A World Created Mostly in One’s Head

Life-changing breakthroughs in the genetic code and human genome are part of Dr Sydney Brenner’s work, for which he received a Nobel Prize for Physiology/Medicine. Rhodes University conferred an Honorary Doctorate on Dr Brenner on the 12 April at the 2014 graduation ceremony.

At the age of 87 Dr Sydney Brenner remains a hard working researcher and daunting intellect. There’s no rambling in his discussion or indulging in what he now knows that he didn’t know at 20.

“The difference is I now know 66 additional years of life. Your life at any age is what you make of it, and you should continue pursuing things that are new to you,” he says.

He’s equally to the point about his rise to giant molecular biology heights: “I was born at the right time, I knew I had a gift for science, I learned how to use libraries very early on in life – a habit that has remained with me – and I knew how to exploit the opportunities presented to me.”

Life for Dr Brenner started in Germiston on Johannesburg’s East Rand where he was born in 1927 and where his parents settled. Jewish immigrants from Eastern Europe, his father repaired shoes and their first home was at the back of his shop.

While at Germiston High School Dr Brenner discovered the public library, which, like many libraries the world over, was established with funding from the Andrew Carnegie Foundation.

A rather unusual young man, Dr Brenner 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 the Germiston Town Council gave him a bursary of 60 pounds to study at Wits University, where in 1942 he started what was to become his lifelong research career.

While at Wits he lived at home, cycled to the local railway station every morning, caught the train to town, then walked to campus. It was here that he started his lifelong research pursuit in the field that fascinated him most: cells and their functions.

Dr Brenner has been directly involved in genetic code and human genome breakthroughs since the 1950s when he worked with the English molecular biologist Francis Crick on elucidating the genetic code. Crick is widely known as the co-discoverer of the structure of the DNA molecule in 1953, together with American molecular biologist James Watson.

Breaking new ground is no easy journey, and, as Dr Brenner 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.”

He gratefully thanks the many people who have helped him along this passage, including his parents “who would have preferred him to become a surgeon or physician”, and his wife and children “who lived with a preoccupied husband and father”.

Throughout his life he has collaborated with outstanding scientists and kindred spirits. Two especially kindred spirits were Crick and Watson in the United Kingdom whom he met while he was doing his PhD at Oxford University from 1952 to 1954.

“I went to Oxford after completing my medical degree at Wits University in 1951,” he explains. “I must add that 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 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.”

He had also decided that the subject he was interested in pursuing was molecular biology, which did not exist at the time.

He applied to the Department of Biochemistry at Cambridge University but never even received a reply. He was subsequently awarded a scholarship by the Commission for the Royal Exhibition of 1851 and was accepted by Oxford University’s Professor of Physical Chemistry, CN Hinshelwood. In October 1952 he arrived in Oxford to begin his PhD in the Physical Chemistry Laboratory.

Life was not easy at Oxford as there were still food rations in the aftermath of World War II, and Dr 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 in 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 also got married to May Covitz and became a father, worked harder than ever before and longed for the food and warmth of South Africa.

He then applied for 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 Jim Watson.

He returned to South Africa at the end of 1954 – he was committed to do so by the terms of the Carnegie Corporation Fellowship. “I started working on a bacteriophage system that we thought might be useful to solve the genetic code. I also continued to work on some theoretical aspects of the genetic code.”

Crick subsequently helped him to secure an appointment at the Medical Research Council Unit in Cambridge, and in December 1956 Dr 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.”

They went their separate ways in 1976: “The centre point of our interests had begun to diverge,” Dr Brenner explains. “Whereas we were both interested in the nervous system, I was far more interested in finding a simple experimental system, which might tell me how brains were constructed, whereas Francis wanted to know about the complex activities of higher nervous systems.”

Five years later Dr Brenner was awarded the Nobel Prize in Physiology/Medicine 2002 (together with Robert Horvitz and John Sulston) for his pioneering work in understanding the principles of animal and neural developmental using the nematode worm.

On receiving the Nobel Prize he remarked that choosing the right organism to work on (the nematode worm) was as important as choosing the right problem to work on.

His achievements are vast and plentiful, and Rhodes is honoured to welcome Dr Brenner to the University to bestow on him an Honorary Doctorate on the 12th April.

Regarding his Honorary Doctorate (of which he has quite a few) he says: “I believe that a scientist should be judged by the quality of the people he has helped to produce and not by prizes or other honours bestowed on him.

“At the same time I am very happy to accept this doctorate, and, better still, it is free. You should always accept something that is free and how wonderful to get a very high degree for doing nothing. Students have to work so hard to get what I am getting just for turning up!”

Dr Brenner last visited Rhodes 66 years ago when he attended a conference held by the National Union of South African Students (NUSAS) in 1948.

“The National Party came to power in June that year and the thrust was to get students to stand together in the battle against what was to become institutionalised apartheid.”

Academically, Dr Brenner has had ongoing involvement with Rhodes since 2001 through the coelacanth genome-sequencing project. It was completed in 2012 and the first results were recently published in the leading international scientific journal, Nature.

He lent his weight to support a funding proposal for a flagship research project focused on the South African coelacanths and their environment, which is now the African Coelacanth Ecosystem Programme.

2013 was the 75th anniversary since the discovery off the coast of South Africa of the first living coelacanth. Dr Brenner explains that fish and sharks are the representatives of the oldest vertebrates, and that the coelacanth and the even older elephant shark from Tasmania tell us that vertebrates started around 500-million years ago and have survived through this extraordinary length of time.

“If you think about it we descended from those very fish, which, 500-million years ago were already very sophisticated animals with brains and blood and all the attributes that vertebrates have,” says Dr Brenner who is currently working on another aspect of the human genome – trying to find clues to our very early history.

“Lodged in our genes are the molecular sequences of these vertebrates because they gave us their genes. This research is an attempt to reconstruct, theoretically, the remnants of these genes. We want to see what the vertebrates and pre-vertebrates gave us. We want to work out what they could they see and smell, and understand how our brains arose.

“I can already do parts of this – I can, for example, tell you how certain molecules in the muscles arose. But this is a long, long conversation.”

Looking to the future of cell regeneration and whether science can regenerate a new brain for Dr 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.”

After the graduation ceremony, Dr Brenner and his brain will head home, which, these days, is “anywhere” he says.

“I spend time researching at institutes in Singapore, California, Europe…I don’t belong anywhere anymore; I belong in an airport.”

He does own a house though, in a small town outside of Cambridge in the United Kingdom, where he has based himself for 50 years.

At 87 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.”