“My Little Spontaneous Blips” and Edited All Manuscripts Before Any of the John Heuser Junior Members of His Unit Submitted Their Work for Publication
Total Page：16
File Type：pdf, Size：1020Kb
R ETROSPECTIVE sonal influence. Katz personally assigned all projects, oversaw all progress through weekly meetings or “pass-throughs” of each individ- ual’s laboratory, and painstakingly reviewed “My Little Spontaneous Blips” and edited all manuscripts before any of the John Heuser junior members of his unit submitted their work for publication. Many remember this lat- o wrote Sir Bernard Katz (1), of the “visualization” of a single molecular event—in ter aspect of his influence as the most wonder- observations that eventually led to his this case, the conformational change that a ful of all. Some have even declared that Katz’s Sbeing awarded the Nobel Prize for dis- synaptic chemoreceptor undergoes when it in- command of the English language and of sci- covering the mechanism of neural secretion. teracts with its neurotransmitter (acetylcholine, entific expression was totally unsurpassed. This “father” of the fields of biophysics and in the case of the nerve-muscle synapse) re- This, despite the fact that Katz was German- neuroscience died of natural causes on 20 sulting in opening of a channel or “pore” in the born and did not emigrate to England until he April 2003, at the ripe old age of 92. He postsynaptic membrane. Individually, these graduated from medical school, forced into continued to live and work in London until molecular reactions create only minute depo- exile by the rise of Nazism. the end, although with diminishing enthusi- larizations of the muscle, the “noise” that Katz Katz followed in the footsteps of the asm after the death 4 years ago of his and Miledi saw when they applied acetyl- great muscle physiologist A. V. Hill, who beloved wife of 54 years, Rita. choline experimentally. But had spoken out strongly against Nazism and Katz’s legacy is immense— during normal synaptic trans- had been instrumental in arranging his es- from the solid scientific foun- mission, when hundreds of cape from Germany (2). Katz admired Hill dation he and his collaborators thousands of acetylcholine so much probably because both men were established in the field of neu- molecules are abruptly released (in Katz’s own words) “united in their en- roscience, to the extraordinary by calcium-activated discharge thusiasm for the possibility of making very number of budding scientists he of many hundreds of synaptic accurate measurements on living tissues, “sired” by welcoming them into vesicles simultaneously, these with relatively simple technical equipment,” his laboratory as postdocs. channel openings act in concert and were “fascinated with establishing pre- Katz was the first person to to completely depolarize the cise quantitative relations and applying a observe tiny electrical “blips” at muscle and make it contract. mathematical theory to the results” (3). the synapse (see the figure), Speaking of one particular equation that on January 4, 2008 which he termed “miniature end- Katz himself derived and that particularly plate potentials” (“endplate” be- pleased him (the equation that gave two sep- cause he was recording from frog arate and independent ways of determining muscle, where the postsynaptic the average number, n, of quantal packets of element is so named). Correlating these elec- neurotransmitter released by each motor ) trical blips with the tiny packages of mem- nerve impulse), Katz quipped, “You may 5 brane (“vesicles”) that had recently been dis- well ask why I make so much out of such a covered by electron microscopy inside the simple formula. The answer, I suppose, is synapse, Katz realized that his blips couldn’t that being mathematically naïve, I see some www.sciencemag.org be individual “hits” of single neurotransmitter beauty in what others with more knowledge molecules upon the postsynaptic membrane. and experience may regard as trivial” (4). He surmised that they must be multimolecu- Katz was blessed by making not one but lar “packets” of nearly uniform size (thus, the Thus, in one lifetime, Katz (with Miledi two major scientific discoveries—discover- term “transmitter quanta”) released by dis- and his earlier collaborators, del Castillo, ies that opened whole new fields in neuro- charge of individual synaptic vesicles. Fatt, and Jenkinson) elucidated the whole biology. When asked on Japanese TV about Some years later, Katz and his chief collab- mechanism of synaptic transmission— what he thought it took to become the out- orator, Ricardo Miledi, finally realized that by from presynaptic neurosecretion by dis- standing scientist he was, Katz answered Downloaded from racking up the gain on their electrical ampli- charge of transmitter quanta from within humbly: “I cannot give a prescription; but fiers, they could indeed recognize individual the synaptic vesicles populating motor it needs a combination of intelligence, molecular “hits” upon the muscle’s postsynap- nerve terminals, to postsynaptic chemore- willpower to overcome setbacks, readiness tic “endplate” membrane. However, these mo- ception by the transmitter-induced opening to follow unexpected leads, plus a good lecular hits came so fast and furiously—and of individual molecular channels or pores mentor and a great deal of luck!” Katz had were so tiny—that they still appeared as elec- covering the muscle endplate membrane. all of these traits in spades. His proteges trical “noise” that could only be resolved into No department was held in higher esteem have been blessed by his influence person- individual events by computer-based Fourier in its day than the Biophysics Unit at ally, and we will all continue to be blessed analysis. Working day and night with the only University College, London, headed by Katz. by Katz’s lasting scientific legacy. computers available in London in those days— For nearly 40 years, aspiring young scientists primitive devices that choked the halls of the came to this laboratory to work under him and References and Notes chemistry department at University College— Miledi. Here, they felt that they were in the 1. B. Katz, Creativity Res. J. 7, 225 (1994). Katz and Miledi went on to describe these in- Mecca of neuroscience, and as such, were be- 2. For a complete description of Hill’s great role in sci- ence in general and his influence on Katz in particu- dividual molecular “hits” in quantitative terms. ing offered a tremendous head start toward be- lar, see B. Katz, J. Physiol. 370,1 (1986). In this way, they achieved the first-ever direct coming the next generation of leading neuro- 3. Personal letter to the author from Sir Bernard Katz, scientists (which many of them did). In this dated 18 January 1994. “hothouse” environment, Katz’s presence was 4. B. Katz, in Neurotransmitter Function,L.C.Sellin, R. The author is in the Department of Cell Biology, Libelius, S.Thesleff, Eds., vol. 13 of Fernstrom Foundation Washington University School of Medicine, St. Louis, always gentlemanly; but it was also intense, in Series (Elsevier, Amsterdam, 1989). MO 63110. E-mail: [email protected] terms of his exemplary intellectual and per- 5. P. Fatt, B. Katz, J. Physiol. 117, 109 (1952). CREDITS:AND B. UNIVERSITY SCHOOL OF MEDICINE; ( WITH PERMISSION FROM JOHN HEUSER/WASHINGTON (TOP) REPRODUCED FATT KATZ (BOTTOM) 1248 23 MAY 2003 VOL 300 SCIENCE www.sciencemag.org.