The Chain of Unexpected Discovery: Xanthopterin-stimulated Renal Mitosis

THE CHAIN OF UNEXPECTED DISCOVERY: XANTHOPTERIN-STIMULA TED RENAL MITOSIS ALEXANDER HADDOW, W. C. J. ROSS, and G. M. TIMMIS* Dedication The authors wish to inscribe this paper to the memory and the genius of Frederick Gowland Hopkins, in Needham's words "essentially the founder of modern biochemistry in the United Kingdom" [1]· Hopkins's towering contributions have been movingly described in Needham's Centenary Lecture in the University of Cambridge in 1961 and in Dale's great obituary appreciation written for the Royal Society [2]—both works of much piety. Among Hopkins's multifarious interests, none can excel in sheer romance that which dealt with insect pigments, an interest which spanned the greater part of his long life. At the age of seventeen he had just left school when he published a note in The Entomologist of 1878 dealing with the natural history of the bombardier beetle {Brachinus crepitans). A decade later (while he was at Guy's Hospital ) came a further paper on the pigments of pierid butterflies, with his suggestion of the importance of the uric acid structure. No fewer than a further four decades were needed before Wieland, again to * Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital , London S.W.3. We wish to acknowledge much scientific discussion with Dr. Adrien Albert, Prof. F. Bergel, FRS, the late Prof. E. Braun-Menendez, and with Prof. E. Boyland. We must also recognize the superb technical skill of the late Prof. E. S. Horning. Little could have been accomplished without the particular help of Mr. P. G. Avis, Dr. R. C. Bray, Dr. J. A. Blair, Dr. A. Brown, Prof. Malcolm Dixon, Dr. G. C. Easty, Mr. J. Edwards, Mr. J. L. Everett, Mr. D. G. Felton, Mr. D. Gilbert, Mr. L. I. Hart, Prof. E. S. Horning, Dr. P. F. Knowles, Dr. G. de Lamirande, Mr. B. Mansfield, Mr. B. C. V. Mitchley, Dr. T. S. Osdene, Dr. J. J. Roberts, Dr. K. V. Shooter, Dr. R. G. W. Spicke«, Dr. L. Wattenberg, and Dr. K. Williams. Our thanks to Dr. Jeffrey Boss of the University of Bristol and our indebtedness to the Royal Society of London for permission to reproduce their portrait of Prof. Sir Gowland Hopkins have already been expressed. Finally, it is a special pleasure to acknowledge the help of the library of the Chester Beatty Research Institute and of Miss A. M. Whitecross in her capacity as devoted amanuensis. Perspectives in Biology and Medicine · Winter 1972 | 177 quote Needham, "succeeded in showing that the wings contain not so much uric acid itself as a number of substances with a complex ring system allied to it. Such was the origin of our understanding of the pterin [pte??? = wing] pigments, an entirely new class of chemical compound. The earlier conclusions had been quite reasonable not only because the pterins give nearly all the colour reactions of uric acid, but because . . . pierid wings contain not only leucopterin and xanthopterin, but also uric acid sometimes in equivalent amounts." Sir Frederick Gowland Hopkins, FRS. (Courtesy the Royal Society of London.) 178 I Alexander Haddow et al. · Xanthopterin-stimulated Renal Mitosis Through the courtesy of the Royal Society we are able to print a reproduction based upon Meredith Frampton's celebrated portrait of 1938, commissioned to memoralise Hopkins's presidency. It will be seen that he has just written the word "Lepidoporphyrin," now known as rhodopterin. Imaginative as it was, the earlier chemistry required much correction, and Dale has described how Hopkins, in his last paper to the Royal Society communicated in his eighty-second year, returned to the pierid pigments and brought their pterin structure into true relation with some of his own observations made more than half a century before. There is evidence from Albert [3] and others that Hopkins had been in some doubt as to the metabolic significance of such observations . Certainly he was to see the great impact of the Munich school in the chemistry of the pyridopyrazines, but not perhaps the key revelation toward which it was leading. He had in fact opened up a field with the widest chemical, biochemical, and biological ramifications, summary allusion to which is...