https://doi.org/10.1136/bmj.d6389 (Published 04 October 2011) Cite this as: BMJ 2011;343:d6389
This year’s Nobel prize in physiology or medicine has been won by three researchers whose work offers insights into the activation and regulation of the immune system. Announcing its decision in Stockholm on 2 October, the awards committee said that the work had opened the way to developing new methods for preventing and treating disease.
The three winners are Bruce Beutler, a professor of genetics and immunology at the Scripps Research Institute in La Jolla, California; Jules Hoffmann, who worked at the University of Strasbourg until 2009; and Ralph Steinman, director of Rockefeller University’s Center for Immunology and Immune Diseases in New York.
Unbeknown to the Nobel Assembly, Dr Steinman had died of pancreatic cancer on 30 September. In a statement issued on 3 October the assembly said that notwithstanding its own statutes, which disqualify posthumous awards, Steinman would keep the prize.
The awards committee said that the scientists’ discoveries could lead to better vaccines and the possibility of stimulating the immune system to attack tumours. “These discoveries,” the committee added, “also help us understand why the immune system can attack our own tissues, thus providing clues for novel treatments of inflammatory diseases.”
Professor Hoffmann and Professor Beutler have received their half of the prize for identifying the sensors of immunity. Professor Hoffmann made his discovery in 1996 in experiments on fruit flies. When he and his co-workers infected them with microbes, those flies with a mutation in a gene called Toll were unable to mount an effective defence and died. Professor Hoffmann concluded that the product of the Toll gene was involved in sensing pathogenic microbes, and that unless it was activated the fly’s defence system would not function. But while fruit flies are useful models, their workings aren’t always identical to those of humans.
It was Professor Beutler who provided reassurance. In 1998 he was searching for a cell receptor that could bind the bacterial product (lipopolysaccharide) responsible for septic shock. His group discovered that mice that were resistant to this product had a mutation in a gene similar to the fruit fly’s Toll gene. It soon became clear that mammals and fruit flies use similar mechanisms to activate their innate immune systems.
“This is an excellent Nobel prize,” said Mark Walport, director of the health research charity the Wellcome Trust in London. “Our understanding of the activation of the immune system has been revolutionised by the work on innate immunity by Jules Hoffmann and Bruce Beutler.”
Dr Steinman received his half of the prize for the 1973 discovery of the role of dendritic cells. He showed that these can activate T cells, the members of the immune cell family that play a key role in adaptive or learnt immunity and in immunological memory.
“He’s the man who realised that dendritic cells were important,” said Peter Lachman, emeritus professor of immunology at Cambridge. “He realised that they were separate from macrophages and that they played a hugely important role in antigen presentation.”
Dr Steinman and others went on to demonstrate the modulating role of the dendritic cells. Responding to signals generated by the body’s innate immune system, these cells play a part in deciding whether to activate the body’s adaptive immunity. While they must react to pathogenic microbes, they must be equally adept at preventing the system reacting inappropriately and turning on itself.
Cite this as: BMJ 2011;343:d6389