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Sydney Brenner, 1927-2019

A scientific giant, Sydney Brenner has died at the age of 92. He was present at the beginning of molecular biology – while in the chemistry department at Oxford, he car-pooled with Dorothy Hodgkin, Leslie Orgel, Jack Dunitz and others over to Cambridge to see Watson and Crick’s new model for the structure of DNA back in April 1953. And he never looked back. He and Crick ended up collaborating for many years. He was the first to realize that there needed to be such a thing as messenger RNA, and was crucial in working out the triplet-code system for amino acids.

Brenner began to feel that the major problems of early (“classical”) molecular biology were either solved or on their way to being solved, and looked for a way to extend his research into the downstream effects of genetics. He turned to simple model organisms to work out more details of genetic and cellular function, famously choosing the C. elegans nematode (here’s a copy of his letter requesting the inital batch!) This was an enormously productive line of research – when he shared the Nobel in 2002, he cited his choice of organism as one of the best decisions he’d ever made. “Without doubt the fourth winner of the Nobel prize this year is Caenohabditis elegans; it deserves all of the honour but, of course, it will not be able to share the monetary award.

They grow quickly, their bodies are transparent, their self-fertilizing nature makes isogenic populations easy to produce and maintain, they produce a large number of interesting viable mutants – Brenner chose well indeed. He and his co-workers worked out the basic map of the organism’s nervous system and much more – the organism has a constant number of cells (959 in the common hermaphroditic form, 1031 in the rarer males), and the lineage and fate of every single one has been studied in detail. Hundreds of papers a year continue to appear on nematode work, and the little guys have certainly not yielded all their secrets yet.

Sydney Brenner won basically every major award a biologist can win, and is considered one of the founders of chemical biology and other fields besides. I very much regret never having had the chance to meet him in person – he was famously well-spoken, with a wit that sometimes had to be edited out in interviews because it cut a bit too close for editorial comfort. For many years, he wrote a column in Current Biology entitled “Loose Ends“, which I always looked forward to reading. This ranged rather widely, from thoughts about research strategies all the way to advice on the perfect practical joke. I remember that column vividly, and I cannot resist quoting it:

I was visiting the W— Pharmaceutical Company in Japan and at the end of the tour I was taken to a meeting room where everybody had gathered. This company made a Japanese herbal remedy concocted from fermented garlic, which was widely used. It was called something like Lycopentane, which sounds like lighter fuel for werewolves, and was so vile tasting that it had to be taken in gelatine capsules. The dose was large, however, and the capsules could not be filled and sold without leaking, so a kit was provided with a dropper bottle and empty capsules.
I said I would like to try the remedy and with much amusement a kit was brought in. I filled a capsule and swallowed it. As it went down, I gave a strangled cry, followed by a gurgle, rolled off the chair and lay motionless on the floor. Through one half-opened eye I observed the reactions of my hosts. They were thunderstruck; the blood had drained from their faces and in the few seconds that I lay there, I could see running though their minds questions such as how to dispose of the body and what to do about my colleague who had observed the event, also with surprise.
The laughter when I rose from the floor was almost hysterical, and, in the end, everybody enjoyed themselves. I am quite famous in Japan for this and every now and then, somebody comes up to me, shaking their head, nudging me and saying “W— Pharmaceutical Company.”
This is a man who will be missed. Here’s to his long, interesting, and productive life!


16 comments on “Sydney Brenner, 1927-2019”

  1. Retired mobiol says:

    I was quite fortunate to meet with Sydney several times in my first job over 30 years ago. He was a consultant that periodically came to our site. We could get 1:1 meetings with him and discuss our projects or anything else that might come up . It was a great experience. He had excellent insight and a great whit. He did, however, also have a great memory so you had better have followed up on his suggestions before he next came by!

  2. Brad Smith says:

    Two memories of Sydney: His comment one year at ASCO that every time we treat a patient we are running an experiment that we should learn from and Don Comb’s retirement symposium at NEB with multiple Nobel Laureates. Sydney’s brilliance outshone them all.

  3. pete says:

    A great mind – and wickedly funny sometimes – I heard him speak several times over the many years. I took some special care in giving a close read to his primary pubs + opinion pieces starting from my tender days right on through a bioscience career.

    The question he crystallized in my head very early on continued to present itself every day in the lab: Do we need to understand the encompassing details of every constituent molecule in the body in order to understand (or make predictions about) how the body works ?

    1. eub says:

      Did he have responses to that question?

      At least as a provocation, I would say yes, we do need to understand everything to understand anything in biology — at least to underscore the contrast with physics or computer science. Biology always seems to surprise us in this direction.

      1. pete says:

        I’d have liked to ask him in that in his still-lucid, later years.

        But I do remember him saying (much earlier on) something to the effect that as the major pillars of molecular biology nearer to being established, the rest would be just filling in the details.

        I’m pretty sure he’d have been the first to agree that that POV was presumptuous, given how components of cell biology once dismissed as “housekeeping” have since been invited upstairs into the grand hall as prime movers & shakers.

      2. Hap says:

        I wouldn’t have assumed you needed to know everything, just the important things. The problem with that (as noted below) is that we don’t seem to know what the important things are, and if you don’t or can’t know that, then you need to know everything. (“The first rule of good tinkering is don’t throw anything away.”) Biology has lots of unknown unknowns.

        1. pete says:

          “The problem with that (as noted below) is that we don’t seem to know what the important things are, and if you don’t or can’t know that, then you need to know everything.”

          …sometimes (a lot of times, in fact) it seems that way. Fascinating expedition, though — but daunting.

  4. Kenneth Crook says:

    Ah yes. Loose Ends. I’d forgotten all about that. Always worth reading.

  5. luysii says:

    Brenner’s work with C. elegans was great, and we now have a complete wiring diagram of its 302 neurons and their 7,000+ connections. However we don’t understand how it works — see an earlier post of Derek’s —

    The situation with the human brain is far worse (and not just because it’s 10^7 – 10^8 larger in terms of neurons and synapses), but for ‘improvement’ such as volume neurotransmission, electrical synapses etc. etc. For more details see —

  6. HFM says:

    I met the man once, when I was 17. I had no idea who he was. This was at a science fair awards ceremony – honestly, I thought he was one of those eccentrics who hang around universities, attracted by the intellectual stimulation and the poorly guarded free food.

    I don’t even recall what we talked about, but once he was out of earshot, I expressed my surprise. That scruffy old man was really smart! Everyone else laughed at me. Yes, you dimwit. He just won the Nobel Prize!

    May there be more where he came from.

  7. jbosch says:

    I had the fortune to meet him after he just had landed in Munich to give a talk at the Max-Planck not knowing that he had become a Nobel laureate while in the air.

    Needless to say that the talk had to be moved from a “regular” conference room to the largest available on campus in Martinsried. His dry comment was along the lines “it’s about time …”

  8. haw says:

    Just going through loose end now- thanks for the tip. What an absolute joy to read.

  9. Julio says:

    His book, My life in Science” gave me the courage to pursue my independent career as a scientist and to stay always “out of the frequency” of what is happening now, as he said, to fid new problems and innovate.

  10. exDrugDiscoverer says:

    As someone that used to work in ‘omics in early discovery while studying biology Sydney’s view on systems biology helped me rediscover humility. May he RIP.

  11. Metastasis says:

    I heard a talk where Brenner said, “Never forget to touch the meat.” He meant something critically important in the modern world: do not lose sight of the actual animal and its biology through a reductive view.

  12. Taco DEL says:

    Also worth pointing out that he (with Lerner) proposed the idea of DNA encoded chemistry.

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