Stephen W. Kuffler

(1913-1980)

MBL Affiliation from 1947 to 1979 as Faculty, Investigator, Trustee, and Corporation Member

Known as the father of modern neuroscience, Stephen Kuffler laid the foundation for our understanding of the nervous system. His mantra that “the good old days are now” holds true even today, thanks in large part to the fundamental research he conducted at the Marine Biological Laboratory (MBL) and beyond.

History knows him as ‘Steve,’ but he was born in 1913 as Wilhelm Kuffler and didn’t adopt his new name until over two decades later. He spent the first 10 years of his life on his family’s estate in Táp, Hungary. But his adventures horseback riding, swimming, and exploring the nearby city ended when he was sent to a Jesuit boarding school in Austria. There, he would become well-versed in Greek, Latin, and the humanities.

Despite being exposed to very little science, he chose to pursue medicine for its “international character.” He would not be disappointed. During the five years it took him to earn an M.D. in Vienna, he spent six months in London and trekked through the Middle East and Egypt to evade the turmoil preceding the Austrian Anschluss.

The Germans ultimately invaded Austria in 1938, during Kuffler’s clinical residency. His paternal grandmother was Jewish, and the hostility of his environment was made all too clear when he had to perform a postmortem on a colleague murdered by the Nazis. He fled to London, and soon after to Sydney, Australia.

There, Kuffler gained footing in experimental science on unexpected ground: the tennis court. He would volley with neurophysiologist and future Nobel Laureate John Eccles, who hired Kuffler as an assistant in his physiology lab at Sydney Hospital. Eccles was using cats to study the neuromuscular junction — the interface between a motor neuron and a muscle. Kuffler was joined by future Nobel Laureate Bernard Katz, who convinced him to take advantage of simpler, non-mammalian systems such as frogs. Thanks to this encouragement, in 1941 Kuffler was the first to master a dissection that allowed him to isolate a single frog nerve fiber and the muscle it innervated.

This feat drew international kudos, and helped earn Kuffler a fellowship at the University of Chicago. Shortly thereafter, he accepted a professorship at Johns Hopkins University School of Medicine. His research career took off. First came seminal studies on skeletal muscle fibers and muscle spindles, then experiments on the mammalian retina and stretch receptor neurons in crustaceans — some of which were conducted at the MBL, where he began spending summers in 1947.

In 1959, Kuffler relocated his team from Johns Hopkins to the Department of Pharmacology at Harvard Medical School (HMS). The team included future Nobel Laureates Torsten Wiesel and David Hubel, Edwin Furshpan, David Potter and instrumentation specialist Bob Bosler. Less than a decade later, Kuffler became the inaugural chair of the HMS Department of Neurobiology, which was the first of its kind in the world. At the time, the notion of uniting experts from various disciplines to study the nervous system, which Kuffler accomplished, was unprecedented.

“Steve knew everyone, and everyone really loved him,” recalls Edward Kravitz, former co-director of the MBL’s Neurobiology course, who joined Kuffler’s HMS team in 1960 and began spending summers at MBL as well. “Steve ran the department like a dad. We didn’t go to Thanksgiving dinner with our families — we went to Steve’s house.” Like many dads, Kuffler was also a notorious punster. “We allowed him one pun a day, but he didn’t follow the rules,” Kravitz says.

In 1963 at the MBL, Kuffler established the first experimental lab classes centered on the nervous system, taught by Dave Potter and Ed Furshpan. Known as the Nerve-Muscle Program, these classes preceded the MBL’s Neurobiology and Neural Systems & Behavior courses. Kuffler’s program drew disciples of diverse disciplines, and was instrumental in introducing them to the budding field of neurobiology.

Kuffler was known for selecting just the right organism for each research question. When Kravitz arrived at HMS, Kuffler and other researchers were working to pinpoint the role of a nervous system chemical called gamma-aminobutyric acid (GABA). Crustaceans such as crayfish and lobsters were the optimal subjects, because they contained inhibitory and excitatory nerve fibers that were large in diameter but small in number. Each nerve fiber branched many times to innervate muscle bundles.

Thanks to the elegant simplicity of this system, Kravitz and his group, with Kuffler’s strong support, demonstrated that stimulating the inhibitory — but not the excitatory — nerves released GABA. This indicated GABA was a particular type of chemical called an inhibitory neurotransmitter. Back then, only two other neurotransmitters had been identified, and GABA was the first inhibitory one.

Kravitz remembers presenting this work for the first time at the MBL, expecting to receive props. Instead, he was met with resistance. Many Americans at that time believed nerve cells only used electrical signals to communicate — not chemicals. When one particularly esteemed scientist stood up and denounced the findings, Kuffler came to Kravitz’s defense.

“Steve would do things like that,” Kravitz says, “but he would always do it in a way that he didn’t offend people.”

In fact, one of Kuffler’s favorite forums was the MBL’s Monday night seminar series, colloquially known as the Fight Club. Here, research titans would discuss — and often debate — their scientific theories. After Kuffler stopped doing experiments on the GABA system, he transitioned to studying the function of glial cells in the nervous system, introducing the use of the leech for those studies.

Kuffler returned to Woods Hole nearly every summer with his wife, Phyllis, and children; their home near Stony Beach was known as a welcoming place filled with lively conversation. Phyllis ran a summer symphony in Woods Hole and was an early organizer of the MBL Club, which to this day promotes activities for MBL families.

“Steve’s sharp mind, good humor and playful interactions with colleagues and their families and students made him beloved and inspiring. All of us enjoyed having the pleasure to work or interact with this joyful and wonderful man,” says Wiesel. A beloved member of the MBL community to the end, Stephen Kuffler died in 1980 and was buried at the Church of the Messiah, Woods Hole.

— By Raleigh McElvery

Selected References

Akkermans, Rebecca (2017) Stephen Kuffler. The Lancet Neurology, DOI: 10.1016/S1474-4422(16)30326-X

Katz, Bernard (1982) Stephen William Kuffler, 24 August 1913-11 October 1980. Biographical Memoirs, Fellows of the Royal Society, DOI: 10.1098/rsbm.1982.0011

Kravitz, E. A., S. W. Kuffler, and D. D. Potter (1963) Gamma-aminobutyric acid and other blocking compounds in crustacea: III. Their relative concentrations in separated motor and inhibitory axons. Journal of Neurophysiology, DOI: 10.1152/jn.1963.26.5.739

Kravitz, Edward A. NEUROBIOLOGY IN THE 60S OR ‘THE GOOD OLD DAYS ARE NOW. Originally published in the International Society for Neuroethology Newsletter.

Nicholls, J. G. (1998) Stephen W. Kuffler: August 24, 1913-October 11, 1980. Biographical Memoirs, National Academy of Sciences (US) 74: 193-208.

von Hoeckendorf, Vincent, and Frank W. Stahnisch (2016) Stephen William Kuffler (1913–1980). Journal of Neurology: DOI: 10.1007/s00415-015-7932-z