For 50 years of brilliant creativity in biomedical science — exemplified by his legendary work on the genetic code; his daring introduction of the roundworm Caenorhabditis elegans as a system for tracing the birth and death of every cell in a living animal; his rational voice in the debate on recombinant DNA; and his trenchant wit.
Sydney Brenner likes beginnings. In the course of his career, he has opened up several major fields. While many scientists are gearing up to explore the new frontiers he has pioneered, Brenner's brain is already fidgeting and scouting around for a fresh path.
In the early 1960s, Brenner emerged as one of the influential leaders of the classical period of molecular biology, the era from 1953 (discovery of the double helix) to 1966 (elucidation of the genetic code). His discoveries are legendary and appear in every biology textbook. He established the existence of messenger RNA (mRNA) — the 'working tape' copy of genetic material from which cells make proteins — and found that each amino acid in a protein is specified by a set of three building blocks, or nucleotides, in the RNA chain, which he termed "codon." He showed that the nucleotide sequence in mRNA dictates the order of amino acids, and that each mRNA chain contains the instructions for a particular protein. He also deciphered the stop codons, which terminate protein synthesis.
Award presentation by Joseph Goldstein
Groucho Marx may hold the distinction of being the funniest comedian who ever lived, but Sydney Brenner, this year’s recipient of the Lasker Special Achievement Award, holds a loftier title — the funniest scientist who ever lived. Like Groucho, Sydney is famous for his flamboyant energy, his creative one-liners, and his insightful monologues on every subject imaginable — not to mention his bushy eyebrows. Fifty years ago, Groucho Marx taught Americans the meaning of the Yiddish word chutzpah when he refused membership in a Beverly Hills country club because he didn’t care to join any club that would elect him as a member. Like Groucho Marx, Sydney Brenner is the personification of chutzpah.
What other scientist would have the chutzpah to present a lecture at Harvard wearing a splashy Hawaiian shirt?
What scientist would have the chutzpah to submit a manuscript to the Royal Society with a fake reference tucked away in the middle of the text, “Leonardo da Vinci (personal communication)”? And when called on the carpet by the editor, fired back that there’s a new Italian postdoctoral fellow working in the lab.
What scientist would have the chutzpah to refuse a knighthood from the Queen of England? I doubt that even Groucho Marx would have the chutzpah to refuse the club at Buckingham Palace.
Errol Friedberg, professor and chair, Department of Pathology, University of Texas Southwestern Medical Center in Dallas, interviews Sydney Brenner, winner of the 2000 Albert Lasker Special Achievement Award. Dr. Brenner is President and Director of Science at The Molecular Sciences Institute in Berkeley, California.
Part 1: Early Education
Growing up in the “relative isolation” of South Africa, Dr. Brenner says he became a self-taught chemist until going on to university there and later to Oxford.
Friedberg: To begin this formally, on behalf of the entire community of past and present molecular biologists, let me extend my congratulations to you on receiving the Special Achievement Award.
This award recognizes your lifetime of contributions to science. Let me start by asking you this: In retrospect, was growing up in the relative isolation of South Africa a good or bad thing for you? And if you were to have your scientific life again, would you do it the same way, or differently?
Brenner: It’s hard to say if it’s good or bad because I can’t do the control experiment. That’s where I grew up, and I think the upshot was that it was good for me. And indeed, if I’d grown up somewhere else, I would have been somebody else. So I think, what it let me do was, of course, to become essentially self-taught. I think lots of people who grew up in South Africa had to exploit their own initiatives in learning about things. So it had that benefit. It inculcated at least one good habit.
Friedberg: How did your interest in science in that part of the world, so early on, evolve to chromosomes and genes?
Brenner: I think like most children, I got interested in nature very early. And then by reading a little book called The Young Chemist by Sherwood Taylor, I got interested in actually doing chemical experiments. So I started my career as a garage chemist, buying chemicals from the local pharmacist and making things according to the prescriptions then, and going forward to more experiments, just on that basis. I then started — still while I was at school — extracting pigments from petals and just doing really cookbook chemistry, on that basis. And of course when I came to university, a whole new realm of biology was opened up to me because in doing first-year medicine studies, I did both zoology and botany. And while I was doing botany, I was able to work for someone (on the faculty). I saw chromatography being practiced, which just taught me how naive I was with my own pigment extractions and partitions. Then I got interested in biochemistry. And I got interested in how are things are determined, of course, through just studying anatomy, physiology, botany and zoology — through biological things. So at that time, I was interested in (what we call) cell physiology. When I started moving towards trying to define something to do research on, I decided that I would work on chromosomes. So that’s how I got into this. And the most formative book at that time was reading Wilson’s The Cell in Development and Heredity.
Friedberg: Then you went to Oxford, and as I recall working with (Cyril) Hinshelwood was not an especially inspiring experience for you.
Brenner: Well, it was. I went to Oxford because I wanted to do something that I thought might be the closest thing to my interest, which I had formulated then as cell physiology. Of course, molecular biology hadn’t been invented yet. And I had been given the chance to work on bacteriophage because he (Hinshelwood) was interested in bacteriophage resistance. And so before I came to Oxford, while I was still in Johannesburg, I read this little book, Viruses 1950, which was my first contact with phage. And that was my first conversion to the whole of that stream, which finally ended up in creating molecular biology. So when I came to Oxford, I had already started to work on phage and bacteria.
And of course, as everybody knows, Hinshelwood was not a great believer in mutation. He thought everything was done (in bacterial cells) by simply (shifting) the balance of the kinetics of reactions amongst the different molecules. And he wrote a book called The Physical Chemistry of The Bacterial Cell, in which he said that one could shift balances (in cells) by intervention of the environment, and then the whole state could become inherited. Now, of course, he was right (to a certain extent. There are states in organisms which are like that, except he chose the wrong subject, the wrong kind of bacteriophage (phenotypes) to investigate. And I think that if you look at how he would have interpreted resistance or virulence (in bacteria), or in fact any of the switches we now know about, like the switch from lysogeny to lysis in a lysogenic bacterium, he was absolutely correct there. But, indeed, you know what I was working on was not in question: These were true phage-resistant mutants. Actually, I think I was able to convince him of that at the end by pointing out to him a phrase I have often liked to use over and over—that there are essential differences between impotence and chastity, although the external behavior could be quite the same.
Part 2: Encounter with Francis Crick
When Brenner met Jim Watson and Crick at Cambridge, he says he realized what his life’s work would be. Brenner and Crick shared an office for some 20-odd years.