Angelo M DiGeorge

BMJ 2009; 339 doi: (Published 09 December 2009) Cite this as: BMJ 2009;339:b5379
  1. Ned Stafford

    Paediatric endocrinologist who discovered the role of the thymus gland in human immunological function

    Angelo DiGeorge was growing more and more excited as he listened to Max Cooper describe “a new concept of the cellular basis of immunity.” DiGeorge, a paediatric endocrinologist in Philadelphia at St Christopher’s Hospital and Temple University School of Medicine, was listening from the audience of the 1965 meeting of the US Society for Pediatric Research.

    Dr Cooper was reporting “experimental evidence” that indicated that the lymphoid system is composed of two distinct cell populations, each with a separate embryological origin and different morphological and functional characteristics. But his evidence was based primarily on research in chickens, not humans. When Dr Cooper showed that he and his University of Minnesota colleagues thought a dual immune system also existed in mammals, the scepticism emanating from the audience was palpable, recalls Dr Cooper, now at the Emory University School of Medicine in Atlanta.

    “It was not a very Darwinian audience,” he said. Audience members tittered when the questioner approached the microphone and quipped that caution was called for when trying to compare the immune systems of chickens with humans.

    DiGeorge was not laughing. When the first questioner finished, he sprang up and hurried toward the microphone, shouting, “That’s it. That’s it. That explains what we have been seeing in Philadelphia.”

    By the time he had finished speaking, the audience was no longer giggling. DiGeorge had a solid reputation. “I could have hugged him,” Dr Cooper said. “He rescued me. His comments changed the whole atmosphere in that room.”

    No trace of a thymus

    DiGeorge had told the audience of his investigations of three infants with tetany because of hypoparathyroidism. After their deaths, autopsies showed no trace of a thymus, an organ that until the early 1960s was thought to have no function. Immunologists had recently recognised an immunological function for the thymus, but he explained that paradoxical finding of plasma cells that produce antibodies in infants born with no thymus, which had not yet come to the attention of these immunologists.

    DiGeorge added that the absence of cellular immunity coupled with retention of humoral immunity he saw at St Christopher’s Hospital in a fourth infant, still alive but whom he suspected had no thymus, seemed to be “completely analogous” with Dr Cooper’s chickens. These findings in humans clearly showed that the thymus is not the source of our antibody producing cells.

    The still living infant with immune problems referred to by DiGeorge eventually died, and the autopsy showed no thymus. DiGeorge coauthored the groundbreaking paper published in Nature that described the syndrome, initially presumed rare, but now known as a common genetic disorder, occurring in more than one in 4000 live births (Nature 1967;214:580-2, doi:10.1038/214580a0). Robert A Good, a founder of modern immunology and at the time Dr Cooper’s mentor at the University of Minnesota, suggested the condition be named the DiGeorge syndrome. It was later learnt that affected patients have a small deletion on chromosome 22, and now the syndrome is commonly called 22q11.2 deletion syndrome, responsible for a long list of symptoms.

    Donna M McDonald-McGinn, programme director of the 22q and You Center at the Children’s Hospital in Philadelphia and a board member of the International 22q11.2 Deletion Syndrome Foundation, said of DiGeorge’s discovery, “It was revolutionary. It had a huge impact. At the time a lot of kids did not survive [DiGeorge syndrome]. It was extremely important for the management of the children.”

    News of his death circulated by Internet around the world among various 22q11.2 deletion syndrome groups. Anne Lawlor, chairwoman of the 22q11 Ireland Support Group, said, “I feel a connection to the man because that is the diagnosis my daughter was given at 15, DiGeorge syndrome.”

    Chemistry degree

    Angelo M DiGeorge was born on 15 April 1921 in Philadelphia, the son of Italian immigrants. He attended Temple University, earning a chemistry degree in 1943 and three years later his medical degree, also at Temple. After completing his internship at Temple University Hospital, he served from 1947 to 1949 as captain and chief of medical service for a US army station hospital in Austria.

    After his return to Philadelphia he met his future wife, Natalie Picarello, a registered nurse. He completed his pediatric residency at St Christopher’s Hospital for Children and did a postdoctoral fellowship in endocrinology at Jefferson Medical College in 1954. DiGeorge joined the department of paediatrics of Temple University School of Medicine in 1952. He was also an attending physician at St Christopher’s, where he became the chief of endocrinology and metabolism from 1961 to 1989 and the director of the Pediatric Clinical Research Center from 1965 to 1982. After retirement in 1991, he became professor emeritus.

    Iraj Rezvani, who in 1971 began a paediatric endocrinology fellowship under DiGeorge, described his mentor as “a superb teacher, a masterful lecturer, a brilliant diagnostician, a caring physician, and a warm-hearted man.” He was also a man of strong convictions and opinions who loved to debate with colleagues, friends, and family. “If he had an opinion, he defended that opinion all the way,” said Dr Rezvani.

    Dr Rezvani, now professor emeritus of paediatrics at Temple University, adjunct professor of paediatrics at Drexel College of Medicine and a paediatric endocrinologist at St Christopher’s Hospital, said that DiGeorge’s discovery is even more remarkable because he was an endocrinologist, not an immunologist, with no access to modern diagnostic equipment.

    The discovery was not luck, though, but the result of a well prepared mind. “He was very well read,” Dr Rezvani said. “He was a true scientist, a great thinker way ahead of his time doing something completely out of the box.” Dr Cooper adds, “He was not an immunologist, but he was a good biologist and a good physician, and he followed his observations and logic.”

    In addition to his wife of 58 years, Natalie, DiGeorge leaves two sons and a daughter.


    Cite this as: BMJ 2009;339:b5379


    • Angelo M DiGeorge, paediatric endocrinologist (b 1921; q 1946, Temple University, Philadelphia), died 11 October 2009 from kidney failure.

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