The Making of a Biochemist

Home , Hans Krebs (biochemist), Otto Heinrich Warburg

book reviews disappearance of kuru as an important In the late 1920s, he looked into the effect TION episode in our understanding of the risks of light on the inhibition by carbon monox- A associated with this type of infectious ide of respiration in living cells. This work process. Informing the wider community of encompassed considerations of photo- these risks may lead to a more helpful debate chemical processes in terms of quantum about the public health policies required chemistry, and the use of the manometer, NOBEL FOUND to minimize the chances of another BSE photoelectric cell and spectroscope. From epidemic. Books such as this are useful in the shape of the curve obtained by plotting this context. the effectiveness of light against its wave- Colin L. Masters is in the Department of Pathology, length, it was possible to deduce the resem- 8 The University of Melbourne, Parkville, Victoria, blance between the respiratory ferment and 3052, Australia. haemins. Warburg was awarded the Nobel prize for physiology or medicine in 1931 for his recognition of the haemin-type nature of the respiratory ferment and its underlying The making principles. The development of Warburg’s theoreti- of a biochemist cal thinking and experimental procedures are Otto Warburgs Beitrag zur ably chronicled in Petra Werner’s introducto- Atmungstheorie: Das Problem der ry essay. Her book is the first volume of an Sauerstoffaktivierung* edition of Warburg’s correspondence Brilliant but flawed: Warburg tended to pettiness. by Petra Werner deposited in the Berlin–Brandenburg Aca- Basilisken-Presse: 1996. Pp. 390. DM136 demy of Sciences. Regrettably, the 143 pub- 1950). In 1925, Keilin demonstrated the Mikulás˘ eich T lished letters covering the period 1906 to 1939 reversible oxidation and reduction of a include only 14 by Warburg, all of which were pigment, which he named ‘cytochrome’, The biochemist Otto Heinrich Warburg to Jacques Loeb. Warburg’s early work was in the thoracic muscles of the adult fly (1883–1970) was a name to conjure with in strongly influenced by Loeb’s book, pub- Gasterophilus intestinalis. This was a crucial the days before molecular biology. In 1908 he lished in 1906, which dealt with artificial event in the history of biological oxidation began to investigate — in part with Otto parthenogenesis and the nature of fertiliza- and helped lead to the interpretation of cell Meyerhof — the respiratory activities of vari- tion in thoroughly physicochemical, reduc- respiration in terms of a sequence of reac- ous materials, such as sea-urchin eggs, avian tionist terms. Loeb immediately recognized tions driven by oxidation and reduction (the erythrocytes and liver tissue. His experimen- in Warburg a kindred spirit, and was pre- ‘respiratory chain’). That Keilin’s achieve- tal results led him to surmise that cellular pared to get him a grant from the Rockefeller ment did not earn him a Nobel prize was, oxidation was linked to the catalytic activity Institute to work in his laboratory, and to help I think, a notable omission. It is unfortunate of iron in cells. him settle in the United States. Before and that his name crops up just once in the book. After returning from the First World War, after the First World War, Loeb — an early That said, the book is an important Warburg continued with his studies of respi- emigré from Germany as a result of source for studying the development of the ration using cancerous tissue, and improved his experiences of anti-Semitism in the aca- chemistry of life from about 1900 to 1930. the manometric method of gas analysis. His demic world — befriended not only Warburg, Mikulá˘s Teich is at Robinson College, University of starting point was that cellular respiration but also Meyerhof and Leonor Michaelis, Cambridge, Cambridge CB3 9AN, UK. was a cyclic reaction. Oxygen combined with who contributed to the development of a iron to produce higher-valency iron, which mathematical theory of enzyme processes. reacted with oxidizable organic material and This emerges from Loeb’s letters to the two in so doing returned to the bivalent state. scientists, which are also included in the Software reviews at www.nature.com Warburg might have obtained the idea of the book. From this week, Nature’s website presents cycle from Meyerhof, who in 1919 and 1920 Outstanding as Warburg was as a scientist, comparative reviews of scientific software. studied chemical changes occurring in mus- even his admiring Nobel prize-winning cle in relation to the work done or the energy research students, Hans Krebs and Hugo Nature has recruited a group of reviewers to liberated as heat. Meyerhof visualized the Theorell, realized that he tended to pettiness. test a wide range of scientific software, breakdown of carbohydrate to lactic acid as There can be little doubt that this fuelled his including graph-making and statistics pack- the anaerobic phase, and the synthesis of car- resentment of Meyerhof, who, with ages, mathematics software, systems for bohydrate as the aerobic phase, of a ‘specific Archibald Vivian Hill, won the Nobel prize bibliography and reference management, carbohydrate cycle’. for physiology or medicine nine years before and more. This week, Sharon Kardia of the Warburg’s investigations of artificial Warburg for work on muscle metabolism. University of Michigan inaugurates the iron-containing systems, which were pre- Werner also refers to Warburg’s selective series at www.nature.com, with reviews of sumed to be analogous to reactions occur- approach to history in two retrospective 16 graph-making packages. ring in living cells, satisfied him that iron monographs: “he cited only Nobel prize Kardia explains the criteria used to evaluate functions as the oxygen-transferring con- winners or widely known persons... and left the packages, and outlines the strengths stituent of a ubiquitous cellular catalyst, others out; thus, later he never mentioned the and weaknesses of each. She calls atten- which he named Atmungsferment (‘respira- name of Jacques Loeb. This retrospective tion to unique features, and suggests who tory ferment’). He was a most inventive account submerged historical reality beneath might benefit from using each package. experimenter. Among the artificial systems an embellished, teleological presentation.” A table of system functions shows which that he studied were the oxidation of amino The English version of Warburg’s first packages possess which capabilities, and acids by haemin charcoal, and the inhibition publication appeared as Heavy Metal Pros- gives performance ratings for each pack- of oxygen uptake by cyanide and urethane. thetic Groups and Enzyme Action (Oxford age, for each of these functions. Each

*Otto Warburg’s Contribution to Respiration Theory: The Problem University Press, 1949) and was critically review is hyperlinked to additional product of Oxygen Activation. reviewed by David Keilin (Nature 165, 4–5; details provided by the manufacturer.