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An Interview with Eric Kandel

2010; Wiley; Volume: 588; Issue: 5 Linguagem: Inglês

10.1113/jphysiol.2009.185231

1469-7793

Brian Robertson,

Neurology and Historical Studies

This is the first in a new series, designed to give our readers some insight into the lives of leading physiologists. To uptown New York, on a typically hot mid-July day, to meet and interview Professor Eric Kandel for The Journal of Physiology. The time is set for 3 pm on a Friday afternoon, in his offices at The New York State Psychiatric Institute, on 40 Haven Avenue (West 168th Street). The building is located at one end of a warren (if one can describe such a huge conglomeration) of buildings associated with the New York – Presbyterian Hospital and Columbia University Medical Center. Here cutting-edge research is carried out right next to patients. As we get out of the taxi there are people in wheelchairs and dressing gowns coming and going. I guess this is a daily reminder to the bench scientists of what it is ultimately all about. Another noticeable point is that many of the buildings are named after munificent benefactors, a reminder not only of the philanthropic nature of many wealthy Americans, but the fact that big money talks and gets big buildings. New Yorkers without a National Health plan must be grateful. We are to meet in Eric's office on the 6th floor and after being warmly welcomed by his extremely efficient and delightful secretary Millie Pellan, with a much-needed bottle of cold water, we wait for the great man to enter. Bang on time, Eric joins us in his large – but not excessively so – office with fine views over the Hudson River. The place is filled with photographs of family, colleagues, special occasions, certificates and I can spot only one easel painting in a gilt frame on the wall. This is no showcase of achievement though, but a working office, where he holds regular meetings with members of his laboratory. One gets an immediate impression of energy and charm from Eric. He is vivacious, certainly, and has a huge glistening smile that would not look out of place in Hollywood. The smile is the bright visual prelude to a very warm welcome with his distinctive windmill-in-high-wind laugh. I had brought my wife Lesley along as ‘assistant’, and he makes a tremendous fuss of her, commenting immediately on a small silver Celtic necklace which reminds him of some items in his extensive collection Art Nouveau; immediately, we are aware that we are in the presence of a sophisticated, urbane and cultured man – he is completely at ease dealing with people. After the traditional pleasantries, I noticed the clock was ticking, and it was already clear that we were well into our hour-only appointment (Millie pins the schedule to the office entry – this is a busy man). Firstly, I thank Eric for his excellent contributions to the David Hubel and Torsten Wiesel Anniversary Special Issue for The Journal, where he contributed a personal memoir (Kandell, 2009a) as well as a Topical Review (Kandell, 2009b) on some recent work from his labs on learning and memory in the hippocampus. ‘It was a pleasure to do so – I have great respect for these men, and their first joint paper was indeed a landmark and worth celebrating’ he says. We talk a little more about Hubel and Wiesel, especially Torsten. ‘He came across as the quieter, more reserved of the two in the early days. I always felt that he was a little under Hubel's shadow. However, later, when he became Head of Neurobiology at Harvard he showed a great deal of inner strength and confidence, which later became more apparent when he joined Rockefeller University in New York. He was an outstanding leader and mentor to many young scientists. A brilliant man.’ Brian Robertson (BR). I met him briefly last year, in Rockefeller, where he still maintains an office. I was extremely impressed with some of the art he has there; he is very knowledgeable about art and artists. Eric Kandel (EK). Yes, he has a superb and eclectic collection of art. We are both passionate about art. Sometimes we compete for the same painting! BR. I want to come back to your interest in art, but first, tell me a little about your background. EK. I was born in Vienna on November 7 1929. I was the second child. My parents were not from Vienna, but from what is now Western Ukraine. My father established a small toy store, where my mother also worked. Vienna at that time was a wonderful, cultured and cosmopolitan city. All this changed, of course, when Hitler annexed Austria. For obvious reasons, which I go into further in my autobiography, our family had to leave Austria. My brother and I left for the USA in April 1939 and our parents in September 1939, a few days before the Second World War started. One of the legacies of my time in Vienna was a profound curiosity concerning the origins of human behaviour – how could a society so cultured become so vicious? I followed this thread in my first degree which was in History and Literature at Harvard University, where I wrote a dissertation on ‘The attitude toward national socialism of three German writers: Carl Zuckmayer, Hans Carossa, and Ernst Junger’. I came to the rather depressing conclusion that many German artists, intellectuals and academics succumbed too readily and embraced to the doctrines of Nazism. As a recent émigré family, we lived in Brooklyn, near my relatives. My father got a job in a toothbrush factory, but later saved enough to open his own clothing store. We lived above the shop, and the modest income supported us through school and me through medical school. He worked in that store until he died in 1978. BR. You still live in Brooklyn? EK. No, we live in the Riverdale section of the Bronx; my wife and I have lived in the same 150-year-old house for several decades. We have wonderful views of the Hudson River. I swim in the pool every day and play tennis regularly. My wife Denise and I collect avidly: French art nouveau furniture, vases and lamps, and a good deal of graphic art, especially that of the Austrian and German Expressionists. BR. To come back to your art collection again, what is your favourite work – or rather, since it is hard to choose a favourite, what would you grab if your house were to go on fire? (Heaven forbid.) EK. Difficult. I think it would be my Gustave Klimt! BR. Fabulous! How lucky you are. EK. I am getting another one for my 80th birthday! We collect a good deal – I would say we are addicted. With some of my Nobel Prize money we bought a wonderful apartment on the Left Bank in Paris. Much of our collection is there too. My wife and I are Francophiles (Denise was born in France), and we hoped that our children, and now our grandchildren, would be able to use the apartment too. We try to get there a couple of times a year. BR. You’ve had a fascinating route to your present position. What would you do if you weren’t, or couldn't be, a scientist? EK. Perhaps an historian. Or a gallery owner! BR. But a scientist you became. Who would you count as your greatest mentor in science? EK. There would be a few, but certainly Harry Grundfest and Dominick Purpura. I did my elective at Columbia University with Grundfest, and there I met and worked with Dominick. Later, I worked with Alden Spencer, and together we made intracellular recordings from the hippocampus. BR. I remember as a PhD student in the early 80's, reading about your work on Aplysia, and seeing how that was beginning to answer the questions of the molecular mechanisms of memory. I was going to Australia to do my PhD, and was dithering whether to work on the hippocampus, or Aplysia, which were plentiful in the Sydney lab. I chose hippocampus, and whilst working on slices, was amazed to read your papers of the 1960's making recordings from hippocampal neurons in vivo! I had a hard enough time with slices then. What skill and patience you guys must have had, and from doing that, to take the reductionist approach and go to a simple organism like Aplysia must have taken some guts. EK (laughing.) Yes. Eccles was very against a reductionist approach. But there were superb precedents from the work of Hodgkin and Huxley, Katz, and of course Steve Kuffler, who was a great inspiration for me. I learned from Kuffler's scientific papers how biological science should be done – the value of matching a scientific question to a suitable preparation. Kuffler taught me to respect the power of invertebrate neurobiology. BR. I have encountered a similar snobbishness about preparations too; one very distinguished pharmacologist I knew couldn't understand why I would give up hippocampus for sensory neurons and patch clamp to study GABA, but he would always slip me the best chemical tools. I think it is good to try different things in ones career, and certainly for you and the neuroscience community at large, the move to Aplysia paid off handsomely. What scientific paper most inspired your work? EK. The classic papers of Hodgkin and Huxley in The Journal of Physiology. We worshipped those papers. Also the work of Katz, on spontaneous and evoked release. Wonderful. I think The Journal of Physiology made a big mistake though in sticking to alphabetical order for so long; young American scientists couldn't understand that and deserted The Journal for that reason. BR. How would you change science education to produce a more scientifically literate population? EK. I think science is taught wrongly – it comes across as boring, which it isn’t. Communication of science has to be improved. BR. What have you sacrificed for science? EK. Zero. Nothing. Science has given me a wonderful life. I love it. When pressed though, I said in a speech I gave several years ago at my birthday party that I could have been a better father when I was younger, and been around more. I was so busy then, and often away. So I said in this speech that I gave myself a ‘B’ in parenthood. (Laughing.) Afterwards, one of my children came up and asked when I was promoted to a ‘B’! They were joking, of course, but I did miss some valuable times. BR. Who is your favourite writer and which one of their books would you recommend? EK. Having spent a whole career occupied with memory, one would be Proust's magnificent ‘À la recherche du temps perdu’. He says so much about memory there. BR. How appropriate – it was he who coined the phrase, and described so well, ‘mémoire volontaire’; it fits with your love of things French too. Any others? EK. Jane Austen's ‘Sense and Sensibility’ and Charles Dickens’‘Bleak House’. I also enjoyed the novel of Siegfried Lenz called ‘The German Lesson’. It is a biographical treatment of his house arrest in the Nazi period. He may have been a Nazi himself and it is a remarkable story. BR. What scientific problem currently occupies you? EK. There are so many! But here are two, quite different in scope. A scientific one is the involvement of a prion-like protein in long-term memory. In neurones from Aplysia and mice, we identified a local ‘marking signal’ for synaptic facilitation. In Aplysia we found that one component of these marking signals requires local protein synthesis. A neurone-specific isoform of cytoplasmic polyadenylation element-binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. The Aplysia CPEB protein is up-regulated in activated synapses; it is required for maintenance of long-term facilitation. Fascinatingly, CPEB is an ideal stabilizer because it has prion-like properties. Prion proteins have the unusual ability to fold into functionally distinct conformations, one of which is self-perpetuating. Our preliminary studies suggest that conversion of CPEB to a prion-like state in stimulated synapses helps to maintain long-term synaptic changes associated with memory storage. It is wonderful to be involved in something so exciting, so potentially important, at my stage of life! BR. A solid element to memory? I guess that answers my next question then, which is if you were marooned on a desert island, with a simple but adequate laboratory, what would you study? EK. How memories can be perpetuated for the lifetime of an individual. BR. How Proustian; you mentioned a second project? EK. This is quite different. I am writing another book (pointing to a large manuscript on the table). This one is about the inter-relationships with art and science, focusing on pre-War European thought. It also includes autism, and there is some discussion about the art of Stephen Wiltshire, an autistic savant, who can draw cities from memory. People said I shouldn't do this, it is too arrogant (laughing). Perhaps it is, but the age I am, and all I have achieved, permit me to do this. It should come out in 2010. BR. I shall look forward to that. What you said reminds me of what the German painter Gerhard Richter says, that as he gets older, he gets more ‘sovereignty’ in his work, he gives himself permission to do things that he wouldn't have done when younger – people tell you that you can't do this or that when you are young. EK. Quite right. I have the advantage of leverage in all sorts of different ways now, so I can use it. I have discussed consciousness with the Dalai Lama and Tina Turner! BR. Tina Turner? EK (Laughing.) Yes! I was invited on to a German television talk show a short time ago. They wanted me to talk about the brain and consciousness, and where it was and so forth. Sitting next to me was this woman I had never heard of called Tina Turner. She asked me some questions, and afterwards gave me a big hug and kiss and thanked me for explaining it all so clearly to her! BR. Marvellous – what an image. Eric, thank you very much for your time, you have been most kind. We wish you a happy 80th birthday. Our time, sadly, was up. Eric had a meeting with one of his group. Gentleman that he is, he showed us to the elevator; we, somewhat elated but exhausted. Age certainly does not diminish his ardour, and we later had a drink to him enjoying the pairing of Tina Turner and the Nobel Laureate, Arts and Science. For a sample of Eric Kandel and Tina Turner, see YouTube: http://www.youtube.com/watch?v=MyX_sd4UmBY&feature=related