16 April 2019
Sydney Brenner (1927-2019) - A baobab has fallen

Image: http://www.nobelprize.org

(Published - 16 April 2019)

On 5 April 2019, A*STAR - the Agency for Science, Technology and Research, which is Singapore’s leading research agency - announced the death of Sydney Brenner. Those of us who knew, or knew of him, immediately understood the impact of the loss of one of the pioneers of 20th century science. I was transported back to my postdoctoral days in his laboratory. I recalled the times he would visit every two months and engage individually with each member of the laboratory. I had so much to reminisce about while sitting at the University of Western Cape Natural Science Faculty graduation this month and seeing our students about to embark on a scientific journey that will definitely transform their lives. The conversations with Brenner showed evidence of a man who read widely, could engage on any topic and bring it back to the science at hand. It helps to remind ourselves of his immense contribution to science.

Brenner was born a South African of Lithuanian descent who, at the age of 15, obtained a scholarship to study medicine at the University of Witwatersrand (WITS) in Johannesburg. Subsequently, he read for his DPhil at Oxford University in the UK and returned to South Africa for a few years before taking up a position at the MRC Laboratory of Molecular Biology at Cambridge where he shared an office for 20 years with Francis Crick, the co-discoverer of DNA.

Brenner is known for his pioneering work in the field of molecular and development biology. Together with John Sulston and Robert Horvitz, they shared the Nobel Prize in Medicine in 2002 for their work on Caenorhabditis elegans. They studied C.elegans to determine how cells divide and create new functions. Brenner used an Ethyl methanesulphonate to induce mutations in the worm and, in turn, these mutations had an effect on organ development. His findings laid the foundation for others such as Sulston and Horvitz to expand on programmed cell death. These three individuals ushered in a new field of human disease research with C.elegans as a model organism for subsequent genetics research.

Brenner’s best-known contribution to scientific research was in 1961 when he, through cleverly designed experiments, discovered that sets of three bases in the DNA sequence signify the correct string of amino acids that must be used by the ribosomes to assemble proteins. He called these three bases “codons”. He was also responsible for identifying two of the 3?stop codons. His contribution to other discoveries included messenger RNA (mRNA) – the molecule that produces amino acids in the cell.

Sydney Brenner was also renowned for his wit. On one occasion, reflecting on his time at Cambridge and bemoaning administration, he is known to have said: ‘You become a mediator between two impossible groups, the monsters above and the idiots below.”

Following on from his directorships of the UK MRC’s Laboratory of Molecular Biology (1979–86) and Molecular Genetics Unit (1986–91), he established the Molecular Science Institute in California in 1996. In 2000 he became the Distinguished Professor at the Salk Institute for Biological Studies. He continued to divide his time between California and Cambridge until 2004 when he settled in Singapore for health reasons.

He contributed significantly to developing scientific capacity in Singapore, and it was during these years, specifically 2001-2007, that I had the privilege of working and publishing with him as a postdoctoral fellow. He established two laboratories specifically for Singapore graduates who returned from completing their PhDs abroad. This environment allowed young scientists to develop their own research projects and follow through with their ideas. This was in contrast to the more common practice of spending a few years doing a postdoc in someone else’s team and at times not having the space or the scope for personal scientific growth.

Much of the interactions that I had with Brenner during these years strengthened my resolve to persevere with projects even though others might attempt to derail it. The one characteristic I did not imbibe from Brenner was his refusal to use slides during a presentation. He was adamant that slides are used to reflect on the past, and he felt that he was very much investigating new areas of scientific enquiry.

Brenner held strong views on the way we conduct scientific research today. He was opposed to the insane drive to publish volumes of papers as a metric for good science. This was eloquently described by him in his tribute to Professor Fred Sanger (http://science.sciencemag.org/content/343/6168/262.full):

“A Fred Sanger would not survive today’s world of science. With continuous reporting and appraisals, some committee would note that he published little of import between insulin in 1952 and his first paper on RNA sequencing in 1967 with another long gap until DNA sequencing in 1977. He would be labelled as unproductive, and his modest personal support would be denied. We no longer have a culture that allows individuals to embark on long-term—and what would be considered today extremely risky—projects.”

This article and others sparked rebuttal and responses by other scientists who attempted to demonstrate that the NIH grant system would support someone of the caliber of the late Professor Sanger. It was evident that Brenner yet again was able to initiate a broader conversation and cause people to reflect on how we do science, and he did so with insight and carefully chosen words.

In 2014 during an interview with Elizabeth Dzeng on “How academia and publishing are destroying scientific innovation”, Brenner used his wit and humor to draw an analogy with the creation of the world (http://bit.ly/BrennerOnPublishing):

“[Sanger] wouldn’t have survived. Even God wouldn’t get a grant today because somebody on the committee would say, oh those were very interesting experiments (creating the universe), but they’ve never been repeated. And then someone else would say, yes and he did it a long time ago, what’s he done recently? And a third would say, to top it all, he published it all in an un-refereed journal (The Bible).”

Brenner pushed interdisciplinary or maybe even non-disciplinary research. He held to the view that the progress made in biology was due to significant contributions of physicists who knew little about biology. He maintained that ignorance of a topic drives innovation. I appreciated his unconventional approach to building research teams when I joined his and Professor Byrappa Venkatesh’s Marine Molecular genetics team in Singapore. Brenner was not concerned that I had no background in marine science. He would meet with me as he did other lab members every 2-3 months and would be keenly interested in the details of how I used bioinformatics approaches to study the puffer fish (Fugu rubripes) genome. I would get a glimpse of how little I knew when he would open his laptop and take out some computer code that he wrote in a language that I had never seen in my life. What did this encourage you to do? Yet, he always encouraged me, and each team member, and often had us laughing at his funny one-liners. The one I always remember is; “Alan you seem to like this idea of systems biology. When I was your age we called it physiology”.

As a community of data scientists in the African Society of Bioinformatics and Computational Biology who straddle a number of disciplines, may the life of Brenner encourage us to strive for interdisciplinary research that catalyzes innovation and creativity. While acknowledging the importance of publishing our scientific findings, we need to hold our respective academic institutions and funding agencies accountable when they use publications as the overriding metric for innovation and scientific performance.

Hamba Kahle Sydney…

Professor Christoffels is the Director of the South African National Bioinformatics Institute (SANBI) at the Faculty of Natural Science

More about Sydney Brenner: https://www.nobelprize.org/prizes/medicine/2002/brenner/biographical/