Hans Thacher Clarke (1887-1972): Chemist and ... - ACS Publications

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Hans Thacher Clarke (1887–1972): Chemist and Biochemist Ronald Bentley Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260

Hans Thacher Clarke, a man of many talents, made distinguished contributions to organic and bioorganic chemistry and was instrumental in nurturing the discipline of biochemistry in the United States. Despite his long and very productive career (1908–1970), his achievements have tended to be overlooked with the passage of time. I was acquainted with him as an author in 1939, and met him in 1946 when I was a Commonwealth Fund Fellow at Columbia University’s College of Physicians and Surgeons. He was then Chairman of the Department of Biochemistry and was invariably known as HT; so he shall be dubbed here. Early History HT was born in England in 1887 to an American father and German mother (1, 2). The middle name, Thacher, derived from his grandfather’s wife, Mary Gray Thacher (1823–1875), who traced her ancestry to the Mayflower. The name derived from her ancestor, Anthony Thacher. Thacher and his wife were the only survivors of the ship Watch and Wait, wrecked in 1653 on an island off Rockport, Cape Ann, MA. Four children from a previous marriage died in the wreck as well as a cousin, the cousin’s wife, and six further children. In compensation, Anthony Thacher was awarded the island by the General Court. He originally named it “Thacher’s Woe” but it is now known as Thacher (or Thatcher on some maps) Island (3). HT’s father and mother were accomplished musicians; HT followed suit, playing clarinet at almost the professional level until an encounter with a scythe in 1960. His first wife, a niece of Max Planck, was a skillful violinist. HT attended University College School, London, from 1896 to 1905 and subsequently studied chemistry at University College itself. At that time, University College had an exceptional group of chemists including William Ramsay, famous for his work with inert gases, and John N. Collie and Samuel Smiles in organic chemistry. HT obtained a B.Sc. degree in 1908 and continued research with Smiles and Alfred W. Stewart. From 1911 to 1913, he spent “three profitable and enjoyable semesters” (2) with Emil H. Fischer (Nobel Laureate in Chemistry, 1902) at the University of Berlin, where he had a nasty encounter with mustard gas [(ClCH2CH2)2S] (4). A further summer was spent at Queen’s University, Belfast, Northern Ireland, with Stewart. These researches earned him a D.Sc. degree from London University. Two of his University College professors, Collie and Stewart, were truly remarkable individuals from the late Victorian era; Collie was also a very distinguished mountaineer and explorer (5) and Stewart wrote 27 mystery novels under the pseudonym John J. Connington (6 ). The Eastman Kodak Years HT’s father, John Thacher Clarke, 1856–1920, the son of a Boston physician, was educated in Germany and became an archaeologist. During excavations at Assos, near Troy, he

Hans Thacher Clarke (1887–1972)

had used a cumbersome glass-plate camera. In the 1880s, to facilitate photography, he developed a small box camera (the “Frena”) that held 40 sheets of celluloid-based film, each measuring 31⁄4 × 41⁄4 inches. A meeting with George Eastman in 1886 led to J. T. Clarke’s appointment to Eastman Photographic Materials Ltd., and he played an important role with Eastman Kodak until his death (7). J. T. Clarke suggested the hiring of Charles E. K. Mees as Director of Research; Mees was appointed in 1912 and proved to be of great value to Eastman Kodak (7). The appointment of Mees provided another connection to University College, since he had worked there on spectroscopy, using photographs to record spectra; in this way Mees had become acquainted with many matters relating to photography. As was the case for many individuals and institutions, World War I initiated events of lasting consequence. Eastman Kodak had previously imported chemicals from Germany but in 1914 was faced with the need to manufacture these materials in the United States. It was natural for George Eastman to invite his associate’s son, a well-trained organic chemist, to synthesize organic chemicals at Rochester; HT remained there from 1914 until 1928 (2). In 1918, Mees offered HT a fulltime appointment in a new section for organic chemistry research. At about this time, the synthetic work to replace the materials previously obtained from Germany was expanded to include the needs of university chemists. HT organized a facility for preparation of “rare organic chemicals”, defined as chemicals required in relatively small quantities exclusively for laboratory purposes such as synthetic or analytical work or experimentation in medical or physical science (8). In addition, technical chemicals acquired in bulk from various manufacturers were repackaged and were made available in

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small amounts. Eastman Kodak was the first commercial firm in the USA to synthesize and distribute rare organic chemicals. By the end of 1922, the Organic Chemicals Division of Kodak had a list of more than 1,300 different chemicals, of which about 700 had been prepared or purified at the Rochester facility. The German company, Kahlbaum, listed a little more than 2,000 organic chemicals; HT was sure that the latter number would be reached within three years (8). In the first two years the work was conducted at a loss of about $30,000. An account of the work at the Kodak Rochester facility was given, probably by Mees, to The Society of Chemical Industry in Montreal (August 31, 1921). The lecture was published as a book under the joint authorship of Mees and Clarke (9), with the title The Preparation of Synthetic Organic Chemicals at Rochester. The problem of the non-availability of German chemicals was clearly defined as follows: “Researches already undertaken had to be abandoned or postponed and in many cases the laboratory curricula had to be modified so as to employ for teaching purposes only such substances as could be obtained in this country [i.e., the USA], and at the beginning of 1915 these were but few.” This publication, apparently not well known, is mainly concerned with the procedures devised by HT. Starting with an improvised laboratory “staffed with a few chemically trained girls [men at that time being out of question]”, new facilities were constructed. They consisted of several rooms, 24 × 12 feet, isolated by fireproof partitions, designed for one chemist and an assistant, together with three 24 × 24foot rooms for special purposes and available to all. The construction and equipment was “on as cheap a scale as possible”; floors were of cement with open gutters and much work was carried out directly on the floors. Pipes for the supply of necessary services (electricity, gas, water) were on the walls. The book contains 3 photographs of the buildings and laboratories and 30 of the generally used equipment; presumably these photographs were used as slides in the original lecture in Montreal. The improvised and rather primitive nature of the equipment is clear from these photographs. It seems likely that there must have been accidents and fires from handling glass flasks on cement floors and from heating distillation vessels, protected by wire gauze, directly with burners. Some preparations are very impressive, if not downright scary. To make capryl alcohol from “castor oil soap”, presumably by a saponification, a large can was raised on a brick framework and heated with massive gas burners, the process requiring five days. A separator allowed recovery of capryl alcohol with water being returned to the kettle. In the absence of ground-glass joints special methods were used to protect rubber stoppers during nitration and bromination procedures. To prepare diphenyl, benzene vapor was passed through an iron tube, heated to a “bright redness”. The apparatus was kept running all the time and produced 300–400 g of diphenyl per week. One wonders how many fires and explosions took place! Although there were patents, HT published little in the way of research before about 1924. However, in 1919, together with Mees, he described a material for preparing yellow photographic filters with improved properties over others, such as picric acid, that were available (10). The yellow material, glucose phenylosazone-p-carboxylic acid, was named “Eastman Yellow”. In 1918, HT published a paper that had clearly required considerable analytical research. With the 186

cutoff of German supplies of the important photographic developing agent Metol (p-methylaminophenol sulfate), “less commendable manipulations of the purveyors of bogus and adulterated developing agents” had become common and needed to be investigated. Typically, HT developed a systematic analytical technique with revealing results (11). A material named “Developing Agent”, acquired in 1916 and claimed by its purveyors to be identical to Metol, contained only 32% of Metol together with 52% of hydroquinone and small amounts of sodium carbonate, sodium sulfite, and potassium iodide. A “Metol Substitute” from April 1916 contained 10% Metol and 18.5% hydroquinone, the remainder being composed essentially equally of cane sugar (sucrose) and sodium sulfite. In this work, HT encountered a total of 25 adulterants. Although the definitive The Story of Kodak, written with the company’s cooperation, contains many references to J. T. Clarke, it is strange that it has no mention of HT (7). The book focuses on photography, and HT’s chemical contributions were essential to the preparation and processing of film. Moreover, there is a depressing coda to the Kodak story. HT had retired from Columbia University in 1956 and subsequently Erwin Chargaff suggested to Kodak that they help to establish a professorship in HT’s honor. Chargaff has written that “The answer I received will remain a monument to American corporate shabbiness” (12). Organic Syntheses and Organic Analysis At the University of Illinois (Urbana), Clarence G. Derick had responded to the chemical shortage by using students during summer vacations to prepare needed materials and in 1917 Roger Adams extended the resources of the university chemical manufacturing department to other laboratories. At that time, it is said that “thirty university and many industrial laboratories bought reagents” (4, pp 151–155). Accounts of syntheses were published annually in the University of Illinois Bulletin. Eventually, four chemists came together to systematize publication of organic syntheses in The Preparation of Organic Chemicals, Volume 1. Thus began the monumental series Organic Syntheses. The chemists were Roger Adams (University of Illinois), James B. Conant (Harvard University), Oliver Kamm (Parke, Davis & Co.), and HT (Department of Synthetic Chemistry, Eastman Kodak). HT was Editor in Chief for Volume 10 (1930) and was a member of the Editorial Board for Collective Volumes 1 and 2 (1932, 1943). In addition to contributing original articles, HT also checked many of the preparations. As late as 1955, he contributed articles on cysteic acid monohydrate and pentaacetyl d-glucononitrite (sic) for Collective Volume 3. A fuller history of Organic Syntheses is available (4, pp 151–155). A consequence of its success was the later publication of related volumes such as Inorganic Syntheses and Biochemical Preparations. HT was already an established author before this work. In 1911, he had published A Handbook of Organic Analysis. Qualitative and Quantitative, which ran to many editions (13). It became a standard text for students, at least in England. I still have my much-used and splattered copy of the 4th edition (1926), 6th impression (1939), purchased in the somber days of October 1939 at a cost of 8 shillings and 6 pence (then approximately $2). An Introduction to the 1911 1st edition by Collie noted that organic analysis, qualitative and quan-

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titative, had “of recent years acquired increasing importance in the training of the chemist”. He also stated that “Clarke’s book covers a very considerable amount of ground, and gives practically all that an average student should need. It will be of great assistance to anyone testing organic substances, and will help to put qualitative organic chemistry on as systematic a basis as qualitative inorganic chemistry has been for many years”. The book contains extensive tables of the properties of compounds and derivatives, many of them determined by HT himself. The illustrations from the pre-ground-glass-joint era are charming; the student is told that for distillation in vacuum, “all stoppers should be of indiarubber”. In 1912, HT followed with a second book, Introduction to the Study of Organic Chemistry (14). Organic Sulfur Compounds and Penicillin HT’s first research publication had been with Smiles in 1909 on the refractive power and chemical activity of some sulfur compounds (15). This work initiated a lifelong interest in organic sulfur compounds that had two consequences of considerable importance. The first concerned vitamin B1 (thiamin). During work on this vitamin, Robert R. Williams and his colleagues had isolated two degradation products, one a pyrimidine, the other a sulfur-containing nitrogenous base. HT’s examination of the latter indicated a thiazole structure and in collaboration with Samuel Gurin he synthesized the sulfur-containing moiety of vitamin B1 in 1935 (16 ). Two years later, Williams and his colleagues achieved the total synthesis of vitamin B1 (17 ). The second sulfur-related consequence came in connection with the USA–UK collaboration from 1943 to 1946 to determine the structure of penicillin with the hope that a chemical synthesis would replace the unpredictable fermentations of those days. His important administrative role in this project must first be noted. The Office of Scientific Research and Development (OSRD) had been set up in 1941 with Vannevar Bush as the director. A subdivision of OSRD, the Committee on Medical Research (CMR), chaired by Alfred N. Richards, had overall responsibility for the penicillin project. HT was asked to supervise the contracts made between the U.S. government and various firms, universities, and institutions and to provide coordination with the work being conducted in the UK. The task was monumental, since more than 800 reports were prepared; they contained what was then regarded as secret information related to the war effort. HT’s contribution to this project has received less appreciation than it deserves. In addition, at least in the early days, HT wrote extensive summaries of the work in progress and of possible conclusions. Thus, number 1 in a series of memos from HT to the contractors, dated January 20, 1944, consists of a summary requiring seven single-spaced typewritten pages. It begins with a suggestion for nomenclature, since by that time two different penicillins had been recognized. One, typically produced by surface growth of Penicillium notatum, was to be named penicillin F after its developer, Howard Florey. The product from submerged fermentation received the next letter in the alphabet, penicillin G. This nomenclature received extensive use until more structural information became available. HT’s memo continued with a discussion of many of the degradation

products and he concluded that the evidence then available suggested that penicillin G had a thiazolidine-oxazolone structure. Other memos provided further summaries and important information to the contractors. For instance, memo 3, May 4, 1944, announced that facilities and experience with X-ray and infrared spectrograms were to be made available for general use. As the mammoth project was terminated, HT played a major role in preparation of the archival volume The Chemistry of Penicillin, which was finally published in 1949 (18). He had chaired a meeting of representatives of the U.S. contractors on January 9, 1946, and prepared a detailed memorandum (memo Number 13) of a proposed organization of the complex mass of information; it had been decided that the individual publication of the 800 reports was not possible. HT left for England a few days later to discuss the proposed arrangements with the UK groups. He was one of the three editors of the volume, the others being Robert Robinson and John R. Johnson. These three individuals authored the first chapter, titled “Brief History of the Chemical Study of Penicillin”. All of the reports are tabulated in The Chemistry of Penicillin. Significantly, probably because of HT’s modesty, there is no mention in that volume of his vital administrative role and none of his memos are mentioned. A reader unfamiliar with the actual circumstances would never gain knowledge of HT’s heroic efforts. HT’s research contribution to the chemistry of penicillin was a study of the reaction between cysteine and formaldehyde made in collaboration with Sarah Ratner (19). The product was characterized as thiazolidine-4-carboxylic acid and the parent compound, thiazolidine, was prepared similarly from β-aminoethyl mercaptan. This 1937 paper was based on the Ph.D. thesis work of Ratner, an early graduate student in HT’s department at Columbia University. As a female graduate student in the late 1930s, Ratner encountered many difficulties, but with considerable fortitude and a high degree of intellectual rigor, these problems were overcome. Subsequently, she worked with Rudolph Schoenheimer’s group developing the use of 15 N as a tracer (see later) and had a long and distinguished independent career, being well known for her work on urea biosynthesis. Her active research continued until a few years before her death in 1999. A comment on the interaction between mentor and student has been recorded: “When ‘H.T.’ [bless his heart !], sincerely intending to be complimentary, remarked ‘Sarah thinks like a man’, Sarah’s response was a somewhat disdainful, ‘Humph’” (20). Times have certainly changed. Such a remark today would be considered inappropriate and might even form part of an official complaint. In a tragic mistake, penicillin had been thought for some time not to contain sulfur. Eventually, sulfur was shown to be present in the degradation product, penicillamine, C5H11NO2S. Penicillamine reacted smoothly with acetone to form a compound termed “isopropylidene penicillamine” (18). It was shown that penicillamine was actually β,βdimethylcysteine and the “isopropylidene penicillamine” was a thiazolidine carboxylic acid; the reaction between penicillamine and acetone was entirely analogous to that between cysteine and formaldehyde. The thiazolidine ring became an important component of the various structures proposed for penicillin, including the now accepted β-lactam. The penicillin work was top secret, but there was a security breach. One participating contractor was Vincent du


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Vigneaud and his colleagues at Cornell University Medical College. One day, Sofia Simmonds, working at Cornell but not involved in the penicillin work, remarked to HT that penicillin obviously was a sulfur-containing compound. HT was considerably taken aback, since this was supposed to be a closely held secret. Simmonds explained: “We all could tell: the labs … leaked benzylmercaptan into the hallway—any V. du V. person knew what that meant” (21). Many years later, I too was aware of the characteristic odor of benzylmercaptan when I opened a box of the ancient reports in the National Archives in 1989—an amazing persistence of odor after more than four decades of storage. Large amounts of benzylmercaptan had been used for the chemical synthesis of penicillamine. Department Chairman at Columbia’s College of Physicians and Surgeons HT’s influence on biochemistry began with his appointment as head of the Department of Biochemistry, College of Physicians and Surgeons, Columbia University, in 1928. He was able to expand and upgrade the facilities and to appoint new faculty members, eventually developing a world-class department. For this development, HT had two general principles in mind. The first was that organic chemistry had a fundamental role in biochemistry—for example, for chemical structures of “natural products”, for the chemical reactivity of groups and compounds, and for the chemical details of the many conversions in metabolic pathways (2). As the historian Robert E. Kohler has noted, “a conscious effort was made to introduce ideas and techniques from organic chemistry into medical research” (22). One consequence was a close association with organic chemical investigations of bacterial polysaccharides carried out by Michael Heidelberger in the Department of Medicine at Columbia University. Another was the development of the isotope tracer technique (see later). HT’s department from about 1940 to 1960 extensively explored the chemico-mechanistic details of intermediary metabolism, the work being heavily dependent on the use of organic chemistry. Major contributions were made to the biosynthesis of fatty acids and cholesterol, amino acids and proteins, and porphyrins, and to elucidating the shikimic acid pathway for formation of aromatic substances. In those times, a well-trained organic chemist could easily take up biochemical problems. There were two advantages: when speaking to biochemists such an individual could claim to be an organic chemist; when speaking to organic chemists the individual was cloaked in biochemistry. An instance of HT’s conviction that organic chemistry was central to biochemistry and medical research was the early appointment of Oskar Wintersteiner, an Austrian organic chemist who had trained at Graz, Austria, with the great microanalyst Fritz Pregl (Nobel Laureate in Chemistry, 1923). Wintersteiner had previously worked with John J. Abel, Professor of Pharmacology at Johns Hopkins University School of Medicine, on chemical studies of insulin and also on progesterone. After leaving Columbia, Wintersteiner had a long and very profitable association with Squibb’s Institute of Medical Research. He and his colleagues there made a very decisive contribution to penicillin chemistry in 1943 when they were the first to obtain penicillin as a crystalline sodium salt (18, 23). 188

The second principle was derived from HT’s experiences in Fischer’s laboratory from 1911 to 1913. He had been surprised to be warned not to ask other members of Fischer’s group what they were doing; many of them were retained as consultants by manufacturing firms that had priority on any patentable discoveries. HT has stated that “This system appeared to me, as it still does, as being at variance with the prime functions of an academic laboratory” (2). He was repelled by Fischer’s dictatorial leadership style and when he came to lead his own research school, the experience led him “to adopt a more liberal attitude toward … students and postdoctoral associates” (24). A distinguishing feature of the department was a large open laboratory for graduate students; HT believed that it was “important that graduate students be located in close contiguity, for they can learn more from one another than from their formal instructors.” For the same reason he encouraged “the greatest possible diversification in the subject matter of departmental researches” (2). Chargaff has emphasized HT’s philosophy: “He belonged to the conscientious generation: every day of his long life he came in early each morning, and there he sat in his shabby office, door open to the corridor; you could see him and speak with him by sticking your head in. His dignity required no ceremony” (12). The department was home to a large number of postgraduate students and visitors and HT welcomed many refugees from the nightmare of the Third Reich. One such individual, Rudolph Schoenheimer, stands out for the development of the isotope tracer technique for the study of intermediary metabolism. Schoenheimer had been forced to leave his position at the Pathology Institute of the University of Freiburg in 1933. Initially, the work involved the stable isotopes 2H and 15N, supplied by Harold Urey who had developed the necessary methods for separating these isotopes; later, 13C and 18O were used (25). The easiest determination of 15N content required mass spectrometry, and a spectrometer was constructed by David Rittenberg, a student of Urey. Rittenberg had been appointed to the department with the specific role of facilitating the use of isotopes. The tracer technique was particularly valuable for revealing that most body constituents are in a dynamic state of constant breakdown and resynthesis. Moreover, the details of many metabolic pathways became amenable to study and the role of “activated” acetic acid as an important metabolic intermediate became apparent. Much work with isotopically labeled acetate was carried out in HT’s department. In a detailed historical account of the development of the tracer technique at Columbia University, it has been pointed out that “it entailed a special social organization: the interdisciplinary group” (22). With separated isotopes supplied as inorganic compounds by a physicist, synthesis of labeled biomolecules required an organic chemist, the construction and operation of complex analytical instrumentation required a physical chemist, and finally a biochemist was needed to study metabolic problems. Much credit is due to HT for fostering this very early example of interdisciplinary research. He obtained critical financial support from Columbia University and foundations, notably the Rockefeller Foundation. He has been described as “generous, modest, never domineering; he let everyone pursue his interests, often sacrificing his own” (22). Thus, at one point, acquisition of a grant in support of the isotope work necessitated termination of HT’s own research



funding—it was the policy of the Rockefeller Foundation to give only one grant at a time to a department. Unhappily, Schoenheimer took his own life in September 1941. He had prepared drafts of three lectures to be delivered under the Edward K. Dunham Lectureship for the Promotion of Medical Sciences at Harvard University’s Medical School one month later. HT, after consultation with other colleagues, completed the writing, delivered the lectures, and saw to their publication; with typical modesty, Schoenheimer was listed as the sole author (26 ). The isotope technique was rapidly expanded, particularly after the end of World War II with the ready availability of radioactive isotopes such as 14C, 3H, and 32 P. These techniques continue to this day to be a fundamental component of experimental biology and diagnostic medicine. From 1931 to 1956, 94 graduate students received doctoral degrees in biochemistry from Columbia University (2). Many went on to distinguished positions and several became faculty members in HT’s department. One graduate student, Konrad Bloch, became a Nobel Laureate in Physiology or Medicine in 1964 for work on the biosynthesis of cholesterol that had its beginnings in work carried out at Columbia in collaboration with Rittenberg. Glass Blowing and Keten One of HT’s many accomplishments was in glassblowing, and as a teenager he had had suitable facilities provided in his home. His biographer has termed him a “master glassblower” and noted that “his bench and shelves were littered with devices for special uses that he had made himself—liquid–liquid extractors, distillation columns, filtering apparatus, and so forth” (1). In 1946, as a guest in HT’s department, I required a source of keten to attempt a new synthesis of acetyl phosphate, then a possible candidate for the role of the “activated” form of acetic acid (27 ). Surprisingly, a “keten lamp”, in perfect working order, was found in the dusty storeroom. I think it may have been one of HT’s products, although I could not find a requirement for keten use in any of his papers. Only recently did I discover that HT had been involved in the very earliest experiments with keten. The first keten, diphenylketen [(C 6H 5) 2C=CO], had been prepared by Hermann Staudinger and in 1905 he used Ketene (in German) for a class of compounds and Keten for the simplest representative, CH2=CO. Two years later, Norman T. M. Wilsmore and Stewart at University College, London, obtained the first evidence for the existence of keten itself by the action of “a strongly heated platinum wire” on acetic anhydride (28). In 1909, Wilsmore and a colleague noted that the spontaneous condensation of keten led to acetylketen, CH3-CO-CH=CO, described by them as a “polymeride of keten” (29). The last paragraph of their paper reads as follows: “Our thanks are due to Mr. H. T. Clarke, who kindly assisted in the carrying out of several of the experiments”. This paper was published just after HT had received his B.Sc. degree (1908) and before his first publication with Smiles. Later Days HT’s scientific achievements were recognized by his election to the National Academy of Sciences in 1942. He undertook many responsibilities for the American Chemical

Society and the American Society of Biological Chemists, becoming president of the latter organization in 1947. From 1951 to 1952 he served as science attaché at the United States embassy in London. He suffered mandatory retirement in 1956 at the age of 68. Despite his unparalleled contributions to Columbia University he was refused a laboratory in which to continue work at the College of Physicians and Surgeons. He subsequently worked at Yale University until 1968 and then at the Children’s Cancer Research Foundation in Boston until 1970, when poor health necessitated his retirement from active research. His last research paper, on the action of hypochlorite on sulfanilate, was published in 1971 (30). The name of Thacher was not lost to chemistry, since by that time work by his two sons, Eric Thacher Clarke and John Thacher Clarke, was being indexed by Chemical Abstracts. After HT’s death, a French version of his classic text on organic analysis was published in 1978 under the title Chimie Organique. Analyse Qualitative et Quantitative. HT—The Person Some of the best personal impressions of HT are given by Chargaff, who joined the Department of Biochemistry at Columbia University in 1935 and subsequently had a long and productive career there (12). He described HT as “a rather tall, aristocratic-looking man with a human face and friendly eyes. His British upbringing, or perhaps his innate temperament, had endowed him with the special kind of shy aloofness that has baffled continentals in their dealings with the English upper class since time immemorial”. HT was not a good lecturer, but “he was a very good organic chemist of the old observance; one of those who liked to putter around in the laboratory with test tubes and small beakers and watch glasses and who was happy when crystals appeared. He belonged to a vanishing species, when science was young and adventurous, when real experiments could still be performed, when the sense of smell still served to identify classes of compounds.” Chargaff also bestows the accolade that “He was, perhaps, the most unselfish scientist” he had encountered. An example of his unselfishness was noted earlier in connection with the isotope work. Warren Weaver of the Rockefeller Foundation, who was deeply involved in providing grants for the isotope work, wrote that “Professor Clarke is not only a distinguished and able biochemist, but he is an utterly trustworthy individual, who characteristically asks for less support than he really needs and merits” (22). One aspect of his personality caused some difficulties for his colleagues. HT, a relatively well-to-do person, had little understanding of the importance of money for those less fortunate, particularly those in junior positions. Salaries negotiated for his faculty members were largely below the average. Moreover, he made little or no effort to retain those tempted by more lucrative offers. A classic case is that of Oskar Wintersteiner. Instead of urging the promotion of this brilliant organic chemist, for whom he had a genuine liking, HT let him go to Squibb as already noted. HT’s life spanned a time of amazing discoveries as well as the disruptions of two world wars. He began his undergraduate studies at University College only 8 years after Buchner’s discovery of the cell-free production of ethanol from carbohydrates. The discipline of biochemistry was only


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just emerging and vitalist concepts were still being debated; organic chemistry was poised for the chemical syntheses of increasingly complex natural products. Three years before his retirement, a DNA structure was proposed; subsequently molecular biology and biotechnology to some extent displaced biochemistry. The emphasis turned to macromolecular structures far removed from the smaller molecules that had intrigued classical organic chemists. HT’s life encompassed an exciting trip from relatively simple carbon compounds with only a few carbon atoms to the new complexities of macromolecules. It is clear that while he would have welcomed the new discoveries, he would have been uncomfortable with the entrepreneurial spirit that characterizes much of academe today. In the best sense of the hackneyed phrase, he was a true “gentleman and scholar”. Acknowledgments I thank the reviewers of the original draft of this paper for helpful suggestions. The photograph of HT was provided by the National Academy of Sciences, through the kind help of the Archivist, Janice Goldblum. Literature Cited 1. Vickery, H. B. Biogr. Mem. Natl. Acad. Sci. 1975, 46, 3. 2. Clarke, H. T. Annu. Rev. Biochem. 1958, 27, 1. 3. Information on Thacher Island was obtained from The Thacher Island Association, PO Box 73, Rockport, MA 01966 by way of their Web site: http://www.lighthouse.cc/thacher/index.html (accessed Dec 2000). 4. Tarbell, D. S.; Tarbell, A. T. Essays on the History of Chemistry in the United States, 1875–1955; Folio Publishers: Nashville, TN, 1986; p 131. 5. Bentley, R. J. Chem. Educ. 1999, 76, 41–47. 6. Kauffman, G. B. J. Chem. Educ. 1983, 60, 38. 7. Collins, D. The Story of Kodak; Harry N. Abrams: New York, 1990; pp 110–121. 8. Clarke, H. T. J. Ind. Eng. Chem. 1922, 14, 836. 9. Mees, C. E. K.; Clarke, H. T. Preparation of Synthetic Organic Chemicals at Rochester; Eastman Kodak Co.: Rochester, NY, 1922.

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10. Mees, C. E. K.; Clarke, H. T. J. Ind. Eng. Chem. 1919, 11, 454. 11. Clarke, H. T. J. Ind. Eng. Chem. 1918, 10, 891. 12. Chargaff, E. Heraclitean Fire; Rockefeller University Press: New York, 1978; pp 64–69. 13. Clarke, H. T. A Handbook of Organic Analysis. Qualitative and Quantitative; Edward Arnold: London, 1911. 14. Clarke, H. T. Introduction to the Study of Organic Chemistry; Longmans Green: London, 1912. 15. Clarke, H. T.; Smiles, S. J. Chem. Soc. 1909, 95, 992. 16. Clarke, H. T.; Gurin, S. J. Am. Chem. Soc. 1935, 57, 1876. 17. Cline, J. K.; Williams, R. R.; Finkelstein, J. J. Am. Chem. Soc. 1937, 59, 1052. 18. Clarke, H. T.; Johnson, J. R.; Robinson, R. The Chemistry of Penicillin; Princeton University Press: Princeton, NJ, 1949. 19. Ratner, S.; Clarke, H. T. J. Am. Chem. Soc. 1937, 59, 200. 20. Bentley, M. B. In An Era in New York Biochemistry: A Festschrift for Sarah Ratner; Pullman, M. E., Ed.; New York Academy of Sciences: New York, 1983; pp 1–4. 21. Hofmann, K. Biogr. Mem. Natl. Acad. Sci. 1987, 56, 554. 22. Kohler, R. E. In Historical Studies in Physical Sciences, Vol. 8; McCormmach, R.; Pyerson, L., Eds.; Johns Hopkins University Press: Baltimore, MD, 1977; pp 257–298. 23. MacPhillamy, H. B.; Wintersteiner, O.; Alicino, J. F. Report S3 from Squibb Institute of Medical Research to OSRD, dated August 3, 1943. 24. Fruton, J. S. Contrasts in Scientific Style. Research Groups in the Chemical and Biochemical Sciences; American Philosophical Society: Philadelphia, PA, 1990; pp 216–218. 25. Hevesy, G. In Biological Applications of Tracer Elements; Cold Spring Harbor Symposia on Quantitative Biology, Vol. 13; The Biological Laboratory: Cold Spring Harbor, NY, 1948; pp 129–150. 26. Schoenheimer, R. The Dynamic State of Body Constituents; Harvard University Press: Cambridge, MA, 1942; reprinted and termed “Second Edition” in 1946. 27. Bentley, R. J. Am. Chem. Soc. 1948, 70, 2183. 28. Wilsmore, N. T. M.; Stewart, A. W. Nature (London) 1907, 75, 510. 29. Chick, F.; Wilsmore, N. T. M. J. Chem. Soc. 1908, 93, 946. 30. Clarke, H. T. J. Org. Chem. 1971, 36, 3816.


Hans Thacher Clarke (1887-1972): Chemist and ... - ACS Publications

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