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Saturday, January 19, 2013

As flies to wanton boys are we to the gods

An earlier post, Discrete genetic modules can control complex behavior, described genetic control of burrowing behavior in deer mice. A reader commented that the results were entirely unsurprising. I wasn't aware of similar results in mammals, but of course this sort of thing has long been known in drosophila, thanks to Seymour Benzer and collaborators.



WSJ: ... When the great California Institute of Technology geneticist Seymour Benzer set out in the mid-1960s to find mutations in fruit flies that affected behavior, rather than mere anatomy, he was ridiculed for challenging the consensus that all behavior must be learned.

Benzer told the geneticist Max Delbrück about the plan to find behavioral mutants; Delbrück said it was impossible. To which Benzer replied: "But, Max, we found the gene, we've already done it!" (Benzer's mother was more succinct: "From this, you can make a living?") He was soon able to identify mutations related to hyperexcitability, learning, homosexuality and unusual circadian rhythms, like his own: Benzer was almost wholly nocturnal.

Since then, thanks to studies of human twins and a rash of genetic investigations in animals, it has become routinely accepted that most things, including personality, sexual orientation and intelligence, are to some degree affected by genes. The University of Virginia's Eric Turkheimer has declared what he calls the "first law of behavior genetics": that all human behavioral traits are heritable.

Benzer started in solid state physics, migrated to molecular biology, and then to neuroscience.
Caltech Oral History:  ... I had my nose on the transistor. It’s like Max Delbrück [professor of biology at Caltech; d. 1981] failed to discover fission, and he had it under his nose. [Laughter] I failed to discover the transistor, because I had three electrodes in there, and I was measuring things—using one to measure what the other one was doing—but I never had the idea of trying to use that arrangement as an amplifier. Instead, I had a different idea; I had the idea of making a crystal amplifier, but it was too sophisticated. It was based on putting a metal layer on top of a semiconductor and using a tunnel effect to control the current that’s passing through, but I never got it to work. Instead, the Bell Labs guy did the most simpleminded thing, which was to have just these two wires next to each other and have one influence the other. It escaped me, and it was under my nose. Some time later, there was a big demonstration of it at Bell Labs. These guys grabbed me and said, “You should have done this.” [Laughter] And they were right. But, you know, maybe to some extent, because I was already into biology at that time, I wasn’t really focused on that problem. Of course, being a graduate student and not being all that able or having big resources [played a role]. But by the time I got my Ph.D. in 1947, I was already interested in biology.

Aspaturian: What had happened?

Benzer: I was always interested in biology. But two things happened. One of the guys in the lab — his name was Lou [Louis L.] Boyarsky—told me about mapping genes on chromosomes, the work that had been done here at Caltech by [Alfred H.] Sturtevant and [Thomas Hunt] Morgan and their group. I thought that was very exciting. And then I read this book by [Erwin] Schrödinger, written around 1944, called What Is Life?, which inspired a number of other people as well—Francis Crick, for one. Max Delbrück was in the book—he had been at Caltech in the thirties, switching from physics to biology—and there’s a chapter in there on Delbrück’s model of mutation. ...

Aspaturian: What brought you to Caltech, the first time you came?

Benzer: During the sixties, I was getting more and more interested in behavior. One reason was my two children. I have two daughters with very different personalities. If you have one daughter, you don’t notice anything, but if you have a second one, you begin to wonder, “Are we doing things differently, or is it genetic?” So I got interested in this general problem of personality and behavior—how much is genetics and how much is environment? And how do you study such a problem? I had actually begun to be interested even before that time. There was a meeting about ’63, I think, at Cold Spring Harbor, where I remember having a conversation with Marshall Nirenberg. We had this feeling that all the molecular biology problems were on the verge of being solved. It was a little bit like the physicists at the end of the nineteenth century saying, “All we have left to do is one more decimal place.” Little did we anticipate all the recombinant DNA technology. So that was another part of it, the fact that molecular biology was going so well, becoming rather crowded. When things get to that stage, you wonder why you should be doing something somebody else is already doing. It’s just redundant. ...

Aspaturian: Would you say that Drosophila is about the most complex organism with which you can get really rigorous results in this kind of research?

Benzer: Well, I don’t know. It depends on what you want to study. You can get rigorous results with humans now. Modern technology makes it almost as easy to work with humans as with flies, and that’s why I have the courage to get into the human business now.

Aspaturian: But there are so many more behaviors to look at in humans.

Benzer: Humans are wonderful. There’s a book on viewing disorders of man, containing 4,000 hereditary disorders in humans, one or two thousand of which have been actually mapped on the chromosome. Many of these have behavioral components, and hundreds affect the eye. There’s a similar book on Drosophila. And we’re finding that more and more of the genes correspond to one another.
See also this video interview of Benzer. Among other things, he discusses specific mutations that control sexual behavior in drosophila (e.g., length of copulation, courtship), learning ability, memory, etc. Of course, these are just flies  ;-)

For more on Max Delbruck, see For the historians and the ladies; for more on physicists and early molecular biology, see The Eighth Day of Creation.

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