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Immune System Pioneers Share America’s Largest Prize in Medicine

Albany, N.Y., April 24, 2009—Ralph M. Steinman, M.D., of Rockefeller University, Charles A. Dinarello, M.D., from the University of Colorado, and Bruce Beutler, M.D., of The Scripps Research Institute in La Jolla, CA—whose groundbreaking discoveries have transformed the field of immunology—have been named the 2009 recipients of the Albany Medical Center Prize in Medicine and Biomedical Research. The $500,000 Prize is the largest award in medicine or science in the United States.

The co-recipients of the Prize, who will share the award, were honored at a news conference and luncheon held today at the Hilton Garden Inn at Albany Medical Center.

“Collectively, the work of these scientists has led to a dramatically better understanding of the human immune system, in health and in disease,” said James J. Barba, president and chief executive officer of Albany Medical Center, who served as chairman of the National Selection Committee. “That knowledge has already directly resulted in new therapies for people with conditions including rheumatoid arthritis, diabetes, Crohn’s disease and cancer. And, the discoveries they have made about how the body senses and responds to infection remain the basis of active research that holds the promise of new and improved vaccines and innovative ways to harness the power of the immune system to better fight viruses and bacterial illness. Their achievements are nothing short of astounding.”

This is the ninth year the Albany Medical Center Prize has been awarded. It was established in 2000 by the late Morris “Marty” Silverman to honor scientists whose work has translated from “the bench to the bedside” resulting in better outcomes for patients. A $50 million gift commitment from the Marty and Dorothy Silverman Foundation to Albany Medical Center provides for the Prize to be awarded annually for 100 years.

Like all vertebrates, the human body has two immune systems that work separately and in combination—adaptive immunity (the more widely understood), which learns to recognize and respond to specific bacteria, viruses and other microbes over time using receptors, or “signaling messengers,” located on white blood cells; and innate immunity, which recognizes and responds instantly (without prior exposure) to fight off the countless infectious agents and microbes people are exposed to daily.

Defined in the early 1900s, knowledge about how adaptive immunity works translated into the development of many effective vaccines including those for measles, polio and influenza.

But the question, “How do you start this immune response?’ had yet to be answered until Drs. Steinman, Dinarello and Beutler effectively figured it out, and forever changed the field of immunology.
 
The first revelation came in 1973 at a lab at Rockefeller University when Dr. Ralph Steinman, who is now the Henry G. Kunkel Professor in Rockefeller’s Laboratory of Cellular Physiology and Immunology, discovered a previously unknown type of white blood cell—which he named the dendritic cell. These pivotal cells turned out to be the “missing link” in innate immunity; as its central regulator, they process germs to initiate the front-line immune response. Dendritic cells, ever watchful for invaders, “tell” other white blood cells called T-cells to multiply and get the immune system ready to “fight the enemy” or they give the word to other cells to ignore agents that will not harm the host.

Dr. Steinman’s work, including his success in growing large numbers of dendritic cells in the lab, opened a new field of study focusing on the role of dendritic cells in immune function, their potential for vaccine enhancement and the treatment of autoimmune disorders and even cancer. For example, in clinical research studies, scientists are putting tumor cells along with dendritic cells into test tubes, allowing the dendritic cells to develop an anti-tumor response. These “revved up” dendritic cells are then put back into a patient in the hopes that they will more effectively fight the tumors. Other dendritic-cell therapies also are being designed to combat allergies.

As studies of dendritic cells show, immune responses can be obviously beneficial, but in some cases our response to disease turns out to be quite harmful. At the heart of the problem is inflammation, which dendritic cells (and, it turns out, many of their protein products collectively known as cytokines) trigger to fight infection. The right amount of inflammation at the right time and in the right place is a good thing. However, if that inflammatory response happens in the bloodstream, it results in sepsis, an overwhelming reaction that is the 10th leading cause of death in the United States. Likewise, an immune response triggered in error against the body’s own tissues results in the runaway inflammation characteristic of autoimmune disorders like lupus and rheumatoid arthritis.

To this end, Dr. Charles Dinarello’s groundbreaking work on anti-cytokine therapies that block the immune system’s inflammatory reaction also opened an entire new field of study in immunology called cytokine biology. In the 1970s, while working at the NIH and later at Tufts University School of Medicine in Boston, Dr. Dinarello identified and purified the body’s key fever-producing molecule, later named Interleukin-1 (IL-1). Dr. Dinarello led the team that first cloned IL-1 in 1984. Released by white blood cells during infections and immune reactions, IL-1 tells the body to produce inflammation.

Dr. Dinarello, currently professor of medicine at the University of Colorado Denver School of Medicine, has since focused on blocking IL-1 to quell inflammation. This work, and the subsequent discovery of many other Interleukins, has resulted in therapies for rare immune disorders and more common ones including Crohn’s disease, diabetes, allergies, rheumatoid arthritis, and graft-versus-host disease in transplant patients. In addition, anti-cytokine therapies and the ability to manipulate cytokines hold promise for treatment and/or vaccination for patients with sepsis, cancer and viral diseases including HIV.

Similarly, Dr. Bruce Beutler, professor and chairman of the department of genetics at Scripps, is famous in scientific circles for defining the role of another key cytokine termed Tumor Necrosis Factor (TNF). In the 1980s, while at Rockefeller University, Dr. Beutler isolated TNF and demonstrated its role as an additional mediator of immune system-generated inflammation. Like the discovery of IL-1, this knowledge has directly resulted in improved outcomes for people with chronic inflammatory diseases; specifically, Dr. Beutler created recombinant inhibitors of TNF, now widely use as Enbrel, a first-line treatment for people suffering from rheumatoid arthritis, psoriasis, ankylosing spondylitis, juvenile rheumatoid arthritis and other autoimmune disorders. The drug works by blocking TNF to reduce inflammation.

In the 1990s, while at the University of Texas Southwestern Medical Center in Dallas, Dr. Beutler went on to discover the key proteins used by the innate immune system to “see” viruses, bacteria, and fungi. These are the TLRs (toll like receptors), which ignite the immune response within minutes of the time an infection begins. The TLRs protect us from infections, but paradoxically, also cause much of the morbidity associated with infections. An immunologist and geneticist, Dr. Beutler is a world leader in “forward genetics,” a technique used to identify critical genes supporting the innate immune system. His work has pointed to several genetic mutations in people who are predisposed to sepsis and other diseases.

Dr. Steinman was born in Montreal in 1943. He received a B.S. from McGill University in 1963, and an M.D. from Harvard Medical School in 1968. Following an internship and residency at Massachusetts General Hospital, he joined Rockefeller University in 1970 as a postdoctoral fellow in the Laboratory of Cellular Physiology and Immunology. He was appointed an assistant professor in 1972, associate professor in 1976, and professor in 1988. He was named Henry G. Kunkel Professor in 1995 and director of the Christopher H. Browne Center for Immunology and Immune Diseases in 1998.

Dr. Beutler was born in Chicago in 1957, and grew up in Southern California. He graduated from the University of California, San Diego in 1976 at the age of 18, and received his M.D. from the University of Chicago in 1981 at the age of 23. He performed an internship and residency at the University of Texas Southwestern Medical Center in Dallas, and was later a postdoctoral fellow and an assistant professor at Rockefeller University. Between 1986 and 2000, Beutler was a professor and HHMI investigator at the University of Texas Southwestern Medical Center. He returned to Southern California in 2000 when he was appointed professor in the department of immunology at Scripps in La Jolla. In 2007 he was named chair of the department of genetics.

Dr. Dinarello was born in 1943 in Boston. He received his medical degree from Yale University and performed a residency at Massachusetts General Hospital. In the 1970s, he was a clinical associate and senior investigator at the National Institutes of Health in Bethesda, MD. Until 1996, he was a professor of medicine and pediatrics at Tufts University School of Medicine and a staff physician at New England Medical Center Hospital in Boston. He joined the faculty at the University of Colorado in 1996. The Institute for Scientific Information lists him as the world’s fourth most cited scientist in the 20 years, 1983-2002.

All three pioneers have extensively published research and have been cited by countless medical and scientific journals including the Lancet, Nature, The New England Journal of Medicine and the Journal of the American Medical Association. They have received numerous other prestigious national and international awards and honors as well as a number of honorary degrees.

For more in-depth biographies of the 2009 winners, and information on previous winners of the Albany Medical Center Prize in Medicine and Biomedical Research, go to: www.amc.edu/Academic/AlbanyPrize.

Albany Medical Center is one of only 125 academic health sciences centers in the nation and the only such health care institution in northeastern New York. With more than 7,000 staff members, this leading not-for-profit health care institution constitutes the largest private employer in Albany.  It includes one of New York’s largest teaching hospitals, Albany Medical Center Hospital (founded in 1849); one of the nation’s oldest medical schools, Albany Medical College (founded in 1839); and one of the Capital Region’s most active fundraising organizations, the Albany Medical Center Foundation, Inc.
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*Questions & Comments:

Greg McGarry
Extension: (518) 262 - 3421
  McGarrG@mail.amc.edu



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