William C. Rose' University of Illinois Urbana 61801
Recollections of Personalities Involved in the Early History of American Biochemistry
Older people are frequently accused of being prone to reminisce, due, it is said, to a practice of living in the past. Regardless of the validity of this accusation, and admittedly it may be true, we elders have an excellent reason, I think, for reminiscing. Through the years, we have seen so many marvelous discoveries in science, even surpassing our wildest fantasies, that we have acquired a respect, or even a reverence, for the events that have served as stepping stones to the eminence of learning upon which we think we now stand-an eminence which, as "time marches on," will most assuredly prove to be merely a slight elevation, or even a mirage, as more and more knowledge is gained. For anyone with an historical interest in science, tracing the path that has been followed in arriving a t the place where we now are becomes an extremely fascinating pursuit. Of even greater fascination, I think, are the personalities-the people-who have been responsible for the exciting events that have transpired along the tortuous, but ever upward, road which we have followed through the years. So, with your indulgence, I propose to reminisce for awhile, bringing to your attention a few of the personalities who have played dominant roles in the early development of American biochemistry. It may come as a surprise to some of you to hear that biochemistry, or physiological chemistry as it was called originally, is a very young science in the United States. I n contrast to other branches of chemistry, biochemistry did not appear in the course offerings of most American universities until near the turn of the century. Medical students teceived instruction in what was known as medical chemistry. This varied in content, but usually consisted of an heterogeneous mixture of elementary inorganic and organic chemistry, a few analytical methods, tests for certain abnormalities in the excreta, and some discussion of the toxicity and identification of the more common poisons. Students, for the most part, regarded the subject as a necessary evil, which they would take, hopefully pass, and then forget as quickly as possible. Even at Harvard, which is regarded by many as the acme of educational perfection, unless one is from Yale,--even a t Harvard a part-time instructor in physiological chemistry was not provided until 1898. Not until 1905, did Haward assign full-time instructors to the subject, in the persons of Lawrence J. Henderson and Carl L. Alsberg. The first biochemistry course in this country was Taken from an after dinner speech given during "Nutrition Emphrtsis Week" at the University of Missouri, Columbia, 1967. Research Professor of Biochemistry, Emeritus. Present address: 405 West University, Champaign, Illinois 61820.
inaugurated a t Yale. This was not due to superior administrative wisdom, but rather to the presence on the faculty of a gentleman of unusual discernment, foresight, and enthusiasm. His name wss Samuel W. Johnson, professor of analytical and agricultural chemistry. As early as 1868, the Governing Board of the Sheffield Scientific School of Yale University appointed a committee, of which Johnson was a member, to devise and bring into being a course of study in biology, designed particularly to meet the needs of prospective students in medicine. This was followed in 1874 by the inauguration of a course in physiological chemistry, largely through the influence of Dr. Johnson, and launched admittedly "as an experiment." Before discussing this course, attention is directed for a moment to the training and activities of Dr. Johnson. After graduating in 1852 from the Sheffield Scientific School, he continued his studies a t Leipzig and Munich. At the latter institution, he came under the influence of Justus von Liebig and M. J. von Pettenkofer, two pioneers in the application of chemistry to the study of living things. There, Johnson's interest in agriculture, and in the role chemistry could play in its development, was greatly stimulated. Upon returning to New Haven, he began immediately to exert his influence for the benefit of those engaged in agricultural pursuits. He made many analyses of commercial fertilizers, exposing those that were worthless; he met with farmers and discussed their problems; and published numerous agricultural reports for the enlightenment of farmers. I n addition, he was a prolific contributor to chemical and agricultural periodicals. Two books brought him much fame in this country and abroad. The first was published in 1868, and was entitled, "How Crops Grow." The second a ~ ~ e a r eind 1870, and was entitled, "How Crops ~ e k h . " I n 1875, through Johnson's influence, the Connect,icut Legislature made a small appropriation to aid in the cost of a two-year program of agricultural experimentation, to be conducted by W. 0. Atwater at Wesleyan University, nIiddletown, Connecticut. Atwater had received the PhD degree under Johnson's direction, and was now a professor at Wesleyan University. The latter institution had agreed to provide space for this new enterprise. Two years later, the State Legislature approved the establishment of the Connecticut Agricultural Experiment Station on a permanent basis, and Johnson became its first director. Thus, the first such experiment station in the United States came into being. At the start, it was housed in two rooms on the lower floor of Sheffield Hall of Yale University. Later, as the amount o f work increased, the Station was Volume 46, Number
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moved to a building of its own on Huntington Street in New Haven, where, to the present time, it has continued to render many services to the State and Nation. In addition to his agicultural activities, Johnson gained an enviable reputation as an outstanding teacher and attracted students from far and wide. Four of these are of particular interest to biochemists, namely, W. 0. Atwater, who has already been mentioned and is well known for his extensive investigations involving the use of a respiration calorimeter sufficiently large to accomodate human subjects; H. P. Armshy, who b e came Director of the Institute of Animal Nutrition, Pennsylvania State College and made use of a respiration calorimeter in studying the metabolism of farm animals; T. B. Osborne, who became a research chemist a t the Connecticut Agricultural Experiment Station, married Johnson's daughter Elizabeth, and justly attained fame because of his remarkable techniques in the isolation, crystallization, and determination of the amino acid content of plant proteins; and Russell H. Chittendeu, about whom we shall have much to say later. Other indications of Johnson's remarkable talents are found in the fact that he was President of the American Chemical Society in 1878; President of the American Association of Official Agricultural Chemists in 1888; and President of the American Association of Agricultural Colleges and Experiment Stations in 1896. Such are some of the qualities of vision and leadership exhibited by the man who successfully exerted his intluence to bring about the launching a t Yale of the first biochemistry course to be offered in this country. As already stated, the first course was begun in 1874. Initially, it was assigned to very modest quarters, consisting of one room fairly well equipped for chemical work and providing accommodations for eight or ten students. In charge of this little laboratory Johnson placed Russell H. Chittenden. The latter had just completed his junior year in the Sheffield Scientific School, and was 18 years of age. The following year Chittenden graduated and, in keeping with the Yale requirements, submitted a thesis entitled, "Glycogen and Glycocoll in the Muscular Tissue of Pecten irradians." The latter is better known, of course, as the common scallop. The thesis was published in the American Journal of Science and Arts; and, at the suggestion of Johnson and with his help, was translated into German and transmitted to Liebig's Annakn der Chemie. Eventually it appeared there. Double publication was not uncommon at the time in view of the slow methods of communication. We shall see that this thesis played an extraordinarily important role in Chittenden's later career. Chittenden continued to teach the course as well as he could, while taking advantage of every opportunity to improve his own knowledge of the subject. Three years after his graduation, or in 1878, he was granted a leave of absence to pursue his training in Germany. There, biochemistry, or physiological chemistry as it was usually denoted, was much further advanced than in the United States or in England. Many German physiologists had come to appreciate the importance of applying chemical techniques to the solution of physiological problems. This accounts for the use in Germany of the term, "Physiological Chemistry," or even "Chemical Physiology." Indeed, for the most part, the subject 760' / Journal of Chemical Education
was regarded as a branch of physiology, and was taught by chemically trained personnel attached to the departments of physiology. Several laboratories had become well-established as centers for this type of research by the time Chittenden arrived in Germany. Among the outstanding investigators in this field were Carl Voit a t Munich, Eugen Baumann at Freiburg, Willy Kuhne a t Heidelberg, E. F. W. Pfluger a t Bonn, and Felix Hoppe-Seyler a t Strassburg. Hoppe-Seyler had the title of Professor of Physiology but also was the recognized head of an "Institute of Physiological Chemistry," said to be the only separate organization of this kind in Europe at the time. At Leipzig, the eminent Carl Ludwig, though primarily a physical physiologist, thoroughly appreciated the importance of the chemical approach and was closely associated with chemicallytrained personnel. Outside of Germany, probably the most active chemically-inclined physiologist was Claude Bernard of the College de France, Paris; but he died in 1878, the year Chittenden went abroad. Chittenden had chosen Hoppe-Seyler as the man under whom he wished to pursue his training and had been accepted for this purpose by the University of Strassburg. However, upon arriving, he was discouraged by the conditions which he encountered there. The laboratories were indeed veritable beehives of activity, but the students were so numerous that little opportunity was afforded for personal contact with and guidance by the distinguished professor. To the young American, both the University and the city seemed drab and unattractive. Furthermore, the laboratories appeared to be poorly organized, and to be lacking in that indefinable quality which, for the want of a better term, may be called "atmosphere." Chittenden reminds us that the city of Strassburg and its University were very different in 1878 from what they became later. At the time of which he speaks, both had recently been acquired by Germany as part of the settlement of the Franco-Pmssian war of 1870. Chittenden rightly felt that his subsequent career would be so vitally affected by the use he made of the ensuing year or two in Germany that he could not afford to jeopardize his future by remaining in an unsuitable environment. With these thoughts in mind, he decided to go to Heidelberg. There, he sought out Professor Willy IGihne and requested permission to work in his laboratory. It was not customary ninety years ago, nor is it today, for a prospective student to present himself without credentials and expect to be admitted by a German professor as a worker in his laboratory. Space usually was, and still is, at a premium. One needed to be fortified with proof of his research qualifications before he could expect to be assigned a desk. Chittenden's credentials were a t Strassburg. The only bit of evidence he had, even in proof of his identity, was his personal visiting card. This he presented to the professor, and assured him that credentials would be forthcoming just as quickly as mail could be received from New Haven. Kiihne appeared not to be impressed by what the young man was saying. Instead, he kept looking a t the visiting card. Finally, he said, "Do you happen to be the Chittenden who published an article on the occurrence of glycogen and glycocoll?" Chittenden admitted that he was. Immediately, the
atmosphere changed. Kiihne went into an adjoining room and returned with the volume of Liebig's Annalen containing Chittenden's paper. He glanced through it for a few moments and said, "This paper contains some interesting observations. This is the first time glycogen has been found in the muscle of an invertibrate; nor do I recall any other observation indicating the occurrence of free glycocoll in tissues. Mr. Chittenden, we shall provide a working space for you." After a month, Kuhne invited Chittenden to serve as his assistant in the lecture demonstrations. Thus began a friendship between the distinguished professor and his young pupil that persisted for more than twenty years until I