/ 7 May 1999

The map maker

Name: John Sulston

Institution: Sanger Centre, Cambridge

Field: Mapping the human genome

Above the reception desk at the Sanger Centre, John Sulston has installed an electronic display, showing the genes of humanity streaming from the sequencing machines in Sanger’s laboratories to the Medical Research Council’s computers nearby. Look at it for a few minutes and you can actually see the very components of the genetic formula for us all.

John Sulston is a cautiously spoken man who wears sandals and sports a beard, not what you expect after reading about the rivalry between him and the American scientist Craig Venter. Sulston and Venter are both sequencing the human genome, but they have adopted different methods. Sulston is funded at the Sanger Centre by the Wellcome Trust, which has built the Genome Campus at a cost of 90-million, while Venter is financed by private enterprise and plans to make as much money as possible for his company, Celera.

The difference between their two scientific approaches is extremely hard for the uninitiated to grasp. Venter is using new automated sequencing machines, which are producing a map of the genome; Sulston says this map will be inferior to the information that is being published on the Internet by the Sanger Centre, and other scientific institutions involved in the Human Genome Project.

Sulston says that Venter’s primary motive is to control a series of patents on information rightly belonging to all humanity. Venter denies this. “The dispute about scientific method,” says Sulston, “may seem like arguing about angels on a pinhead, but I find it a terrible shame that this important moment in human history is being sullied by this act.”

Sulston compares mapping the human genome to an archaeologist attempting to decipher an ancient stone tablet. “You look at all the squiggles and you know there are amazing discoveries to be made. But as you first hold it in your hand, you haven’t a clue what they mean. You need a Rosetta Stone to help you interpret it.”

It is difficult to see how work on worms fits into the biological definition of humanity, but all kinds of creatures help to explain human gene functions. Surprising similarities are being found between genes in widely differing creatures. If a protein works in a particular way in a worm, it is likely to work in the same way in a yeast or a human being.

“We need to know the genes and the proteins that they make. We need to know how the genes are switched on and off in the right place at the right time, how they come together to make assemblies, and how those assemblies come together to make cells, and how those cells make the animal. There is a whole series of levels which are now being worked on. But at the bottom lies the DNA information – it’s like the atomic level.”

Since Venter announced his project, a race has been under way. Last month, the international Human Genome Project, which principally consists of four US laboratories and the Sanger Centre, but also involves 350 smaller labs worldwide, estimated that it would have a working draft of the human genome by next spring. “It’s really speeded things up. As always, competition sharpens people’s minds.”

Although this is an international effort, the Cambridge scientists may be driven by a slightly proprietorial instinct because of the university’s reputation as the birthplace of biochemistry and genetics. Dr Fred Sanger, who won two Nobel prizes for his work there in the biochemistry department – the first for sequencing insulin, and the second, in 1980, for developing the chemistry to read the genetic code – still has an admittance pass for the centre which is named after him. At the age of 80, he regularly visits Sulston.

I asked Sulston what effect the human genome would have on humanity’s view of itself. “There are these big important steps. Galileo, a great hero of mine, took us away from the idea that we were the centre of the universe. The theory of evolution took us away from the conviction that we were a unique life form. And this work will eventually tell us what makes our brains work and therefore our minds. It will tell us what we are.”

Will some important human mystery vanish with this knowledge? “This has never been a problem to me. There are many rainbows within the rainbow. There are bigger mysteries beyond this. One frontier will be to understand our own complex nervous systems. Beyond that we will want to understand how our brains work and give us the sensation of consciousness. We have survived knowing that the earth is not flat; we survived the theory of evolution. Can we survive the understanding of consciousness, I wonder?”