IMMUNOLOGICAL TOLERANCE AS A DEVELOPMENTAL PHENOMENON

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Abstract
MY ATTRACTION to research and to the general problems of resistance and immunity can be directly traced to events of an internship thirteen years ago when I was stimulated by the clinical problem of neonatal sepsis. In my first attempts to understand some of the underlying mechanisms, I was drawn irrevocably into the center of scientific ferment which was then growing in the Department of Pediatrics at the University of Minnesota. Here McQuarrie had brought under one roof, nearly simultaneously, Robert Good, Lewis Thomas, Chandler Stetson, Lewis Wannamaker, and Floyd Denny. To each of them, as teacher, colleague, and abiding friend, I acknowledge an enduring debt, for they exposed me to their imaginative ways of thinking habits of productivity, high scientific standards, and devotion to truth. My colleagues of the subsequent years—Robert Bridges, Donald Eitzman, John Robbins, and Joseph Bellanti—have each contributed their ideas, hard work, and enthusiasm to building the body of data for which this Mead Johnson Award is bestowed. We are signally honored and are sincerely grateful to the American Academy of Pediatrics and to the donors of the prize. When the startling discovery of immunologic tolerance was made by Peter Medawar and his colleagues in 1953, our minds were prepared to accept the premise that profound immunologic deficiencies were characteristic of the neonatal period. The few clinical and experimental data available until then indicated clearly that the newborn infant was a poor antibody former, dependent upon an umbrella of transplacental antibody until the third or fourth month of life; that he was highly susceptible to bacterial and certain viral infections; and that he was deficient in localizing inflammatory stimuli. Medawar's disclosure was that perinatal injection of spleen cells from a donor mouse permanently endowed the recipient with a capacity to retain an otherwise unacceptable homograft. This experiment seemed to confirm the prediction of Sir McFarlane Burnet that foreign tissues or antigens which were encountered by the fetus during certain critical periods of development were endowed with self-markers of structural proteins, and, therefore, not recognized as foreign.

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