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College. After gaining Higher School endocrinology he was invaluable to his Our sympathy goes to Bill’s wife Certificate he was awarded a Kitchener colleagues who appreciated what one Margaret, his three daughters and his Scholarship that enabled him to go to described as his high standards and grandchildren. King’s College London to take a BSc. sceptical integrity about science. He then went to Edinburgh on a Ann Silver scholarship from the Agricultural A trademark of his experiments was (using contributions from Hal Dixon, Alan Findlay, Research Council (ARC) to do a PhD their simplicity. This is exemplified by James Fitzsimons, James Hickson, Arieh Lew, Miranda with Catherine Hebb. Though offered a an experiment in the late 1970s. It had Potter (née Harrison) and David Tolhurst). junior lectureship in Edinburgh, he been established that when a muscle- opted to move to The Physiological derived preparation of ATP was used in Laboratory in Cambridge where he measurements of Na+-K+-ATPase the Paul Lauterbur remained for the rest of his working enzyme activity was less than that 1929–2007 life, first as an ARC Fellow and then as obtained with ATP prepared from yeast. a member of the academic staff. The suspected inhibitory contaminant was eventually identified as vanadate, Bill was elected a Member of The then attracting interest as a possible Physiological Society in 1955 and mediator of the diuretic effect of atrial served on the Committee from 1980 to distension. However, when sodium 1984. News of his death prompted a orthovanadate was injected into rats its flow of emails from his Cambridge diuretic effect was small and transient. colleagues and ex-students. Woven On being consulted by the colleagues together here, these highlight his involved in this experiment, Bill’s standing as a physiologist, a teacher reaction, to the surprise of all Paul Lauterbur, who has died aged 77 from and a good and wise friend. concerned, was ‘What a huge effect!’ kidney disease, published the first He set out to prove that the apparently Bill’s lab was a solitary affair, untidy, magnetic resonance image in a short letter disappointing result was attributable to to Nature in 1973 (242, 190-191). Though full of antique equipment with reprints dehydration. An anaesthetized rat fitted all over the place. Although constantly the name he coined for the technique – with an intravenous cannula was put on zeugmatography - never caught on, the at the bench his publication list is short. an old-fashioned balance and a He was always reluctant to publish method has revolutionised medical imaging, primitive but ingenious feedback particularly of soft tissues. An estimated 60 unless he felt he had something worth system set up to keep the rat’s weight writing about. His preference, when he million or more magnetic resonance constant by intravenous infusion. imaging (MRI) scans are now carried out did publish, was for a letter to Nature. Vanadate induced a diuresis comparable He enjoyed discovering novel, each year. The invention of MRI won to the animal's weight in a few hours. A Lauterbur many prizes and awards, important, and frequently counter- beautiful experiment, with the intuitive phenomena that would act as a culminating in the 2003 Nobel Prize for simplicity only profound expertise can Physiology or Medicine jointly with the stimulus to others to head off in new deliver. directions. He preferred, in his own British physicist Peter Mansfield. quiet way, to lead the pack rather than Bill was a dedicated teacher and an to follow, and a letter to Nature is a Paul Lauterbur enjoyed being something of excellent and caring Director of Studies time-honoured way of doing just that. a scientific maverick. As a teenager he built in King’s College. His lectures on Having cracked a problem, or his own basement chemistry laboratory, and endocrinology are remembered for their demonstrated something important, he would recall as an early inspiration a clarity, logical progression, and the vast was content to let others sort out the chemistry teacher who let him get on with amount of fascinating information boring bits while he moved on to new doing self-designed experiments ‘while the conveyed at a speed that allowed but always fertile ground. rest of the class got a lecture’. The lifelong copious note taking (although, independence of mind led him to give up Bill worked largely alone though early according to one student, this was at the MRI research in his 70s, as he joked, ‘just collaborative work included studies on expense of an aching hand). in time for the Nobel’, to work on the the synthesis of acetylcholine in brain, possible pregenomic chemical origins of life. carrier proteins for thyroxine and Progressive ill health meant that in his triiodothyronine, the role of the carotid later years Bill became increasingly Paul Lauterbur was born in Ohio in the body in the regulation of erythropoiesis, reclusive but as a young man he had a American Midwest, and got his Bachelor the secretion of progesterone by the passion for exotic cars. These included degree from Case Institute of Technology adrenal gland, and absorption of a red Gordon-Keeble – a British car of (now part of Case Western University) colostrum in the newborn calf. Later, which only 100 were built, two of them before being drafted into the US army. As his main interest was in the regulation being owned by fellow physiologists in he described in a 2003 interview with of blood volume. As a willing source of the Cambridge Lab. Another enterprise Physiology News (55, 12-15), it was in the updated and critical wisdom on all was making his own trousers and shirts Army that he first got to use an NMR aspects of kidney function and which he did with some success. spectrometer, publishing several papers.

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Following return to civilian life and A century ago in J Physiol paper of a staggering 25 Lucas published in completing graduate school, Lauterbur The Journal between 1904 and 1914. became an Associate Professor at the State University of New York (SUNY) in Stony As many readers will already know, the full Academics in those days were clearly Brook. Here he carried on pioneering work archive of J Physiol is now available on particular about their affiliations. Lucas does with multinuclear and particularly 13C NMR, Highwire, and can be reached from The not list any degrees but gives his personal including the first 13C NMR studies of Society web site. This allows one to see affiliation as ‘Fellow of Trinity College’, while proteins. In the summer of 1971 he got what was being published 25, 50 or even Fletcher and Gowland Hopkins also give involved with an NMR instrument company 100 years ago. their college details. in Pennsylvania, and the seed that led to the idea of MRI was planted when he The four papers in J Physiol (35.4) The volume also includes a paper from the watched living tissue experiments there. He (http://jp.physoc.org/content/vol35/issue4/) Department of Physiology at UCL (then run often recounted the story of how he made come from just two universities, Cambridge by Ernest Starling) by David Henriques de the first notes of the basic concept of MRI and UCL (March 1907). The authors include Silva. Silva later worked at King’s College, on a napkin in a hamburger restaurant later a future Nobel Laureate, Frederick Gowland collaborating with W D Halilburton among that night. Back at Stony Brook that autumn Hopkins (Nobel 1929), a brilliant others, and seems to have had biochemical he did the pioneering work single-handed, experimental physiologist killed in a WWI inclinations; his later papers cover many often using the NMR machine at night, and flying accident (Keith Lucas), and the subjects, often with a focus on digestive making early images of simple ‘phantoms’ Cambridge ur-pharmacologist W E Dixon. juices and blood. (capillary tubes of water and heavy water) Two authors are among the UK founding and of seashells collected by his elder fathers of sciences that ‘spun off’ from The final paper in volume 35.4 is the only daughter Sharyn. Lauterbur liked to point physiology – biochemistry (Gowland one not to come from a physiological out, in discussions on the beginnings of Hopkins) and pharmacology (Dixon) - or laboratory. This is W E Dixon’s The action MRI, that Nature only published the seminal perhaps even three if one views Keith of alcohol on the circulation, detailing 1973 paper after he had argued long and Lucas as the father of UK biophysics The experiments on humans, dogs, cats and hard with their original rejection of it, and papers run the full gamut of the rabbits (!) to try and determine absolutely also that SUNY’s patent department thought experimental systems of the day, ranging whether alcohol is a cardiac stimulant or the whole idea of MRI too far-fetched to from amphibian and crustacean nerves in depressant. The following excerpt patent. Lucas’ work, through frog muscle, to particularly caught my eye: rabbits, cats, dogs and humans. Through the 1970s Lauterbur’s lab at Stony ‘If moderate doses of alcohol well diluted Brook became a focus for others interested Papers 100 years ago came in all sizes. with water be administered to animals or in the idea of imaging with NMR, and once When I started in physiology J Physiol had men the pulse rate does not alter. I have MRI machines became a reality in the early a reputation for printing very long papers. tried these experiments over and over again 1980s he worked tirelessly to convince This may well be an ancient tradition, as and always with the same results. The radiologists that the technique would volume 35.4 opens with a paper by Fletcher popular fallacy that alcohol quickens the provide new data not available from CT and Gowland Hopkins that runs to a hefty pulse is clearly derived from the conditions (computed tomography) scans. He took 62 pages, albeit the smaller pages of the under which alcohol is usually taken. It is great satisfaction from the way that new pre-1994 Journal. Fletcher and Hopkins’ well known that excitement of any kind applications of MRI in science and medicine paper on Lactic acid in amphibian muscle is quickens the heart and alcohol is generallv continued to emerge, stating in 2003 that heavy on methodology, with an Appendix taken under exciting circumstances.’ among developments of MRI that had most even giving the (heroic?) numbers of frogs There is a highly entertaining account of gratified him were its use in ‘functional used in each experiment! Their painstaking Dixon’s career written by Alan Cuthbert in imaging’ of things like brain activity and experimentation does, however, give a his 2001 W D M Paton Memorial Lecture heart movements. picture of the conditions under which muscle lactate is produced that holds good (Cuthbert AW (2001). Brit J Pharmacol 133, 945–950). In 1984 Lauterbur married for the second to this day. Cuthbert wryly points out that though Dixon time, to the American physiologist Joan was the founding father of pharmacology in Dawson (then at UCL), and they moved to Keith Lucas’ paper includes some delightful Cambridge, Cambridge never got round to the University of Illinois at Urbana. He is diagrams of the self-designed and built making him a Professor. Dixon was a survived by Joan, their daughter Elise, and equipment he used to deliver brief stimuli to professor, however, as for many years he his son and daughter from his first nerves (e.g. his Fig. 2). Lucas worked in a held a lectureship in Cambridge marriage. special vibrationally-shielded basement simultaneously with a Professorship at room in the Cambridge Physiological King’s! Cuthbert quotes Dixon’s motto as Austin Elliott Laboratory, inherited after his tragic early ‘Dire n’est rien , faire est tout’, and tells a death by his former student E D (later fascinating story of how Dixon almost Paul Christian Lauterbur, pioneer of 13C NMR discovered neurotransmission almost a and co-inventor of MRI. Nobel Laureate, Baron) Adrian. Lucas’ paper employs the member of the US National Academy of amphibian sciatic nerve – gastrocnemius decade before Otto Loewi. Sciences (1985) and Honorary Member of The muscle prep still in use (one hopes) in Physiological Society (2004). undergraduate physiology labs. It is one Austin Elliott

Physiology News | No. 67 | Summer 2007 | www.physoc.org