Aaron J. lhde University of Wisconsin Modison 53706
An Inquiry Into the Origins of Hybrid Sciences: Astrophysics and Biochemistry
Besides the traditional disciplines like physics, chemistry, astronomy, biology, and geology, modern science is characterized by a growing number of hybrid sciences: biochemistry, astrophysics, geochemistry, chemical physics, molecular biology, geophysics, and biophysics. Of these, biochemistry and astrophysics are clearly the earliest of the hybrid sciences to become firmly established. I t is of interest to inquire into the processes mhirh result in the development of hybrid sciences. Do they represent a merging of common interests as peripheral inquiries of the parent sciences begin to overlap? Or do they possibly arise out of peculiar problems of one of the parent sciences with very little contribution from the other? Or possibly, may a hybrid science arise de novo as the result of circumstances independent of either of the sciences which ultimately become foster parents to the hybrid? At the risk of being pedantic, I must make it clear that I consider a hvbrid science to be in existence onlv a t such a time as scientists would clearly refer to i t as a vocation. If one were to write a comprehensive history of biochemistry he would quite certainly have some things t o say about chemical relationships in biological organisms in antiquity. I would argue that in including such material one is dealing with the subject matter of biochemistry, although the science did not yet exist. For purposes of this discussion, I shall consider a science to exist only when practitioners of the science earn their living by working in the field. As a consequence of this position, the two sciences under examination became vocations approximately a century ago, when a few investigators were referred to as astrophysicists and others came to be spoken of as physiological chemists. I consider the term physiological chemistry t o be, for all practical purposes, synonymous with biochemistry. It is also necessary to include agricultural chemists within the category. The term biological chemistry or biochemistry did not be-
-The Cover Professor Aaron J. Ihde, the 1968 Dexter Awmd recipient, is presently Professor of Chemistry and History of Science and Chairman of Integrated Liberal Studies at the University of Wisconsin where he received his doctorate. Previously he has had positions at ButJer University, Harvard University, and Western Reserve University. He served as chairman of the Division of History of Chemistry for three years and has been active in other professional societies. The Dexter Award, estahlished in 1956 by the Dexter Chemical Corporation and administered by the Division of History of Chemistry, includes a $1000 prize and a plaque and is given each year "to generate further interest in the history of chemistry." This paper is Professor Ihde's award address.
come common until the twentieth century began. However, those persons who spoke of themselves as physiological chemists, plant chemists, agricultural chemists, soils chemists, and animal chemists, mere clearly laying the foundations of what came to be called biochemistry. Astrophysics
The circumstances surrounding the origin of astrophysics are reasonably simple. The science arose very suddenly when a contribution out of physics, the spectroscope, provided a tool whereby astronomers could raise questions about the nature of stellar bodies (chemical composition) which they could not seriously raise before. To he sure, the spectroscope ultimately became adaptable to questions which transcended that of chemical composition (temperature, dissociation and aggregation of matter, stellar motion) but the new hybrid science was clearly born out of the unanswerable questions of the astronomers and the tool of the physicists (1). It is of passing interest to note that the physical tool developed out of the prohlems of chemical identification faced by the chemist, Robert Runsen ( 2 ) . It was soon used very effectively in chemistry for identification of elements in mixt,ures and even for the discovery of unknown elements. The spectroscope was applied soon after its discovery to the chemical identification of elements on the sun and stars. In 1863 William Huggins announced in England that the solar spectrum revealed some of t,he same lines as wereo associated with elements known on eart,h. Anders Angstrom of Smedeu identified hydrogen in the sun. Further applications of spectroscopy to celestial problems mere made by Pietro Secci in Rome, Lewis M. Rutherfnrd in New York, and Hermann C. Vogel in Berlin. By the end of the 1860's evidence for a new element on the sun, helium, mas uncovered through spectroscopy by 6 . Norman Lockyer in England and P. Jules C. Janssen in France. Thus, astrophysics grew out of the alacrity with which astronomers brought into use an instrument developed by physics. Bunsen, the chemist, had a problem of identification of elements from their flame colors. Gustav Kirchhoff, the physicist, showed him how to solve the problem. Together they developed the instrument (3). Kirchhoff immediately went on to work out the theoretical consequences of emission and absorption of light. The astronomers took over from t,here and created the hybrid science of astrophysics. Biochemistry
The creation of biochemistry is not so simple. It did not arise through biologists taking over a chemical Volume 46, Number 4, April 1969
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contrihution-or vice versa. The origin and growth of biochemistry is vastly more complex. Actually, the science of biochemistry was conceived t,wice. The first birth was abortive, however. Iatrochemistry was based on the premise that the body is a chemical system, whose processes are chemical processes. The healthy body has its chemical operations in a state of balance, the diseased body suffers from chemical imbalance. The job of the chemist is to for more than a century to achieve their goals but were doomed to failure. The state of knowledge for both biology and chemistry was inadequate to achieve the desired objectives. By the time that Sylvius formalized iatrochemistry into a medical system the subject was already expiring. A rebirth of biochemistry took place in the last half of the nineteenth century. It is this development that I wish to examine since it grew into the viable science of today. A foreshadowing is evident among the scientists of the Chemical Revolution. Not only was Lavoisier interested in thc nature of combustion, but in the nature of respiration, which he looked upon as a form of biological combustion. Together with Laplace he studied the heat evolution of a guinea pig in an ice calorimeter, obtaining a reasonably accurate agreement with the ice melted by glowing charcoal or a candle (based on COXevolved) ( 4 ) In later experiments with Armand SBguin he extended his conclusions to human respiration (5). At the same time, photosynthesis came under examination in the laboratories of Priestley, Ingenhousz, Berthollet, Senebier, and de Saussure (6). While thcsc investigations involved chemical behavior of biological systems they hardly represent the creation of the science of biochemistry. In this age, scieutists were still unclassified as chemists or physicists. Wide ranging experiments were commonplace and investigators failed to categorize their area of investigation. This mould be true for several more generations. Humphry Davy might write a hook on agricultural chemistry without creating a new hybrid science (7). In searching for t,he roots which led to aviable science of biorhemistry, that is, one characterized hy suhseqnent rontinuity of investigation, one keeps returning to thc publication of Jnstus von Liebig's "Animal Chemistry" in 1812 (8). Despite his tendency to ignore the contribut,ions of his predecessors and despite his numerous errors of fact and concept, Liebig gave to animal chcrnistry a body of information and a foundat,ion of theory that served for a half century as a focus for rhemists intcrested in biological materials and physiologists interested in chemical function. Puhlication of his hook occurred when his career was a t its height, when his students were being sought for niches in the universities of the world, and when his fame outside Germany had reached its pinnacle. It is ironical that Liebig's influence in the field of animal chemistry should have become so great. He parried out one experiment on living animals, and that had been done more thoughtfully by Boussingault before him (9). As an organic chemist he had never systematically directed his investigations toward hiological materials. As an analyst hc had developed a 194 / Journal of Chemical Educafion
highly successful procedure for the determination of carbon and hydrogen, but his method was of principal importance in thc study of pure compounds. When applied to alhuminous materials it would only prove misleading in the hands of Mulder, and of Liehig himself. Other contemporaries had gained a sounder understanding of biological relationships. Carl Sprengel recognized 15 elements which played a role in plant growth (10). J. B. J. D. Boussingault mas laying the foundations of agricultural experimentation on his farm in Alsace. His work included not only careful experiments on soil fertilky aud plant growth, but on animal physiology and nutrition as well (11). In fact, animal physiology was entering a vigorous period in the hands of Johannes Miiller and Fran~oisMagendie. Xevertheless it was Liehig who boldly rode to the attack, bringing before thc scient,ificworld a tract which enthusiastically pointed out how chemistry might assist physiology, while frequently ignoring what had already been done hy ot,hers, or misintcrpret,ing its significance. This action had had a prelude in the publication of his work on organic chemistry in 1840 (12). Criticism of that hook's shortcomings failed to det,er Liebig from moving ahead, albeit with a trifle bet,ter judgment. He could not resist needling the physiologists for their ignorance of chemistry while pointing out how the rhemists could be of help to them if they would only rooperate by raising the right questions. Rut he did not wait for their questions. He raised his own and sought to show, through the application of logic and rhemiral knowledge, the road t,o deeper understanding (13). His own associates at Giessen were now grappling with analytical prohlems which mould lead to a better chemical understanding of biological suhstances. Heinrich Will in particular mas t,alented in this direction (especially the Will-Varrentrapp method for organic nitrogen). However, experiment,al activities under his o m direction mould soon grind to a halt. When he look the professorship a t Munich in 1852, it mas 011 vondition that he not he required to direct, a laboratory. Although suffering from poor health, he cont.inried to at,trart standents to rhcmistry with his enthusiastic lcrtnres, and he continued his writing. The latter, however, had beromc increasingly polemical during the 1840's and continued so throughout the last two decades of his Mr. Ife entered int,ohitter qnarrels mit,h Dnmas, 13crzelius, Mulder, and Pwsleur, as \ d l ns wit,ll lcsscr men. Criticisms of statements in his books frequently led to corrections in later editions. On occasion, he nyould be gracious toward his critics, but frequently he could bc devastating in rebuttal. Despite all of this, the "Animal Chemistry" served as a st,imulusto biochemical controversy and investigation. Much speculation in the book ultimately proved mithout foundat,ion. Severtheless, it raised questions and these could he exposed to expcrimental investigation. Voit, a former student of Liehig, wrote in 1865 (14) r\ll thefie chcmie;tl discoveries, to which Liebig so largely contrihuted, gave him his fruitful conceptions concerning the processes in the animal body. Before him the observations were like single building-stones withoot interrelation, and it required a mind like his to bring them into ordered relation. It is s, scrvioe which tho physiologists of our own day do not sufficiently recog-
nisc. In order t o appreciate this one has only to read physiological papers written before the publication of his books and afterward in order to witness how his writings changcd the mcntsl attitude toward the processes in the organism. The chemical discoveries on which he based his conclusions were, in fact, mattcrs of general knowledge, but i t was he who applied them to the proecsses of living things. Scientific progress is determined by the cstablishment of correct interpretations and the creation thereby of new pathway8 and problems. A schoolboy has a better knowledge of many things than the wisest man had formerly; and he laugh8 a t the ignorance of his forefathers because he does not understand the history of the human mind.
Coincident with Liebig's book, physiology was being established on an experimental basis by Johannes Miiller, Fran~oisMagendie, and their students. The school of Miiller, composed of Helmholtz, Du BoisReymond, Schmmn, Virchow, Kolliker, and Henle, was direrted toward physical experimentation but Claude Bernard, Magendie's greatest student, was pursuing his master's chemical bent to open up still further frontiers in this area. Kot surprisingly, the most active interest in the two decades following 1842 was in metabolism and animal heat. Conservation of heat, or more properly energy, was being developed in this period. Helmholtz mas oue of the active participants in the work. Students of Liebig (Regnault, C. Schmidt, Voit) figured prominently in the studies on respiration and calorimetry which were made near the middle of the century. Voit and Pettenkofer, working a t Munich, improved calorimetry to the point where direct studies could be made on human beings by 1870. Such studies continued to be popular through the rest of the century, possibly to the detriment of other biochemical problems. Even by the time Liebig died in 1870, some of his principal ideas, particularly that muscular work consumes proteins, had been discredited (15). Auother type of emphasis became apparent in the work of Felix IIoppe-Seyler for whom the first institute and uuiversity chair of physiological chemistry was rreated at Strassburg in 1872. Although educated in medicine and having served as assistaut to Virchow for four years, Hoppe-Seyler's leanings were strongly chemical. Before taking the Strassburg post he was professor of applied chemistry at Tiibingen. In 1862 he isolated hemoglobin in crystalline form; in 1871 he discovered invertase. A student, Friedrich Miescher, isolated nurleic acid from pus cells in 1869. Since the subst,ance cont,ained hoth nitrogen and phosphorus, as does lecithin-a substance which had held HoppeSeylcr's attention, Hoppe-Seyler proceeded to investigate nucleic acid himself. In 1871 he isolated such a substaure from yeast. The Strassburg laboratory attracted many students and quickly became a principal rent,er for study of biochemistry. In 1871 Richard Maly of Innsbrwk started puhlicalion of his dahresbericht uber die Fortschritte der Tierchcmie. This annual sought to bring together a review of cxperimental progress in all aspectasof physiological (man :1nd animals) chemist,ry. Maly held a professorship of "applied medical rhemistry." His experimental rontributions were of little importance but his Jahresberich1 was of enormous value t,o workers in the field. Hoppe-Seyler founded a journal, Zeitschrift ,fur physiologische Chemie, in 1877. Besides the center a t Strassburg, and that of Voit and Pettenkofer at Munich, a center of biochemical research
was arising a t Heidelberg even though Willy Kiihne held a professorship of physiology. His education in medicine included mork under Virehow in Berlin, Carl 1,udmig in Leipzig, and Bernard in Paris. He took the rhair a t Heidelberg when Helmholtz moved to Berlin. Resides doing significant mork on muscle and nerve physiology, Iciihne carried out ext,ensivestudies on the chemistry of proteins. He isolated trypsin from panrreatic juice and int,roduced the term "enzyme" for such substances as pepsin and trypsin. A certain dudism is evident in the German branch of hiorhemistry. We note on the oue hand those hiochemists like Voit and Pettenkofer who \\.ere thermochemirally inclined and thosc exemplified by HoppeSeyler and Willy IGihne who were working a t the romposition and rhemical nature of tissue components. 13ut alongside these two schools there was a third, arising directly out of the Liebig interest in agriculture. The rise of agricultural experiment stations in Germany took place very rapidly after the publiration of Liebig's principal hooks. The expcriment stations were to a significant degree concerned with practical problems of agriculture and there developed in them a marked iit,tention to t,he composition of foods and feeds, aud the productivity of farm animals thereon. The Wolff feeding tables, generated at the station a t Mockern (near Leipzig) att,ained widespread acceptance in circles dealing with scientific agriculture. These st,ations were also concerned with the nutrition of plants and much at,tention was given to the analysis of soils and fertilizers and thc response of plants thereto. By the end of the niueteenth century there had developed in Germauy a viable biochemistry characterized by three largely independeut paths: (1) heat and respiration, (2) tissue components, and (3) agricultural rhemistry. This pattern mas also reflected later on the American scene, perhaps not surprisingly, because most of the American chemists with biochemical leanings were trained in German universities and experiment stations. Samuel W. Johnson, educated under Liebig, had cnormous influence not only in the development of the Sh?ffieldSrientific School at Yale, hut in t,he creation of t,hc first ngricultural expcriment station in the U. S., that in Connecticut. New Haven quickly became a render for teaching and investigation of biochemistry in America after Johnson was joined by Itussell Chittenden. The latter took a position a t the Sheffield school soon after his return to America following studies in t,he laboratory of Kiihne. Chittenden's enthusiasm for teaching the subject, coupled with his research productivity soon attracted large numbers of young men to his laboratory, which, by the turn of the century was justly famous. In fact, it is possible to trace the original staffing of many physiological chemistry departments in medical schools and agricultural chemistry departments in agricultural schools in the United States directly to Chittenden's laboratory a t Yale (16). Summary
I t appears probable that hybrid sciences have their origins in a unique stimulus. Certainly, the questions characterizing a hybrid science are in the air even if they are not being openly asked. The stimulus without. the incipient questions would fall on sterile ground. Volume
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The questions, however, are of very little significance as long as a reasonable mode of attack is not availahle. In the case of astrophysics, the questions regarding rhcmiral composition of sun and stars mere dormant sinre there was, in 1850, no apparent way to answer them. Once the spectroscope becamo available the xnsnxrs could be eagerly sought, and mere. Without t,he spertroscope thcre could have been no astrophysics. Of course, if Rnnsen and Kirchhoff had not introduced the spertroscope there is a good probability that someone else mould have done so before many years had ~ a s s e d . The study of both emission and absorption spectroscopy had been carried on for several decades hefore they assembled the instrument (17). The emergence of biochemistry is vastly more diffuse. One rannot point. to a tangible instrument which made it possible to answer questions regarding chemical behavior of biological systems although there is no question that tools have stimulated biochemical investigat,ion (18). Nevertheless, it would appear that a stimrdus was present, t h k time in the form of Liebig's book, "Animal Chemistry." The hook not only raised questions and stimulated others to raise questions, hut sought to construct hypothetical answers in the form of a theoretical system. It was the availability of this theoretical system which encouraged investigation, as well as attracted criticism which served as t,he major stimulus to the emergence of biochemistry as a hybrid science. Acknowledgement
The research support of the National Science Foundation in making this st,udy is gratefully acknowledged. Literature Cited (1) PANNEKOEK, A,, "A History of Astronomy," Interscience Publishers (division of John Wilcv & Sons. Inc.). New York, 1961; pp. 389-93; A B E ~ I , " G . , he ~ i s t b r yof A&ronomy," Abelard-Sehumnn, New York, 1952, pp. 187-196, 201-202. RIRCHHOFF, G., AND BUNSEN, R., Ann. Physik, 110,161-89 (1860); Phil.Mag., [4] 20, 89-109 (1860). PEARSOX, T. H., AXD IHDE, 8 . .I., J. CHEM.EDUC.,28, 269-70 (1951).
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(4) LAYOISIER, A. I,., A N D LAPLACE, P. S. DE, "Memoire sur In chalenr," Gauthiws-Villars, Paris, 1920, pp. 57-78 (reurinted from Mem. Amd. Sei.. 355-408 (1780). . , Also see XENDELSOHN, IL, "Heat and Life," Harvard IJnivrrsity Press, Cambridge, 1964, pp. 146 ff. ( 5 ) LAYOISIEH, A. L., and S ~ G U I N A,, , A m . Cliim, 91, 318-34 (1814). ( 6 ) NASH,L. R., "Plants and the Atmosphere," Harvard Univ. Press, Cambridge, Mass., 1952. (7) DAVT,HUMPIIRY, "Elcmente of Agrioultural Chemistry, in a course of lecturcs for the Board of Agriculturc." Longman, Hurst,, Reos, Ormc, and Brown, London, 1813. (8) LIEBIG,JUSTUS,"Animal Chemistry, or Orgsnic Chemistry in its Application to Physiology and Pathology," edited from the author's manuscript by Wm. Gregory, Taylor and Walton, London, 1842. A German edition was puhlifihed simultaneously in Braunschweig, and an American edition in Cambridge, Mnss. An easily available and ~ o f u edition l is the facsimile reprint of thc Cambridge cdition of 1842 pnbliahed by Johnson Reprint Corp., New York in 1964. This edition has s long and very perceptive introductory essay by Frcderic L. Holmes. (9) LIEBIG, J.. "Animal Chemistry," Camhridge Edn., pp. 272-80. (10) SPRENGEL, C. S., "Die Lehre vom Dunger oder Besohreibong aller bei der Lmdwirthschaft gebrauchlicher vegetabilischer, animaliseher, und mineralisoher Dungermatcrialien nebst Erklarun~ihrer Wirkungsart," 2nd ed., Lcipzig, 1845, pp. 4 5 4 6 . C. A., "A Source Book of Agricultural Chemistry," (11) BROWNE, Chranica Botsnica Co., Waltham, Msss., 1944, pp. 239-52. (12) LIEBIG,J., "Organic Chemistry in Its Application to Agriculture and Physiology," edited from the author's manuscript by Lyon Playfair, Taylor and Walton, London, 1840. There was a simultaneous German edition. For further information on editions of this and the "Animal Chemistry" see Browne, C. A,, in Moulton, F. R. (Editor), "Liebig and After Liebig, A Century of Progress in Agricultural Chemistry," Am. Assoe. Adv. Science, Washington, 1942, p. 1. F. L., Reference (a), pp. xriv-xxv. (13) HOLMES, (14) Quoted from Lusk, G. in "Endocrinology and Metabolism," vol. 8, Appleton and Co., New York, 1922, p. 46. (15) Ibid., pp. 24-56; MCCOLLUM, E. V., "A History of Nutrition," Hooghton, MiWin Ca., Boston, 1957, pp. 115-133; SCHELAR, V., J. CHEM.EDUC.,41, 226-29 (1964). R., "The Development of Physiological (16) CHITTENDEN, Chemistry in the United Ststcs," Chem. Catalog Co., New York, 1930, passim. (17) PEARSON, T . H., A N D IHDE,A. J., Reference (3). (18) IHDE,A. J . , , A c l e X ~ I International C o q . H i s t . Sciences, 4, 142-47 (1968). ~
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