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Organotherapy, British physiology, and discovery of the internal secretions

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References

  1. C.-E.Brown-Séquard and A.d'Arsonval, “De l'injection des extraits liquides provenant des glandes et des tissues de l'organism comme méthode thérapeutique,” Comp. Rend. Soc. Biol., 9th sér., 3 (April 18, 1891), 248–250. For a discussion of the events leading up to this communication, see my paper, “Brown-Séquard's Organotherapy and Its Appearance in America at the End of the Nineteenth Century,” Bull. Hist. Med., 50 (1976), in press.

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  2. I discuss these developments in detail in Chapters 1 and 2 of “Origins of the Hormone Concept: Internal Secretions and Physiological Research, 1889–1905,” Ph. D. diss., Yale University, 1976.

  3. George R.Murray, “Note on the Treatment of Myxoedema by Hypodermic Injections of an Extract of the Thyroid Gland of a Sheep,” Brit. Med. J.2 (October 10, 1891), 796–797, and G. Oliver and E. A. Schäfer, “On the Physiological Action of Extract of the Suprarenal Capsules,” Proceedings of the Physiological Society, March 10, 1894, J. Physiol., 16 (1894), i–iv.

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  4. “The Pentacle of Rejuvenescence,” Brit. Med. J., 1 (June 22, 1889), 1416.

  5. Ibid.

  6. Ibid.

  7. G.Variot, “Trois expériences sur l'action physiologique du suc testiculaire injecté sous la peau, suivant la méthode de M. Brown-Séquard,” Comp. Rend. Soc. Biol., 9th sér., 1 (June 29, 1889), 451–454.

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  8. “Dr. Brown-Séquard's Hypodermic Fluid,” Brit. Med. J., 2 (July 6, 1889), 29.

  9. Ibid.

  10. “The New Elixir of Youth,” Brit. Med. J., 2 (August 29, 1889), 446.

  11. For the context of such attitudes, see Richard D.French, Antivivisection and Medical Science in Victorian Society (Princeton, N.J.: Princeton University Press, 1975).

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  12. This criticism probably refers to the fact that Brown-Séquard observed that if debility were due to seminal loss, increased vigor might result from seminal retention. He had advocated sexual excitement without ejaculation to some of his patients. See Brown-Séquard, “Seconde note sur les effect produits chez l'homme par des injections sous-cutanées d'un liquide retiré des testicules frais de cobaye et de chien,” Comp. Rend. Soc. Biol., 9th ser., 1 (June 15, 1889), 420.

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  13. “The Recent Experiments of Dr. Brown-Séquard,” Brit. Med. J., 2 (July 27, 1889), 229. Thejournal claimed that its objections were quoted out of context by the author of this tract and, further, that the charges of barbarity were not justified because it was common agricultural practice to castrate animals to improve the flavor of the meat.

  14. “Dr. Brown-Séquard's Experiments: A Member of the Medical Profession Writes,” Brit. Med. J., 2 (August 10, 1889), 347.

  15. Brown-Séquard, “Note on the Effects Produced on Man by Subcutaneous Injections of a Liquid Obtained from the Testicles of Animals,” The Lancet, 2 (July 20, 1889), 105–107. This article is clearly written and provides an excellent summary of Brown-Séquard's ideas concerning the testicular fluid. It is based on his three notes to the Society of Biology: “Des effects produits chez l'homme par des injections sous-cutanées d'un liquide retire des testicules frais de cobaye et de chien,” “Second note ...,” and “Troisième note sur les effets des injections sous-cutanées de liquide testiculaire,” Comp. Rend. Soc. Biol., 9th. ser., 1 (June 15, June 15, June 22, 1889) 415–419, 420–422, 430–431.

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  16. “Before Our Time,” letter of the editors of Lancet to Brown-Séquard, The Lancet, 1 (1965), 315.

  17. Brown-Séquard, “Note on the Effects,” pp. 106–107.

  18. “Dr. Brown-Séquard's “Elixir of Life” (New York, from our own Correspondent),” The Lancet, 1 (January 4, 1890), 57–58.

  19. Ibid.

  20. “Charles Edward Brown-Séquard,” in Encyclopaedia Britannica, 11th ed., IV, 674.

  21. Brown-Séquard served between 1860 and 1863. He greatly influenced J. Hughlings Jackson (1835–1911) during this visit. See J.M.D.Olmsted, Charles-Edouard Brown-Séquard: A Nineteenth Century Neurologist and Endocrinologist (Baltimore: The Johns Hopkins Press, 1946), p. 107.

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  22. Ibid.

  23. See the correspondence between February 3 and May 3, 1891, in LéonDelhoume, De Claude Bernard a d'Arsonval (Paris: J.-B. Baillière & Fils, 1939), pp. 357–402. Cited hereafter as Delhoume, Correspondence.

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  24. , p. 360. Letter of February 13, 1891. D'Arsonval wrote: “I have sent some liquid to Dr. Jacquard; I have likewise received a letter from London from Dr. Fanton-Cameron; I await your orders to dispatch (it).” I have been unable to locate any biographical information on Fanton-Cameron.

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  25. , p. 364. Letter of February 19, 1891.

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  26. , p. 365. Unfortunately, these letters were not published. Delhoume, editor of the correspondence between d'Arsonval and Brown-Séquard, notes in a footnote: “Brown-Séquard, in four consecutive letters from the 17 to 22 of February, gives some directions to d'Arsonval for the shipments of testicular fluid to England and requests him notably to address some to Doctors Fanton-Cameron, Brudenell Carter and to Professor Horsley, of London.”

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  27. Robert Brudenell Carter (1828–1918) was an ophthalmic surgeon. He served on the staff of both The Times and The Lancet. See d'ArcyPower, “Robert Brudenell Carter,” in Plarr's Lives of the Fellows of the Royal College of Surgeons of England (London: Royal College of Surgeons, 1930), I, 201–203; “RobertBrudenellCarter, F.R.C.S.,” The Lancet, 2 (1918), 607; and “R. Brudenell Carter, F.R.C.S.,” Brit. Med. J., 2 (1918), 502–503.

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  28. See below.

  29. Delhoume, Correspondence, p. 366.

  30. Ibid., pp. 368–369. Letter of February 26, 1891. See also Brown-Séquard, “De l'injection des extraits liquides,” p. 248, for a summary of this procedure.

  31. Delhoume, Correspondence, p. 385. Letter of March 29, 1891.

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  32. Stephen Paget does not mention this trip in his biography, Sir Victor Horsley: A Study of his Life and Work (New York: Harcourt, Brace and Howe, 1920).

  33. Delhoume, Correspondence, pp. 394, 396–397, 402.

  34. “Report of the Clinical Evening of the Harveian Society, January 7, 1891 (sic),” Brit. Med. J., 1 (January 30, 1892), 229.

  35. Paget, Sir Victor Horsley, pp. 54–67.

  36. EdwinClarke, “Victor Alexander Haden Horsley,” in Dictionary of Scientific Biography, ed. C. C.Gillispie, I (New York: Charles Scribner's Sons, 1972), 518–519, and Paget, Sir Victor Horsley.

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  37. VictorHorsley, “Note on a Possible Means of Arresting the Progress of Myxoedema, Cachexia Strumipriva, and Allied Diseases,” Brit. Med. J., 2 (February 8, 1890), 287.

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  38. J. C.Spence, “George Redmayne Murray,” in Dictionary of National Biography, 1931–1940, ed. L. G.Wickham Legg (London: University Press, 1949), pp. 638–639. See also Paget, Sir Victor Horsley, pp. 65–66, n. 1.

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  39. Murray also held the post of lecturer in bacteriology at the Durham University College of Medicine.

  40. Cited in Paget, Sir Victor Horsley, pp. 65–66. Horsley was referring to the work of Moritz Schiff (1823–1896), Professor of Physiology at Geneva. In 1884, Schiff published the results of his experiments on thyroid grafts. He suggested that ground thyroid gland might, like grafts of thyroid gland, be effective in eliminating the symptoms which followed experimental thyroidectomy; cf. A. Herzen and E. Levier, ed., Moritz Schiff's gesammelte Beiträge zur Physiologie, IV (Lausanne: B. Benda, 1898), 391.

  41. Paget, Sir Victor Horsley, p. 66.

  42. Murray, “Note on the Treatment of Myxoedema”.

  43. Murray credited Horsley with the suggestion. The French investigator Jacques Abelous (1864–1940), however, claimed that this mentor Charles Bouchard (1837–1915), Professor of General Pathology at the Faculty of Medicine in Paris, had recommended this treatment as early as 1887; see J.-E.Abelous, “La physiologie des glandes à sécrétion interne: corps thyroide et capsules surrénales,” Revue générale des sciences pures et appliquées, 4 (1893), 275.

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  44. Murray, “Note on the Treatment of Myxoedema,” p. 796. Murray was referring to Horsley's conclusions in the Brown Lectures of 1885. Note that both Kocher and von Eiselsberg had been students of Theodor Billroth (1829–1894) of Vienna.

  45. Murray, “Note on the Treatment of Myxoedema,” p. 797.

  46. Ibid.

  47. Ibid.

  48. E.Gley, “Note préliminaire sur les effects physiologiques du suc de diverses glandes et en particulier du suc extrait de la glande thyroide,” Comp. Rend. Soc. Biol., 9th ser., 3 (April 18, 1891), 250–251. Gley was Professeur agrégé at the Faculty of Medicine in Paris.

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  49. This seems generally to have been the case for the use of organ extracts as therapeutic agents. On April 16, 1891, Brown-Séquard wrote d'Arsonval urging him to present a communication to the Society of Biology on the following Saturday because “the thing is in the air — especially in Italy”; cf. Delhoume, Correspondence, p. 400.

  50. E. HarryFenwick, “The Diuretic Action of Fresh Thyroid Juice,” Brit. Med. J., 2 (October 10, 1891), 798.

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  51. Ibid. Presumably, Fenwick thought the accumulation of fluid to be due to malfunctioning of the kidneys.

  52. VictorHorsley, “Remarks on the Function of the Thyroid Gland: A Critical and Historical Review,” Brit. Med. J., 1 (January 30, February 6, 1892), 215–219 and 265–268.

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  53. See the British Medical Journal for the year 1892. The successful treatment of myxoedema by feeding of fresh thyroid was reported in October.

  54. “The Treatment of Myxoedma,” Brit. Med. J., 2 (October 29, 1892), 965.

  55. VaughanHarley, “The Pathogenesis of Pancreatic Diabetes Mellitus,” Brit. Med. J., 2 (August 27, 1892), 452–454. Harley was the son of George Harley (1829–1896), who, under William Sharpey (1802–1896) at University College, began the first class of practical physiology in England. The elder Harley was also the first in England to repeat Brown-Séquard's experiments on adrenal extirpation; see Sir Edward Sharpey-Schafer, History of the Physiological Society during Its First Fifty Years, 1879–1926, supplement to the Journal of Physiology, December 1927 (London: Cambridge University Press, 1927), p. 2. According to papers published in the Journal of Physiology, Vaughan Harley was Assistant Professor of Pathology in 1895. He later became Professor of Chemical Pathology; see Sharpey-Schafer, History of the Physiological Soceity, p. 108.

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  56. G. R.Murray, “Remarks on the Treatment of Myxoedema with Thyroid Juice, with Notes of Four Cases,” Brit. Med. J., 2 (August 27, 1892), 449–450.

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  57. Harley, “The Pathogenesis of Pancreatic Diabetes Mellitus.”

  58. “Physiology in 1892,” Brit. Med. J., 2 (December 31, 1892), 1442. For discussion of studies of pancreatic physiology, see below.

  59. “Report of the Clinical Evening of the Harveian Society”, and A. Ambrose, letter to the editor in “Letters, Notes, and Answers to Correspondents,” Brit. Med. J., 2 (July 16, 1892), 163.

  60. R.Mansell-Jones, “Pancreatic Juices in Diabetes,” under “Notes, Letters etc.,” Brit. Med. J., 1 (January 7, 1893), 50.

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  61. HectorW.G. Mackenzie, “The Treatment of Diabetes Mellitus by Means of Pancreatic Juice,” Brit. Med. J., 1 (January 14, 1893), 63–64.

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  63. W.Hale White, “On the Treatment of Diabetes Mellitus by Feeding on Raw Pancreas and the Subcutaneous Injection of Liquor Pancreaticus,” Brit. Med. J., 1 (March 4, 1893), 452–453.

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  64. C.-E.Brown-Séquard, “On a New Therapeutic Method Consisting in the Use of Organic Liquids Extracted from Glands and Other Organs,” Brit. Med. J., 2 (June 3 and 10, 1893), 1145–1147, 1212–1214.

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  65. C.-E.Brown-Séquard, “On a New Therapeutic Method Consisting in the Use of Organic Liquids Extracted from Glands and Other Organs,” Brit. Med. J., 2 (June 3 and 10, 1893), 1213.

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  66. “Animal Extracts as Therapeutic Agents,” Brit. Med. J., 1 (June 17, 1893), 1279.

  67. Ibid.

  68. Ibid. The experiments cited were those of J. Rose Bradford on the kidney, Minkowski and von Mering on pancreatic diabetes. Langlois and Abelous on the adrenals, and Horsley and “others” on the thyroid.

  69. Ibid.

  70. Ibid. Brown-Séquard denied that the extracts were harmful when prepared properly; see Brown-Sequard and d'Arsonval, “Rejet de l'emploi de tous les antiseptiques autre que la glycerine et l'acide carbonique pour la préparation des extraits organiques destinés aux injections thérapeutique sous-cutanées,” Comp. Rend. Soc. Biol., 9th ser., 3 (July 4, 1891), 535–536; and Brown-Séquard and d'Arsonval, “Innocuité de l'injection dans les sang d'extraits liquides du pancreas, du foie, du cerveau, et de quelques autres organes,” Comp. Rend. Soc. Biol., 9th ser., 3 (October 24, 1891), 722–725.

  71. These arguments are simular to those advanced by Putnam in the United States; see James J.Putnam, “Recent Observations on the Functions of the Thyroid Gland; and the Relation of Its Enlargement to Graves's Disease; Also Remarks on the Therapeutic Use of Sheeps' Thyroids and of Other Organic Extracts,” Boston Medical and Surgical Journal, 130 (February 8, 1894), 153–159.

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  72. Brown-Séquard refers to a brochure published in Paris in 1878 by a Dr. Mattei called “De la resorption de la liqueur séminale; de son action excitante sur l'homme et sur la femme;” see Brown-Séquard, “Nouveaux faits relatifs a l'injection sous-cutanée, chez l'homme, d'un liquide extrait de testicules de mammifères,” Achives de physiologie normale et pathologique, 5th ser., 2 (1890), 201–208. Presumably, it is to this work that the British Medical Journal was referring.

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  73. Oliver practiced medicine in Harrogate between 1876 and 1908. His practice was seasonal, and he spent the winter months in London. See Richard D.French, “George Oliver,” in Dictionary of Scientific Biography, ed. C. C.Gillespie, X (New York: Charles Scribner's Sons, 1974), 204–206. I thank Dr. French for kindly allowing me to see the manuscript of this article prior to its publication.

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  74. Schäfer succeeded John Burdon Sanderson as Professor of Physiology at University College in 1883. See LeonardHill, “Sir Edward Albert Sharpey-Schafer, 1850–1935,” Obituary Notices of Fellows of the Royal Society, 1 (1932–1935), 401–407; and Sir Charles Scott Sherrington, “Sir Edward Sharpey-Schafer and His Contributions to Neurology,” Edinburgh Med. J., n.s., 42 (1935), 393–406.

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  75. SirHenryDale, “Accident and Opportunism in Medical Research,” Brit. Med. J., 2 (1948), 451–455.

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  76. Ibid., p. 454.

  77. The tension between these two approaches constitutes a major theme in the history of endocrinology. The “crisis” of medical endocrinology which emerged in the 1920's effected a reevaluation of the relative merits of medical and physiological research for the progress of this field. Cf. Diana LongHall, “Biology, Sex Hormones, and Sexism in the 1920's,” Phil. Quart., 5 (1973–74), 84.

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  78. E. A. Schäfer, “Oliver-Sharpey Lectures on the Present Condition of Our Knowledge Regarding the Functions of the Suprarenal Capsules,” delivered before the Royal College of Physicians of London on April 7 and 9, 1908, Brit. Med. J., 2 (May 30, June 9, 1908), p. 1281. See also H. Barcroft and J. F. Talbot, “Oliver and Schäfer's Discovery of the Cardiovascular Action of Suprarenal Extract,” Postgraduate Medical Journal, 44 (1968), 6–8.

  79. Schäfer's testimony before the second Royal Commission on Vivisection in British Parliamentary Papers, 57 (1908), 430; cited in French, “George Oliver,” p. 205, and Sherrinton, “Sir Edward Albert Sharpey-Schäfer,” pp. 396–397.

  80. Dale, “Accident and Opportunism,” p. 454.

  81. Schäfer, “Oliver-Sharpey Lectures,” p. 1281.

  82. Ibid. The question put to the applicants had been, “What is the use of the suprarenal glands?”

  83. Oliver and Schäfer, “On the Physiological Action of Extract of the Suprarenal Capsules,” p.i.

  84. Ibid., pp. ii–iii.

  85. Ibid., p. iv. They reported, “The physiological effect of this solution, as to the mode of preparation of which we are wholly ignorant, proved to be precisely the same as that of our own extracts.”

  86. White's Materia Medica, Pharmacy, Pharmacology and Therapeutics was published in 1892.

  87. White, “On the Treatment of Diabetes Mellitus.”

  88. Edward A. Schäfer, “Address in Physiology on Internal Secretions,” delivered at the annual meeting of the British Medical Association at London, August 2, 1895, The Lancet, 2 (August 10, 1895), 321–324.

  89. Ibid., p. 321.

  90. Ibid.

  91. Ibid.

  92. Ibid.

  93. Ibid.

  94. Ibid.

  95. See J.vonMering and O.Minkowski, “Diabetes mellitus nach Pankreasexstirpation,” Archiv für experimentelle Pathologie und Pharmakologie, 76 (1890), 371–387.

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  96. Schäfer, “Address in Physiology on Internal Secretions,” p. 322.

  97. Ibid. Schäfer credited this opinion to Munk, whom I have been unable to identify further.

  98. See Abelous, “La physiologie des glandes à sécrétion interne.”

  99. Schäfer, “Address in Physiology on Internal Secretions,” p. 322.

  100. Ibid. Schäfer was referring to data published in G. Oliver and E. A. Schäfer, “On the Physiological Action of Extracts of Pituitary Body and Certain Other Glandular Organs. (Preliminary Communication),” J. Physiol., 18 (1895), 278.

  101. Smith's earlier work concerned the study of the histological changes which followed thyroidectomy. The project Schäfer describes had been suggested by Horsley. Smith was a John Lucas Walker Student in Pathology at Cambridge. See J. LorrainSmith, “On Some Effects of Thyroidectomy in Animals,” J. Physiol., 16 (1894), 378–409.

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  102. Schäfer, “Address in Physiology on Internal Secretions,” p. 322.

  103. Ibid.

  104. A summary of these comments was inserted by the editors; Schäfer's complete comments on the pituitary were not published.

  105. Schäfer, “Address in Physiology on Internal Secretions,” p. 322.

  106. Ibid.

  107. Ibid.

  108. Over the next few years, internal secretions were often referred to as “drug-like” substances.

  109. Schäfer, “Address in Physiology on Internal Secretions,” p. 322. Note that Schäfer completely rejected the antitoxic theory of adrenal function, although he thought the theory might explain thyroid physiology.

  110. Ibid.

  111. Ibid., p. 324.

  112. Ibid.

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    Merriley Borell

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Borell, M. Organotherapy, British physiology, and discovery of the internal secretions. J Hist Biol 9, 235–268 (1976). https://doi.org/10.1007/BF00209884

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