Paul Fatt

Paul Fatt
FRS
Born(1924-01-13)13 January 1924
Chicago, IL
Died28 September 2014(2014-09-28) (aged 90)
London, UK
Known for
  • Quantal theory of neurotransmitter release
  • T-tubules
Spouses
  • Ione Copplestone
  • Gertrude Falk
  • Carla Wartenberg
Children
  • Michael Fett
  • Laura Fett
  • Harriet Fett
  • Ilsa Fatt
Scientific career
WorkplacesUniversity College London
ThesisNeuro-muscular transmission (1950)
Bernard Katz

Paul Fatt FRS (13 January 1924 – 28 September 2014) was a British neuroscientist, who was a professor at University College London. With Bernard Katz, he developed the "quantal hypothesis" for neurotransmitters.[1][2][3][4]

Early life and education

Paul Fatt was born in Chicago, IL, on 13 January 1924, in a Jewish-American family. His parents, Annie (née Arkin) and David were immigrants from eastern Slovakia (then Austro-Hungarian empire) and Lithuania (then Russian Empire), respectively. Paul had an elder brother Irving (1920–1996), a chemical engineer, and a younger brother Milton (1929–2011), a mathematician.[5] Paul Fatt went to Grant’s Elementary School in Chicago. During those years, Paul spent his Saturdays exploring the Field Museum and other museums along the Lake Michigan waterfront. From those visits he acquired an interest in biology.[6][5]

In 1938 the Fatt family moved from Chicago to Los Angeles, CA, where Paul attended Mount Vernon High School, then Fairfax High School, and then Los Angeles City College.[5]

Military service

When Japan attacked Pearl Harbor in December 1941, and the USA entered World War II, Paul Fatt enlisted in the Army as a reservist. After an initial military training in California, he was transferred to Lexington, KY, and assigned to 291st Field Artillery Battalion where he was trained in localization of the enemy artillery sources, using artillery sound ranging. In 1944, Fatt was promoted to the rank of T4 sergeant, and sent via Liverpool to France. Having landed in October 1944 on the Omaha Beach, Fatt and his troop were first stationed near Cherbourg and assigned to guarding military railway transports. Then, the battalion was moved eastward and, on January 1, 1945, entered the Western Front near Aachen where he and his troop survived an attack by Luftwaffe. From there, the troop moved further east, crossing the Rhine and then Elbe rivers. There they remained stationed until the war's end.[6][5]

Fatt spent several months in Étretat , France, then a month in Shrivenham, England, where he tried to restart his studies, taking courses in mathematics. Eventually, in 1946, the American soldiers were transported back to the U.S. by a Navy aircraft carrier. Paul travelled back to Los Angeles to reconnect with his family.[6][5]

Career and research

After returning from Europe, Fatt enrolled in a course on biochemistry and biophysics at Berkeley, which a financial asisstance from the G.I. Bill made possible. There, he collaborated with Vernon Brooks, who recommended him to A. V. Hill. Hill invited Fatt to his laboratory in London. Thus, in 1948, Paul joined the Hill's Biophysics Research Unit at University College London (UCL), still with the help from the G.I. Bill. Under the mentorship of Bernard Katz, first at the Marine Biological Association in Plymouth, then in London, Fatt studied depolarization of the neuromuscular junction (a.k.a. motor end plate) by acetylcholine in squid and crayfish.[6][5] He was one of the pioneers in the use of glass microelectrodes for the neurophysiological research.[1] Extending this research to vertebrate[note 1] motor end plates, Fatt and Katz studied the miniature end plate potentials (MEPPs) and demonstrated their quantal and spontaneous nature. The quantal aspect meant that the amplitudes of the MEPPs were integer multiples of the minimum value. The spontaneous aspect was evident from the time course of those potentials, which turned out to be a Markov process.[2] Fatt and Katz found evidence that MEPPs resulted from small amounts of acetylcholine released by the presynaptic cell.

Having completed his PhD thesis, Fatt moved on to study synaptic inhibition in crustacean motor end plates. He showed that inhibition relied on an increase in conductance of the muscle cell membrane.[7] To follow this interest, in 1952, Fatt moved to Australia to join the lab of John Eccles at the John Curtin School in Canberra. Working on cat motoneurons, inhibitory interneurons and sensory neurons, Fatt discovered that synaptic inhibition in mammals, as in crustaceans, relied on increased membrane conductance to chloride ions (Cl−).[8] He described in detail the electrophysiological properties of the two classes of muscle afferents (i.e., Ia fibers and Ib fibers), as well as their synaptic targets.[9] Also, in Canberra, Fatt developed new experimental techniques: a double-barrel microelectrode,[10] and an improved, more stable micromanipulator, which made those discoveries possible.[5]

In 1956, Paul Fatt returned to London and took up a position as reader in the Biophysics Department at UCL.[5] There, he collaborated with Bernard Ginsborg, and further investigated the mechanisms of synaptic inhibition; particularly, the ions involved in it.[11] The two discovered calcium-dependent action potentials in crayfish muscle cells.[12] Subsequently, Fatt and Jacques Boistel confirmed that Cl− current was responsible for inhibition of the crayfish muscle cells. Then, they discovered that GABA was the neurotransmitter responsible for that inhibition.[13] In another line of research, Fatt and Gertrude Falk, described the electrical properties of the muscle cells.[14][15] With a hypothesis of a system of internal membranes that was continuous with the sarcolemma, they explained an apparent discrepancy between membrane impedance values, measured vs. estimated from the observed cell size. The measured impedance was several times higher than expected.[note 2] These observations, along with electron microscopic images obtained by Hugh Huxley[16] and Sally Page,[17] led to the discovery of T-tubules.[18]

From 1964 to 1985, Fatt and Falk studied signal transduction in vertebrate photoreceptors. Fatt attempted to explain the signal amplification mechanism by which a single photon absorbed by rhodopsin could elicit a measurable electrical response in a retinal bipolar cell.[19][20] Although those studies generated important hypotheses about the mechanisms of phototransduction, which informed the work done by others and resulted in later discovery of the role of G proteins and cGMP, Fatt's experimental results in that period were not as groundbreaking as his earlier research.[21] In 1985 Fatt stopped his research, and—four years later—retired from UCL.[5]

Political views and activity

Fatt was an active member of the Labour Party since 1950s. Sometimes, after lunch, he would go from door to door, soliciting support for the party. He joined Pugwash and Campaign for Nuclear Disarmament, and participated in marches and rallies, giving emotional speaches to warn against the risk of nuclear war. In 1983, Fatt authored a memorandum, signed by several fellows, opposing Margaret Thatcher's election as an honorary fellow of the Royal Society. He left the Labour Party in 2003, protesting against the party's support for the invasion of Iraq.[5][22]

Personal life

While in Australia, Paul Fatt married Ione Copplestone (1926–2016). They had three children: Michael (b. 1954), Laura (b. 1955) and Harriet (b. 1957). The marriage did not last, however, and Fatt returned to England in 1956, while Ione stayed in Australia. Several years later, Paul married Gertrude Falk (1925–2008) whom he had met during a scientific conference in Seattle where they both presented their respective research results. Paul and Gertrude had daughter Ilsa (b. 1963) who later became a jewellery designer.[23] In 1965, Fatt obtained British citizenship. Following his separation from Gertrude, Fatt married freelance translator Carla Wartenberg (1934–2019) in 1985, and the couple remained together until his death. Paul died peacefully on 28 September 2014 at his home in Hampstead.[5]

Awards and honours

In 1969, Paul Fatt was elected to the Fellowship of the Royal Society.[4]

Footnotes

  1. ↑ This research was done on frogs (Rana temporaria),[1], as well as lizards (Lacerta dugesii) and tortoises (Testudo graeca).[2]
  2. ↑ These experiments were done on frog sartorius muscles and crayfish limb muscles.

References

  1. 1 2 3 Fatt, P.; Katz, B. (1951-11-28). "An analysis of the end-plate potential recorded with an intracellular electrode". The Journal of Physiology. 115 (3): 320–370. doi:10.1113/jphysiol.1951.sp004675. ISSN 0022-3751. PMC 1392060. PMID 14898516.
  2. 1 2 3 Fatt, P.; Katz, B. (1952). "Spontaneous subthreshold activity at motor nerve endings". The Journal of Physiology. 117 (1): 109–128. doi:10.1113/jphysiol.1952.sp004735. ISSN 0022-3751. PMC 1392564. PMID 14946732.
  3. ↑ "Sir Bernard Katz Award". Biophysical Society.
  4. 1 2 Cull-Candy, Stuart; Ashmore, Jonathan (2014). "Paul Fatt 1924–2014". Nature Neuroscience. 17 (12): 1634. doi:10.1038/nn.3873. ISSN 1546-1726. PMID 25413090.
  5. 1 2 3 4 5 6 7 8 9 10 11 Ashmore, Jonathan F. (2016-01-01). "Paul Fatt. 13 January 1924 — 28 September 2014". Biographical Memoirs of Fellows of the Royal Society. 62: 167–186. doi:10.1098/rsbm.2016.0005. ISSN 0080-4606.
  6. 1 2 3 4 Ashmore, Jonathan (2013). "An interview with Paul Fatt" (PDF). physoc.org. Archived from the original (PDF) on 2017-10-27. Retrieved 2017-10-27.
  7. ↑ Fatt, P.; Katz, B. (1953). "The effect of inhibitory nerve impulses on a crustacean muscle fibre". The Journal of Physiology. 121 (2): 374–389. doi:10.1113/jphysiol.1953.sp004952. ISSN 0022-3751. PMC 1366081. PMID 13085341.
  8. ↑ Eccles, J. C.; Fatt, P.; Koketsu, K. (1954-12-10). "Cholinergic and inhibitory synapses in a pathway from motor-axon collaterals to motoneurones". The Journal of Physiology. 126 (3): 524–562. doi:10.1113/jphysiol.1954.sp005226. ISSN 0022-3751. PMC 1365877. PMID 13222354.
  9. ↑ Eccles, J. C.; Fatt, P.; Landgren, S.; Winsbury, G. J. (1954-09-28). "Spinal cord potentials generated by volleys in the large muscle afferents". The Journal of Physiology. 125 (3): 590–606. doi:10.1113/jphysiol.1954.sp005183. ISSN 0022-3751. PMC 1365631. PMID 13212722.
  10. ↑ Coombs, J. S.; Eccles, J. C.; Fatt, P. (1955-11-28). "The specific ionic conductances and the ionic movements across the motoneuronal membrane that produce the inhibitory post-synaptic potential". The Journal of Physiology. 130 (2): 326–374. doi:10.1113/jphysiol.1955.sp005412. ISSN 0022-3751. PMC 1363415. PMID 13278905.
  11. ↑ Fatt, P.; Ginsborg, B. L. (1958-08-06). "The ionic requirements for the production of action potentials in crustacean muscle fibres". The Journal of Physiology. 142 (3): 516–543. doi:10.1113/jphysiol.1958.sp006034. ISSN 0022-3751. PMC 1356760. PMID 13576452.
  12. ↑ Fatt, P.; Ginsborg, B. L. (1958-02-17). "The production of regenerative responses in crayfish muscle fibres by the action of calcium, strontium and barium". The Journal of Physiology. 140 (2): 59–60P. ISSN 0022-3751. PMID 13514709.
  13. ↑ Boistel, J.; Fatt, P. (1958-11-10). "Membrane permeability change during inhibitory transmitter action in crustacean muscle". The Journal of Physiology. 144 (1): 176–191. doi:10.1113/jphysiol.1958.sp006094. ISSN 0022-3751. PMC 1356779. PMID 13599117.
  14. ↑ Fatt, P. (1964-03-17). "An analysis of the transverse electrical impedance of striated muscle". Proceedings of the Royal Society of London. Series B, Biological Sciences. 159 (977): 606–651. Bibcode:1964RSPSB.159..606F. doi:10.1098/rspb.1964.0023. ISSN 0950-1193. PMID 14130855.
  15. ↑ Falk, G.; Fatt, P. (1964-04-14). "Linear electrical properties of striated muscle fibres observed with intracellular electrodes". Proceedings of the Royal Society of London. Series B, Biological Sciences. 160 (978): 69–123. Bibcode:1964RSPSB.160...69F. doi:10.1098/rspb.1964.0030. ISSN 0950-1193. PMID 14142170.
  16. ↑ Huxley, H. E. (1964-06-13). "Evidence for Continuity Between the Central Elements of the Triads and Extracellular Space in Frog Sartorius Muscle". Nature. 202 (4937): 1067–1071. Bibcode:1964Natur.202.1067H. doi:10.1038/2021067b0. ISSN 0028-0836. PMID 14207194.
  17. ↑ Page, Sally G. (1964). "The organisation of the sarcoplasmic reticulum in frog muscle". Journal of Physiology. 175: 10P–11P.
  18. ↑ Page, S. G. (1968). "Fine structure of tortoise skeletal muscle". The Journal of Physiology. 197 (3): 709–715. doi:10.1113/jphysiol.1968.sp008583. ISSN 0022-3751. PMC 1351757. PMID 5666182.
  19. ↑ Falk, G.; Fatt, P. (1966). "Rapid hydrogen ion uptake of rod outer segments and rhodopsin solutions on illumination". The Journal of Physiology. 183 (1): 211–224. doi:10.1113/jphysiol.1966.sp007861. ISSN 0022-3751. PMC 1357537. PMID 5945249.
  20. ↑ Falk, G.; Fatt, P. (1968). "Conductance changes produced by light in rod outer segments". The Journal of Physiology. 198 (3): 647–699. doi:10.1113/jphysiol.1968.sp008631. ISSN 0022-3751. PMC 1365287. PMID 5685293.
  21. ↑ Fatt, P. (1979-08-02). "Decline of the calcium hypothesis of visual transduction". Nature. 280 (5721): 355–356. Bibcode:1979Natur.280..355F. doi:10.1038/280355a0. ISSN 0028-0836. PMID 223059.
  22. ↑ "Tony Blair - Prime Minister, Iraq War, Labour Party | Britannica". Encyclopedia Britannica. Archived from the original on 2025-07-08. Retrieved 2026-05-21.
  23. ↑ Joffe, Lawrence (1 April 2008). "Gertrude Falk". The Guardian. Archived from the original on 2024-12-04. Retrieved 2026-05-04.

Jonathan F. Ashmore, PAUL FATT 13 January 1924 — 28 September 2014, in: https://royalsocietypublishing.org/doi/pdf/10.1098/rsbm.2016.0005

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