Collip, James Bertram

(b. Thurold Township, near Belleville, Ontario, 20 November 1892; d. London, Ontario, 19 June 1965),

endocrinology.

Collip’s father, James dennis Collip, operated a vegetable and flower shop in Belleville; his mother, Mahala Vance, was a former schoolteacher. At the age College, University of Toronto. In 1912 he received his B. A. graduating at the head of his class, then went on to obtain the M.A. in 1913 and a Ph.D. in biochemistry in 1916. His graduate training was under the direction of A. B. Macallum, whom he succeeded in 1928 as professor of biochemistry at McGill University.

In 1915 Collip received his first academic appointment, as lecturer in biochemistry at the University of Alberta. Here he had a heavy teaching load in a department depleted of staff by the war, but he was nevertheless able to continue his research. In 1916 he published the first of his many contributions to medical literature, a paper entitled “Internal Secretions,” which he had presented to the Alberta Medical Association. (An earlier abstract of the paper with A. B. Macallum given at the British Association for the Advancement of Science was published at London in 1914; in their reports of 1913, p. 673, Collip’s name appears as “collop.”) Although in the nature of a review, it reveals Collip’s thinking in this field, which was to be his major interest. His early papers, however, were concerned mainly with the comparative blood chemistry of vertebrates and invertebrates. He recorded some new findings on the alkali reserve of plasma, acid-base exchange, and osmotic pressure of blood serum. In 1920 he wrote On the Formation of Hydrochloric Acid in the Gastric Tubercules of the Vertebrate Stomach, which included many of his own observations made while working toward his Ph.D.

In 1921 Collip was awarded a Rockefeller Traveling Fellowship to visit laboratories in North America and England. This proved to be a decisive turning point toward a career in endocrine research. His first visit was to Toronto, where there was intense interest in the development of a pancreatic extract to combat diabetes. This possibility so caught Collip’s imagination that he gave up the fellowship to become an assistant professor in the department of pathological chemistry at Toronto. He was subsequently asked by J. J. R. Macleod, head of the department of physiology, to join the group working with Banting and Best on the new hormone “insulin.”

Historically there was strong evidence to suggest that the pancreas had a major role in the control of sugar metabolism. It was known that surgical removal of the pancreas in the dog led to a diabetic condition as a reult of which the animal rapidly died. Many unsuccessful attempts had been made to extract the pancreas and obtain a fraction which would effectively maintain diabetic dogs. Unfortunately the pancreas contains—in addition to cells producing insulin—cells that produce powerful digestive enzymes and these presumably destroyed the hormone in extraction processes. In the autumn of 1921 extracts had been prepared from dogs whose pancreatic ducts had been ligated (such a procedure is followed by a degeneration of the enzyme-producing tissue but not of the insulin-producing cells) and from fetal pancreas obtained from slaughterhouses. Those showed activity in depancreatized dogs but toxic impurities and difficulty of preparation prevented their practical application to the treatment of patients with diabetes. Collip rapidly developed a method for the preparation of insulin from cattle or hog pancreas, employing alcohol in varying concertrations to obtain a differential precipitation of impurities. The resulting extract was sufficiently pure to allow the clinical group to test its action in humans. The first clinical results with insulin were published in March 1922 by Banting, Best, Collip, Campbell, and Fletcher, under the title “Pancreatic Extracts in the Treatment of Diabetes Mellitus.” Over the short interval of two years the Toronto group published fifteen fundamental papers and ten communication-abstracts that constituted an extensive contribution to knowledge of insulin and carbohydrate metabolism. In 1923 Banting and Macleod were the first Canadians to receive the Nobel Prize in physiology and medicine; in recognition of the parts played by their collaborators, they shared the monetary gifts with Best and Collip.

With the breakup of the group of collaborators in Toronto, Collip returned to Edmonton in 1922 to continue research as professor of biochemistry; he earned the D.Sc. in 1924 and the M.D. in 1926. During five years in Edmonton, he made some of his most important contributions to medicine by relating the hormonal control of calcium and phosphorus metabolism to an active principle in the parathyroid gland. This original work was published in 1926 as “The Extraction of a Parathyroid Hormone Which Will Prevent or Control Parathyroid Tetany and Which Regulates the Level of Blood Calcium,” The extensive discoveries made in this field at Edmonton are presented in Collip’s Harvey Lectures of 1925–1926.

In 1927, at the age of thirty-five, Collip became chairman and head of the department of biochemistry at McGill University. The next eleven years were the most productive of his career and, with a large group of distinguished collaborators that included David L. Thomson and Hans Selye, he published more than 200 papers. They contributed to nearly every facet of endorcrinology, particularly to pituitary function. Most of the projects centered on Collip, who had the remarkable ability to handle large concentrates of glands, purify them to manageable proportions, and separate out various hormone function. His restless and inquisitive nature led him to explore one area rapidly and then pass on to another. Many other laboratories benefited therefore, from his original observations as they proceeded to develop them. Throughout his life Collip explored areas of research in which it seemed directly possible to discover new treatments for human diseases.

The confusing field of female sex hormones and “ovary-stimulating substances” of the placenta attracted the attention of the McGill group; and as a result of their studies one of the group, J. S. L. Browne, isolated the female sex hormone estriol and prepared the first orally active estrogenic preparation that could be used clinically.

Collip’s interest in placental gonadotrophic hormones led him to the complex problems of the production by the anterior lobe of the pituitary of gonadotrophic and other trophic hormones. In the early 1930’s little was known of the nature or even the number of different hormones this part of the pituitary produced, and new animal models (chiefly the hypophysectomized rat) had to be developed to allow their assay. By 1933 Collip had separated pituitary growth hormone essentially free from both adrenocorticotrophic hormone (ACTH) and thyrotrophic hormone (TSH), which tended to run closely together in pituitary gland extracts. The preparation of seperated “pure” hormones allowed extensive investigations of their often complicated actions. ACTH was prepared in sufficiently pure form to be administered to patients. Unfortunately, it was not used to treat any of the diseases against which it is now known to be effective.

The preparations of ACTH, although not pure, were tolerated by patients and the activity was such that corticoid hormones were stimulated in sufficient amounts to be active against inflammatory reactions, rheumatism, arthritis, and various collagen diseases—conditon which were later shown by Hench and Kendall at the Mayo Clinic to respond to corticoid treatment. During many experiments with fractions containing TSH it was noticed that after repeated injections the initial stimulating response was lost and that the blood serum of the animal would inhibit the action of the hormone in other animals. Collip envisioned the development of “anit-hormones” as a normal physiological means of maintaining hormone homeostasis. This theory created great interest; and although it was later shown that closely bound nonspecific proteins and not the pure hormones probably led to this reaction, it focused attention on the possible influence of immune reactions in endocrine therapy.

In 1938 Collip abandoned research to devote most of his time to the organization of medical research in Canada, first as a member of the newly created Associate Committee for Medical Research of the National Research Council and later as chairman, succeeding Sir Frederick Banting. He was also medical liasion officer to the United States. He was decorated for his work by both the Canadian and United States governments. After the war Collip continued his administrative responsibilities as director and chairman of the Medical Advisory Committee of the National Research Council until his retirement at the age of sixty-five.

In 1941 Collip resigned his position in the department of biochemistry to become the Gilman Cheney professor of endocrinology and director of the Institute of Endocrinology at McGill. Although not participating personally in the research in his new laboratory, he closely followed its work. During these years the staff of the laboratory published thirty-eight papers containing significant contributions to such widely separated fields as experimental traumatic shock, motion sickness, audiometry, and blood preservation.

In 1947 Collip resigned from McGill to become dean of medicine at the University of Western Ontario and director of the department of medical research at the new Collip Medical Research Laboratory. Here he formed an active research group, and many graduate students benefited from training in his department. By 1965 more than 125 publications had originated from this laboratory. Collip retired as dean of medicine in 1961 but continued as director of the laboratory until his sudden death in 1965.

Many honors were bestowed on Collip for his pioneer investigations in endocrinology. His election in 1925 to the Royal Society of Canada and in 1933 to the Royal Society of London recognized his early achievements. He received honorary degrees from nine Canadian universities and from Harvard (1936), Oxford (1946), and the University of London (1948). Among Collip’s awards are the Canadian Medical Association’s F. N. G. Starr Award (1936), the Flavell Medal of the Royal Society of Canada, the Cameron Prize at Edinburgh, and the Banting Medal (1960). He was a fellow of several medical colleges and a member or honorary member of many Canadian and foreign scientific societies.

Collip never aspired to be a public figure; and his modesty and inherent shyness made him reluctant to lecture or give papers, even to scientific audiences. At first meeting he gave the impression of abruptness, but one soon realized that behind this manner were shyness and great personal charm. Collip had strong family ties and made many lasting friendships. He found little time for his hobbies of bridge, billiards, badminton, and golf.

BIBLIOGRAPHY

I. Original Works. Collip’s writings, alone or with collaborators, include, “Internal Secretions,” in Canadian Medical Association Journal (Dec. 1916), 1063–1069; On the Formation of Hydrochloric Acid in the Gastric Tubercules of the Vertebrate Stomach, University of Toronto Studies, Physiological Series, no. 35 (Toronto, 1920), 1–46; “Pancreatic Extracts in the Treatment of Diabetes Mellitus,” in Canadian Medical Association Journal, 12 (Mar. 1922), 141–146, written with F. G. Fletcher; “The Original Method as Used for the Isolation of Insulin in Semipure Form for the Treatment of the First Clinical Cases,” in Journal of Biological Chemistry, 55 (Feb,1923), 40–41; “The Extraction of a Parathyroid Hormone which Will Prevent or Control Parathyroid Tetany and Which Regulates the Level of Blood Calcium,” ibid., 63 (Mar. 1925), 395–438; THe Parathyroid Glands (New York, 1925–1926), the Harvey Lectures; “The Pvary-stimulating Hormone of the Placenta,” in Nature (March 22, 1930), 1–2; “Placental Hormones,” in Proceedings of the California Academy of Medicine (1930), 38–73; “Further Clinical Studies on the Anterior Pituitary-like Hormone of the Human Placenta,” in Canadian Medical Association Journal, 25 (1931), 9–19, written with A. D. Campbell; “The Adrenotrophic Hormone of the Anterior Pituitary Lobe,” in Lancet, 12 (1933), 347–350, written with E. M. Anderson and D. L. Thomson; “Preparation of a Purified and Highly Potent Extract of Growth Hormone of Anterior Pituitary Lobe,” in Processdings of the Society for Experimental Biology and Medicine of New York, 30 (1933), 544–546, written with H. Selye and D. L. Thomson; “Thyrotrophic Hormone of Anterior Pituitary,” ibid., 680–683, written with E. M. Anderson; “Preparation and Properties of an Antithyrotropiv Substance,” in Lancet, 30 (1934), 784–790, wrtitten with E. M. Anderson; “The Production of Serum Inhibitory to the Thyrotropic Hormone,” ibid.. 76–79, written with E. M. Anderson; “Diabetogenic, Thyrotropic, Aderntropic and Parathyrotropic Factors of the Pituitary,” in Journal of the American Medical Association, 104 (1935), 827, 916; “John James Rickard Macleod (1876–1935),” in Biochemical Journal, 29 (1935), 1253–1256; “Recent Studies on Anti-hormones,” in Annals of Internal Medicine, 9 (1935), 150–161; “Endocrine Organs,” in Hawk and Bergeim, eds., Practical Physiological Chemistry, 11th ed. (Philadelphia, 1937), ch. 26, written with D. L. Thomson; “Results of Recent Studies on Anterior Pituitary Hormones,” in Edinburgh Medical Journal, 45 (1938), 782–804, the Cameron Lecture; The Antihormones,” in Biological Review, 15 (1940), 1–34, written with D. L. Thomson and H. Style; “Adrenal and Other Factors Affecting Experimental Traumatic Shock in the Rat,” in Quarterly Journal of Experimental Physiology, 31 (1942), 201–210, written with R. L. Nobel; “Recollections of Sir Frederick Banting,” in Canadian Medical Association Journal, 47 (1942), 401–405; “Science and War,” ibid., 49 (1943), 206–209; “Alexander Thomas Cameron 1882–1947,” in Biochemical Journal, 43 (1948), 1, written with F,.D. white; and “Professor E. G. D. Murray—An Appreciation,” in Canadian Medical Association Journal, 92 (1965), 95–97.

II. Secondary Literature. A biographical notice is R. L. Noble “Memories of James Bertram Collip,” in Canadian Medical Association Journal, 93 (1965), 1356–1364. Papers by members of his laboratory staff include J. S. L. Browne, “The Chemical and Physiological Properties of Crystalline Oestrogenic Hormones,” in Canadian Journal of Research, 8 (1933), 180–197; E. G. Burr and H. Mortimerm, “Improvements in Audiometry at the Montreal General Hospital,” in Canadian Medical Association Journal, 40 (1939), 22–27; O.f. Denstedt, Dorothy E. Osborne, Mary N. Roche, and H. Stansfield, “Problems in the Preservation of Blood.” ibid., 44 (1941), 448–462; and R. L. Noble, “Treatment of Experimental Motion Sickness in Humans,” in Canadian Journal of Research and Experiment, 24 (1946), 10–22.

R. L. Noble