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EDWARD C. KE N DALL March 8, 1886_May 4,1972 BY DWIGHT J. INGLE . . . ~ EDWARD CALVIN KENDALL isolated thyroxine from the thyroid gland; he and associates crystallized glutathione and estab- lished its chemical structure; and he and associates isolated a series of steroid compounds from the adrenal cortex and con- tributed importantly to the determination of the structure and synthesis of several of them. With Philip S. Hench, he con- ceived the idea that cortisone might be useful in treating rheumatoid arthritis, and they planned clinical studies that confirmed the hypothesis. Kendall also initiated and partici- pated in a number of related studies. During his professional life he was called "Nick" by close friends and by his wife. He was referred to as "The Chief" by some of his laboratory associates, but commonly he was ad- dressed with deference, as "Doctor Kendall." Edward C. Kendall, the third child of George S. and Eva F. Kendall, was born March 8, 1886, at South Norwalk, Connecti- cut. The home was a citadel for religious teachings. The father, a dentist by profession, took an active interest in com- munity affairs. Edward attended the Franklin Elementary School and, for two years, South Norwalk High School. He spent a year at Stamford High School preparing for college. During these years he excelled in mathematics and became interested in the work of a foundry and a machine shop. In his 249

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250 BIOGRAPHICAL MEMOIRS teens, he set up a shop in the attic of his home; there he built electrical apparatus and did machine work. At Stamford High School Kendall developed an interest in chemistry. It was enhanced by his brother-in-law's stories of an amateur chemist who developed a secret process for making high-quality writing paper. This much admired brother-in- law graduated from Columbia University in 1900, and this in- fluenced Edward to enter there four years later. Edward concentrated his attention on chemistry and, as a college senior, he wrote a thesis under the guidance of Professor H. C. Sherman. During the summer of 1908, he served as a laboratory instructor in the department of biochemistry. He was awarded a scholarship for post-graduate work in biochem- istry and received an M.S. degree in tune 1909. He then became the first recipient of the Goldschmidt Fel- lowship and began research on amylase, an enzyme of the pan- creas. Kendall observed that the amount of reducing sugar produced by given amounts of amylase varied considerably, and he identified sodium chloride as the factor causing the vari- ability; the presence of the salt enhanced the activity of amy- lase severalfold. His first paper reported this research in the Journal of the American Chemical Society; Professor Sherman was co-author. He received the Ph.D. from Columbia in June 1910. (Hereafter, I shall refer to my subject as Dr. Kendall, for I addressed him thus for forty years.) In his memoirs, Dr. Kendall tells of departing from the sheltered, restricted life of his boyhood; but he cites specifically only that he played cards on Sundays and that he once tested the consequences of saying "God damn" out loud. As an adult, he was not overly religious, but he was more puritanical than many who practice religion loudly. These early years must have been important in the development of his quiet, scholarly demeanor and self-discipline. He continued to keep physically

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EDWARD C. KENDALL 251 fit throughout his adult life. He had participated in high school sports and, in college, he was a bow oar in a four-man shell. On September 1, 1910, Dr. Kendall began working in the chemical laboratory of Parke Davis and Company; his assign- ment was to isolate the hormone of the thyroid gland. He stayed five months. He found that punching a time clock was annoying, and he was disappointed by the intellectual isola- tion. There were no seminars, and he found himself working, in competition with another chemist who was assigned the same problem. After returning to New Yorl; City, he accepted an invitation to occupy and equip a new laboratory in St. Luke's Hospital. In the beginning, he worked without salary but was given funds for supplies and equipment. Eventually a salary of $1200 a year was provided, but it was never increased. Dr. Kendall continued research on the thyroid gland. Near the end of the nineteenth century, Professor Eugen Baumann, a physiological chemist at the University of Freiburg, had pre- pared iodine-containing extracts of thyroid glands that were useful in treating clinical hypothyroidism. Baumann's partially purified principle was named iodothyrin. The findings of Baumann served as a starting, point for Dr. Kendall. By 1913 he had purified the active principle about a hundredfold. The method of bioassay was to measure changes in the urinary nitro- gen of dogs. The biologic activity of the partially purified preparations was also demonstrated in hypothyroid patients. The research was not appreciated by the clinical staff of the hospital, whose attitude toward the partial purification of the iodine-containing compound seems to have been "So what?" At about tins time the hospital administrator sent Dr. Ken- dall a box of cereal with a letter directing him to analyze the contents. The letter and the cereal were thrown summarily into the wastebasket. Not then or ever would the young chemist

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252 BIOGRAPHICAL MEMOIRS take orders of this sort or accept distraction from his own goals. This and similar incidents formed the basis of his determina- tion to move to a research-oriented institution. It was Professor Clarence M. Jackson, soon to become a great teacher of anatomy at the UniversitY of Minnesota. who ~ ~11 ~~ Ir ~~ ~_11 _ ~ 1 _ ~ cola Or. Kendall ot ctevelopments at the Mayo Clinic and sug- gested that he apply to Dr. Louis B. Wilson, Director of Labora- tories, for a position. Dr. Henry S. Plummer, a many-sided genius, was involved in the treatment of diseases of the thyroid and in studies of its pathologic physiology. Drs. Will and Charlie Mayo were interested in diseases of the thyroid. Dr. Kendall was invited to join the staff of the Mayo Clinic and he began his research there on February 1, 1914. He was con- cerned with two projects: first, the isolation of the hormone of the thyroid gland, and second, the determination of the amount of the acid-insoluble fraction of thyroid glands re- moved surgically from patients so these data could be corre- lated with other clinical and laboratory findings. Baumann had prepared iodothyrin by boiling thyroid tis- sue with 10 percent sulfuric acid to hydrolyze the proteins; Dr. Kendall came to use repeated treatment with hot dilute sodium and barium hydroxides followed by separation of the acid-insoluble material. Near the end of 1914, an acid-in- soluble fraction that contained 47 percent iodine had been prepared. At this point, ethanol was used as a solvent. On December 23, a sample was dissolved in a small amount of ethanol and evaporation started. The young chemist was tired and fell asleep. When he awakened, the ethanol had evapo- rated, leaving on the bottom of the beaker a white crust sur- rounded by a ring of yellow waxy material. When more ethanol was added, the latter material dissolved but the white crust did not. When the residue was analyzed the following, morning, it was found to contain 60 percent iodine. During the day, more of the crust alas prepared. On Christmas morn-

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EDWARD C. KENDALL 253 ing, some of the white crust was dissolved in ethanol that con- tained a small amount of sodium hydroxide. The addition of a few drops of acetic acid precipitated crystals. This pure com- pound was later named "thyroxin" and, still later, when it was found to be an amino acid with an amine group, an "e" was added to make the name "thyroxine" (The ending "ine" indi- cates the chemical class to which the compound belongs.) Some hypothyroid patients were treated with the crystalline hor- mone; it was fully active in relieving the symptoms of thyroid deficiency. A year later, Edward C. Kendall married Rebecca Kennedy of Buffalo, New York. To Dr. Kendall and "Becky," four chil- dren were bornHugh, Roy, Norman, and Elizabeth. Before coming to the Mayo Clinic, Dr. Kendall had applied for a position at the Rockefeller Institute and was bluntly turned down by its director, Dr. Simon Flexner. This rankled the younger man and, in 1916, he took special satisfaction in reading a paper, "Isolation ill Crystalline Form of the Iodine- Containing Compound of the Thyroid Gland," at a session of the Federation of American Societies for Experimental Biology, chaired by Dr. Flexner. Efforts to identify the structure of thyroxine and to synthe- size the compound extended over the next ten years; they re- sulted in failure. Dr. Kendall described thyroxine incorrectly as triiodo-hexahydro-oxindolepropionic acid. In 1926, Dr. C. R. Harington of University College, London, identified the nu- cleus of thyroxine as the tetra-iodo derivative of thyronine and he synthesized thyroxine. At that point, the Mayo Clinic closed its research on the chemistry of the thyroid hormone. Dr. Kendall was already an important scientist and was to accomplish goals more significant than the isolation of thy- roxine; but he was not then, nor was he to become, a great chemist. His formal training in chemistry had been brief, and from the time he had received his Ph.D., he no longer worked

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254 BIOGRAPHICAL MEMOIRS with a master. A stubborn man, throughout his life he held that his intuitive beliefs were valid until the evidence against them became overwhelming. Other chemists had advised him over and over that his proposed structural formula for thy- roxine was incorrect. Usually, when confronted with proof that a belief was incorrect, he would accept it with good grace; but undue faith in his own ideas and resistance to the sug- gestions of others characterized his whole life as a scientist. Yet, in another sense, these foibles may have been necessary for his noble aims, his tenacity, and, hence, his great achievements. As Albert Szent-Gyorgyi said, "Discovery consists of seeing what everybody has seen, and thinking what nobody has thought." The research interests of Dr. Kendall shifted to studying the specific compounds involved in the effect of thyroxine on oxi- dation in the body. Attention was focused on cysteine and gluta- thione. Since the latter compound could not be purchased, the Mayo group became involved in a program to crystallize it and prepare it by synthesis. The compound was first isolated, ana- lyzed, and named by Professor F. Gowland Hopkins of Cam- bridge Universi ty in 1921. Bernard F. McKenzie and Dr. Harold L. Mason were collaborators of Dr. Kendall in isolating glutathione in crystalline form and in identifying it as a tri- peptide of glutamic acid, cysteine, and glycine. This was ac- complished independently of the isolation of crystals of gluta- thione and determination of structure by Professor Hopkins. The two groups agreed that the compound is glutamyl-cys- teinyl-glycine. It was first synthesized by Dr. C. R. Harington. The Section of Biochemistry at the Mayo Clinic was in- volved in basic research, graduate education, and performing clinical biochemistry. The last-named function was directed by Dr. Arnold E. Osterberg, first research associate of Dr. Kendall at the Mayo Clinic. It was Osterberg who suggested the name "thyroxin." Although Dr. Kendall participated in graduate

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EDWARD C. KENDALL 255 education to a small extenthe held the rank of professor since 1921he would permit few distractions to his research. He was never to become a sitting scientist; he was almost always at the bench. In the fall of 1929, Albert Szent-Gyorgyi, who, throughout his life made discoveries and stimulated the research of others, be- came a visiting scientist in Biochemistry at the Mayo Clinic. Szent-Gyorgyi had isolated small amounts of a substance that he first named "hexuronic acid." It is widely distributed in plants and animals and relatively large amounts are in the adrenal cor- tex. Fresh beef adrenal glands were made available to Dr. Szent- Gyorgyi, and he isolated substantial amounts of the compound during the eight months he spent in Dr. Kendall's laboratories. Hexuronic acid was later identified as vitamin C and given the name "ascorbic acid." The initiation of research on adrenal glands in Dr. Ken- dall's laboratories coincided with the publication of convincing evidence that an extract of beef adrenal glands would sustain life in adrenalectomized animals and would reverse the symp- toms of Addison's disease in human patients. Several investi- gators claimed to have achieved this during the 1920s, but the first to publish statistically reliable evidence (1927) for the pro- longation of life in adrenalectomized animals was Professor Frank A. Hartman at the University of Buffalo. In 1930, Hart- man and Katherine A. Brownell at Buffalo and J. J. Pfiffner and W. W. Swingle at Princeton University prepared extracts of the adrenal cortex that would sustain adrenalectomized ani- mals indefinitely, would revive them from a state of adrenal crisis, and would relieve the symptoms of patients with Addi- son's disease. The efficacy of the Pfiffner-Swingle extract was demonstrated on patients with Addison's disease by Dr. Leonard G. Rowntree of the Mayo Clinic. Dr. Rowntree came to Dr. Kendall with a plea to prepare adrenal cortical extract. The challenge was accepted, but Dr. Kendall looked beyond the

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256 BIOGRAPHICAL MEMOIRS immediate clinical need toward the isolation and chemical identification of the hormone of the adrenal cortex. During the early 1930s, Dr. Giles A. Koelsche, a Fellow in Biochemistry, carried out an important study of the effects of thyroxine and of adrenal cortical hormones on nitrogen bal- ance in dogs. It is generally believed that the hormones of each gland are catabolic. This is true when they are given in excess, but Koelsche demonstrated experimental conditions in which physiological doses of adrenal cortical hormones favor a posi- tive nitrogen balance and anabolism. Dr..Joseph L. Svirbely came to the Mayo Clinic for one year, did sophisticated bio- logical studies, then returned for several summers. Svirbely had contributed importantly to the identification of hexuronic acid as vitamin C during his association with Dr. Szent-Gyorgyi at Szeged, Hungary. Dr. Frank C. Mann supported the research of Dr. Kendall in two important respects. First, he was director of the Insti- tute of Experimental Medicine of the Mayo Clinic, which car- ried out all animal experimentation. Dr. Mann performed all of the adrenalectomies on dogs used by the Kendall group in bioassay procedures and research. Second, Dr. Mann was a member of Mayo's Board of Governors for a number of years. He was one of the effective spokesmen for the Clinic's labora- ~ , ~ - . ~ . . ~ , . tory investigations. He was a great experimental surgeon and physiologist, and a pathologist of broad interests, who had im- portant Insights Into the complexities of life and disease. Dr. Kendall and Dr. Mann were, in unique ways, strong personali- ties. Each had a warm personal regard for the other, but Dr. Mann was well aware of Dr. Kendall's foibles as a scientist. Dr. Kendall's knowledge of physiology was shallow; he did not appreciate the complexity of cause-and-effect relationships, and he did not fully appreciate the extent of biological variability. He was also given to making premature announcements of laboratory results. All of this exasperated Dr. Mann. On one

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EDWARD C. KENDALL 257 occasion, a brash young biochemist who came to the Institute to do research and bioassays on adrenalectomized dogs was questioned by Dr. Mann about his knowledge of physiology. The new Fellow replied that, since he was trained in biochem- istry, he had good basic knowledge of physiological processes. Dr. Mann replied, "I know more than two hundred biochemists and not a damn one of them knows any physiology." When the remark was repeated to Dr. Kendall, he said, "I know more than two hundred physiologists and not one of them knows any bio- chemistry." Some members of the Clinic staff and some members of the Board of Governors questioned the wisdom of supporting basic research in the Section of Biochemistry. So long as Drs. Will and Charlie Mayo ran the clinic, they supported lair. Kendall's programs. Dr. Charlie especially would come frequently to Dr. Kendall's laboratory bench to chat and keep in touch with progress. When the Mayo brothers began to turn over more and more administrative responsibilities to committees, the re- search program of Dr. Kendall was in some danger. He had to appear before the Board each year and resell the program. These were depression days and the Mayo Clinic did not accept any outside support for any of its functions. Dr. Kendall could plead a cause with quiet optimism, always promising early progress. But there were years in which there was little progress to report. Dr. Mann was in a position to scuttle Dr. Kendall's program but did not. He would express misgivings, then sup- port the continuation of the research. There was no true in- consistency in this, for Dr. Mann understood better than most physicians the necessity for basic research, that it is errant, and that years of effort may go by without discovery. In 1928, when I was an undergraduate student, a physician friend gave me a publication containing "before and after" pictures of a ten-vear-old girl in whom treatment with thy- roxine at the Mayo Clinic had corrected cretinism within a few

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258 BIOGRAPHICAL MEMOIRS months. There was a remarkable spurt in growth. I wrote a letter to Dr. Kendall. I received a reply to each of my questions about this patient. In 1932, I heard him speak on thyroxine at the University of Minnesota School of Medicine. After the lecture I wrote to him and was again treated with kind con- sideration. I was told that he note aimed to isolate the hormone of the adrenal cortex. I was studying the work performance of adrenalectomized rats: The general technique was to anesthe- ~ze one rat warn sodium phenobarbital, weight the gastrocne- m~us muscle won ~~u grams, and stimulate it electrically to lift the weight three times per second. Normal rats could continue work of the stimulated muscle for more than fourteen days. When the adrenal glands were removed, the amount of work accomplished began to fall below that of sham-operated animals within two hours, and muscular responsiveness was lost within a day. I had shown that ability to work was lost because of ~ ~ _ _ _ . , 1 1 1 . 1 ~ off 1 circulatory failure and that the state of shock was due to absence of the adrenal cortex rather than of the adrenal medulla. When I asked Dr. Kendall for a sample of adrenal cortical extract, he suggested that I first test lactyl epinephrine. He had an intuitive guess that since the adrenal glands contain both lactic acid and epinephrine, the two compounds might be linked together to form the hormone of the adrenal cortex. He be- lieved that he had extracted this compound from adrenal glands, but the evidence was tenuous. A final ether extract contained lactic acid and gave a positive test for the catechol grouping. He believed that synthetic lactyl epinephrine was prepared in his laboratory, again basing chic concl',sion an th`> finding that an ether-soluble product contained lactic acid and gave a positive test for the catechol grouping. There was no proof that lactic acid and epinephrine were chemically bonded. Dr. Kendall had injected this latter product into dying adrenal- ectomized dogs and had observed temporary improvement in some of them; I found the product to have an epinephrine-like = . ~ _ ~ ~ ~ ~ ., - ^ ~ _

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EDWARD C. KENDALL 1930 281 Function of the suprarenal gland. Introduction. Proc. Staff Meet. Mayo Clin., 5: 133-35. With H. L. Mason and B. F. McKenzie. Crystalline glutathione. l. Biol. Chem., 87:xli. A study of glutathione. III. The structure of glutathione. l. Biol. Chem., 87: 55-79. With H. L. Mason and B. F. McKenzie. A study of glutathione. IV. Determination of the structure of glutathione. I. Biol. Chem., 88:409-23. 1931 With I. E. Holst. The oxidation of cobaltous cysteine. I. Biol. Chem., 91 :435-74. Chemical study of active constituents of suprarenal gland. I. Biol. Chem., 92:1vi; also in Proc. Staff Meet. Mayo Clin., 6:296 (A). The removal of traces of oxygen from nitrogen; a convenient appa- ratus for studies in oxidation-reduction potentials. Science, 73: 394-97; also in Proc. Staff Meet. Mayo Clin., 5: 199-200~1930) (A). The consideration of some of the glands of internal secretion from a chemical viewpoint. Endocrinology, 15: 357-64. With J. E. Holst. Oxidation of cobaltous cysteine. Proc. Soc. Exp. Biol. Med., 28:674-75. 1932 Chemical studies of the suprarenal gland. l. Biol. Chem., 97:iv-v; also in Proc. Staff Meet. Mayo Clin., 7:135-36 (A). Studies on experimental suprarenal deficiency. Proc. Staff Meet. Mayo Clin., 7:595-96. Further studies on experimental suprarenal deficiency. Proc. Staff Fleet. Mayo Clin., 7: 664-65. 1933 With B. F. McKenzie. Separation of the active principle essential to life from the suprarenal gland. Proc. Staff Meet, Mayo Clin., 8: 90-92. With H. L. Mason, B. F. McKenzie, and C. S. Myers. The physio- logic action and chemical nature of the active principle in the suprarenal gland essential to life. J. Biol. Chem., 100: 1ix-lx.

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282 BIOGRAPHICAL MEMOIRS Chemical nature of the hormone of the suprarenal cortex essential to life. Proc. Staff Meet. Mayo Clin., 8:392-95. 1934 With H. L. Mason, B. F. McKenzie, C. S. Myers, and A. G. Koelsche. The chemical nature and physiologic activity of the hormone of the suprarenal cortex. l. Biol. Chem., 105:xlv-xlvi. With H. L. Mason, B. F. McKenzie, C. S. Myers and G. A. Koelsche. Isolation in crystalline form of the hormone essential to life from the suprarenal cortex: its chemical nature and physiologic properties. Trans. Assoc. Am. Physicians, 48: 147-52; also in Proc. Staff Meet. Mayo Clin., 9:245-49 (A). 1935 Suprarenal cortical hormone. Minn. Med., 18:71-73. With H. L. Mason, B. F. McKenzie, C. S. Myers, and W. D. Allers. Recent developments in the investigation of the hormone of the suprarenal cortex. Proc. Staff Meet. Mayo Clin., 10:245~6. Vitamins from a chemical viewpoint. Med. Clin. North Am., 19: 447-86. With G. A. Koelsche. The relation of the suprarenal cortical hor- mone to nitrogen metabolism in experimental hyperthyroidism. Am. J. Physiol., 113:335~9. Adrenal cortex extract. i. Am. Med. Assoc., 105: 1486-89. Glutathione. In: Cycloped ia of Med icine, ed. by G. M. Piersol. Philadelphia: F. A. Davis Co. 1936 With R. M. Wilder, A. M. Snell, E. J. Kepler, E. H. Rynearson, and Mildred Adams. Control of Addison's disease with a diet re- stricted in potassium: a clinical study. Proc. Staff Meet. Mayo Clin., 11: 273-83. With W. D. Allers and H. W. Nilson. Studies on adrenalectomized dogs: the toxic action of potassium. Proc. Staff Meet. Mayo Clin., 11 :283-87. With H. L. Mason and C. S. Myers. Concerning the chemical nature of the hormones of the adrenal cortex. Proc. Staff iMeet. Mayo Clin., 11:351-52. With H. L. Mason, C. S. Myers, and W. D. Allers. A physiologic and

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EDWARD C. KENDALL 283 chemical investigation of the suprarenal cortex. .T- Biol. Chem., 114:1vii-lviii. With i. L. Svirbely. Vitamin C and the adrenal cortical hormone. Am. J. Physiol., 116: 187-93. With H. L. Mason and C. S. Myers. The chemistry of crystalline substances isolated from the suprarenal gland. If- Biol. Chem., 114:613-31. With D. i. Ingle. Survival of the adrenalectomized nephrectomized rat. Am. .T- Physiol., 117: 200-203. With H. L. Mason and C. S. Myers. Chemical studies of the supra- renal cortex. II. The identification of a substance which pos- sesses the qualitative action of cortin: its conversion into a dike- tone closely related to androstenedione. .T Biol. Chem., 116: 267-76. 1937 With W. D. Alters. Maintenance of adrenalectomized dogs without cortin through control of the mineral constituents of the diet. Am. I. Physiol., 118: 87. With D. J. Ingle and H. W. Nilson. The effect of cortin on the concentrations of some constituents of the blood of adrenalecto- mized rats. Am. l. Physiol., 118:302. With R. M. Wilder, A. M. Snell, E. J. Kepler, E. H. Rynearson, and Mildred Adams. The intake of potassium, an important con- sideration in Addison's disease. A metabolic study. Arch. Intern. Med., 59:367-93. With H. L. Mason, W. M. Hoehn and B. F. McKenzie. Studies in the chemistry of the suprarenal cortex. The structure and physio- logic activity of compound B: its relation to compound A and Reichstein's corticosterone. Proc. Staff Meet. Mayo Clin., 12:136. With H. L. Mason, W. M. Hoehn, and B. F. McKenzie. Studies in the chemistry of the suprarenal cortex. The probable position of the undetermined atom of oxygen. Proc. Staff Meet. Mayo Clin., 12:270. With H. L. Mason, W. M. Hoehn, and B. F. McKenzie. Chemical studies of the suprarenal cortex. III. The structures of com- pounds A, B and H. J. Biol. Chem., 120:719. The chemical constitution and physiologic activity of crystalline products separated from the suprarenal cortex. Trans. Assoc. Am. Physicians, 42: 123.

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284 BIOGRAPHICAL MEMOIRS A chemical and physiologic investigation of the suprarenal cortex. Cold Spring Harbor Symposium on Quantitative Biology, 5:299. With D. J. Ingle. The significance of the adrenals for adaptation to mineral metabolism. Science, 86: 18. With D. I- Ingle. Atrophy of the adrenal cortex of the rat produced by the administration of large amounts of cortin. Science, 86: 245. 1938 Metabolic processes influenced by certain ductless glands. Proc. Staff Meet. Mayo Clin., 13:379; also in Endocrinology, 24:798-805. The influence of cortin, insulin and glucose on the metabolism of potassium. Proc. Staff Meet. Mayo Clin., 13:519. With H. L. Mason and W. M. Hoehn. Chemical studies of the supra- renal cortex. IV. Structures of compounds C, D, E, F and G. i. Biol. Chant., 124:459. With E. V. Flock, ]. L. Bollman, and F. C. Mann. The effect of the intravenous injection of glucose and other substances on the concentration of potassium in the serum of the dog. J. Biol. Chem., 125:57. With E. V. Flock, J. L. Bollman, and F. C. Mann. The influence of cortin and sodium chloride on carbohydrate and mineral me- tabolism in adrenalectomized dogs. l. Biol. Chem., 126:679. With D. l. Ingle. \Veights of adrenal glands in rats fed different amounts of sodium and potassium. Am. i. Physiol., 122:585. With D. l. Ingle and G. W. Higgins. Atrophy of the adrenal cortex in the rat produced by administration of large amounts of cortin. Anatomical Record, 71:363-72. 1 939 Influence of some of the ductless glands on metabolic processes. Endocrinology, 24:798. Report of the International Congress of Physiologists at Zurich. Proc. Staff Meet. Mayo Clin., 14:78. 1940 Glutathione. In: Cyclopedia of Medicine, p. 791. Philadelphia: F. A. Davis Co.

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EDWARD C. KENDALL 285 With B. B. Wells. A qualitative difference in the effect of com- pounds separated from the adrenal cortex on distribution of electrolytes and on atrophy of the adrenal and thymus glands of rats. Proc. Staff Meet. Mayo Clin., 15: 133-39. The function of the adrenal cortex. Proc. Staff Meet. Mayo Clin., 15:207-304. With B. B. Wells. The influence of corticosterone and C~7-hydroxy- dehydrocorticosterone (compound E) on somatic growth. Proc. Staff Meet. Mayo Clin., 15: 324-28. The influence of the adrenal and thyroid on gluconeogenesis in phlorhizin diabetes. Proc. Staff Meet. Mayo Clin., 15:493-96. With B. B. Wells. The influence of the adrenal cortex in phlorhizin diabetes. Proc. Staff Meet. Mayo Clin., 15: 565-73. With D. l. Ingle. Influence of amorphous fraction from adrenal cortex on efficiency of muscle. Proc. Soc. Exp. Biol. Med., 45: 602-6. Some observations of the physiologic activity of the thyroid. Trans- actions of the American Association for the Study of Goiter, pp. 265-71. 1941 With B. B. Wells. The influence of the hormones of the adrenal cortex on ketonuria in rats treated with phlorhizing. Proc. Staff Meet. Mayo Clin., 16: 113-16. Hormones. Annual Review of Biochemistry, 10: 285-336. The function of the adrenal cortex. J. Am. Med. Assoc., 116:3294-98. The adrenal cortex. Archives of Pathology, 32:464-501. With F. H. Stodola. Studies on steroid ,8-ketols. I. The partial syn- thesis of 16-keto-sterone acetate. I. Org. Chem., 6: 837~40. With F. H. Stodola and B. F. McKenzie. Studies on steroid p-ketols. II. A new partial synthesis of 5-androstene-3,16,17-triol: an intermediate in the preparation of 16-hydroxytestosterone. Org. Chem., 6:841-44. 1942 With W. J. Eversole and Robert Gaunt. The effect of adrenal steroids in water intoxication. Am. l. Physiol., 1 3~: 378. Hormones of the adrenal cortex. Endocrinology, 30:853.

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286 BIOGRAPHICAL MEMOIRS With Robert Gaunt and W. I. Eversole. Influence of some steroid hormones on lactation in adrenalectomized rats. Endocrinology, 31 :84-88. With Frank H. Stodola. Studies on steroid ,8-ketols. III. A partial synthesis of 3,17-diacetoxy-5-androstene-16-one. I. Org. Chem., 7:336. With R. M. Reinecke. Method of bioassay of hormones of the adrenal cortex which influence deposition of glycogen in the liver. Endocrinology, 31 :573. 1943 With R. M. Reinecke. A comparison of the influence of some crystal- line hormones of the adrenal cortex on the deposition of glycogen in the liver. Endocrinology, 32:505-8. With R. D. Williams. Influence of thiamine on induced hyperthy- roidism. Arch. Intern. Med., 72: 185-95. 1944 With F. R. Heilman. The influence of 11-dehydro-17-hydroxycorti- costerone (compound E) on the growth of a malignant tumor in the mouse. Endocrinology, 34:416-20. 1946 With B. F. McKenzie and W. F. McGuckin. Steroids derived from bile acids. I. The preparation of 3~-hydroxy-~ 11-choleric acid from desoxycholic acid. .t Biol. Chem., 162:555-63. With L. L. Engel, V. R. Mattox, B. F. McKenzie, and W. F. Mc- Guckin. Steroids derived from bile acids. II. 3~-hydroxy-11, 12-dibromo-cholenic acid and related compounds. l. Biol. Chem., 162:565-70. With R. B. Turner, V. R. Mattox, L. L. Engel, and B. F. McKenzie. Steroids derived from bile acid. III. Derivatives of ~9 -choleric acid with substituents at C3 and Cat. J. Biol. Chem., 162:571-84. With V. R. Mattox, R. B. Turner, L. L. Engel, B. F. McKenzie, and W. F. McGuckin. Steroids derived from bile acids. IV. 3,9-Epoxy- ~-cholenic acid and closely related compounds. J. Biol. Chem., 164:569-86. With R. B. Turner, V. R. Mattox, L. L. Engel, and B. F. McKenzie.

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EDWARD C. KENDALL 287 Steroids derived from bile acids. V. Introduction of oxygen at Car, . J. Biol. Chem., 166: 345-65. 1947 Steroids derived from bile acids. IV. 3,9-Epoxy-~-cholenic acid, as an intermediate in the partial synthesis of dehydrocorticosterone. Recent Progress in Hormone Research, 1:65-81. 1948 With V. R. Mattox. The preparation of 3-keto-~4-steroids. l. Am. Chem. Sac., 70:882-83. With B. F. McKenzie, V. R. Mattox, and L. L. Engel. Steroids de- rived from bile acids. VI. An improved synthesis of methyl 3,9-epoxy-~-cholenate from desoxycholic acid. I. Biol. Chem., 173:271-81. \\lith V. R. Mattox, R. B. Turner, B. F. McKenzie, and L. L. Engel. Steroids derived from bile acids. VII. The probable stereochemical configuration of some derivatives of the bile acids. .l Biol. Chem., 173: 283-94. With B. F. McKenzie and V. R. Mattox. Steroids derived from bile acids. VIII. Catalytic hydrogenation of methyl 3~-hydroxy-12- keto-~9 ~~-cholenate and related compounds. J. Biol. Chem., 175:248-63. With V. R. Mattox and B. F. McKenzie. Hemibydrohalides of 3(cz)- hydroxy steroids. l. Am. Chem. Soc., 70:2662. The influence of the adrenal cortex on the metabolism of water and electrolytes. Vitamins and Hormones, 6: 277-327. 1949 The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehy- drocorticosterone: compound E) and of pituitary adreno-cortico- tropin hormone arthritis: preliminary report. Proc. Staff Meet. Mayo Clin., 24: 181-97. With P. S. Hench, C. H. Slocumb, A. R. Barnes, H. I,. Smith, and H. F. Polley. The effects of the adrenal cortical hormone 17- hydroxy-l l-dehydrocorticosterone (compound E) on the acute phase of rheumatic fever: preliminary report. Proc. Staff Meet. Mayo Clin., 24:277-97.

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288 BIOGRAPHICAL MEMOIRS Some observations on the hormone of the adrenal cortex designated compound E. Proc. Staff Meet. Mayo Clin., 24:298-301. The chemistry and partial synthesis of adrenal steroids. In: The Adrenal Cortex. Annals of the New York Academy of Sciences, 50: 540~7. With P. S. Hench, C. H. Slocumb, and H. F. Polley. Effects of en- docrine secretions: the effect of cortisone and of ACTH on rheu- matoid arthritis and acute rheumatic fever. Seventh Interna- tional Congress on Rheumatic Diseases, May 31, 1949. Reprinted from Rheumatic Diseases. 1950 Studies related to the adrenal cortex. Fed. Proc., 9:501-5. With R. G. Sprague, M. H. Power, H. L. Mason, A. Albert, D. R. lMathieson, P. S. Hench, C. H. Slocumb, and H. F. Polley. Ob- servations on the physiologic effects of cortisone and ACTH in man. Arch. Intern. Med., 85:199-258. With P. S. Hench, C. H. Slocumb, and H. F. Polley. Effects of corti- sone acetate and pituitary ACTH on rheumatoid arthritis, rheu- matic fever and certain other conditions. Arch. Intern. Med., 85: 545-666. Cortisone. Chemical and Engineering News, 28:2074-77. With V. R. Mattox. The mechanism of elimination of hydrogen bromide from a-bromo keto-steroids through formation of hydra- zones. l. Am. Chem. Soc., 72:2290. With C. H. Slocumb, H. F. Polley, and P. S. Hench. Effects of corti- sone and ACTH on patients with rheumatoid arthritis. Proc. Staff Meet. Mayo Clin., 25:476. With V. R. Mattox. Steroids derived from bile acids. IX. Diphenyl- carbinol and diphenylethylene derivatives. i. Biol. Chem., 185: 589-92. With V. R. Mattox. Steroids derived from bile acids. X. Preparation of bromo derivatives of some 3-keto steroids. J. Biol. Chem., 185: 593-99. With V. R. Mattox. Steroids derived from bile acids. XI. Prepara- tion of 3-keto-~4-steroids. l. Biol. Chem., 185: 601-14. Cortisone. Annals of Internal Medicine, 33:787-96; also in Neue Medizinische Welt, No. 35/36, pp. 1-19. With P. S. Hench, C. H. Slocumb, and F. H. Polley. Effects of corti-

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EDWARD C. KENDALL 289 sone and pituitary adrenocorticotropic hormone (ACTH) on rheumatic diseases. I. Am. Med. Assoc., 144: 1327-35. The story of cortisone. Hospital Management. With P. S. Hench, C. H. Slocumb, and H. F. Polley. The anti-rheu- matic effects of cortisone and pituitary ACTH. Transactions and Studies of the College of Physicians of Philadelphia, 18 (4 ser.~: 95-102. 1951 With V. R. Mattox. Steroids derived from bile acids. XII. Adrenal cortical hormones: introduction of a double bond. i. Biol. Chem., 188:287-97. Cortisone. Quarterly of Phi Beta Pi, 47:187-98. With G. M. Higgins and Kathryn A. Woods. Some observations on the physiologic activity of 6-dehydrocortisone (diene). Endocri- nology, 48: 175-88. The development of cortisone as a therapeutic agent. Antibiotics and Chemotherapy, 1: 7-15. With G. A. Fleisher. Preparation and absorption spectra of steroids with 2,4-dinitrophenylhydrazone groups at C-20 and C-21. l. Org. Chem., 16: 556-72. With G. A. Fleisher. Steroids with a glyoxal side chain at C-17 and related compounds. J. Org. Chem., 16: 573-85. The development of cortisone and hydrocortisone as therapeutic agents. American Academy of Orthopedic Surgeons: Instructional Course Lectures, vol. 8, pp. 60-67. The development of cortisone as a therapeutic agent. (Nobel lecture, Dec. 11, 1950) Stockholm: Kungl. Bokthyckeriet P. A. Norstedt and Soner. Alfred Nobel: the man and his prizes. Proc. Staff Meet. Mayo Clin., 26:417-37. The adrenal cortex and rheumatoid arthritis. British Medical iour- nal, pp. 1295-99. 1952 Title F. B. Colton, W. R. Nes, D. VanDorp, H. L. Mason, and A. {. L.aVine. Steroids derived from bile acids. XIII. Introduction of the 17-hydroxyl group in the partial synthesis of cortisone. I. Biol. Chem., 194:235-45.

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290 BIOGRAPHICAL MEMOIRS With F. B. Colton. Steroids derived from bile acids. XIV. Halogen and other derivatives of a -pregnant. i. Biol. Chem., 194: 247-60. With V. R. Mattox, G. Woroch, and G. A. Fleisher. Steroids derived from bile acids. XVI. Preparation of 6-dehydrocortisone. i. Biol. Chem., 197:261-70. With W. F. NIcGuckin. Steroids derived from bile acids. XVII. Dehydrobromination of 3-keto-4-bromosteroids with 2,4-dini- trophenylhydrazine. i. Am. Chem. Soc., 74:3951. Hormones of the adrenal cortex in clinical medicine. (Cameron Prize Lecture) Edinburgh Medical journal, 59:1. With W. F. McGuskin. Steroids derived from bile acids. XVIII. Introduction of the 4,5-double-bond of cortisone. I. Am. Chem. Soc., 74:5811. With R. B. Turner, V. R. Mattox and W. F. McGuckin. Steroids de- rived from bile acids. XIX. Barbier-Wieland degradation of the 11-keto series. i. Am. Chem. Soc., 74:5814. With V. R. Mattox, R. B. Turner, W. F. McGuckin, and E. I. H. Chu. Steroids derived from bile acids. XX. Degradation of 3a!, 9~-epoxy-11-ketonorcholanic acid to A, 9,`-epoxy-11-ketoetio- cholanic acid. I. Am. Chem. Soc., 74:5818. Acceptance of Kober Medal for 1952. 'Trans. Assoc. Am. Physicians, 65:52. 1953 Hormones of the adrenal cortex in health and disease. Proceedings of the American Philosophical Society, 97:8-11. Hormones of the adrenal cortex. Bulletin of the New York Academy of Medicine, 29:91-99. 1960 With Zolton G. Hajos. Tetrahydro-3,4-furandione. I. Preparation and properties. I. Am. Chem. Soc., 82:3219. With Zolton G. Hajos. Tetrahydro-3,4-furandione. I. Dioxolane and dioxane derivatives. J. Am. Chem. Soc., 82:3220.

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