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An epiphany working on Bence Jones protein


Lessons learnt from Pauling and Burnet
Gerald Edelman Scientist
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This may be the time to say something about what you learn from the faults of great men, because I did learn something from both Pauling and from Burnet. When, I don't remember the date, I'm not good at chronology, but in the mid to late '60s I was invited for the first time to a very large scientific symposium – the Kaiser Foundation symposium –and I remember it for several reasons. One is that I had a suite at the Fairmont Hotel in San Francisco with even whiskey bottles in the room – that wasn't bad. The second was I had an honorarium that seemed humongous at the time – something like $750. And the third was the scary part: when I looked at the program, which I hadn't seen before... as it arrived in the room, guess who was speaking first, and I was speaking second? Linus Pauling was speaking first about his antibody theory. Well, that threw me into a sort of terror because I was about to give a speech that said that he was wrong. So I called up a friend at Stanford who knew him and I said, 'Do you think you can rig a dinner – we've got one day, and I know it's an imposition...' And, by golly, he pulled it off.

So there we were – my friend and I with Pauling and his wife. Pauling, you remember, had two Nobel Prizes – one in chemistry and the other in international peace, the Peace Prize, because of his interest in nuclear events and disasters – and all that evening, all he could talk about was nuclear containment and, let me put it this way, when you're in Linus's presence you were forced to admire. And so everyone was admiring and I couldn't get a word in edgewise until I finally said, 'Sir, there is just one thing I wanted to tell you. You see, we've been working on antibody molecules and we've cleaved them and they have polypeptide chains linked by disulphide bonds and, furthermore, different antibodies have different amino acid compositions.' And that's about as far as I got. He went right back to nuclear containment. So the next day I said, 'You know, you'd better take it easy here.' He got up and he gave an absolutely brilliant lecture. I was despondent. And at a certain point he showed a figure of the instructional theory on his slide, and he said this is one of the polypeptide chains of the antibody molecule. And I said, 'My God, he understood everything.' So I got up and I said, 'Well, you'd better stick to the facts.' And I think that doesn't necessarily make for a good lecture but I... I did my best. I came back to my chair and there on the chair was a piece of paper that said: 'Edelman, send reprints, Pauling.' And that was the end of that.

And now my second anecdote is about the other great figure who's a biologist. When Joe and I were working on this antibody and Bence Jones thing, he visited us. Completely different kind of personality; and that's an important thing to realize about science and personality: there's no one way of being. He came and he said, 'Well, what are you doing? And I said, 'Well, sir, we're working on the structure of the antibody molecule.' And he said, 'That's a total waste of time – what are you doing that for? Chemistry just makes things worse.' And I said, 'Well, if you don't do that, you see, we're selectionists like you, and if you can't count how many members in the repertoire it won't work. Supposing it's only five and it's not a...' He said, 'Mathematics is even worse than chemistry. Don't worry, young man, my theory is correct.' And he walked away. And I remember thinking: is he stupid? And then... no, the funny thing was his theory was correct, but I learned from each of them two things: the first one was from Pauling who would have... and you know he had a big role in the double-helix story... who would have abandoned instructionism if he had only gone up to the cellular level, but he stayed all at the molecular level. And one of the lessons in biology is that you'd better look at a multilevel system, because at the cellular level, and this is where Burnet came in, you had something called immune tolerance in which you did not make antibodies to your own proteins when you were developing. That's like The Hound of the Baskervilles when the guard said that the hound did not bark... the dog did not bark. And Pauling didn't know that. Had he known that he would realize you can't wrap an antibody molecule around nothing. And so the whole phenomenon of immune tolerance, to me, it meant it couldn't be that way. What I learned from Burnet was you can be right the way he can be, but you can't be really precise unless you look down a level and do the whole thing in terms of molecular structure as well as the cellular behavior. Those two lessons I learned from great scientists and they were very, very important in conditioning the way I responded later.

US biologist Gerald Edelman (1929-2014) successfully constructed a precise model of an antibody, a protein used by the body to neutralise harmful bacteria or viruses and it was this work that won him the Nobel Prize in Physiology or Medicine in 1972 jointly with Rodney R Porter. He then turned his attention to neuroscience, focusing on neural Darwinism, an influential theory of brain function.

Listeners: Ralph J. Greenspan

Dr. Greenspan has worked on the genetic and neurobiological basis of behavior in fruit flies (Drosophila melanogaster) almost since the inception of the field, studying with one of its founders, Jeffery Hall, at Brandeis University in Massachusetts, where he received his Ph.D. in biology in 1979. He subsequently taught and conducted research at Princeton University and New York University where he ran the W.M. Keck Laboratory of Molecular Neurobiology, relocating to San Diego in 1997 to become a Senior Fellow in Experimental Neurobiology at The Neurosciences Institute. Dr. Greenspan’s research accomplishments include studies of physiological and behavioral consequences of mutations in a neurotransmitter system affecting one of the brain's principal chemical signals, studies making highly localized genetic alterations in the nervous system to alter behavior, molecular identification of genes causing naturally occurring variation in behavior, and the demonstration that the fly has sleep-like and attention-like behavior similar to that of mammals. Dr. Greenspan has been awarded fellowships from the Helen Hay Whitney Foundation, the Searle Scholars Program, the McKnight Foundation, the Sloan Foundation and the Klingenstein Foundation. In addition to authoring research papers in journals such as "Science", "Nature", "Cell", "Neuron", and "Current Biology", he is also author of an article on the subject of genes and behavior for "Scientific American" and several books, including "Genetic Neurobiology" with Jeffrey Hall and William Harris, "Flexibility and Constraint in Behavioral Systems" with C.P. Kyriacou, and "Fly Pushing: The Theory and Practice of Drosophila Genetics", which has become a standard work in all fruit fly laboratories.

Tags: The Hound of the Baskervilles, Linus Pauling, Macfarlane Burnet, Joe Gally

Duration: 4 minutes, 57 seconds

Date story recorded: July 2005

Date story went live: 24 January 2008