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Biographical Memoirs: Volume 44 (1974)

Chapter: 5. Howard Bishop Lewis

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Suggested Citation:"5. Howard Bishop Lewis." National Academy of Sciences. 1974. Biographical Memoirs: Volume 44. Washington, DC: The National Academies Press. doi: 10.17226/567.
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Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

136 BIOGRAPHICAL MEMOIRS The electron. In: Encyclopaedia Britannica,.Vol. 8, pp. 323-27. Chicago, Encyclopaedia Britannica, Inc. 1948 Lattice vibrations and specific heat of diamond. Naturforschung, 3a:607-11. Normal vibrations of a crystal lattice. 20: 161-65. 1949 Zeitschrift fur Reviews of Modern Physics, With C. F. Squire. Electromagnetic induction in a superconductor. Phys. Rev., 76:685-86. (L) 1950 Electric and magnetic forces on superconductors. Soc., 94:453-58. With N. Muench. Electromagnetic forces on a superconductor. Phys. Rev., 79:967-70. Physics for adventure. Phys. Today, 3 (6) :20-21. Proc. Am. Phil. 1951 On the spirit of physics. Phys. Today, 4 (2) :g-10. Principles of Quantum Mechanics. New York, McGraw-Hill Book Co., Inc. vii + 288 pp. 1952 Description of the physical world. In: The Scientist Looks at His World, pp. 5-32. Philadelphia, University of Pennsylvania Press. With R. H. Pry and A. L. Lathrop. Gyromagnetic effect in a superconductor. Phys. Rev., 86: 905-7. Phys. Rev., 88: Temperature dependence of electrical resistance. 1321-23. Theory and practice in engineering. Phys. Today, 5 (9) :4-5. 1954 Robert Andrews Millikan. In: The American Philosophical So- ciety Year Book, pp. 440-44. Philadelphia, The American Philo- sophical Society.

WILLIAM VERMILLION HOUSTON 137 1955 Philosophy in the twentieth century. Proceedings of the Philo- sophical Society of Texas, 20: 7-15. With H. E. Rorschach. Motion of nuclei in liquid helium. Phys. Rev., 100: 1003-7. Physics in engineering. Am. J. Phys., 23:610-14. 1956 Objectives of engineering education. nology, 8: 12-14, January. Journal of Petroleum Tech- 1960 Waves and Particles. Columbus, Ohio State University Press. 18 pp. (First Annual Alpheus W. Smith Lecture.) Electrons and nuclei in ideal crystals. In: Modern Physics for the Engineer, by L. N. Ridenour and W. A. Nierenberg, pp. 83-107. New York, McGraw-Hill Book Co., Inc. 1963 Some observations on the theory of electrons and atomic nuclei in solids. Phys. Today, 16:26-36. 1966 With D. R. Smith. Mechanical forces on a superconducting film. Physical Review Letters, 16:B552 1-2 and 2-2. Are electrons real? Am. J. Phys., 34:351-57. Particles and fields in physics. The Physics Teacher, 4:158-60. 1967 With D. R. Smith. Motion of magnetic flux in superconducting strips. Phys. Rev., 163:431-34.

HOWARD BISHOP LEWIS November 8, ~ 887- March 7, 1954 BY WILLIAM C. ROSE AND MINOR J. COON HOWARD BISHOP LEWIS died in Ann Arbor, Michigan, on March 7, 1954, after a prolonged illness. Thus ended the career of a dedicated and talented teacher, and a sound and skillful investigator. For thirty-two years he had served the University of Michigan with distinction as head of the Depart- ment of Biological Chemistry in the School of Medicine. In 1947, the University, in appreciation of his remarkable services and national reputation, conferred upon him a distinguished professorship entitled the John Jacob Abel University Professor- ship in Biological Chemistry. In addition to his departmental duties, Lewis was director of the College of Pharmacy from 1933 to 1947. Lewis was born on a farm near Southington, Connecticut, on November 8, 1887, the son of Frederick A. and Charlotte R. (Parmelee) Lewis. Little information is available concerning his early life; he left no record of his boyhood, nor of the influences that motivated him in pursuing a scientific career. However, his scholarly temperament was revealed even before he entered college. Prior to his sixteenth birthday, he graduated from high school as valedictorian of his class. He had a special interest in the classics. During the year of waiting to meet the age require- ment for admission to Yale, he mastered, by self-instruction, a two-year course in high school Greek. At Yale, he won the 139

140 BIOGRAPHICAL MEMOIRS Chamberlain Prize for the best entrance examination in the Greek language. Lewis entered the freshman class of Yale College in 1904 and was awarded the Bachelor of Arts degree four years later. The record shows that his devotion to Greek and Latin per- sisted, though he graduated "with honors in physical sciences." He stood fourth in a class of three hundred and eighty. During his college years he was the recipient of prizes in Latin composi- tion, chemistry, and calculus. Most of the two years immediately following his graduation (1908-1910) was occupied in teaching at Hampton Institute, Hampton, Virginia, and at the Centenary Collegiate Institute, Hackettstown, New Jersey. During half of the second year, he began graduate study in chemistry at George Washington University. Apparently, Dr. Isaac K. Phelps, onetime member of the chemistry faculty at this institution, played an important role in encouraging Lewis to pursue his training in biochem- istry. He, like Lewis, was a Yale graduate and a native son of Connecticut, and seems to have regarded biochemistry, a rela- tively new branch of chemistry at the time, as a particularly inviting field for a young scientist. Lewis entered the Graduate School of Yale University in the fall of 1910. His program of training was directed by Pro- fessor Lafayette B. Mendel, a man of remarkable charm, peda- gogic skill, and research acumen. During his last two years at Yale, Lewis served as Professor Mendel's laboratory assistant. He was awarded the degree of Doctor of Philosophy in 1913. During much of his college career Lewis found it necessary to finance his training by tutoring and other extracurricular activities. During one summer, Professor Mendel obtained em- ployment for him in the laboratories of the Connecticut State Hospital at Middletown. This was not an unusual experience for financially needy students in Mendel's laboratory. Several in turn were privileged to engage in such employment. The

HOWARD BISHOP LEWIS 141 position paid a small stipend in addition to room and board. More importantly, it afforded an opportunity for the student to acquire valuable experience in clinical laboratory techniques, while leaving sufficient time for him to exercise his originality in the pursuit of an independent research project. Lewis used the occasion to study the nature of the antigen in the Wasserman reaction. Following the completion of his training for the doctorate, Lewis accepted an instructorship in physiological chemistry in the School of Medicine of the University of Pennsylvania. He held this position for two years (1913-1915~. Sometime during the latter year, he was invited to assume responsibility for the teaching and research programs of the Division of Physiological Chemistry ~ in the Chemistry Department of the University of Illinois. He accepted this challenge and began his new duties on the Urbana campus in the fall of 1915. There, single- handedly, except for the modicum of help received from a part- time student assistant, he organized and taught a general course in physiological chemistry and three graduate courses dealing with special topics. In addition, he attracted a number of stu- dents to work toward advanced degrees under his direction. Between the Pennsylvania and Illinois assignments, Lewis married Mildred Lois Eaton, daughter of the late Dr. Edward Dwight Eaton, President of Beloit College from 1886 to 1917. She passed away in 1961. Two daughters, Charlotte Barber and Elizabeth Parmelee, survive. Lewis remained at the University of Illinois until 1922, when he was called to head the Department of Physiological Chemistry ~ at the University of Michigan. There he continued to display his genius as a teacher, as an investigator, and as an administrator. But his influence did not stop at the borders of the campus. His wide knowledge of medical sciences and The name alas later changed to the Division of Biochemistry. The name was later changed to the Department of Biological Chemistry.

142 BIOGRAPHICAL MEMOIRS medical education led many outside organizations to seek his services. For fifteen years he was a member of the National Board of Medical Examiners, a position which required an in- credible amount of arduous labor. From 1936 until his final illness he was a member of the Council on Foods and Nutrition of the American Medical Association. From 1945 to 1948, he was a member of the Division of Medical Sciences of the Na- tional Research Council, and for five years he was chairman of the Michigan Nutrition Council. As for organizations more closely associated with his specialty, Lewis was intimately involved in the activities of the American Institute of Nutrition as a councilor ~ 1 94 1-1 942), vice presi- dent ~ 1 942-1 943), and president ~ 1 943-1 944) . During the long period in which the American Society of Biological Chemists had no paid officials, Lewis, with rare skill and efficiency, per- formed the laborious task of being its secretary (1929-1933~. Subsequently, he was elected to the offices of vice president 1933-1935), president ~ 1935-1937), and councilor ~ 1937- 1940 and 1941-1942) of the Society. One of his greatest con- tributions to science was the dedicated manner in which, for many years, he managed the Placement Service of the Federation of American Societies for Experimental Biology. With a min- imal allowance for secretarial help, he brought together many young scientists seeking employment and institutions seeking personnel. Partly because of these services, and partly because of his love of people, Howard Lewis probably knew personally more biochemists and related scientists than any other indi- vidual in this country. At various times in his busy career, Lewis was a member of the editorial boards of five periodicals, namely, the Journal of Biological Chemistry, the Journal of Nutrition, Chemical Re- views, Physiological Reviews, and the Proceedings of the Society for Experimental Biology and Medicine. On several occasions he was honored by being chosen to deliver special lectures. In

HOWARD BISHOP LEWIS 143 1932, he was the Beaumont Lecturer of the Wayne County Medical Society; in 1941, he was Lecturer of the Harvey Society of New York; and in 1948, he was the Henry Russel Lecturer of the Research Club of the University of Michigan. Membership in professional societies, other than those al- ready mentioned, included the American Chemical Society, the American Physiological Society, the American Pharmaceutical Association, the American Association for the Advancement of Science (fellow), the Society for Experimental Biology and Medicine, and the American Medical Association (associate). In 1949 he was elected a member of the National Academy of Sciences. A review of Lewis's many outside activities leads one to wonder how he could have accomplished so much while suc- cessfully carrying the full-time responsibilities of a large and active department. Despite his many professional duties, Lewis always seemed to find time for healthful recreation. He loved the o~t of It TATL_.L___ ]_ ·_ ~ . . vvt~er nits moon at the moment called for a game of tennis or a long walk in the country, he pursued the pastime with zeal and alacrity. One of his favorite hobbies was gardening. He seemed to take special delight in seeing plants grow. Perhaps this was an echo of earlier experiences as a boy on a Connecticut farm. He was an expert bridge player; and not the least im- portant of his hobbies was his lifelong interest in philately. His knowledge of stamps is said to have amazed all who heard him talk about them. He lectured frequently to interested groups on such topics as "Pioneers in Philately"; "The Literature , Aid Ally r clllly DlaCK'; and "Some Early Charity Stamps." Sometimes the lectures were illustrated with Blues. En one occasion he spoke on "Philately and Medicine" before the Detroit Academy of Surgeons. The next day, one of the physicians in the audience, who also was a Regent of the University, wrote in part as follows: "Your talk last night was a masterpiece.... I was actually thrilled.... It was an extremely of Phil~t-=l~r,,. ELI ~~ _ Hi_ ~' ~ ~ ~1:~1 ~~ ~ ~ ^.~ ~~ was a .. ,

144 BIOGRAPHICAL ME M OIRS interesting evening . . . such a refreshing, and altogether unusual evening." Howard's knowledge and appreciation of music continued As a young instructor in Philadelphia, he enjoyed the symphonies, the operas, and the other musical entertainments afforded by the city. One of his associates of that period describes this quality of Howard's character as follows: and grew throughout his career. "These were the years when grand opera was being first brought to Philadelphia. Our chief, Alonzo E. Taylor, as well as the rest of the laboratory family, were all enthusiastic dev- otees—Howard in particular. Assembling in the laboratory a morning after an evening of opera we were plunged immedi- ately into a vigorous discussion of the opera in some detail. Howard had an amazing memory of all the plots and in particu- lar of the musical themes in each. I relished these occasions, for my previous laboratory contacts had suggested that art and chemistry should not be too intimately mixed." ~ Later, music became a common interest of the Lewis family. Each member, except Howard, acquired a proficiency in the use of one or more instruments. Thus a trio could be assembled and a delightful concert rendered at a moment's notice. Many happy hours were spent in this way, to the edification, not only of the instrumentalists themselves, but of their many friends who were privileged to hear the concerts. Perhaps the secret of Howard Lewis's success in so many areas of human endeavor is to be found, not only in his inherent native ability, but also in the spirit which he displayed in the performance of every undertaking. Whether work or play was the object to which he was about to devote his seemingly in- exhaustible store of energy, he approached it with enthusiasm and zest, as though its doing was a new adventure never before experienced. He gave his very best to every enterprise. Not only was he a hard worker; he was a hard player as well. ~ From a letter to Mrs. Lewis from the late Dr. Wm. H. Adolph.

HOWARD BISHOP LEWIS 145 During the forty-one years of his professional career, Lewis participated in the training of many students. Sixty-six re- ceived the Doctor of Philosophy degree under his direction, and many others were awarded the Master of Science degree. As to undergraduates, one may conservatively estimate that in excess of five thousand were privileged to take one or more of his formal courses. The effect these trainees have had, and will continue to have, upon biochemical and medical progress is incalculable. In truth, Lewis's influence "marches on." In research, Lewis displayed both originality and ingenuity. With the collaboration of his students and colleagues, he pub- lished an impressive list of scientific articles covering a broad range of topics and requiring the application of a multiplicity of technical skills in the successful elucidation of the topics covered. During the early years of his career, he became interested in the in vivo formation of hippuric acid following the administration of benzoic acid. He returned to this problem from time to time as new aspects of the conjugation occurred to him. He observed in man that, after doses of 6 to 10 g of sodium benzoate, the elimination of hippuric acid takes place rapidly, 85 to 90 percent of the theoretical yield being recovered in the urine within a period of five to six hours. In these tests, the output of urea was diminished, indicating the probability that the nitrogen of the hippuric acid had its origin largely in nitrogen that normally is excreted in the form of urea. In later investi- gations, a quantitatively less important peculiarity was noted by the author in human subjects, for which he had no satis- factory explanation. This was a marked decrease (50 to 70 percent) in the output of uric acid during the first four hours after administering the sodium benzoate, as compared with the excretion during the corresponding periods of the fore and after days. Most of Lewis's experiments on the metabolic fate of benzoate were conducted on rabbits. The animals were maintained ex- clusively on a diet of milk, which has a very low glycine con-

146 BIOGRAPHICAL MEMOIRS tent. Despite the fact that this procedure largely deprived the subjects of exogenous glycine, the total amount of hippuric acid formed from a given dose of benzoate was not significantly diminished. Furthermore, even large doses of benzoate did not induce a noticeable increase in the output of total nitrogen. Thus the source of the glycine used in the conjugation is not to be found in an increased tissue decomposition. In a single ex- periment in which the bile was drained away from the intestine, the output of hippuric acid was not decreased. This appeared to exclude glycocholic acid as a significant source of the glycine. On the other hand, in all of the rabbit experiments, the distri- bution of nitrogen in the urine showed, as in the human sub- jects, a decrease in the output of urea. Evidently, in this species also, the nitrogen of the glycine used in the conjugation was derived from nitrogen that ordinarily is excreted as urea. Studies of the rate of hippuric acid excretion afforded results of particular interest. The output during a six-hour period was greatly augmented when an abundant supply of glycine was given along with the benzoate. A similar, though less marked erect was induced oy one simultaneous administration of DL- serine and benzoate. These results were interpreted by the author as indicating that serine can be rapidly converted into glycine tor the purpose In question. Other amino acids and related compounds—alanine, cystine, leucine, aspartic acid, glycolic acid, glycolaldehyde, etc.—were found to be without effect upon the rate of synthesis of hippuric acid. In other experiments, the administration of benzyl alcohol yielded hippuric acid at a rate only sli~htlv less than that ob- ~ , ~ , served after the administration of an equivalent amount of sodium benzoate. Obviously, the alcohol is readily oxidized to the corresponding acid, at a rate which is at least as rapid as the conjugation of glycine and benzoate. That the liver may be the site of the conjugation was indicated when it was observed that animals poisoned with hydrazine, a substance known to

HOWARD BISHOP LEWIS 147 exert detrimental effects upon the liver, excrete much less hip- puric acid in a six-hour period than do normal animals receiv- ing comparable doses of benzoate and glycine. Under these conditions, the diminished output of hippuric acid was shown not to be due to a slower rate of absorption of the components from the intestine, nor to an injurious effect of the hydrazine upon the kidneys. Throughout his professional career, Lewis was much in- terested in the metabolic behavior of the physiologically important sulfur compounds, particularly the amino acids cystine and methionine. Among his many contributions to this topic, the following may be noted. In extension of the observations of others, in which white rats were the experimental animals, Lewis found that cystine may be a limiting factor in the nutrition of dogs receiving a low protein diet. Thus the quality of a ration, as measured by its ability to maintain nitrogen equilibrium, may be enhanced by the addition of small amounts of cystine. Furthermore, the supplementing effects of proteins of different sources, when in- corporated in the basal, low protein ration, were proportional to their cystine content. These findings in adult dogs, like the earlier Investigations conducted in other laboratories upon growing rats, seemed to demonstrate that cystine is an indis- pensable dietary component. Later, the role of methionine, and the ability of cystine to replace it in part, were recognized. Many of Lewis's investigations were concerned with the oxidation of cystine and its derivatives as measured by the distribution in the urine of inorganic sulfate, ethereal sulfate, and the so-called "unoxidized" sulfur compounds. Rabbits usually served as the subjects. Free cystine, as its sodium salt, was found to be oxidized to inorganic sulfate without increas- ing significantly the output of unoxidized sulfur compounds. This occurred rather rapidly, with 60 to 85 percent of the sul- fate being recovered within 24 hours. When, however, mod- . . .

148 crate doses (0.5 to 1.0 g per kilogram of body weight) were administered for several days to either fasting or fed rabbits, renal casts and protein appeared in the urine accompanied by a diminution in the excretion of nonprotein nitrogen and creat- inine. A further indication of renal injury was the marked rise in the nonprotein nitrogen of the blood. When the amino acid was administered subcutaneously, the results were variable. Oxidation largely to inorganic sulfate still occurred; but kidney damage, owing to the excretion of unchanged cystine, was ob- served in some cases. The degree of injury appeared to depend upon the rate at which the amino acid was absorbed from the . . . . site of injection. Though cystine undergoes oxidation with considerable ease in the animal body, this is not true of certain derivatives of this amino acid. Thus, phenyluraminocystine is oxidized to a very limited extent, and increases markedly the output of un- oxidized sulfur. This behavior of the compound was interpreted by Lewis as indicating the probability that deamination ordi- narily precedes the oxidation of the amino acid. Furthermore, since phenyluraminocysteine was excreted after feeding phenyl- uraminocystine, the author suggests that perhaps the first step in the catabolism of cystine may be its conversion into cysteine. In line with this suggestion are the observations that thiolactic and thioglycolic acids are readily oxidized when fed to rab- bits, or injected subcutaneously, whereas dithiodiglycolic acid is not. Perhaps, he says, only mercapto compounds, or sub- stances readily converted into them, are oxidized with ease in the animal body. Lewis points out that such a generalization, if true, applies only to aliphatic compounds, since neither thio- phenol nor thiocresol, in which, of course, the sulfhydryl group is attached directly to the benzene ring, is oxidized in the animal BIOGRAPHICAL MEMOIRS organism. The fate of several other compounds related chemically to cystine was tested by Lewis and his colleagues. Definite, but

HOWARD BISHOP LEWIS served r 13 149 variable, increases in the output of inorganic sulfate were ob- following the oral administration of cysteic acid or taurine. Insofar as oxidation of these compounds occurred, it is believed to have been associated with the activity of the intestinal microflora. The accuracy of this conclusion is attested by the fact that, following the subcutaneous introduction of either cysteic acid or taurine, all extra sulfur appeared in the organic sulfur fraction of the urine. The excretion and dis- tribution of the extra sulfur after the oral or subcutaneous ad- ministration of peptides containing glycine and either cysteic acid or taurine did not differ significantly from the findings with the free sulfonic acid. Neither S-carboxymethylcysteine, isocysteine, nor thiourea underwent oxidation when injected subcutaneously into rabbits. After the oral administration of S-carboxymethylcysteine, a slight increase in urinary sulfate was observed, which again is believed to have been due to activities of the intestinal flora. S-Benzyl derivatives of homo- cysteine and cysteine were not oxidized significantly. However, deamination probably occurred as shown by an increase in a-keto acids in the urines. Thus, deamination may take place even though further catabolic change is blocked by the pres- ence of a nonlabile group. In growth studies involving the use of young white rats, Lewis confirmed the observations made elsewhere, that taurine is not capable of improving the quality of rations known to be deficient in cystine and methionine. Also, cysteic acid, di- benzoylcystine, and the betaine of cystine are incapable of pro- moting the growth of animals upon such diets. On the other hand, diglycylcystine and dialanylcystine are readily utilized for growth purposes, while the dianhydride of dialanylcystine iS not. Lewis investigated the cystine content of hair from several specie~, and conducted experiments designed to determine the relationship of the sulfur-containing amino acids to the growth

150 BIOGRAPHICAL MEMOIRS and composition of hair. It was observed that, within certain limits, the cystine and total sulfur content of the hair of white rats tended to vary with the content of the sulfur-containing amino acids in the diet, and to some extent with the age of the rats. Hair from young rats had a significantly lower cystine and total sulfur content than hair from adult animals. Hair from rats receiving a diet known to be deficient in cystine and methionine resembled in composition hair from young animals. However, retardation of growth per se, as illustrated by a lysine deficiency, did not produce hair low in cystine and total sulfur. In general, the cystine and methionine requirements for body growth seem to take precedence over the requirements for the production of hair. Later experiments demonstrated, as was to have been expected, that methionine is just as effective a supple- ment as cystine in inducing the growth and a normal cystine content of hair. One would expect that the curious metabolic anomaly known as cystinuria would be of very special interest to one who had devoted so much time and energy in elucidating the biochemical behavior of sulfur compounds. And so it was. First, Lewis and his colleagues presented evidence indicating that cystinuria probably is not so rare a condition as had previously been thought. This conclusion was based upon the results of tests upon urine samples obtained from about 11,000 healthy young men and women. For the most part, the samples were procured in connection with the medical examinations given to entering students at the University of Michigan and at two neighboring institutions. The tests revealed four students whose urines regularly contained cystine crystals, and hence were in- tensely cystinuric. Samples from twenty-five additional indi- viduals, though devoid of cystine crystals, consistently responded positively, in varying intensity, to color tests for the amino acid. Several individuals were subjected to extended investigation. The data obtained with one young man, who seemingly was in

HOWARD BISHOP LEWIS 151 excellent health except for the excretion of cystine, showed that the output of cystine varied rather closely with the total nitrogen content of the urine, and not with the cystine content of the diet. Indeed, the subject could completely oxidize to sulfate doses of 2 to 3 g of cystine. Obviously, the excreted cystine must have been derived from endo':,enous sources. Like results were obtained with other subjects. Invariably, the administration of cystine, whether isolated from hair, or derived from the patient's own urine, was without effect upon the cystine excretion, but induced a large increase in the sul- fate content of the urine. A similar experiment in which cysteine hydrochloride was ingested led to increases in the out- put of both cystine and sulfate. When D~-methionine was given, much extra cystine appeared in the urine, accompanied by a moderate rise in sulfate. Strangely, less extra cystine was excreted after a given dose of methionine when the subject was consuming a high protein diet (124 g daily) than when he was ingesting a moderate protein intake (55-60 g daily). This suggested to Lewis the possibility that the utilization of the precursor of urinary cystine in cystinuria occurs more readily under conditions of a high level of protein metabolism. No evidence was obtained for the presence in the urine of a com- plex containing cystine. Furthermore, both in children and in adults, the loss of cystine in the urine did not alter the cystine content of the hair and nails. No cystine could be detected in the sweat of a patient with pronounced cystinuria. Lewis's interest in amino acids was not restricted to cystine and methionine, though they seem to have been uppermost in his thoughts. His scientific curiosity included the origin, func- tions, and metabolic deportment of many amino acids. Ex- tensive experiments were devised to determine the relative rates at which amino acids are absorbed from the alimentary tract, their influence on blood composition, and their effectiveness in the formation of glycogen. In studying absorption, use was

152 BIOGRAPHICAL MEMOIRS made of the well-known technique devised by Cori. For this purpose, the amino acids, as their sodium salts, were admin- istered by stomach tube to white rats. The extent of the absorption was measured in each case at the end of a period of three hours by killing the animal, removing its alimentary tract, and determining the amount of unabsorbed amino acid remaining in the tract. Incidentally, Lewis confirmed Cori's statement that the rate of absorption is independent of the absolute quantity and the concentration of the amino acid in . . the Intestine. The results obtained with each amino acid were expressed in terms of the "absorption coefficient" of the compound, which, by definition, is the milliequivalents absorbed per 100 g of body weight per hour. The figures are not reproduced here; it is sufficient to state that the absorption coefficients of the amino acids tested may be arranged in the following descending order: glycine, alanine, cystine (expressed as cysteine), glutamic acid, valine, methionine, leucine, isoleucine, and isovaline. Thus, of the above, glycine was absorbed most rapidly and iso- valine least rapidly. No significant difference could be detected in the absorption coefficient of the natural Inform of an amino acid and that of its -counterpart. In later experiments, attention was directed to the effects of structural changes on the rates of absorption of several amino acids, all of which were derivatives of propionic acid. The data revealed that ¢-alanine (natural ~-alanine) its absorbed more rapidly than is ,8-alanine, and serine more rapidly than iso- serine. These findings led Lewis to postulate that the rate of absorption is decreased as the amino group of a compound is moved away from the carboxyl. In like manner, a comparison of the absorption rates of alanine and serine on the one hand, and of ,8-alanine and isoserine on the other, seemed to indicate that the replacement of a hydrogen atom by a hydroxyl group diminished the rate of absorption. It would be interesting to

HOWARD BISHOP LEWIS 153 know whether a similar relationship exists between structure and alimentary absorption in amino acids other than those derived from propionic acid. Changes in the distribution of nonprotein nitrogenous con- stituents of the blood were determined following the adminis- tration of a number of amino acids. Rabbits were the experi- mental animals. The amino acids investigated were glycine; the Informs of alanine, ~lutamic acid, asinine, and lysine; and the -forms of alanine and aspartic acid. Each amino acid was administered, usually orally, in an amount equivalent to 0.182 g of amino nitrogen per kilo of body weight. Blood samples were taken before the amino acid was given, and at intervals of 3, 6, 12, and usually 30 hours thereafter. Each sample was analyzed for nonprotein nitrogen, urea nitrogen, and amino acid nitrogen. From the nitrogen distribution values, it was evident that glycine and ~-alanine are absorbed very rapidly, but that glycine undergoes deamination less rapidly than any of the other amino acids. In studies of glycogen formation, the oral administration of either a- or D~-alanine to white rats which had been de- prived of food for 24 hours resulted in a rapid deposition of glycogen in the liver. On the contrary, after administration of glycine or ~-leucine, the hepatic glycogen values were similar to those of control animals. The monosodium salt of -glutamic acid induced a slight increase in liver glycogen. In later experiments, the glycogenic effects of certain amino acids, after three-hour absorption periods, were found to proceed in the following descending order: DL- and ~-alanine (essentially the same), D~-serine, D-alanine, and D~-isoserine. No glycogen formation could be detected after the administration of ,8- alanine. Several of Lewis's papers dealt with the metabolism of phenylalanine. After the oral or subcutaneous administration of this amino acid to rabbits, significant amounts of phenyl-

154 BIOGRAPHICAL MEMOIRS pyruvic acid appeared in the urine. However, no phenylpyruvic acid was excreted when the amino group was blocked by the formation of the ureido derivative of the amino acid. This observation was interpreted as indicating that oxidative de- amination is a necessary step in the metabolism of phenyl- alanine and must occur prior to the opening of the benzene ring. No evidence was obtained for the excretion of p-hy- droxyphenylpyruvic acid. In some experiments, after relatively large doses of phenylalanine, slight increases in the output of phenaceturic acid were observed. Apparently, under such con- ditions, part of the phenylpyruvic acid may be oxidized to phenylacetic acid, which is then conjugated with glycine and excreted without undergoing further oxidation. Of particular interest was the observation that the daily administration of phenylalanine to white rats in doses exceeding 0.3 g per 100 g of body weight per day, and for consider- able periods of time, led to the excretion of homogentisic acid. This appears to have been the first time that alcaptonuria has been consistently produced experimentally. The observation was interpreted by Lewis as lending support to a concept, which was controversial at the time but now is generally accepted, namely, that homogentisic acid is a normal intermediate in the metabolism of phenylalanine. In experiments of a different kind, Lewis observed that N- methylglycine (carnosine) can undergo demethylation in the animal body, and thereby serve as a source of glycine for hip- puric acid formation. On the other hand, a comparable reaction with N-ethylglycine does not occur. In studies of histidine metabolism, five of eight rabbits that received large doses of this amino acid by mouth responded by excreting urocanic acid. However, no urocanic acid was ex- creted after the subcutaneous administration of like doses of histidine. Severe toxic manifestations were exhibited by every animal that excreted detectable amounts of urocanic acid, while

HOWARD BISHOP LEWIS 155 those that failed to show the presence of this acid in the urine displayed no signs of intoxication. These findings led Lewis to question the assumption that urocanic acid is quantitatively an important intermediate in the normal metabolism of histi- dine. Doubtless he would have altered this opinion in the light of currently accumulated evidence. Lewis verified the strange report in the literature that pregnant women frequently excrete histidine. Of the urine samples obtained from 169 pregnant females, 85 percent showed the presence of histidine in excess of the normal traces. In contrast, of the urine samples collected from 59 nonpregnant women and 50 men, only 9 percent showed the presence of excess histidine. No logical explanation is available to account for the excretion of this amino acid. The phenomenon does not occur until the third month of pregnancy, and consequently cannot be used as an early diagnostic aid. Lewis and his colleagues were among the first to attempt the dietary replacement of an essential amino acid by a related compound for purposes of growth. As is well known, a diet containing 18 percent of gliadin as the chief source of nitrogen is incapable of supporting normal growth in young white rats. The factor limiting growth under such conditions is the low lysine content of the food. The addition of this amino acid to the basal ration greatly increases the rate of gain in body weight. It seemed reasonable to assume that some compound closely related to lysine might be transformed into the amino acid, and thereby improve the quality of the basal diet. With this possibility in mind, growth tests were made with several caproic acid derivatives as dietary supplements, namely, norleucine, a-hydroxycaproic acid, ~-hydroxycaproic acid, ~-aminocaproic acid, and a-hydroxy-~-aminocaproic acid. All proved to be totally incapable of serving in place of the missing lysine, and consequently are not convertible into it. In the light of more recent investigations in other laboratories, in which the a-hy- .. . . . . , . .

156 BIOGRAPHICAL MEMOIRS droxy analogues of several amino acids have been shown to be capable of serving in place of the corresponding amino acid, it seems very odd that a-hydroxy-~-aminocaproic acid was not con- verted into lysine. The most likely explanation of the negative results is the probability that the test compound underwent catabolic changes, possibly involving the c-amino group, before oxidation and amination could occur in the a-position. ~ . ~ , ~ Toward the end of his career, Lewis became interested in a toxemia known as lathyrism. This condition is associated with the prolonged consumption of large amounts of legumes of the genus Lathyrus. The toxemia is said to be rather common in India, in northern Africa, and in other areas where legumes of this genus constitute a high percentage of the daily diet. Those afflicted with the malady experience muscular weakness, lameness, and paralysis of the extremities. Lewis was able to induce the disease in young white rats (adult rats are more resistant) by feeding diets containing 50 percent of a finely ground meal prepared from decorticated sweet peas (Lathyrus odoratus;, or from the seeds of certain other varieties of Lathy- rus. Pathological examinations of the long bones of the leg revealed lesions similar to those observed in acute scurvy. How- ever, the administration of ascorbic acid, which normally is synthesized by the rat, exerted no preventive effect. The active principle was found to be readily extractable with cold water or 30 percent ethyl alcohol. From meal pre- pared from Lathyrus sylvestris Wagneri, the species having the greatest toxicity of the ten varieties tested, Lewis succeeded in concentrating the active agent about forty times. Since then, the possibility has been suggested that more than one deleterious compound may be present in Lathyrus legumes. One such com- ponent has been isolated and identified as 3-~^y-~-glutamyl)- . . . . amlnoproplonltrlle. The above outline of some of Lewis's publications, though very incomplete, may give the reader an idea of the breadth

HOWARD BISHOP LEWIS ~ 1 1 157 of his research activities. Many aspects of protein metabolism, other than those described, were explored by him, as may be seen by examining his extensive bibliography. In addition, his interests included problems in carbohydrate metabolism, as illustrated by papers on the behavior of certain pentoses, man- nose, and inulin in the animal organism. He investigated the metabolism of a number of branched-chain aliphatic acids, described new examples of ,0-oxidation, and conducted a series of studies on the hydrolysis of esters of dicarboxylic acids by liver lipase. Even the physiological effects and the metabolic fate of several toxic agents, notably hydrazine and its derivatives and selenium compounds, did not escape his attention. A multi- tude of miscellaneous topics, too numerous to be described in detail, came under his scientific scrutiny. Among the strikingly unique contributions may be mentioned a comparative bio- chemical study of the urine of the horned lizard, the nitrogenous components of the blood and urine of the turtle, and the nitrog- enous metabolism of the earthworm. Truly, his versatility knew no bounds. Shortly after his death, the Executive Faculty of the School of Medicine at the University of Michigan paid its respects to Howard Bishop Lewis by approving unanimously an appropriate testimonial to be recorded in its minutes and transmitted to his family. Excerpts from that expression of esteem, as phrased by his colleagues, may serve as a tatting conclusion to this survey of his life and work. It reads in part as follows: "It is difficult to appraise the inspired work of Dr. Lewis, and to make a true evaluation of his vital years of service to the medical profession. To understand the magnitude of his in- fluence, it is necessary to comprehend his remarkable ability and unusual skill in dealing with the training of his students and the administrative functions of his offices.... He taught the value of ideals and high standards of accomplishment, and gave to his pupils many guiding principles which have contributed

158 BIOGRAPHICAL MEMOIRS to their enduring happiness and success in the profession of medicine and allied fields of science.... "Dr. Lewis was as great and as honorable and as respected as the University he loved so much. May his students and colleagues reap the full benefit of the inspiration which he has left with us." THE AUTHORS are deeply grateful to the late Mrs. H. B. Lewis for supplying much of the information herein recorded concerning her husband's early life and nonprofessional interests, and for permitting us to see and make use of the contents of letters written to her by close friends following Howard's death. We are also indebted to Dr. A. A. Christman, a former student, friend, and colleague of Dr. Lewis, for supplying many of the scientific facts not otherwise available, and for rendering very substantial assistance in the preparation of the bibliography. !

HOWARD BISHOP LEWIS BIBLIOGRAPHY KEY TO ABBREVIA TIONS 159 Am. J. Pharm. Educ. _ American journal of Pharmaceutical Education Am. J. Physiol. American Journal of Physiology Ann. Internal Med. Annals of Internal Medicine Ann. Rev. Biochem. Annual Review of Biochemistry Cyclo. Med., Surg., Specialties Cyclopedia of Medicine, Surgery, and Specialties i. Am. Chem. Soc. Journal of the American Chemical Society I. Am. Dietetic Assoc. Journal of the American Dietetic Association i. Am. Med. Assoc. Journal of the American Medical Association J. Biol. Chem.—Journal of Biological Chemistry I. Rich. State Med. Soc. journal of the Michigan State Medical Society I. Nutrition- Journal of Nutrition I. Pharmacol. Exp. Therap. journal of Pharmacology and Experimental Therapeutics Oral Surg., Oral Med., Oral Pathol. - Oral Surgery, Oral Medicine, and Oral Pathology Proc. Soc. Exp. Biol. Med. - Proceedings of the Society for Experimental Biology and Medicine 1912 The behavior of some hydantoin derivatives in metabolism. I. Hy- dantoin and ethyl hydantoate. l. Biol. Chem., 13:347-56. The value of inulin as a foodstuff. i. Am. Med. Assoc., 58:1176-77. 1913 The behavior of some hydantoin derivatives in metabolism. II. 2- Thiohydantoins. l. Biol. Chem., 14:245-56. With B. H. Nicolet. The reaction of some purine, pyrimidine, and hydantoin derivatives with the uric acid and phenol reagents of Folin and Denis. J. Biol. Chem., 16:369-73. 1914 With E. NI. Frankel. The influence of inulin on the output of glucose in phlorhizin diabetes. J. Biol. Chem., 17:365-67. Studies on the synthesis of hippuric acid in the animal organism. I. The synthesis of hippuric acid in rabbits on a glycocoll-free diet. I. Biol. Chem., 17:503-8. Studies in the synthesis of hippuric acid in the animal organism. II. The synthesis and rate of elimination of hippuric acid after benzoate ingestion in man. I. Biol. Chem., 18: 225-31.

160 BIOGRAPHICAL MEMOIRS 1915 With A. E. Taylor. A study of the protein metabolism under con- ditions of repeated hemorrhage. I. Biol. Chem., 22:71-75. With A. E. Taylor. On the predominance of the liver in the forma- tion of urea. l. Biol. Chem., 22:77-80. The behavior of some hydantoin derivatives in metabolism. III. Parabanic acid. I. Biol. Chem., 23:281-86. 1916 With W. G. Karr. Studies in the synthesis of hippuric acid in the animal organism. III. The excretion of uric acid in man after ingestion of sodium benzoate. I. Biol. Chem., 25:13-20. The metabolism of sulfur. I. The relative elimination of sulfur and nitrogen in the dog in inanition and subsequent feeding. I. Biol. Chem., 26:61-68. With W. G. Karr. A comparative study of the distribution of urea in the blood and tissues of certain vertebrates with especial reference to the hen. l. Am. Chem. Soc., 38: 1615-20. With W. G. Karr. Changes in the urea content of blood and tissues of guinea pigs maintained on an exclusive oat diet. J. Biol. Chem., 28: 17-25. (A . 1917 The metabolism of sulfur. II. The influence of small amounts of cystine on the balance of nitrogen in dogs maintained on a low protein diet. l. Biol. Chem., 31: 363-77. \Vith L. M. Smith. A study of the normal metabolism of the guinea pig. J. Am. Chem. Soc., 39:2231-39. Edith W. G. Karr. Tl~e phenol excretion of guinea pigs maintained Am. l. Physiol., 44:586-90. On an exclusive oat diet. 1918 With M. E. Newell. The occurrence of lichenase in the digestive tract of invertebrates. I. Biol. Chem., 33: 161-67. With E. A. Doisy. Studies in uric acid metabolism. I. The influ- ence of high protein diets on the endogenous uric acid elimina- tion. I. Biol. Chem., 36:1-7. With M. S. Dunn and E. A. Doisy. Studies in uric acid metabolism.

HOWARD BISHOP LEWIS 161 II. Proteins and amino acids as factors in the stimulation of endogenous uric acid metabolism. l. Biol. Chem., 36:9-26. Some analyses of the urine of reptiles. Science, 48:376. 1919 The antiscorbutic value of the banana. I. Biol. Chem., 40: 91-101. 1920 The metabolism of sulfur. III. The relation between the cystine content of proteins and their efficiency in the maintenance of nitrogenous equilibrium in dogs. J. Biol. Chem., 42:289-96. Title L. E. Root. Amino acid synthesis in the animal organism. Can norleucine replace lysine for the nutritive requirements of the white rat? I. Biol. Chem., 43:79-87. 1921 Studies on the synthesis of hippuric acid in the animal organism. IV. A note on the synthesis of hippuric acid in the rabbit after exclusion of bile from the intestine. I. Biol. Chem., 46:73-75. \Vith A. A. Christman. Lipase studies. I. The hydrolysis of the esters of some dicarboxylic acids by the lipase of the liver. Biol. Chem., 47 :495-505. With M. S. Dunn. The action of nitrous acid on casein. J. Biol. Chem., 49: 327~ 1. With M. S. Dunn. A comparative study of the hydrolysis of casein and deaminized casein by proteolytic enzymes. i. Biol. Chem., 49: 343-50. With G. Stearns. Diet and sex as factors in the creatinuria of man. Am. J. Physiol., 56: 60-71. 1922 With L. E. Root. The metabolism of sulfur. IV. The oxidation of cystine in the animal organism. l. Biol. Chem., 50:303-10. With D. A. McGinty. The metabolism of sulfur. V. Cysteine as an intermediary product in the metabolism of cystine. J. Biol. Chem., 53:349-56. With R. M. Hill. The hydrolysis of sucrose in the human stomach. Am. J. Physiol., 59:413-20.

162 BIOGRAPHICAL MEMOIRS 1923 With R. C. Corley. Studies in uric acid metabolism. III. The influence of fats and carbohydrates on the endogenous uric acid elimination. i. Biol. Chem., 55:373-84. With E. C. Hyde. Lipase studies. II. A comparison of the hy- drolysis of the esters of the dicarboxylic acids by the lipase of the liver. l. Biol. Chem., 56: 7-15. With H. Updegraff. The reaction between proteins and nitrous acid. The tyrosine content of deaminized casein. I. Biol. Chem., 56:405-14. With W. H. Griffith. Studies in the synthesis of hippuric acid in the animal organism. V. The influence of amino acids and related substances on the synthesis and rate of elimination of hippuric acid after the administration of benzoate. l. Biol. Chem., 57:1-24. With A. A. Christman. Biochemical studies on allantoin. I. The influence of amino acids on the excretion of allantoin by the rabbit. J. Biol. Chem., 57:379-95. With W. H. Griffith. Studies in the synthesis of hippuric acid in the animal organism. VI. The influence of the protein of the diet on the synthesis and rate of elimination of hippuric acid after the administration of benzoate. I. Biol. Chem., 57:697- 707. 1924 With H. Updegraff and D. A. McGinty. The metabolism of sulfur. VI. The oxidation of cystine in the animal organism. Second paper. J. Biol. Chem., 59:59-71. With R. M. Hill. The metabolism of sulfur. VII. The oxidation of some sulfur compounds related to cystine in the animal organism. I. Biol. Chem., 59:557-67. \Vith R. M. Hill. The metabolism of sulfur. VIII. The behavior of thiophenol and thiocresol in the animal organism. I. Biol. Chem., 59:569-75. With H. Updegraff. A quantitative study of some organic con- stitutents of the saliva. l. Biol. Chem., 61:633-48. With D. A. McGinty and C. S. Marvel. Amino acid synthesis in the animal organism. The availability of some caproic acid de- rivatives for the synthesis of lysine. l. Biol. Chem., 62:75-92. Sulfur metabolism. Physiological Reviews, 4:394-423.

HOWARD BISHOP LEWIS 1925 163 The metabolism of sulfur. IX. The effect of repeated administra- tion of small amounts of cystine. J. Biol. Chem., 65:187-95. Some contributions of chemistry to the art and science of medicine. I. Erich. State ~led. Soc., 24:1-7. Insulin. Annals of Clinical Medicine, 3:623-33. 1926 With D. A. McGinty. Lipase studies. III. The hydrolysis of the esters of the dicarboxylic acids by the lipase of the liver. I. Biol. Chem., 67: 567-77. With R. H. Wilson. The metabolism of sulfur. X. The determina- tion of cystine in the urine. I. Biol. Chem., 69:125-31. With G. T. Lewis. The metabolism of sulfur. XI. Can taurine replace cystine in the diet of the young white rat? l. Ball. Chem., 69:589-98. With S. Izume. The influence of hydrazine and its derivatives on metabolism. I. The effect of substitution in the hydrazine mole- cule upon the hypoglycemic action of hydrazine. l. Pharmacol. Exp. Therap., 30:87-93. NVith S. Izume. The influence of hydrazine and its derivatives on metabolism. II. Changes in the non-protein nitrogenous con- stituents of the blood and in the metabolism of injected glycine in hydrazine intoxication. i. Biol. Chem., 71:33-49. With S. Izume. The influence of hydrazine and its derivatives on metabolism. III. The mechanism of hydrazine hypoglycemia. ]. Biol. Chem., 71:51-66. The role of the inorganic elements in nutrition. 68:950-58. 1927 Dental Cosmos, With G. T. Lewis. The metabolism of sulfur. XII. The value of diglycyl-cystine, dialanyl-cystine, and dialanyl-cystine dianhy- dride for the nutritive requirements of the white rat. i. Biol. Chem., 73:535-42. With R. H. Wilson. The cystine content of hair and other epi- dermal tissues. ]. Biol. Chem., 73:543-53. With G. T. Lewis. The metabolism of sulfur. XIII. The effect of elementary sulfur on the growth of the young white rat. I. Biol. Chem., 74:515-23.

164 BIOGRAPHICAL MEMOIRS With M. G. Bodey and I. F. Huber. The absorption and utilization of inulin as evidenced by glycogen formation in the white rat. I. Biol. Chem., 75:715-23. \Vith F. H. Wiley. The distribution of nitrogen in the blood and urine of the turtle (Chrysemys pinta j. Am. J. Physiol., 81: 692-95. 1928 With S. L. Diack. Studies in the synthesis of hippuric acid in the animal organism. VII. A comparison of the rate of elimination of hippuric acid after the ingestion of sodium benzoate, benzyl alcohol, and benzyl esters of succinic acid. {. Biol. Chem., 77:89-95. Occurrence of cystine in sweat of cystinurics. Proc. Soc. Exp. Biol. Med., 26: 69-70. With P. Hodgson. Physical development and the excretion of creatine and creatinine by women. Am. l. Physiol., 87:288-92. With hi. W. Johnston. Comparative studies of the metabolism of amino acids. I. Changes in the non-protein nitrogenous con- stituents of the blood following administration of amino acids. T. Biol. Chem., 78:67-82. 1929 With S. A. Lough. The metabolism of sulfur. XIV. A metabolic study of a case of cystinuria. I. Biol. Chem., 81:285-97. With H. D. Lightbody. The metabolism of sulfur. XV. The rela- tion of the protein and cystine content of the diet to the growth of the hair in the white rat. I. Biol. Chem., 82:485-97. Edith H. D. Lightbody. The metabolism of sulfur. XVI. Dietary factors in relation to the chemical composition of the hair of the young white rat. i. Biol. Chem., 82:663-71. NVith R. H. Wilson. Comparative studies of the metabolism of amino acids. II. The rate of absorption of amino acids from the gastrointestinal tract of the white rat. I. Biol. Chem., 84: 51 1-31. With L. F. Catron. The formation of glycogen in the liver of the young white rat after the oral administration of glycerol. J. Biol. Chem., 84:553-59. With R. L. Grant and A. A. Christman. Exogenous arginine as the

HOWARD BISHOP LEWIS 165 precursor of creatine in the dog. Proc. Soc. Exp. Biol. Med., 27:231-33. lg30 With R. H. Wilson. Comparative studies of the metabolism of amino acids. III. The formation of glycogen after oral adminis- tration of amino acids to white rats. I. Biol. Chem., 85:559-69. \Vith G. Stearns. The metabolism of sulfur. XVII. The rate of oxidation of ingested cystine in the organism of the rabbit. I. Biol. Chem., 86: 93-105. With F. H. Wiley. The action of nitrous acid on casein. II. T. Biol. Chem., 86:511-28. 1931 With M. F. O'Connor. Cystinuria and tuberculosis. American Review of Tuberculosis, 23: 134-38. With M. M. Miller. Glycogen formation in the white rat after oral administration of xylose. Proc. Soc. Exp. Biol. Med., 28:448-49. With N. F. Shambaugh and D. Tourtellotte. Comparative studies of the metabolism of the amino acids. IV. Phenylalanine and tyrosine. l. Biol. Chem., 92:499-511. 1932 \Vith S. A. Lough. The metabolism of sulfur. XVIII. The distri- bution of urinary sulfur in the rabbit after the administration of monobromobenzene. l. Biol. Chem., 94:739-47. With A. K. Silberman. The tyrosine content of cocoons of various species. I. Biol. Chem., 95:491-94. NAlith J. P. Chandler. Comparative studies of the metabolism of the amino acids. N1. The oxidation of phenylalanine and phenyl- pyruvic acid in the organism of the rabbit. l. Biol. Chem., 96:619-36. With M. M. Miller. Pentose metabolism. I. The rate of absorption of d-xylose and the formation of glycogen in the organism of the white rat after oral administration of d-xylose. I. Biol. Chem., 98: 133-40. NVith M. M. Miller. Pentose metabolism. II. The pentose content of the tissues of the white rat after the oral administration of d-xylose. I. Biol. Chem., 98:141-50. With A. White. The metabolism of sulfur. XIX. The distribution

166 BIOGRAPHICAL MEMOIRS of urinary sulfur in the dog after the oral administration of monobromobenzene as influenced by the character of the dietary protein and by the feeding of ~-cystine and D~-methionine. I. Biol. Chem., 98:607-24. The occurrence of cystinuria in healthy young men and women. Ann. Internal Nfed., 6:183-92. Cystinuria: a review of some recent investigations. Yale Journal of Biology and Medicine, 4:437-49. The chemistry and metabolism of the compounds of sulfur. Ann. Rev. Biochem., 1:171-86. The role of amino acids in the animal organism. I. Cystinuria and cystine calculi, a surgical and medical problem. J. Mich. State ~led. Soc., 31 :249-53. The role of amino acids in the animal organism. II. The physiology of the amino acids. I. Mich. State Med. Soc., 31:307-13. 1933 With B. W. Chase. The metabolism of sulfur. XX. The rate of absorption of D~-methionine from the gastrointestinal tract of the white rat. i. Biol. Chem., 101: 735-40. \Vith A. K. Silberman. Pentose metabolism. III. The rate of ab- sorption of l-rhamnose and the formation of glycogen in the organism of the white rat after oral administration of l-rhamnose. J. Biol. Chem., 101 :741-51. With V. l. Tulane and A. A. Christman. Studies in the synthesis of hippuric acid in the animal organism. VIII. Hydrazine in- toxication and hippuric acid synthesis in the rabbit. J. Biol. Chem., 103:141-50. With V. J. Tulane. Studies in the synthesis of hippuric acid in the animal organism. IX. A comparative study of the rate of synthesis and excretion of hippuric and phenaceturic acids by the rabbit. J. Biol. Chem., 103: 151-60. With A. K. Silberman. Glycogen formation after oral administra. tion of mannitol to white rats. Proc. Soc. Exp. Biol. Med., 31 :253-55 The chemistry and metabolism of the compounds of sulfur. Ann. Rev. Biochem., 2: 95-108. 1934 With R. W. Virtue. The metabolism of sulfur. XXI. Comparative

HOWARD BISHOP LEWIS 167 studies of the metabolism of Cystine and D~-methionine in the rabbit. I. Biol. Chem., 104: ~ 9-67. With R. W. Virtue. The iodometric determination of cystine in the urine. l. Biol. Chem., 104:415-21. With S. A. Lough. The reaction of nitrous acid with cystine and related sulfur-containing compounds. i. Biol. Chem., 104:601 - 10. With B. W. Chase. Comparative studies of the metabolism of amino acids. VI. The rate of absorption of leucine, valine, and their isomers from the gastrointestinal tract of the white rat. I. Biol. Chem., 106:315-21. With W. C. Lee. The effect of fasting, refeeding, and of variations in the cystine content of the diet on the composition of the tissue proteins of the white rat. i. Biol. Chem., 107:649-59. The progress of biochemistry. Review of Volume 3 of the Annual Review of Biochemistry. Science, 80:291-92. 1935 With R. L. Grant. Some products of partial hydrolysis of silk fibroin. I. Biol. Chem., 108: 667-73. With L. Frayser. The metabolism of sulfur. XXII. The cystine content of the hair and nails of cystinurics. I. Biol. Chem., 110:23-27. With B. H. Brown. Specific rotation of cystine excreted in cys- tinuria. Proc. Soc. Exp. Biol. Med., 32: 1100-~. The chemistry and metabolism of the compounds of sulfur. Ann. Rev. Biochem., 4: 149-68. Editorial review. The chief sulfur compounds in nutrition. T. Nutrition, 10:99-116. Sulfur. Cyclo. Med., Surg., Specialties, 8:922-29. With A. Bendana. The utilization of inulin for growth by the young white rat. l. Nutrition, 10:99-116. 1936 With B. H. Brown and F. R. White. The metabolism of sulfur. XXIII. The influence of the ingestion of cystine, cysteine, and methionine on the excretion of cystine in cystinuria. J. Biol. Chem., 114:171-84.

168 With F. R. White and i. White. BIOGRAPHICAL MEMOIRS 1937 The metabolism of sulfur. XXIV. The metabolism of taurine, cysteic acid, cystine, and of some peptides containing these amino acids. I. Biol. Chem., 117 : 663-71. With B. H. Brown. Cystine in normal and cystinuric human blood. Proc. Soc. Exp. Biol. Med., 36:487-88. 1938 With E. V. Heard. The metabolism of sulfur. XXV. Dietary methionine as a factor related to the growth and composition of the hair of the young white rat. I. Biol. Chem., 123:203-10. With E. Papageorge. Comparative studies of the metabolism of the amino acids. VII. Experimental alcaptonuria in the white rat. J. Biol. Chem., 123:211-20. With E. T. Papageorge and M. M. Frohlich. Excretion of homo- gentisic acid after oral administration of phenylalanine to al- captonuric subjects. Proc. Soc. Exp. Biol. Med., 38:742-45. With I. I. Routh. The enzymatic digestion of wool. I Biol. Chem., 1 24: 725-32. With W. D. Block. The amino acid content of cow and chimpanzee hair. ]. Biol. Chem., 1 25:561-70. With P. C. fen. Availability of dibenzoylcystine for growth of the young white rat. Proc. Soc. Exp. Biol. Med., 39:301~. 1939 With P. C. Jen. The metabolism of sulfur. XXVI. The metabolism of the betaine of cystine. I. Biol. Chem., 127:97-103. With R. A. Gortner, fir. Quantitative determination of selenium in tissues and feces. Industrial and Engineering Chemistry, Analytical Edition, 11:198-200. With S. F. Velick and J. White. The synthesis of dicholylcystine and cholylcysteic acid. i. Biol. Chem., 127:477-81. Vitamins in theory and practice. Ann. Internal \led., 1 3: 749-54. With R. A. Gortner, Jr. The retention and excretion of selenium after the administration of sodium selenite to white rats. l. Pharmacol. Exp. Therap., 67:358-64. With L. D. Abbott, fir. Comparative studies of the metabolism of

HOWARD BISHOP LEWIS 169 the amino acids. VIII. Glycine precursors. Availability of N- methylglycine, lYr,N-dimethylglycine, and betaine for the syn- thesis of hippuric acid by the rabbit. J. Biol. Chem., 131:479-87. Sulfur metabolism. Cyclo. Med., Surg., Specialties, 10:125-34. 1940 With i. Schultz and R. A. Gortner, fir. Dietary protein and the toxicity of sodium selenite in the white rat. l. Pharmacol. Exp. Therap., 68:292-99. With I. Schultz. The excretion of volatile selenium compounds after the administration of sodium selenite to white rats. i. Biol. Chem., 133: 199-207. With R. L. Garner. The metabolism of proteins and amino acids. Ann. Rev. Biochem., 9:277-302. 1941 The significance of the sulfur-containing amino acids in metabolism. Harvey Lectures, 36:159-87. With L. D. Abbott, [r. Comparative studies of the metabolism of the amino acids. IX. Glycine precursors. Availability of N- ethylglycine and glycolic acid for the synthesis of hippuric acid by the rabbit. I. Biol. Chem., 137: 535~3. With B. H. Brown. The metabolism of sulfur. XXVII. The distri- bution of sulfur in the ultrafiltrates of blood plasma. l. Biol. Chem., 138:705-16. With B. H. Brown. The metabolism of sulfur. XXVIII. The cystine content and sulfur distribution of ultrafiltrates of plasma after the administration of ~-cystine and D~-methionine to rabbits. I. Biol. Chem., 138:717-26. Charles Wallis Edmunds. Am. l. Pharm. Educ., 5:245-48. With F. R. Blood. The metabolism of sulfur. XXIX. S-Carboxy- methylcysteine. J. Biol. Chem., 139:407-12. With F. R. Blood. The metabolism of sulfur. XXX. Thiourea. I. Biol. Chem., 139:413-20. End products of nitrogen metabolism in animals. Biological Symposia, 5: 20-30. 1942 With W. J. Darby and J. R. Totter. The preparation of 4 (5~- hydroxymethylimidazole. J. Am. Chem. Soc., 64:463-64.

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Biographic Memoirs: Volume 44 contains the biographies of deceased members of the National Academy of Sciences and bibliographies of their published works. Each biographical essay was written by a member of the Academy familiar with the professional career of the deceased. For historical and bibliographical purposes, these volumes are worth returning to time and again.

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