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Volume 25, Number 3, 2020 HEART NEWS AND VIEWS www.ishrworld.org ISHR International Society for Heart Research THE NEWS BULLETIN OF THEEuropean INTERNATIONAL Section SOCIETY FOR HEART RESEARCH XXIV WORLD CONGRESS BEIJING, CHINA BERLIN, GERMANY OCTOBER, 2020 JUNE 12-15, 2022 8 7 THE HEART OF THE MATTER In this Issue: LIFE IN THE KREBS LAB – CIRCA 1980 ■ The Heart of the Matter: Life in s a practicing cardiologist, and as one of Professor Krebs’s last graduate stu- the Krebs Lab – Circa 1980 . .. 1 dents, I recently read a portrait by Dr. Mark Nicholls in the European Heart ■ President’s Letter ............6 Journal (1). I read it with personal interest. While the accounts are accurate ■ A 2022 World Congress in Berlin . 7 (and well presented), the author probably has never met Hans Krebs. Until late in his ■ Report on the Chinese Section life, Krebs also had no particular interest in the heart. Therefore, I would like to share Meeting .....................8 some personal recollections from my time in the Krebs lab (1978-1981). ■ 2018 Peter Harris Distinguished Scientist Award .............11 I have fond memories of the ■ JMCC Editors’ Update ........12 Metabolic Research Laboratory ■ Report on the Australasian in Oxford, mostly because of Section Meeting .............14 Krebs’ infectious enthusiasm for ■ 2018 Research Achievement science, and, because of a con- Award .....................17 genial group of coworkers. They ■ Meetings Calendar. 17 came both from Britain, and from all over the world. In the lab, we called our leader simply the “Prof.”. Krebs was an unas- suming person of extraordinary discipline, a superior mind, well Fig 1: The Prof (right) with the author in front of the deserving his nickname. No one new perfusion apparatus for the isolated working rat would argue with him. heart in 1978 (Circ Res. 2019, 124: 1291-3. PMID. 31021725). Finding my way to the Krebs Lab: I am sometimes asked: “How did you end up in the Krebs lab?” I am still strug- gling to find the right answer. Like every medical student, I had once memorized the Krebs cycle. I was attracted by its logic, and on a personal note, I knew that Krebs had come to England from Germany. During my cardiology fellowship at the Brigham in http://ees.elsevier.com/jmcc/default.asp Boston, I got hooked on cardiac metabolism through my mentor, Dr. Michael Lesch. for online submission Perhaps it was my ambition to excel that I contacted Krebs when I read an article about of manuscripts 1 THE NEWS BULLETIN OF THE INTERNATIONAL SOCIETY FOR HEART RESEARCH his lab in Oxford. Admittedly, I took the first step by writing to all agree with this answer, today even more than ever before. A year Krebs with a proposal to study branched-chain amino acid metabo- later, in 1981, Krebs concluded in a masterful editorial in Nature lism in isolated heart muscle cells. Krebs would not have any of it, that metabolic cycles enhance the efficiency of energy transfer (5). and he showed little interest at first. Both concepts are probably correct, but, when it came down to it, Krebs readily drew on his medical experience honed as a medical Krebs and the heart: In fact, throughout his career, Krebs had resident (Assistenzarzt) in Lichtwitz’s clinic at Hamburg, and in avoided to study metabolism of the heart or the brain (Brian Ross, Thannhauser’s clinic at Freiburg in the early 1930s, after four years personal communication). Even Lionel Opie, one of the fathers of of training in the laboratory of Otto Warburg. Incidentally, Warburg cardiac metabolism and a Rhodes Scholar in the Krebs lab in the was a physician himself. Hence, Warburg’s interest in cancer cell late 50s, was not able to write a paper with Krebs. However, in metabolism. It was his way of thinking, Krebs liked to say, although 1970 Krebs had agreed to serve as one of the founding editors of Krebs had not practiced medicine in nearly 50 years, when I was the Journal of Molecular and Cellular Cardiology, together with in his lab. Perhaps his medical training had also influenced Krebs Lionel Opie and Richard Bing. The whole initiative of starting a to stay focused and to exercise care with the resources available to new journal I find amazing because 50 years ago, cardiology was him. On the one hand, we were instructed to order only reagents of dominated by hemodynamics and imaging. Indeed, very few people the highest quality for the lab. On the other hand, no used envelope thought in terms like “molecular” and “cellular” cardiology. Krebs was ever discarded. Envelopes were slit open and served as scrap supported the cause, I think, simply by lending his name to the new paper, sometimes to capture an elusive thought, and always to write adventure. As an aside, Krebs was eager to read manuscripts. When down the day’s “to-do” list. The Prof. set the example. he reviewed manuscripts, he taught me how to be detailed, con- structive, and decisive. It may sound trivial, but such habits may have contributed to the Prof’s profound insights into the fundamental processes of life. Continuing with my story, Krebs took the second step a few weeks Waste not, want not. This is what he said at the end of his Nobel later, by interviewing me during a layover between two flights at Lecture in 1953: The concept of evolution postulates that living Logan Airport in Boston. Things happened rather quickly thereaf- organisms have common roots, and in turn the existence of com- ter. Another few weeks on, my family and I were in Oxford – myself mon features is powerful support for the concept of evolution. The with instructions to develop my own experimental tools under the presence of the same mechanism of energy production in all forms guidance of Reg Hems (about whom I will talk later). Looking of life suggests two other inferences, firstly, that the mechanism of back, I shudder at taking such a great risk without thinking of the energy production has arisen very early in the evolutionary process, consequences. All came to a good end, though, and I credit the sup- and secondly, that life, in its present forms, has arisen only once (6). port from my wife and children for this, as will be described below. Unity in diversity: The Metabolic Research Laboratory never had Leader by Example: Krebs led his team by example and stayed more than a dozen members, but they were an ideal mix of both close to the bench until the end of his life. Perhaps, not surprisingly, senior and junior investigators, working on about half a dozen (or his last original, first author paper (on the fungicidal action of ben- more) distinctly different projects at a time. A special feature of zoic acid) appeared in the Biochemical Journal, two years after his the lab were its collaborators or “honorary members”. Prominent death (2). As of today, the paper has been quoted over 300 times. among them was Frederic (Larry) Holmes, professor for the History Another paper, with Pepe Viña, and Guillermo Saez as lead authors, of Science at Yale University, traveling to Oxford regularly to inter- and Krebs as the corresponding author, was also published in the view the Prof. and to review material for Krebs’ masterful biogra- same year (3). In this paper, they showed that rapid autooxidation phy (7). of the amino acid cysteine is the reason for the toxic effects of cys- teine in liver cells. In fact, on the day before he died in 1981, Krebs It was Krebs’ quiet influence that during the week the lab was lit- reviewed and interpreted the latest experimental results for this erally “humming” in the same rhythm, with a coffee break at 11:00 paper (Guillermo Saez, personal communication, December 2020). am and a tea break at 3:00 pm. Attendance was expected, but not mandatory. In hindsight, I realize that both breaks amounted to two Physician-Scientist: Paradoxically, in spite of the fame he had short informal lab meetings every day. Back then, it was sometimes attained in biochemistry, Krebs considered himself, first and fore- a challenge for me to fit in the protocols for my working heart per- most, a physician. A physician who was drawn to examine bio- fusions (8) into this schedule. But the main effect on all of us was chemical phenomena in their physiological context. He liked to the same: Someone cared (Fig. 1). call metabolism “biochemistry with a purpose”. For example, when asked about the main function of the citric acid cycle, in 1980, Krebs Our meetings were held in the lab’s library, one flight of stairs answered: “There are about a dozen functions of the cycle” (4). We above the lab. Krebs was of relatively small stature, but, even in his 2 VOLUME 25, NUMBER 3, 2020 late 70s, he always took two stairs at a time while going upstairs, Epstein from Harvard. It was a big surprise for me to see my for- wasting no time. There are many anecdotes about Krebs being mer boss waiting in line behind me carrying his tray of cuvettes parsimonious with both time and resources, as already mentioned. for running an assay. We both waited for our turn at the lab’s only More importantly, Krebs often referred to his “time to think” when dual-beam spectrometer. Another message is: We were all equal, he was washing the glassware for his own experiments, or when he be it in front of the spectrometer, or be it within the lab. A further was meticulously tending to his large garden in Abberbury Road.