Maclyn McCarty

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A 1946 retirement resulted in McCarty being asked to head a specialized 1922-established laboratory. This lab was the scientific home of Rebecca Lancefield, who developed a major classification system. His work, combined with hers, made it clear that conditions affecting the joints and the heart resulted in infections several weeks later. The causal chain of events still eludes us. McCarty attacked this problem by studying both the biology and Rockefeller Hospital patients with acute rheumatic fever.

Together with his students and collaborators, over the next 20 years, McCarty's work changed the understanding of the organism from a gram-positive streptococcus with a particular serological characteristic to one of the best characterized bacterial species. Work on bacterial cell-wall anatomy and chemistry was just beginning. His work led to the isolation of the streptococcal cell wall as a structural entity suitable for anatomic inspection by electronmicroscopy. Chemical dissection led to characterization of the group A–specific polysaccharide and the peptidoglycan, and the identification of its serological specificity in the terminal hexosamine. In order to prove this specificity, he first had to identify and purify a specific enzyme that cleaved hexosamine (a hexosaminidase) from a soil organism. Treating the polysaccharide with this enzyme abrogated its serological reactivity. McCarty further demonstrated the precise configuration of the hexosamine linkage by synthesizing both α- and β-N-acetyl-glucosamine ovalbumin and showing that only the second reacted with group A antisera. A similar analytical strategy indicated that the polysaccharide of group C streptococci differed by having a terminal β-N-acetyl galactosamine as the serological determinant.

In parallel, McCarty studied patients with rheumatic fever admitted to the Rockefeller Hospital as well as valuable specimen collections from military outbreaks of the disease during World War II. He and his collaborators found that antibody responses to several streptococcal antigens were significantly higher in the group of individuals that developed acute rheumatic fever than in individuals with uncomplicated infection. However, the response to unrelated antigens, for instance, diphtheria toxoid, was not enhanced. He found that group A streptococci secreted unusually high amounts of DNase, and established a test for the detection of antibodies produced in response to this antigen. This led to the discovery that streptococci were able to produce multiple isozymes of DNase. He purified human C-reactive protein through crystallization, produced a highly specific antiserum, and, using this much simpler and more sensitive test, found that C-reactive protein levels responded more rapidly and reliably than other inflammatory markers and could serve as the most accurate indicator of rheumatic inflammatory activity. Measuring C-reactive protein levels to detect inflammation is routine now in medical practice.

In his later years, McCarty increasingly served as a statesman of the biomedical sciences. He served for 14 years as the physician-in-chief of the Rockefeller University Hospital, and as a trusted adviser and the vice president of the Rockefeller University. Outside the university, his leadership was sought by the New York City Health Research Council, the Helen Hay Whitney Foundation, the Institute of Medicine (as a charter member), and numerous university visiting boards. For more than 40 years, as editor, he placed his stamp of excellence and integrity on the Journal of Experimental Medicine. He was a member of the United States National Academy of Sciences, the American Academy of Arts and Sciences, and the American Philosophical Society.

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