History of Medicine

 

TWO DOCTORS WITH ACROMEGALY

 

                Dr. Leonard Portal Mark, born in 1855, son of the British Consul in Marseille, enjoyed an uneventful childhood, studied medicine, and entered practice in London. He was also draughtsman in the St. Bartholomew Hospital Pathology Department (medical illustrator). At age 24 he noted a stuffed feeling in the left ear, followed by pain in the left face, sensitivity to light in his eyes, frequent runny nose, fatigue, and frequent headaches. Eventually he noted enlargement of glove, shoe, and hat sizes, protuberance of his jaw and lower lip, and problems with chewing his food. Amazingly, he failed to see that anything serious was wrong until one day, 25-6 years after his symptoms started, he suddenly realized that he must have acromegaly. For years, he admitted, looking in the mirror every day, “there was a typical acromegalic literally staring me in the face.”

Leonard Mark, ages 24 and 57 (from Acromegaly:A Personal Experience)

Yet, he failed to see the diagnosis. Consulting his St. Bartholomew Hospital colleague, Archibald Garrod (a pioneer in inherited diseases of metabolism and discoverer of alkaptonuria), Mark discovered that Garrod and other physician friends, even his brother and his dentist, knew the diagnosis and assumed that he was aware of it. They had simply avoided discussing an unpleasant topic with him.

          Seven years later, at the age of 57 (1912), Dr. Mark published a memoir recounting his symptoms. He wrote that “I felt some resentment having been kept in the dark for so many years.” But this feeling passed away and soon, “I realized that my friends had acted for the best.” He felt that in some ways he had benefitted psychologically from not knowing that he had a serious malady.

          Pierre Marie, a student and colleague of Charcot, whose name

Pierre Marie (Wikipedia)

is most often connected with Charcot-Marie-Tooth disease, a form of muscular dystrophy, described, in 1886, 2 cases with typical features, naming the syndrome “acromegaly” (enlarged extremity). He distinguished it from myxedema and Paget’s disease. Previous similar cases were pulled from the literature and, the following year, Oskar Minkowski noted an association of acromegaly with enlargement of the sella turcica and, perceptively, suggested that giantism might be another form of the same disease process. Dr. Mark’s symptoms, then, began

One of Pierre Marie's 2 cases (Rev Med)

 

before Marie’s report, but the medical world was aware of it soon after. Mark lived to the age of 75, though it was probably not a comfortable life.

         The Latin word pituita means phlegm. Galen believed that the pituitary was a structure that funneled waste products from the brain to the nose in the form of phlegm. Though other possible functions of the gland were subsequently discussed, no real progress was made (primarily because of its inaccessibility) until the reports of Marie and Minkowski.

         Leonard Mark’s autobiography made it across the Atlantic in an ironic way. William Coley, a talented young surgeon at New York Hospital, was consulted in 1890 by a 17-year-old woman, Bessie

William Coley (Nat Library Medicine)

Daschiell, seeking help for a non-healing injury to her right hand. Coley biopsied the swelling, revealing a “round cell sarcoma” of the bone. Bessie underwent an amputation of her right arm below the elbow but succumbed to metastatic disease 2 ½ months later. The incident deeply affected Coley himself and Daschiell’s closest friend, John D. Rockefeller Jr., who considered Daschiell his “adopted sister” (she was the sister of a close school friend).

     Coley, now driven to study sarcomas, found in the hospital records a case of a German immigrant whose large bone sarcoma, incompletely resected from the neck, had disappeared after a serious bout of erysipelas (a streptococcal infection). Coley tracked the man down and found him, amazingly, to be tumor-free and healthy, 6 years after the surgery. Coley treated future sarcoma patients by infecting them with streptococci, later with injections of fluid from cultured combinations of bacteria, usually streptococci and Serratia marscescens. A significant minority improved or were cured, as were occasional non-sarcoma patients. However, because radiotherapy became popular and the side effects of the vaccine treatment could be severe, his treatment languished. His methods were opposed particularly by James Ewing, a prominent pathologist at Cornell University Medical College, where Coley worked.

     Rockefeller, also stunned by Daschiell’s rapid death, saw the need to fight cancer and provided major funding for a new Memorial Hospital near the Cornell site that eventually became the Memorial Sloan-Kettering Cancer Center of today. He remained friends with Coley.

     A number of years later, when Coley was 51 years old (1913) and vaguely aware of enlarging hands and feet, a friend gave him a copy of Leonard Mark’s autobiography. The friend had received it from an anonymous source, apparently an attempt to discredit Coley. Coley read it in detail. It is unclear whether he already suspected that he had acromegaly, but after reading the book he certainly realized it. He downsized his practice. He apparently did not undergo pituitary surgery but left instructions for his brain to go to his friend, Harvey Cushing, for study. He also suffered from bleeding ulcers and in his seventies died of bowel gangrene from previous adhesions.

Only in modern times has interest in what is now called “immunotherapy” of cancer been revived. Coley is frequently cited as the father of this approach. The plethora of cytokines, including “tumor necrosis factor,” uncovered in recent years has reopened the field on a much more scientific basis.

         Coley never met Leonard Mark, but he must have been deeply impressed reading the story of a colleague on the other side of the ocean who, possibly like himself, took time to appreciate the significance of the slow changes in his physiognomy.

 

 

SOURCES:

Mark, L P, Acromegaly: A Personal Experience. Balliere, London, 1912.

Aron, D C, “The Path to the Soul: Harvey Cushing and Surgery on the Pituitary and its Environs in 1916.” Perspect Biol Med 1994; 37 (4): 551-65.

Kaplan, S A, “The Pituitary Gland: A Brief History.” Pituitary 2007; 10: 323-25.

Marie, P, “Sur Deux Cas d’Acromégalie.” Revue de Médecine 1886; 6: 297-333.

Cohen, H, “Pierre Marie 1853-1940.” Proc Royal Soc Med 1953; 46: 1047-1054.

Hall, S S. A Commotion in the Blood: Life Death, and the Immune System. 1997; Henry Holt & Co.