Nobel laureate Sydney Brenner escaped poverty in his native South Africa – and apartheid, to which he resisted by raising funds for black students – to become a key figure in the golden age of molecular biology . With the help of a translucent worm, the scientist, who died at the age of 92 in Singapore, provided vital clues to understand diseases such as cancer, Alzheimer's and AIDS.
When James Watson and Francis Crick clocked the double helix structure of the DNA molecule in 1953, decades of scientific discoveries followed in which Brenner's discoveries were fundamental. Not the least of these was the "central dogma" of biology: the idea that our DNA code instructs the construction of proteins that sustain life in our cells.
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For nearly 40 years, Brenner worked at the molecular biology laboratory MRC (Medical Research Council) in Cambridge, where he shared an office with Crick. A sign that they held – "Reading the mind rots" – has denied their dazzling work in pushing the boundaries of their profession.
Showing such irreverence, Brenner presented a manuscript to the Royal Society of London with a false reference – "Leonardo da Vinci (personal communication)". When Brenner obtained his second Lasker Award for medical science, Nobel laureate Joseph Goldstein described it as "shameless" personified.
Brenner's biographer, Errol Friedberg, noted that his contempt for the rules made him the "scourge of universities and administrators of institutions". All flashpoints, however, tended to be obscured by the great progress made by Brenner in molecular biology.
At the Cambridge laboratory, at the end of the 60s, he undertook an ambitious search for a model organism to study the development of complex animals at the genetic level – an unexplored territory at the time. He found his match in Caenorhabditis elegans, a millimeter-wide transparent worm that would have led him to the 2002 Nobel Prize in Physiology or Medicine for "seminal discoveries on the genetic regulation of organ development and programmed cell death", which "shed new light on the pathogenesis of many diseases".
Later affiliated with the Molecular Sciences Institute in Berkeley, California, Brenner shared the honor with John Sulston of the Wellcome Trust Sanger Institute in Cambridge and H Robert Horvitz of the Massachusetts Institute of Technology.
With the three men as a champion, C. elegans pushed forward a new understanding of how our cells are programmed to proliferate, specialize and die. He became the first animal to have sequenced his complete genome, an important precedent for the Human Genome Project.
The DNA of the humble worm turned out to be surprisingly similar to humans – helping to understand how our cells grow uncontrollably to cause cancer and why they die in excess in neurodegenerative disorders, heart attacks and AIDS . Choosing the right animal to work in biology, Brenner saw, was as important as asking the right questions.
"Without a doubt," the Nobel Prize winner of the year was in his Nobel conference Caenorhabditis elegans; deserves all the honor but, obviously, it will not be able to share the prize money ".
Sydney Brenner was born in Germiston, South Africa, in 1927, to Jewish parents who emigrated from Eastern Europe. His father, a cobbler, could neither read nor write, although he could speak English, Yiddish, Russian and, after moving to South Africa in 1910, in Afrikaans and Zulu.
The young man's first home was in the back of his father's shoe store, two rooms that resembled perpetually of leather stinkers. The public library became a refuge, and it was there that it found 1929 The science of life, the volume in three volumes, written by HG Wells, who first turned it into biology.
Brenner entered the medical school at the University of the Witwatersrand in Johannesburg, at the age of 15. He did not like clinical practice, attracted by the research laboratory. In 1952, he won a scholarship to study with the chemist and future Nobel laureate Cyril Hinshelwood at Oxford. He received a doctorate in 1954.
In England, Brenner met with May Covitz Balkind, a fellow student from Witwatersrand who had traveled to London to study psychology. They were married from 1952 until his death in 2010. Survivors include three children and a stepson.
Under Hinshelwood, Brenner joined a thriving group of thinkers who were forming the new field of molecular biology. On a cold morning, in April 1953, he and three colleagues crowded into a car and went to the Cavendish Laboratory in Cambridge, England, to see the model of Watson and Crick's double DNA helix with their eyes .
The moment was "the watershed in my scientific life," Brenner wrote in his biographical notes for the Nobel Prize. Brenner joined the Cavendish Lab in 1957 and, in a collaboration with Crick that year, deduced that the DNA was read as a triplet code, with each unit of three bases (named A, T, C or G) corresponding to one of 20 protein blocks. The laboratory formally joined later in the biology groups of the university to become the MRC laboratory of molecular biology.
With the future Nobel prize winner François Jacob at the Pasteur Institute and Matthew Meselson at Harvard, Brenner demonstrated in 1961 the existence of the messenger RNA. The molecule, they discovered, is a key intermediary between DNA and proteins – a translated version of the genetic code that is sent to direct synthesis in cell protein production factories.
Brenner's greatest abilities, as described in his 2001 memoir, My life in science, they were in "getting things started". For him, the fun of science was in the "opening game".
And so with a basic knowledge of DNA developed at the end of the 60s, he turned his attention to a new project: to study the development, in particular the brain, of higher organisms. After abandoning the more exotic animal models, Brenner tried to grip, recruit his children and friends to collect soil from their backyards and holidays abroad. It is established C. elegans: a rapidly growing, self-fertilizing, transparent creature with a simple nervous system that could be seen under an electron microscope.
From tip to tail, Brenner's team mapped the entire cellular anatomy of the brain and spinal cord of the worm. Worms with strange morphologies or behaviors, such as abnormal locomotion or feeding, were of particular interest.
From these samples, Brenner worked backwards to understand which defective neurons could cause behavior, and therefore which genes in those neurons had been mutated.
At Cambridge, Brenner advised John Sulston, who developed techniques to track everything C. elegans cell divisions from the fertilized egg adult 959-cells. The enterprise has yet to be repeated in another organization. Horvitz, also a researcher with Brenner's team, identified the key C. elegans genes involved in the control of cell death.
In addition to his research work, Brenner held management positions at the Medical Research Council in Cambridge. In 1996, he founded the Institute of Molecular Sciences in Berkeley, California. He remained director there until 2001, when he joined the Salk Institute for Biological Studies in La Jolla, California. His old friend Crick, who died in 2004, also worked at the Salk Institute.
Brenner also helped launch the Molecular and Cell Biology Institute in Singapore, where he became an honorary citizen.
In the 90's, Brenner wrote a column in the journal Current biology called "Loose Ends" (later renamed "False Starts"). The most popular of his pieces were his columns "Uncle Syd", a series of letters to his imaginary consultant "Dear Willie", with practical joke ideas and career advice for the young scientist as he passed from graduate student to retired professor .
To the committed scientists looking for a polite way to reject expensive invitations in time for the meetings, he suggested the following answer: "Dear X, I regret not being able to accept your invitation because I can't attend your meeting. Best regards. "
His colleagues praised him as "the funniest scientist I ever lived", a title that Brenner much preferred to the "father of the worm". Behind the witty exterior was a scientist who fervently believed in solving problems but who knew when to go through an enigma and leave it to the younger minds to play with.
"I firmly believe that ignorance is important in science," he said The New York Times in 2000. "If you know too much, you start to understand why things will not work. That's why it's important to change course to gather more ignorance."
Sydney Brenner, a South African biologist, born January 13, 1927, died on April 5, 2019
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