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October 3, 2011

Nobel Prize In Physiology Or Medicine

Awards: Three researchers share prize for their work on immunity

Sarah Everts

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Beutler Scripps Research Institute
Beutler

Hoffmann CNRS
Hoffmann

Steinman Rockefeller U
Steinman

For their pioneering work in innate and adaptive immunity, Bruce A. Beutler, Jules A. Hoffmann and the late Ralph M. Steinman were today awarded the 2011 Nobel Prize in Physiology or Medicine. These fields of research have revealed the foundation of how our bodies detect, fight, and remember invading pathogens.

The Nobel Committee has never announced a prize award posthumously, but, according to Agence France Presse, it will allow Steinman’s award to stand. He died on Sept. 30, a fact that was unknown to the assembly at the time of its award announcement. In the past, the committee has allowed awards to stand when the recipient died between the announcement of the award and its official presentation in Sweden in December.

The prize winners’ research “has opened up new avenues for the development of prevention and therapy against infections, cancer and inflammatory diseases,” according to the Nobel Prize announcement. In addition, the trio’s “fantastic discoveries” also help explain how vaccines work, said Hans-Gustaf Ljunggren, a member of the Karolinska Institute, the home of the awards in Sweden.

Half of the roughly $1.5 million prize will be given to Jules A. Hoffmann and Bruce A. Beutler for their work in the 1990s on innate immunity, which is the body’s first line of defense against invading pathogens.  It is unknown how Steinmann’s share of the prize money will be distributed.

Hoffmann, 70, of the Molecular & Cellular Biology Institute at France’s National Center for Scientific Research (CNRS) in Strasbourg, discovered that fruit flies that lacked the gene for a receptor protein called Toll died during bacterial and fungal invasions.

It turns out the Toll receptor is a fruit fly’s first line of defense against foreign invaders; Toll’s activation leads to the destruction of the pathogen and the triggering of an inflammation response that further blocks microbial attack. “There’s a very famous photo of a dead fly from Hoffman’s work” that did not survive an attack from pathogen microbes, says Felix Randow, who studies innate immunity at MRC Laboratory of Molecular Biology in Cambridge, England. “It’s iconographic. This prize is well deserved.”

Two years after Hoffmann’s 1996 discovery of Toll, Beutler, 53, a geneticist at the University of Texas Southwestern Medical Center, discovered the equivalent of the fruit fly’s Toll in mice, which he named Toll-like receptor (TLR). This mouse receptor binds lipopolysaccharides on invading bacteria, which stimulates the innate immune system.

These two receptors “were the tip of the iceberg,” Randow says. With Toll and TLR in hand, researchers soon managed to identify other components of the innate immunity network, he adds.

Steinman is one of the prize winners for his discovery of the role dendritic cells play in adaptive immunity, the body’s second line of defense against invading pathogens.

Dendritic cells “are the command center” of the body’s immune system, explains Alexander Betz, who studies adaptive immunity at MRC Laboratory of Molecular Biology. After the initial detection of foreign invaders by the Toll or TLR receptors, dendritic cells process the danger signals from these receptors and then instruct other immune cells called T cells to fight infection and develop a memory of the invading pathogen, Betz explains.

According to a 2007 feature on Steinmann in the Journal of Experimental Medicine, his work in the 1970s “generated a spirited debate about whether [dendritic] cells were a new class of white blood cells or merely an artifact. Many opponents thought they were too rare to make a difference” (DOI: 10.1084/jem.20071995).

Steinmann, a cell biologist at Rockefeller University, proved that these dendritic cells are the “hub” of our immune system, a discovery that informs all of modern immunology research, Betz adds.

When Steinman was diagnosed with pancreatic cancer four years ago, he extended his life by “using a dendritic-cell-based immunotherapy of his own design,” notes a Rockefeller University press announcement.

The Immune System © 2011 Nobel Prize Committee for Physiology or Medicine
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2011 American Chemical Society
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