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PANORAMA: 1998

Britain to Decode One-Sixth of All Human Genes
by John Newell, former Science Editor, BBC World Service

A MAJOR centre for genetic research, the Wellcome Trust Genome Campus, was formally inaugurated at Cambridge in eastern England. The new centre plans to decode one-sixth of the human genome, the complete genetic blueprint for building a human, by 2002. This means it will make a massive contribution to the international Human Genome Project, which aims to decode the entire human genome by the same date.

The gene sequencing centre on the campus is named after Fred Sanger, the Cambridge scientist who won two Nobel prizes for discovering how to sequence first proteins, and then DNA. The sequences of bases, chemical sub-units along the length of DNA in genes, are what determine the structures of the protein molecules the genes are the blueprints for.

The scientists in the Sanger centre aim to find the exact sequence of five hundred million of the three thousand million bases which make up human DNA. Along the way they will find the exact structure of perhaps 20,000 of the roughly 100,000 genes which together form the plan for building a human being.

Once the "Book of Man'', as it has been called, has been written then the information in it will be there for future scientists and doctors to use for all time. Using it they will be able to develop more and more sophisticated techniques for gene therapy and genetic engineering.

The Director of the Sanger Centre is Dr John Sulston. He sees it as very much part of an interactive group. Says Sulston "It's styled like a small university campus and the idea of a campus is that you have independently growing institutes which are complementary to one another, so the whole is greater than the sum of the parts. So here there is the Sanger Centre, there is the European Bioinformatics Institute which stores huge masses of data, and the Human Genome Project Resource Centre which supplies technical know-how to all the several labs in the United Kingdom who are involved in gene sequencing. And there is a conference centre created in and around a 200-year old listed manor house."

From the beginning of the Human Genome Project there has been generally good cooperation between different labs around the world involved in sequencing human genes. It is an expensive process, and no-one wants to waste time and money duplicating another lab's work if it can be avoided, though understandably there has been intense competition to work on some areas of the genome which are known to have, somewhere hidden in them, genes of special medical interest. Now people from the principal labs involved around the world have an annual meeting to sort out who does what.

Human genes are arranged in twenty-three pairs of microscopic rods, chromosomes, found in all the cells of our bodies with the exception of the reproductive cells, where the pairs are reduced to single chromosomes which recombine into pairs when a sperm fertilises an egg. The chromosomes have been divided up between different labs. John Sulston's team has undertaken to sequence a large fraction of chromosome 22, the whole of chromosome 1, and much of the female sex chromosome the - X chromosome.

"There's an advantage in taking on these vast tracts of DNA in advance, because one can prepare the way," says John Sulston. "Chromosomes contain between one and two hundred million bases each, and this is not something you can attack all at once. You have to break it down and go through a mapping operation, in which the broken pieces of the chromosome are sorted out rather like a jigsaw puzzle. And you then take a series of such pieces and do the sequencing job."

The Sanger Centre's target is to accelerate up to a point where they are sequencing about one hundred million bases a year, two million every week. International collaboration is close and friendly but there is also an element of sporting competition, a race to go fastest. "Of course there is," says Sulston. "The better we know a lab the harder we compete!" The BRCA gene predisposing to breast cancer is among those that have already been pinpointed at the Sanger Centre, as more recently has a gene for ovarian cancer. Identifying such genes helps in early diagnosis and early treatment of cancer and other diseases. Later it will hopefully lead to radically new treatments.

But, says John Sulston: "Sequencing is done for reasons which go beyond the immediate biomedical benefits. If you want to look at a car or a television set you need a workshop manual. Having the complete set of instructions for building a human body is the foundation for an excellent workshop manual. It will be the basis for the much longer task of finding out exactly what they all do.''

Dr John Sulston, Director
Sanger Centre, Wellcome Trust Genome Campus, Hinxton Hall
Cambridge, United Kingdom, CB10 1SA
Telephone: +44 1223 49050/1/2
Fax: +44 1223 495054

  

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