/ 5 April 2003

Gene game has just begun

Sydney Brenner won the Nobel Prize for Medicine last year and is one of South Africa’s most distinguished scientists. He looked up at the whale skeleton suspended just above his head and quipped: “Now I know how Jonah felt.”

Germiston-born Brenner (76) has been called the “Groucho Marx of science” for his infamous irreverence and his stream of one-liners. He was speaking from a podium at the Whale Well in the South African Museum, Cape Town, in a lecture on Humanity’s Genes.

His lecture, the closing act of the Human Genome in Africa conference, peeked into the future. Carried on the wave of revolutionary genetic research and discoveries under way, it is a future full of possibility, he said.

The sequencing of the human genome “is the beginning and not the end of the game”, Brenner told several hundred guests. “This is the dawn of the human sciences.”

Brenner said it would soon be possible to put the genes of every person in the world into a test tube. But even if only 100 000 human genomes could be captured and analysed, our understanding of disease and human development would be greatly advanced. Such numbers would allow researchers to discount environmental and other factors, and would enable scientists to be much more precise about the workings and frailties of the human body. “A genome is knowledge about the future. It’s like a horoscope, except it’s true.”

Brenner was a child prodigy who taught himself to read at the age of three and who went to the University of the Witwatersrand at 14. Working at a laboratory in Cambridge 40 years ago, Brenner discovered much about the way cells are generated and then destroyed by studying a tiny nematode worm known as Caenorhabditis elegans.

Brenner chose the worm because the adults are complex organisms yet consist of fewer than 1 000 cells. Brenner was soon able to unravel its entire genetic sequence.

This path-breaking work helped lay the ground for the sequencing of the human genome, completed last year. C. elegans was “nature’s gift to science”, Brenner said.

Understanding mental disease was one of the great mysteries still to be tackled in medicine and science. Analysing the human genome would likely provide answers, he said.

Other scientists who attended the conference at the Spier Estate in Stellenbosch pondered the likely effects of research into the human genome. Decisive advances against killer diseases are on the cards, they said.

“The field is exploding,” said Matthew Berriman, a biologist at the Wellcome Trust Sanger Institute, which works with the malaria parasite. “We are beginning to get a handle on a number of important diseases.”

The sequencing of the genome would speed up research, Berriman told the conference. “We cannot underestimate how much it can speed up hypothesis-driven research. It means people don’t have to waste time looking for genes. It also means researchers can data-mine for a particular gene or spot where it is active.”

Part of understanding disease was understanding its history, said Stewart Cole, head of the bacterial molecular genetics unit at the Institut Pasteur in France. Cole, who specialises in tuberculosis, said an estimated one in three people around the world are infected with TB. Southern Africa is particularly hard hit.

Genomic research has enabled scientists to revise earlier notions that TB was a strain of disease that humans had contracted from domesticated animals, Cole said. Genetic mapping suggested the human and animal strains of TB once shared a progenitor, but evolved independently. “Genomics is once again rewriting the textbooks,” he said.

Human genomic research could also explain much about the evolution of skin colour, scientists said.

Michelle Ramsay, head of the molecular genetics laboratory at the University of the Witwatersrand, said early hominids were probably light-skinned under their protective layering of hair. But we probably began to develop a darker pigmentation as hair was lost from the body during evolution and sweat glands became the main thermoregulators.

Ramsay said that pigmentation remained well-hidden in the genome, and the research had not yet yielded the exact relationship between genetic mutation and skin colour.

Adrian Hadland is a chief research specialist for the Human Sciences Research Council