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Contradictions in science

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My attraction to darkness and how that led to RNA translation
Gerald Edelman Scientist
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At the same time something else happened in the field of neurobiology. It became increasingly significant that synapses were unbelievably complex structures; that synapses changed their strength through a whole variety of different mechanisms, but the one that arrested my attention and that of my colleagues, Peter Vanderklish and Vince Mauro, was that the RNA was sometimes brought right to the synapse from the body of the cell. You remember the cell of a neuron is over here, and then there's an extended structure called an axon, and there are a set of structures called dendrites, and I remind you that axons make synapses with dendrites amongst others. And what was astonishing was this. That sometimes ribosomes and message and other proteins were brought along these... these linear structures from the soma – from the body where the nucleus is – to the synapse, and then when the synapse becomes active, translation begins right there. That was astonishing. And it does change synaptic strength; that's well-known. So we got rather interested and we started to work.

What we have found so far is a bit out of the ordinary but not yet open to a full picture. And what we found was that it isn't necessarily so that you work by cap scanning; that in fact these sequences, particularly the ones that were complementary – in other words wherever there was a G there was a C, wherever there was an A there was a U, etc... when you looked at those you could show that, having certain of those sequences was enough to enhance translation. And so what we came into was the discovery of a whole set of translational enhancers. Well, we aren't finished yet, but it looks like that this process is much more predominant than people have thought, and in fact the idea is that these complementary enhancers which bind the ribosome don't necessarily do it at the cap, and there's really very little evidence so far that there's this true scanning. So we're still in an indeterminate phase where we trying to find out all the mechanisms... but the name of this story is one of opening up a whole reinterpretation of translational events themselves.

Now, I don't know why he said it, but Woese – is that how you pronounce his name, Ralph? – said that as far as evolution is concerned, translation is the key process. I don't quite understand that myself but it is of course terribly important in realizing what the genes have to say in making it function... what they have to say... function in the cell. So we actually came – because of my tendency to think in terms of theoretical matters – to a notion that the ribosome is actually a control element. It actually controls its own fate. And so Mauro and I put out a so-called ribosome filter hypothesis which said that. That it isn't just a little tape head and that's all; it's a most sophisticated structure, and indeed I hope that we may even be able to show those proteins which were the site of my wrong-headedness, turned out to be modulators of how this thing controls what's happening when the message comes through and gets read.

Anyhow, I come back to this notion that I started with – namely, why did I ever get interested in that? Well, partly because of darkness. I am attracted to this notion that... that style in science differs amongst different people and I know that my own, as far as I can diagnose my own, involves a certain romantic attraction to darkness. Wherever I see the contradiction or unresolved issues that can be subject to experimentation, I am attracted. So I'm often asked this about my own work; why did I leave immunology? Well, in one sense I never left it because I never entered it. It was... I don't want to be condescending about that, but I really didn't feel that I wanted to be in science a specialist in some particular area. I was much more interested in the idea of saying, 'Well, what defines the difference between an open science and a closed science?' And if it isn't that grandiose, what makes the difference between a problem which you advance the thing step by step, versus a problem where you say, hey, you know what, this just doesn't make sense. And I'm much more attracted to that. Sometimes, of course, it's nonsense but... and sometimes the work I do is nonsense but in... in effect, it is valuable I think to reflect on cues and clues as to how you want to work, and it may even be, although I've never exercised this, useful to young people, to give them a kind of picture, a panorama, of types of science.

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: Peter Vanderklish, Vince Mauro, Carl Woese

Duration: 5 minutes, 1 second

Date story recorded: July 2005

Date story went live: 24 January 2008