by Michael Mohammadi

One of the more influential books I read in graduate school had nothing to do with material that I would be tested on. The book was “Steve: Remembrances of Stephen W. Kuffler” by U.J. McMahan, a biography of one of the greatest neurophysiologists, and one of the most passionate scientists of the 20th century. I recently re-read this biography and it once again made me realize why I love science and discovery. Here I give a brief overview on his contributions to neuroscience and hopefully give some insight into his passion for truth. I skip over many of the details that can be found in his biography or the many lectures and notes written about him posthumously.

Kuffler is considered the “father of modern neuroscience” and in fact he created the first neurobiology program, now one of the best in the world, at Harvard University. He began as a greek and latin major, eventually attending medical school in Vienna. His early work with Sir John Eccles (1963 Nobel Laureate) and Bernard Katz (Nobel Prize in 1970) in Australia was some of the fundamental studies on synaptic transmission. Kuffler eventually came to the USA to work at Johns Hopkins university at the Kresge Eye Institute. There he was involved ground breaking research on receptive fields in the visual system.

John G. Nicolls wrote of Kuffler’s approach to mentoring and science

“No one had greater disdain than Steve did for sloppy thinking or sloppy experiments. Yet this attitude was never translated into unkindness at the personal level. A somewhat sharp but subtle wit was his instrument for deflating pomposity or countering aggression. During experiments he worked; you would try again and again and again, all day and late at night, and again the next day until you got good recordings you could rely on. Single mindedness and dedication during experiments were in contrast to the relaxed, vague, almost amorphous approach with which long-term projects were discussed in the first place.”

I can recall in a rigorous synaptic physiology course with Dr. Danny Weinreich (himself also a passionate, great lecturer and scientist) learning the seminal papers from Kuffler’s time. While I didn’t immediately grasp the eloquence and depth of Kuffler’s work (the Journal of Physiology papers seemed endless and there were many of them!) there was no comparison to modern-day publications. Each paper told a story. The story included the “good” data and the “bad” data, and a valid, scientific argument for each. The papers would build to a conclusion that, though often challenged, was so simple and understandable it could easily be interpreted and challenged. This is the foundation of good science. We as scientists must make our work easy to understand and repeat, and we must want to be challenged and occasionally be wrong. Today’s scientists seem so afraid to be incorrect, but in Kuffler’s day that was just part of the excitement.

A majority of scientists today are known for a technique or two, or continuously use a specific animal model such as C. Elegans (worm), Drosophila (fruit fly) or some type of rodent (rat/mouse). Kuffler’s approach to science was inspiring. He didn’t limit himself or his lab to a single technique or species. A specific problem was defined and then he would acquire whatever tools, people or animals were necessary to address the problem. Interestingly, another hero of mine, the Nobel Prize winning physicist and equally as passionate scientist Richard Feynman was also said to approach science in this “everything even the kitchen sink” approach to understanding nature and the universe.

There are numerous reviews and websites giving the details of Kuffler’s contributions so I won’t give an extensive analysis here. It is important though to mention a few of his key contributions to our understanding of physiology:

early work on the role of Ca2+ in the end plate potential

ON and OFF cells in the retina

discovering the primary inhibitory neurotransmitter in the brain (GABAA) using crustaceans

work on sensory innervation

the importance of contrast in the development of the vision (rather than simple diffuse light) in rodents

seminal work on the physiology of glial cells (in the leech)

many seminal studies of the basis of synaptic transmission (brilliantly using the frog heart as a prep)

While some of the work Kuffler did was alone in a lab, many major discoveries came from work with others. It is said that he had a knack for finding the right person, or people, to address a specific questions. Kuffler’s Rolodex in science would be akin to that of Francis Ford Coppala’s in Hollywood. Briefly, he worked for John Eccles, with Bernard Katz, and mentored some of the biggest names in the field including Torsten Wiesel, David Hubel, and Eric Kandel. The list of collaborators, most of whom are top names in the world, National Academy members and Nobel Laureates is extensive and beyond the scope of this mini-bio!

Kuffler’s biography details relationships formed within his lab; scientific, romantic, or just friendships (sometimes all three). I won’t go into these in detail as I do not have first hand knowledge,but I urge you to read his biography. A key partnership that he is given credit for bringing together are Torsten Wiesel and David Hubel and allowing their early work to publish as just “Hubel and Wiesel”, intentionally occluding his own name so they could grow their careers. The pair eventually won a Nobel prize (1981) for their work on the visual system. Kuffler never was awarded a Nobel Prize and some speculate it was purely political (which the Nobel has become, look for an upcoming post on this!). Even without sciences grand prize, those in neuroscience know that the contributions that Kuffler made go well beyond any award or prize.*

Kuffler passed away on October 11, 1980 in Woods Hole, MA. I am fortunate enough to take a trip or two each summer to the Marine Biological Labs and it is one of my favorite things about my job. With the beauty of Cape Cod, the excitement of the students and the amazing seafood, it is quite easy to see why Kuffler loved the time he spent there. His last 20 years were spent at Harvard Medical School and his grand legacy lives on in national and international lecture series, awards and the many stories told by his friends.

Of Kufflers integrity and passion for people, John G. Nicolls wrote:

“The only sign I saw of a double standard in his conduct was the contrast be- tween his own lack of consideration for himself and the infinite trouble he would go to for colleagues who were in need of help.”

Steve: Remembrances of Stephen W. Kuffler

I would recommend this biography to any inquisitive mind or scientist, especially those in neuroscience that want to gain a better understanding of where the field came from. On this Friday evening as you leave your office and perhaps head to a local watering hole to imbibe truth or a cocktail, raise a glass to Dr. Stephen W. Kuffler- a rigorous scientist, respected and loved mentor and the founder of what we now call neurosciences.

Cheers!

*About his not winning a Nobel Prize, I like to think he would have agreed with Feynman in his statement:

“Honors, and from that day to this, always bothered me. I had trouble when I became a member of the National Academy of Science, and I had ultimately to resign. Because there was another organization, most of whose time was spent in choosing who was illustrious enough to be allowed to join us in our organization. Including such questions as: ‘we physicists have to stick together because there’s a very good chemist that they’re trying to get in and we haven’t got enough room…’. What’s the matter with chemists? The whole thing was rotten . Because the purpose was mostly to decide who could have this honor. OK? I don’t like honors.” – Richard Feynman