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Dr. Stephen Malawista

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Dr.  Stephen Malawista Obituary
MALAWISTA, DR. STEPHEN Dr. Stephen Malawista, Professor of Medicine and former Chief of Rheumatology at Yale University, who supervised the group that discovered Lyme disease and whose laboratory research on white blood cells led to seminal discoveries in a variety of inflammatory diseases, including gout, died on September 18, 2013 at his home in Hamden. He was 79. He succumbed to a 5-year battle with metastatic melanoma, his family said in announcing his death. Dr. Malawista was the son of Lawrence Malawista, a New York City real estate developer, and Ann Marlowe (later Straus), a theatrical producer and former chairman and president of the Board of the Berkshire Theatre Festival. He attended the Berkshire School in Sheffield, MA and graduated magna cum laude from Harvard College. After completing his MD degree at Columbia University College of Physicians & Scientists, he trained as a house officer at Yale under Paul Beeson, an expert in infectious diseases and the origin of fever. Inspired to study inflammation, he interrupted his clinical training to spend two years under the tutelage of Bert LaDu and Jay Seegmiller at the National Institute of Arthritis and Metabolic Diseases (NIAMD), followed by a Special Fellowship of the NIAMD at Yale under Aaron Lerner. He joined the Yale faculty in 1966 where, during 21 years as Chief of Rheumatology, he built what began as a one-man operation into a major, internationally recognized Section that fostered the careers of many renowned physician scientists, including that of his first year fellow, Allen Steere, the co-discoverer of Lyme disease. In the fall of 1975, Steere was 4 months into his postdoctoral training in rheumatology at Yale when he was contacted by his former colleague at the CDC, David Snydman, then acting director of preventable diseases at the CT State Health Department, about an unusual clustering of "juvenile rheumatoid arthritis" cases in the towns of Lyme, Old Lyme and East Haddam. Malawista, recognizing the potential significance of this outbreak, supported Steere's suspending his research in the laboratory to determine what was going on in Lyme. "If we could solve the problem of 'Lyme' arthritis" - a name coined by Malawista - "it would give us entree to all sorts of other diseases," Malawista told the NYTimes in 1976. "It would be very exciting. Lyme arthritis could be the key to much of what we don't know about arthritis." He later often said that Lyme disease was "Infectious in origin, rheumatic in expression." Interviews of the people living in those three CT towns linked arthritis to a preceding skin rash similar to one associated with tick bites in Europe. A year later, Steere and Malawista published the seminal paper reporting the results of their initial investigation and their postulate that the arthritis was due to a tick-transmitted pathogen. Over the next decade, they were at the forefront of research that led to the elucidation of Lyme disease-its natural history, antiquity, epidemiology, pathogenesis, etiology, molecular biology and diagnosis, treatment, and prevention by vaccination. Prior to the discovery of Lyme disease, Malawista was already well known for his research on the motility and function of white blood cells in the context of the inflammatory response. His custom and pleasure had been to study these inflammatory mechanisms in the context of human disease-especially gout-and he continued this line of work, adding Lyme disease to the panoply of human inflammatory states he studied. His early work in gout, an arthritis triggered by white blood cell ingestion of urate crystals, showed that colchicine worked to reduce gouty inflammation by its actions on the white blood cell microtubules, the hollow tubes that make up the skeleton of the cell whose assembly are responsible for cell division and motility. His work on the cellular events leading to an attack of acute gouty arthritis pinpointed the monocyte white blood cell as the driver of inflammation, recruiting neutrophils (another type of white blood cell) to propagate the inflammatory paroxysm, a model illustrated in his 2011 FASEB Journal publication Bunbury's Dream, adapted from the image Bunbury, Henry William, 1750-1810: "Origin of the Gout". His years at Yale were punctuated by multiple sabbaticals in Paris, France where he continued studies of neutrophils in the laboratory of Marcel Bessis. Following up on an observation made earlier by Bessis and H.U. Keller that after gently heating a neutrophil, its body would simply "walk away" and detach from its nucleus, he showed that this "headless" marauder retained its ability to seek out, eat and kill bacteria. Decades later, in 2012, similar anucleate soldiers were shown to form in vivo as neutrophils die, producing "nets" capable of continuing a defense until new recruits arrive. Although Bessis died in 1994, Malawista returned to Paris each year for several weeks to continue his studies with Anne Chevance de Boisfleury, their long-standing research assistant. His most recent work, published in June, revealed that a neutrophil could "pilfer the cargo" of another neutrophil that had ingested particles, performing a Houdini act that left the violated cell intact. Malawista's achievements were summed up in his citation for the 1994 Distinguished Investigator Award of the American College of Rheumatology, "Malawista is one of the most creative investigators of our time. He thinks in a bright and focused way about problems. He recognizes the kernels of the unknown in them, surrounds them with the known, and searches through this mechanism for insight in how to answer the questions that exist." Malawista received numerous other honors and awards for his achievements, including the Ciba-Geigy/International League Against Rheumatism Prize (1985), shared with Steere for the discovery and elucidation of Lyme disease; President, American College of Rheumatology (1991-92); Fellow, American Association for the Advancement of Science (1998); Docteur Honoris Causa, University of Paris Ren Descartes (1998); Master, American College of Rheumatology (1999); the Guggenheim Fellowship (2001); the Paul Klemperer Medal and Lecture of the New York Academy of Medicine (2002); and the Gold Medal (highest award) of the American College of Rheumatology (2003). He served on the Advisory Committee for the Harvard-MIT Division of Health Sciences and Technology (1989-2003); and was a Founding Fellow of the Biotechnology Study Group at New York University (since 2000). Raised by a mother with a love of theatrical arts, Malawista's other passion was singing and dancing, and he often performed with his beloved wife of 44 years, Tob Anne Miller Malawista, who founded the vocal chamber music group The Mirror Visions Ensemble with Richard Lalli (Yale Professor of Music) and Scott Murphree (Adjunct Professor of Voice, NYU Steinhardt School). Continued.......

Published in The New Haven Register on Sept. 22, 2013
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