History of Science DOI: 10.1002/anie.200702929 Karl Lohmann and the Discovery of ATP Peter Langen and Ferdinand Hucho* adenosine triphosphate · history of science · Lohmann, Karl “Scientific research is the one Olym- pic competition which awards Gold Medals only. To be second means being last”, says Carl Djerassi, one of those unlucky scientists. He succeeded in synthesizing the pregnancy hormone progesterone and paved the way to the formulation of “The Pill”. The Pill and its “father” were never distinguished by a Nobel Prize. The list of those left out is long, perhaps longer than could be beneficial for the prize of all prizes. Our topic in this Essay is not the injustices though, but rather a curiosity—a scientific breakthrough, a truly fundamental dis- covery not honored with the Nobel Prize—the isolation and elucidation of the structure of ATP by Karl Lohmann. We don)t mean to criticize the Nobel Prize, nor the mode by which it is awarded, nor the committees involved. Rather we would like to discuss why an undoubtedly great discovery was passed over. Prize bashing in the case of the Nobel Prize is by far less suitable than foranyotherawards.Themerenumbers render a just award impossible: In some years there are several worthy scientific accomplishments, but unfortunately, for each field there is only one prize per year (which can be shared by a max- imum of three persons). As to scientific breakthroughs not recognized with a Nobel Prize, medical science is hit hardest. Not only is the definition of the field vague—a prize is awarded for Physiology or Medicine— but of the two alternatives, the first is undoubtedly favored. Moreover, al- though tremendous progress in surgical procedures, for example, in cardiology or oncology, is saving thousands of lives per year, these areas are held in low esteem in Stockholm and are perhaps judged as “crafts” rather than intellec- tual accomplishments. But even when topics of theory are involved, physiology at its best, disturbing gaps are evident: There was never a Nobel Prize for the proof that DNA is the carrier of heredi- tary traits; the discovery of the funda- mental principle of allosterism was not honored with the Prize. Chemists can also list examples of oversight: Didn)t the 1,3-dipolar cycloaddition, now in the focus again in connection with “click chemistry”, deserve the Prize? What about the rearrangement in cation chemistry that bears the name of its discoverer and is an essential tool in all modern synthetic laboratories? The Discovery of ATP—The Most Important Accomplishment in Biochemistry without a Nobel Prize? We won)t discuss physics, literature, peace (especially fraught with false decisions), or even mathematics, which was excluded by Alfred Nobel from the beginning. Let us turn our attention instead to Karl Lohmann, to this quiet researcher who never uttered bitter words about his lack of Nobel Prize. One of us (P.L.), who was a graduate student in his research group in Berlin- Buch, confirms this from many years of personal contact. Karl Lohmann never even mentioned the great discovery of his epoch. In 1929 Lohmann isolated ATP, adenosine triphosphate, from muscle and liver extracts. [1] Actually, Justus von Liebig had first isolated the com- pound, he referred to it as “inosinic acid”, the deamination product of the adenine nucleotide, 80 years earlier from meat extracts. The elucidation of the structure, initially controversial, was in close com- petition with Fiske and Subarrow. [2] Lohmann succeeded through acid hy- drolysis of the colorless substance which provided two moles of phosphoric acid, one mole of adenine, and one mole of d- ribose-5-phosphate. [3] The correct struc- ture of adenosine-5’-triphosphate was finally confirmed 20 years later by Alexander Todd, in due style: by chem- ical synthesis. [4] Life’s Energy Reservoir Synthesis of the acid anhydride ATP requires energy, which can be recovered by hydrolysis of the compound. Thus ATP is the chemical energy reservoir per se—this and all the rest is textbook knowledge and will not be summarized here. But how could it be that this truly fundamental discovery did not receive the honor of a Nobel Prize? Let us look into the course of Lohmann)s scientific life. There we might find some hints; we shall not be able to present a secured explanation. Karl Lohmann was born April 10, 1898, in the northern German town of Bielefeld. His father was a farmer in the province of Westphalia. In World WarI he served as an artillerist on the “west front”. After the war he studied chemis- try in Münster and Göttingen. In 1924 he obtained his doctorate degree with a thesis entitled (translated from Ger- man) “Chemical Investigations of the [*] Prof. Dr. F. Hucho Institut für Chemie und Biochemie Freie Universität Berlin Thielallee 63, 14195 Berlin (Germany) Fax: (+ 49) 30-8385-3753 E-mail: hucho@chemie.fu-berlin.de Prof. Dr. P. Langen Herkulesstrasse 21 16321 Bernau (Germany) Essays 1824 # 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2008, 47, 1824 – 1827