One of my heroes died! Sydney Brenner, Germiston boykie, Witsie and a real mensch, died. Always a heavy smoker, he only lived one thousand five hundred and ninety five C. elegans life cycles. Or 92 years. He was amazing. Some colleagues called him “the funniest scientist who ever lived.”
So what was he famous for? For his research fellow Caenorhabditis elegans, who is pictured below. And also for RNA. Syd was short, but this colleague was only 1mm long – and transparent. Syd could see right through him . .
Brenner realized he needed a simpler animal to study than the fruit
fly, a standard organism used in laboratories. He settled on
Caenorhabditis elegans, or C. elegans, a tiny,
transparent roundworm that dwells in the soil, eats bacteria and
completes its life cycle in three weeks. That worm has spun off many
developments, starting with the decoding of the human genome.
The worm is, of course, an invertebrate, but Syd said as it was a hermaphrodite worm with occasional males he would call it a PERVERT-ebrate. Using the worm, Dr. Brenner and his colleagues first worked out methods for breaking a genome into fragments, multiplying each fragment in a colony of bacteria, and then decoding each cloned fragment with DNA sequencing machines. His colleagues John Sulston and Robert Waterston completed the worm’s genome in 1998, and they and others used the same methods to decode the human genome in 2003.
Another major project, made possible because of the worm’s transparency, was to track the lineage of all 959 cells in the adult worm’s body, starting from the single egg cell. This feat, accomplished so far for no other animal, made clear that many cells are programmatically killed during development, leading to the discovery by H. Robert Horvitz of the phenomenon of programmed cell death. The topic assumed an importance that transcended worm biology when it emerged that programmed cell death is supposed to occur in damaged human cells, and when that process is thwarted, we call it cancer! The humble worm’s DNA has turned out to be surprisingly similar to our own, helping us understand how our cells grow uncontrollably to cause cancer and why they sometimes die in excess.
For their work on programmed cell death, Dr. Brenner, Dr. Sulston (who died last year) and Dr. Horvitz were awarded the Nobel Prize in Physiology or Medicine in 2002. So the worm was good for him and colleagues would teasingly call him “the father of the worm.” In his Nobel lecture, Syd remarked, “Without doubt, the fourth winner of the Nobel Prize this year is Caenorhabditis elegans; it deserves all of the honor but, of course, it will not be able to share the monetary award.”
Long before he got the Nobel Prize, Dr. Brenner had been the first to conclude that there must be some means for copying the information in DNA and conveying it to the cellular organelles that manufacture proteins. That intermediary, now known as messenger RNA, was discovered in 1960 in an experiment devised by Dr. Brenner and others. Many people, including Dr. Brenner himself, believed he should have been awarded a Nobel Prize for his and Dr. Crick’s work on the genetic code. About his Nobel Prize he said, “In fact, to me this is my second Nobel prize. I just failed to get the first one.”
For years he wrote a tongue-in-cheek column called Loose Ends and later False Starts in which he’d offer advice and comment on matters scientific. To busy scientists seeking a polite way to turn down time-consuming invitations to meetings, he suggested the following reply: “Dear X, I regret I am unable to accept your invitation as I find I cannot attend your meeting. Yours sincerely.”
He held positions at Cambridge and at the Salk Institute in San Diego, where he was appointed, as he termed it, “extinguished professor.”
Insights into the nature of the cell would alternate with his playful scientific inventions, like Occam’s broom — “to sweep under the carpet what you must to leave your hypotheses consistent” — or Avocado’s number, “the number of atoms in a guacamole.” **
For a short time he had been director of the Cambridge Laboratory of Molecular Biology, but he did not much enjoy working as an administrator: “You become a mediator between two impossible groups,” he said, “the monsters above and the idiots below.”
In his last column he decided he’d need another job, writing When one stops doing a job, one should immediately go and look for another one, if only to provide an excuse for not doing all the mundane things one has promised to attend to after retirement, so he wrote a personal service ad: Elderly, white, male, column writer, seven years experience, self-employed scientist, explorer, adventurer, inventor and entrepreneur seeks young, naive, preferably female editor of newly formed scientific journal with a view to obtaining un-refereed access to as wide an audience as possible. Has good title for a column: ‘The Well-deserved Rest.’ Please write, quoting circulation and impact factor.
As well as a good writer he was a great talker, it was hard for any listener not to fall under his spell. He spoke slowly and precisely in a lingering South African accent, his sentences long and perfectly constructed and often ending with a joke.
He tells of abandoning religion when very young on his way to Hebrew school when he had to walk through a rough part of town in Germiston. He got beaten up by a gang. “As I stood there, I said Shema Yisrael, Adonai Elohenu, Adonai Ehad, but nothing came. I got beaten up, nobody helped me and I said forget it. That sort of thing stuck in my mind. To me it was just a lot of nonsense, basically.
**see Occam’s razor and Avogadro’s number for the real things.