When The Rockefeller Institute for Medical Research was founded in 1901, infectious diseases were a public health concern of urgent proportions. Pneumonia alone claimed the lives of more than 50,000 people a year in the United States, and laboratories and physicians across the world were focused on stemming the ravaging effects of Streptococcus pneumoniae. Approaching the problem from a biochemical perspective, Rockefeller researchers led by Oswald T. Avery laid open the complex biological, immunological and pathological properties of the bacterium, thereby laying the groundwork for the development of innovative therapies and establishing immunochemistry as the most effective means to define disease-causing microbes. For his exhaustive research on the pneumococcus, Dr. Avery was awarded the 1947 Albert Lasker Basic Medical Research Award.
At the turn of the century, German bacteriologist Friedrich Neufeld discovered that S. pneumoniae exists in different strains, each of which produces a signature immunological response in a host. Dr. Neufeld classified three major strains of the bacterium, and researchers at The Rockefeller Institute Hospital identified a fourth soon after. By 1912, they had also created a largely successful serum against type I pneumococcus, which they determined to be the most prevalent type. Dr. Avery, who joined the hospital as a research assistant in 1913, was first assigned to test the effectiveness of the new antiserum. By 1921, he had significantly improved upon it, but he was convinced early on that the best way to combat the bacterium was to get to the bottom of its immune specificity, particularly its biochemical nature.
Hypothesizing that specificity might be conferred by the protective capsule surrounding virulent types of the bacterium — and absent from avirulent strains — Dr. Avery and his colleagues first compared the germ-free blood serum and urine of pneumonia patients to virulent cultures of the bacterium and observed the presence of the same immune-responsive substances in both. “Specific soluble substances” (SSS) as he called them, led to the development of a diagnostic method that was dramatically faster than the previously used method of analyzing patient cultures.
The experiment also bolstered Dr. Avery’s controversial theory that the bacterium’s immunological agent was not part of the germ itself, and his next step was to break down the capsule of each pneumococcal type so he could analyze its chemical constituents. Working with Michael Heidelberger, a noted chemist at The Rockefeller Institute Hospital, Dr. Avery determined by 1923 that the SSS are indeed part of the protective capsule rather than the germ, and that — contrary to the scientific wisdom that assigned the job of antigen to proteins only — the capsules are made of carbohydrates, specifically complex polysaccharides composed of sugar molecules. Dr. Avery began referring to pneumococcus as “the sugar-coated microbe.” To silence the remaining skepticism — which held that an undetected protein contaminant was the real cause of immune specificity — Dr. Avery, with Walter Goebel, another chemist at the hospital, completed an in-depth series of experiments creating artificial antigens by combining common, unantigenic proteins with the individual disaccharide components of each pneumococcal capsule.
By the time of his retirement in 1948, Dr. Avery’s work on the pneumococcus had produced the most comprehensive knowledge of any known infectious microbe. In addition to identifying the source of its immune specificity, he, along with various colleagues, delineated the immunological relationships of the intracellular components of the bacterium; identified the enzymes and reduction-oxidation systems responsible for metabolic regulation in pneumococcal cells and characterized their roles in virulence; established general principles governing the antigenic power of all pneumococci; and designed methods subsequently used for the antigenic analysis of other microorganisms. In his later research, Dr. Avery also became one of the founders of modern genetics, as leader of the Rockefeller team including Maclyn McCarty and Colin M. MacLeod that in 1944 identified DNA as the carrier of hereditary information. Dr. Avery shared the 1947 Lasker Award with Homer Smith of New York University School of Medicine.
CAREER
Dr. Avery was born in Halifax, Nova Scotia, Canada, in 1877 and moved with his family to New York City 10 years later. Following undergraduate studies at Colgate University, in which he excelled at literature, public speaking and debate, he entered the Columbia University College of Physicians and Surgeons, from which he received his M.D. in 1904. In 1907 he accepted a research and teaching position at the Hoagland Laboratory, a privately endowed bacteriological research center in Brooklyn, New York. Dr. Avery received United States citizenship in 1918 and served as captain in the U.S. Army Medical Corps during World War I. He became a member of The Rockefeller Institute in 1923 and continued his research there until his retirement in 1948. During his career, Dr. Avery served as president of the American Association of Immunologists, the American Association of Pathologists and Bacteriologists and the Society of American Bacteriologists. He was a member of the National Academy of Sciences and The Royal Society. In addition to the Lasker Award, he received a Pasteur Gold Medal from the Swedish Medial Society, a Passano Award, and a Copley Medal from The Royal Society. Dr. Avery died in 1955.