2007 Lasker Awards announced

Ralph Steinman of the Rockefeller University in New York will receive the 2007 Albert Lasker Award for Outstanding Basic Medical Research for his discovery of dendritic cells and his work in elucidating their function as sentinels of the immune system, the Albert and Mary Lasker Foundation announced on Saturday (September 15). The two inventors of mechanical and animal-derived prosthetic heart valves, Albert Starr of the Providence Health System in Portland, OR, and Alain Carpentier of H?pital Europeen Georges Pompidou in Paris, will share the Albert Lasker Award for Clinical Medical Research for their contributions to open-heart surgery. This year's Mary Woodard Lasker Award for Public Service will go to Anthony Fauci, head of the National Institute of Allergy and Infectious Disease, for his work on a government program to treat HIV/AIDS in the developing world, and a nationwide biodefense strategy in the US.

In the early 1960s and 70s, immunologists investigating T and B cell function isolated a spleen-derived suspension of "accessory cells" that appeared to be necessary to activate immune cells in vitro. Although some speculated that these cells were macrophages, no one knew which component of the pool was responsible for initiating the reaction. As a postdoc in the lab of Zanvil Cohn, an expert on macrophages, Steinman decided to find out. "We thought [activation] was the key thing," Steinman said in a recent interview.Upon culturing the pool of splenic cells, he noticed a rare cell type that on first glance resembled a macrophage. Unlike macrophages, however, these star-shaped cells lacked lysosomal compartments and were "sending out processes and probing their environment," Steinman said. In 1973, he published the first characterization of what he called dendritic cells, soon after demonstrating that they were the crucial players in the accessory cell mix, with a potency at least 100 times greater than that of the other splenic cells.Because dendritic cells were rare and difficult to isolate, researchers initially overlooked the significance of Steinman's discovery. "It took many years of painstaking experimentation to convince the leaders of immunology that dendritic cells were really important," said Joseph Goldstein, chair of the Lasker Awards selection committee. Together with Gerold Schuler, Steinman showed that Langerhans cells, which maneuver throughout the uppermost layer of the skin, were actually young dendritic cells. Later work demonstrated that these immature cells picked up foreign antigen from the body's periphery, then travelled to the lymph nodes where, as mature dendritic cells, they spurred immune cells into action. The differentiation of dendritic cells would come to define "the pivotal control point for the immune response," Steinman said. Steinman's work laid the foundation for current research on the use of dendritic cells as therapeutic vaccines for cancer and HIV. "I was delighted that dendritic cells were selected for the Lasker," said Steinman.

The award to Starr and Carpentier will honor their invention of prosthetic heart valves. In 1958, Starr and the late Lowell Edwards started working on the first mechanical heart valve, made out of silicon and hard Teflon. The device, which Starr implanted in the first patient two years later, revolutionized cardiology. "Before his prosthetic, patients with valvular disease would die," said Carpentier.

But the synthetic material from which the valves were made caused blood clots, requiring patients who got them to take blood thinners for the rest of their lives. Carpentier, a surgical resident in Paris at the time, believed he could solve the problem by transplanting valves from pig hearts, on which clots would not form. He knew, however, that the foreign tissue would be rejected by the immune system. To the dismay of his surgical mentor, he enrolled in a PhD program at the University of Paris to find a chemical treatment that would make the animal tissue tolerable to humans. He soon discovered that glutaraldehyde did the trick, and in 1968, he and a colleague implanted the first glutaraldehyde-treated valve in a patient. When Starr learned of the advance, he offered to help Carpentier commercialize the device through the company Edwards had created to manufacture his and Starr's mechanical valves. Thus, two would-be competitors became collaborators. Today more than 300,000 patients worldwide receive valve replacements annually, and Starr and Carpentier remain close friends. Carpentier went on to develop surgical methods to repair rather than replace heart valves. "He not only wrote the book on valve repair," said Starr of Carpentier, "he developed the alphabet that made up the words."

Anthony Fauci, the director of the, NIAID will receive the award for his work orchestrating the $15 billion President's Emergency Plan for AIDS Relief (PEPFAR) program, which supports 114 countries in creating prevention, treatment and care plans for the disease. Fauci recognized HIV as major public health crises when it first emerged in the 1980s. He re-focused his laboratory's efforts to study the molecular mechanism of HIV infection, and was the 10th most-cited HIV/AIDS researcher between 1996 and 2006. "Because of his scientific credibility, and his unflappable confident manner," said Goldstein, "he has been able to convince members of the legislature and the government, who are not that enthusiastic about science," to devote resources to public health issues. The award also honors Fauci's development of Project Bioshield, a cohesive national strategy for responding to the threat of bioterrorism in the wake of the attacks of September 11, 2001. "It's humbling," said Fauci "to be recognized for something that I feel privileged and honored to have been a part of." Fauci's influence as a scientist is commensurate with his influence as an advisor on science to the government, as well to the public. "I do wear many hats," said Fauci, "but that just makes each individual hat all the more exciting." The awards, which carry an honorarium of $150,000 each, will be presented during a luncheon ceremony at the Pierre Hotel in New York City on Friday, September 28. Edyta Zielinska mail@the-scientist.comAndrea Gawrylewski contributed reporting to this article.Links within this article:Ralph Steinman http://www.rockefeller.edu/research/abstract.php?id=150Albert and Mary Lasker Foundation http://www.laskerfoundation.orgA.S. Fauci, "First Person: Anthony Fauci," The Scientist, May 5, 2003. http://www.the-scientist.com/article/display/13734/R.M. Steinman and Z.A. Cohn, "Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution," J Exp Med, May 1, 1973. http://www.the-scientist.com/pubmed/4573839R.M. Steinman and M.D. Witmer, "Lymphoid dendritic cells are potent stimulators of the primary mixed leukocyte reaction in mice," PNAS, October, 1978. http://www.the-scientist.com/pubmed/154105Gerold Schuler http://www.cancerresearch.org/cvc2002/gerold_schuler.html G. Schuler and R.M. Steinman, "Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro." J Exp Med, 161:526-46, 1985 http://www.the-scientist.com/pubmed/3871837K Inaba et. al., "Dendritic cells as antigen-presenting cells in vivo," Int Rev Immunol, 6(2-3):197-206, 1990. http://www.ncbi.nlm.nih.gov/sites/entrezI. Mellman, "Where Next for Cancer Immunotherapy," The Scientist, Jan, 2006. http://www.the-scientist.com/article/display/18859K. Travis, "Deciphering immunology's dirty secret," The Scientist, January 1, 2007. http://www.the-scientist.com/article/display/39377Edwards Lifesciences http://www.edwards.comPod-cast with Fauci on HIV research, The Scientist, September 5 2007. http://www.the-scientist.com/podcasts/theweek/2007/09/05/President's Emergency Plan for AIDS Relief http://www.pepfar.gov/Project Bioshield http://www.whitehouse.gov/infocus/bioshield/