The origin of tissue culture is commonly dated to 1907 and credited to Ross Harrison at Hopkins Medical School. But an unpublished letter from the 1942 offers a different interpretation and gives priority to Montrose Burrows with important contributions for the development of cell culture by Franklin Mall at Hopkins and Alexis Carrel at the Rockefeller Institute in New York City. The early development of tissue culture is reviewed and its applications in modern biology and medicine are briefly outlined.
HarrisonRG. Observations on the living developing nerve fiber. Proceeding of the Society of Experimental Biology and Medicine1906; 4: 140–143.
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HarrisonRG. Observations on the living developing nerve fiber. Anatomical Record1907; 1: 116–118.
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CarrelABurrowsMT. Cultivation of adult tissues and organs outside of the body. Journal of the American Medical Association1910; 55: 1379–1331.
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The 1942 letter by Burrows was loaned to me in April 1955 by Dr Victor A McKusick (1921–2008), then Assistant Professor of Medicine at the Johns Hopkins Medical School. Dr McKusick later became chief of medicine at Hopkins and developed the field of human genetics. I made a typed copy of Burrows’ letter at the time, which was before photo copy machines. I was then a fourth-year medical student, working part-time in the tissue culture laboratory of Dr George Otto Gey (1899–1970), one of the early tissue culturists. At the top of my copy I had typed simply that the letter was ‘to an inquirer into his tissue culture work.’ No envelope was available and I did not copy the letter’s salutation. In 1955 I did not anticipate that 61 years later this letter would be of historical significance. Identification of the addressee would be interesting, but its absence does not diminish the historical importance of the letter’s content and Burrows’ own words. A search for the original letter was made in the Chesney Archives at The Johns Hopkins Medical Institution and was not found in the materials there relating to Dr McKusick or Dr Gey. Burrows died in 1947. Under the 1976 U.S. Copyright Act, copyright protection lasts for the life of the author plus 70 years. Thus, publication of Burrows’ letter should be legally permissible in 2017.
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Arthur Hertzler (1870–1946) practiced medicine and surgery in Halstead, KS, where he established a hospital. He is most noted for his 1941 autobiography, Horse and Buggy Doctor (Garden City, NY: Blue Ribbon Books), describing medical practices in his time.
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Simon Flexner (1863–1946) received his medical degree from the University of Louisville in 1889 and trained in pathology under William Welch at Johns Hopkins. His early reputation came from his studies on dysentery which identified shigella organisms as a common cause – e.g. S flexneri. He investigated an epidemic of meningococcal meningitis in New York City during the winter of 1904–05. He determined by animal experiments that the infection could be treated by intrathecal administration of a specific antiserum produced in his laboratory. This success prompted the building of the Rockefeller Hospital in 1908. Simon’s brother, Abraham Flexner, compiled the 1910 ‘Flexner Report,’ which led to a major reformation of American medical education. By all accounts, Simon Flexner’s wise direction of the Rockefeller Institute (1902–1935) and the freedom he allowed its investigators accounted for the Institute’s ‘immense achievements’ in medical research.
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CornerGW. A history of the Rockefeller Institute 1901–1953, origins and growth, New York City: The Rockefeller Institute Press, 1964, pp. 160–160.
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William MacCallum (1874–1944) was a Canadian-born pathologist who trained under William Welch at Hopkins and succeeded him there in 1917. He made several fundamental medical discoveries. While a medical student during a summer vacation in Canada, MacCallum discovered exflagellation in a malarial parasite of birds – a key step in its life-cycle in erythrocytes. Later, he recognized the separate functions of the thyroid and parathyroid glands. Flexner F. Obituary: William George MacCallum. Science 1944; 99: 290–291.
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Mall established the Department of Embryology in the Carnegie Institute of Washington at Hopkins, 1914–1917. He revolutionized teaching gross anatomy courses by including embryology and histology. He helped found three journals: the American Journal of Anatomy, the Anatomical Record, and the Journal of Morphology. See Osler W. Obituary: Franklin Paine Mall. The Lancet 1917; 1: 841.
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SabinFR. Biographical memoir of Franklin Paine Mall, 1862–1917. National Academy of Sciences of the United States of America Biographical Memoirs1934; 16: 65–122.
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RubinLP. Leo Loeb’s role in the development of tissue culture. Clio Medica1977; 12: 33–56.
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Samuel Meltzer was a German-trained physiologist who studied the mechanism of swallowing. He originated intra-tracheal insufflation, which is employed in general anesthesia, allowing intrathoracic surgery. Three years before the discovery of insulin by Banting and Best in 1922, Metzler prepared a pancreatic extract which lowered blood sugar in experimental diabetes but did not pursue this finding, Corner GW. A History of the Rockefeller Institute 1901–1953, origins and growth, 1964, pp.117–120.
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Later, when the Institute was ‘solidly on its feet,’ it suffered ‘from too much attention.’ Newspaper reporters spoke with irritation of the Rockefeller Institute’s ‘anti-publicity department.’ See Flexner JT. An American saga. The story of Helen Thomas and Simon Flexner. Boston: Little, Brown and Co., 1984, p.444.
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WitkowskiJA. Dr. Carrel’s immortal cells. Medical History1980; 24: 129–142.
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HayflickLMoorheadP. The serial cultivation of human diploid cell strains. Experimental Cell Research1997; 25: 585–621.
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Soupault R. Alexis Carrel, 1873–1944. Paris: Librairie Plon, 1952.
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Many writers remarked on Carrel’s extraordinary manual dexterity – e.g. tying a surgical knot with his thumb and index finger inside a kitchen match box. See Time Magazine, November 13, 1944, p.88. Carrel gained newspaper notoriety for saving a newborn with a potentially fatal bleeding condition (melena neonatorum) by suturing the father’s radial artery to the infant’s popliteal vein – a vessel with ‘the diameter of a matchstick and the texture of wet cigarette paper.’ Modern microsurgery is performed with a binocular surgical microscope. Carrel’s surgical skill plus his fixation on aseptic surgical conditions contributed to his early successes in tissue culture.
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CarrelABurrowsMT. Cultivation of tissues in vitro and its technique. Journal of Experimental Medicine1911; 13: 387–396.
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BurrowsMT. A study of the relation between function and growth in body cells. Kansas University Science Bulletin1922; 14: 475–503.
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Carrel A and DeHelly G. The treatment of infected wounds. H. Child, translator. London: Baillière, Tindall and Cox, 1917.
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CarrelAEbelingAH. Antagonistic growth principles of serum and their relation to old age. Journal of Experimental Medicine1923; 38: 419–425.
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BakerLDCarrelA. Effect of the amino acids and dialyzable constituents of embryonic tissue juice on the growth of fibroblasts. Journal of Experimental Medicine1926; 44: 3979–406.
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Carrel A. ‘Foreword’ in Parker RC. Method of Tissue Culture. 1st ed. New York: Paul B. Hoeber, 1938, pp.xi-xxi.
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Carrel A and Lindbergh CA. The culture of organs. New York: Paul B. Hoeber, 1938.
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Carrel A. Man, the unknown. New York: Halcyon House 1935. This book was widely read in America and translated into 20 languages. In it Carrel proposed that countries could be governed best by an ‘iatocracy’ – a specially educated cadre of physician rulers. This work became controversial because it touched on eugenics and euthanasia and, as some asserted, had fascist overtones. A reviewer in 1988 wrote, ‘It strikes the modern reader as a potpourri of contradictory data and strongly ideological statements on the nature of man.’ See Moulin AM. Alexis Carrel. L’Ouverture de l’homme. Bulletin of the History of Medicine 1988; 62: 505-506. Three works of Carrel were published posthumously – Prayer in 1948, and Voyage to Lourdes in 1950, and Reflections on Life in 1952.
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Soupault R. ‘Catalogue des Oeuvres Publiées par Alexis Carrel’ in Alexis Carrel, 1873–1944. Paris: Librairie Plon, 1952, pp.277-294.
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CarrelAIngebrigtsenR. The production of antibodies by tissues living outside of the organism. Journal of Experimental Medicine1912; 15: 287–291.
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HarveyAM. Johns Hopkins – the birthplace of tissue culture: the story of Ross G. Harrison, Warren H. Lewis and George O. Gey. The Johns Hopkins Medical Journal1975; 136: 142–149.
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WillmerEN. ‘Introduction’ in Cells and Tissues in Culture. Methods: Biology and Physiology1965; Vol. 1, New York: Academic Press, pp. 1–17.
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TaylorMWA history of cell culture. In: TaylorMW (ed). Viruses and man: a history of interactions, New York: Springer, 2014, pp. 41–52.
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StrangewaysTSP. Tissue culture in relation to growth and differentiation, Cambridge: W. Heffer & Sons, 1924.
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WilsonD. Tissue culture in science and society. The public life of a biological technique in twentieth century Britain, Basingstoke: Palgrave Macmillan, 2011. pp.10 and 13.
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HallLA. The Strangeways Research Laboratory: archives in the contemporary medical archives centre. Medical History1996; 40: 231–238.
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CushingH. The life of Sir William Osler1940; Vol. II, London: Oxford University Pressp.604.
