Indian132 Guest J Physiol Editorial Pharmacol 2004; 48(2) : 132–136 Indian J Physiol Pharmacol 2004; 48(2) Guest Editorial REMEMBERING SIR BERNARD KATZ (1911–2003) True science recognizes no boundaries and it is best exemplified by the life of Sir Bernard Katz, an ideal role model for a generation of physiologists and pharmacologists and who was instrumental in the “Quantum” jump in the knowledge of synaptic physiology. Max Katz, the father of Bernard Katz, was a Jew fur trader in Tsarist Russia but had left Russia in 1904 and settled in Germany, where he met and married Eugenie Rabinowitz, a woman of Polish origin. Bernard Katz was born in Leipzig, Germany on 26th March 1911. As a child till 6 years, Bernard Katz was a citizen of Russia but became stateless because of the Russian Revolution and later, ironically his statelessness made it easy for him to escape from Nazi oppression and leave Germany inspite of the fact that he was a Jew and Hitler was at the helm when Bernard Katz left Germany. Katz's early schooling was at Konig Albert Gymnasium in Leipzig and the atmosphere was ‘completely unorthodox and liberal’ as he himself has put it and ‘he chose to learn Latin and Greek rather than more mathematical options as it gave him more time to play chess in the cafes of Leipzig’. Despite this, and inspite of having had his share of anti-Semitic experiences, he did well at school and went on to study Medicine at the University of Leipzig in 1929. After finishing his pre-clinical examination in 1931, he combined his undergraduate work with part-time physiological research under the guidance of Martin Gildemeister. His first work on muscle stretch and impedance resulted in two research papers and also in getting him Siegfried Garten prize and helped him secure M.D. degree. After completing his medical degree in 1934, he continued to work in Leipzig hospital by which time he had read about A V. Hill and had realized that his research work had similarities with that of A. V. Hill and decided to leave Germany and work under him at the University College of London (UCL). At the beginning of February 1935, Katz left Germany and reached the doors of Department of Physiology, UCL, in a few days after travelling by train and ferry and ultimately reached his destination, Prof. A. V. Hill with just 4 pounds in his pocket along with a recommendation letter from Gildemeister. Indian J Physiol Pharmacol 2004; 48(2) Guest Editorial 133 A. V. Hill was a great man, not only as Hodgkin and Andrew Huxley. They were a scientist (he had already been honoured then engaged in the research that led to with Nobel Prize in 1922), but also as a the discovery that the overshoot of action good human being and had a great potential results from an influx of Sodium influence on Katz for the rest of his life. As ions. Along with this discovery, Katz's other Bernard Katz puts it, “It was an outstanding early work included the discovery of the piece of good luck to have been taken on as phenomenon of inward (‘anomalous’) an apprentice to A. V. Hill, it was the rectification. Bernard Katz worked as a decisive influence on my life and career. He Reader in Physiology at UCL from 1950 to was the person from whom I have learned 1951 and later succeeded his mentor A. V. more than anyone else, about science and Hill as the Professor of Biophysics and the about human conduct. A. V. Hill was the headed the department of outstanding most naturally upright man I have ever distinction till 1978. known. To be associated with a man of his stature at a formative period of one's life is By 1950s, unraveling the mystery of indeed a great gift of fortune”. the regulation and transmission of nerve impulses and neuro-muscular transmission Katz worked under A. V. Hill from 1935 had become the key areas of research. Two to 1939 and received his Ph.D. in 1938. In major extrinsic factors were driving the 1939, a month before the start of the Second research in this direction. One was the need World War, he left to Australia to work to understand the effects of organocholine with John Eccles, another renowned and organophsphorous compounds, the basis neurophysiologist, at the Sydney Hospital of nerve gases and the other was the as a Carnegie Research Fellow, during possibility that the detailed understanding which time he worked on synaptic physiology of the basis of generation and transmission and neuro-muscular transmission. In 1941, of nerve impulse and neuro-muscular he became a naturalized British Citizen and transmission would help in medicine like soon after served as a radar officer at New the treatment of some of the diseases of the Guinea in the Royal Australian Air Force nervous system. Hence the choice made by till the end of the war. Meanwhile, he met Katz in the immediate postwar years was Marguerite Penly (Rita) of Cremore, New influenced by these factors as well as by Southwales who incidentally was not a Jew his mentor A. V. Hill, who was already and they got married immediately after the involved in this field of study and was also war. A month after the wedding, in 1946, a wartime Cabinet Scientific Adviser under Katz returned to UCL as Assistant Director Winston Churchill and there was an urgent of Research in Biophysics and Henry Head felt need to solve these questions. Uppermost Fellow of the Royal Society. among the mysteries of neural signal transmission was how the discrete electrical In the immediate postwar period, impulses of a nerve fiber cross the large although based at UCL, Katz spent most of gap observed at each nerve junction with his time working at Cambridge and at its target cell and bring about response marine laboratory Plymouth with Alan quickly and faithfully. Dale had already 134 Guest Editorial Indian J Physiol Pharmacol 2004; 48(2) shown that the transmission was not receiving cell. As the signal strength rises electrical but chemical and that acetylcholine through increased frequency of impulses, was involved at the neuromuscular junction. this is mirrored rapidly by a stepwise Katz unraveled the detailed biochemistry of increase in the release of acetylcholine the dynamic cycle and also the central role packets across the junction. Katz proved the of acetylcholine and its key enzymes and first perception of neural function at the went on to show that even when a nerve is molecular interaction level, the basis of all inactive, the acetylcholine cycle at the later understanding of neural function junction continues transmitting tiny at the molecular level. He, with his ‘bleeps’. His major discovery was that this fellow colleagues at UCL established all the resting signal does not depend on individual important features of synaptic transmission, molecules but it depends on the release of like the role of calcium in vesicular release, small packets of transmitter substance, the enzyme cycles involved in the production which cross the junction and bring about and inactivation of transmitter substances, an electrical response in the muscle fiber. the effects of transmitters on the post This is brought about by the action of synaptic membrane which was the basis of acetylcholine acting on the ‘receptors’ at the later discovery of ‘ion channels’, and also end plate, opening ‘aqueous pores’ in the that all these processes are highly vulnerable muscle membrane leading to the influx of to disruption. The influence of his work is cations and thus bringing about the inestimable, not only in physiology, but also electrical response. Thus, Bernard Katz in pharmacology where his suggestions of a spoke on 12 December 1970, while receiving mechanism for partial agonism and the first the Nobel Prize for this seminal work, “Some rigorous demonstration that d-tubocurarine 20 years ago, using the method of was a competitive antagonist became the intracellular recording, Paul Fatt and I building blocks for future extensive research came across something quite unexpected. In in pharmacology. the absence of any form of stimulation, the end-plate region of the muscle fiber is not Bernard Katz's perception of a problem completely at rest, but displays electric and his uncanny instinct for separating activity in the from of discrete, randomly the important from the trivial were recurring ‘miniature’ end-plate potentials. legendary. Characteristically he would Numerous experiments have shown that approach a fundamental problem that each miniature end-plate potential arises appeared to be settled and by tackling the from the synchronous impact of a large question in a new manner, he would open multi-molecular quantum of acetylcholine up fields that had never been dreamt of. spontaneously discharged by the adjacent His realization of the importance of ‘small nerve terminal”. and unpromising spontaneous ‘bleeps’ recorded by the instrument at the neuro- Katz went on to show that the single muscular junction’ eventually led to the ‘packet’ of molecules, characteristic of the discovery of quantal transmitter release at resting signal, is the minimum amount that the neuro-muscular junction. Similarly, the can produce a corresponding signal in the importance he attached to the ‘apparent Indian J Physiol Pharmacol 2004; 48(2) Guest Editorial 135 increase in the noisiness of the recorded the world. He led the department signal when acetylcholine was present’ and with outstanding distinction till 1978 his subsequent work on this noise analysis when he retired as professor but gave, although indirect, information about continued as a Honorary Research Fellow how single ion channels would probably till his death on 20 April 2003 actively behave.