Profile: Sydney Brenner

A LUCKY ACCIDENT

Nobel laureate DR SYDNEY BRENNER has devoted his long career to understanding the story of life

BY HEATHER DUGMORE

Who are we? Where did we come from? Where are we going? These giant questions are the life work of Dr Sydney Brenner (BSc 1945, BSc Hons 1946, MBBCh 1951, DSc honoris causa 1972), pioneer of modern molecular biology. It’s said of him that no one better understands genomes and evolution.

Genomes are an organism’s complete set of DNA, or genetic material – its instructions for life.

From Brenner’s standpoint there’s no room for self-importance as he attributes all evolution to chance. “It is not purposeful. There is no creator,” he says. “Our main conclusion from studying the history of genomes is that all the major changes, from prokaryotes to eukaryotes, from unicellular to multicellular, from invertebrates to vertebrates, from apes to humans, are the products of lucky accidents that could not have been predicted.”

Neither could it have been predicted that he would still be a leader in genetics at the age of 92. He is currently scientific advisor at the Agency for Science, Technology and Research (A*STAR), Singapore, and adjunct professor at the Lee Kong Chian School of Medicine, Nanyang Technology University, Singapore.

Though physically frail now, he works relentlessly. “I do not do anything but work. I am beyond all those other things,” he says.

In 2016, Brenner conceived the idea of a lecture series covering 10-billion years, from the origin of the universe to the changes modern humans are making through science, technology, language and culture. This Evolution Club brought 24 renowned scientists and thinkers to Singapore “to discuss evolution in all its variety and complexity”.

The lecture series culminated in a musthave science book for general readers, the recently published Sydney Brenner’s 10-on-10: The Chronicles of Evolution (published by Wildtype Books and edited by Dr Shuzhen Sim of Wildtype Media Group and A*STAR’s Dr Benjamin Seet).

Harvard professor George Church’s evocative description is that the book “throws ten logs on the fiery topics of evolution” and offers “many insights into the near and far future”.

The questions that still absorb and drive Brenner are about things like how our brains work, and the impact of new technologies. “Will genetic engineering allow us to create new sources of food, and will we be able to create new minds in computers? These are new elements in a complex world, and they will bring about new changes.”

KNOW THY WORM

Dr Sydney Brenner developed new methods for DNA sequencing and was awarded the 2002 Nobel Prize in Physiology/Medicine (with H Robert Horvitz and John E Sulston) for his work on a model organism for understanding human biology and programmed cell death. On receiving the prize he remarked that choosing the right organism to work on (the nematode worm Caenorhabditis elegans) was as important as choosing the right problem to work on. Brenner linked specific genes to specific effects on organ development.

ENDLESS QUEST

Life for Dr Sydney Brenner started in Germiston. As a schoolboy at Germiston High School, Brenner discovered the public library and became obsessed with biochemistry. He read everything he could find on the subject and tried to discover why flowers have their distinctive colours.

At age 15 he received a bursary of 60 pounds from the Germiston Town Council to study medicine at Wits, and he enrolled in 1942. He lived at home, cycled to the local railway station every morning, caught the train to town, then walked to campus.

“I was not a good medical student and had an erratic career, brilliant in some subjects, absolutely dismal in others. By then I had already decided that I wanted to pursue a research career in cells and their functions and that I needed to go abroad because I would rather be a small frog in a big pond than a large tadpole in a big pond. South Africa was also very isolated then and the politics were not acceptable.”

In October 1952 he arrived in Oxford to begin his PhD in the Physical Chemistry Laboratory. Molecular biology as a subject did not exist at the time.

Life was not easy at Oxford in the aftermath of World War II, and Brenner and other “colonial” students were treated as outsiders. Fortunately he made some firm friends with fellow outsiders like Jack Dunitz, a crystallographer, and Leslie Orgel, a theoretical chemist, both of whom remained lifelong friends and colleagues.

“We had many discussions on DNA, for I had come to Oxford with two half ideas, both of which were more than half wrong,” he recalls. “One was a way of working out the structure of DNA using dyes and the other was how nucleic acids could participate in the synthesis of proteins.”

In April 1953 his life changed when he heard about two researchers at Cambridge, Francis Crick and Jim Watson, who had solved the structure of DNA. He immediately headed over there to see their model. “This was the watershed in my scientific life. The moment I saw the model and heard about the complementing base pairs I realised that it was the key to understanding all the problems in biology we had found intractable – it was the birth of molecular biology.”

During this time he married May Covitz, became a father and was awarded a Carnegie Corporation Travelling Fellowship, which took him to the United States to visit other laboratories on a drive across America with Watson.

Crick subsequently helped him to secure an appointment at the Medical Research Council Unit in Cambridge, and in December 1956 Brenner and his family left South Africa for England.

“I spent 20 years sharing an office with Francis Crick and many new and exciting ideas (both right and wrong) were generated from our conversations.”

Breaking new ground is no easy journey. As he says in his autobiography A Life in Science, published in 2001: “Living most of the time in a world created mostly in one’s head does not make for an easy passage in the real world.”

Looking to the future of cell regeneration and whether science can regenerate a new brain for Brenner to extend his extraordinary life, he replies: “Cell regeneration is already happening but it would take 20 years to programme a new brain for me – so there is no point. Fortunately the existing one is surviving and that is good.”

At 92 he regards his own mortality with respectful indifference: “I live, and one day I will stop; that is all.

“Until that day I will continue to be excited by scientific research. Science is something one is tied to for life, and the endless quest for knowledge will continue as long as humans exist.”

SYDNEY BRENNER INSTITUTE FOR MOLECULAR BIOSCIENCE

The Sydney Brenner Institute for Molecular Bioscience at Wits is a multi-disciplinary research institute which investigates the molecular and genomic aetiology of diseases among African populations. The institute aims to enable the development of solutions to some of Africa’s greatest health challenges.