鈥淚t鈥檚 a history book, a shop manual and, most importantly, a textbook of
medicine,鈥� says Francis Collins, head of genome research at the National
Institutes of Health near Washington DC. 鈥淏ut it鈥檚 written in a language we
don鈥檛 quite understand yet.鈥�
鈥淭he sequence is only the first level of understanding of the genome,鈥� Craig
Venter says. 鈥淭he next steps are clear. We must define the complexity that
ensues when this relatively modest set of about 30,000 genes is expressed.鈥�
As the genome has been assembled, the publicly funded Human Genome Project
and Celera have been cataloguing millions of variations between the thirty or so
people whose DNA was sequenced. The idea is to find variations that cause or
predispose people to different diseases.
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But most faulty genes will have quite small effects, and their influence will
depend on other genes, and on the environment. And according to Jean-Michel
Claverie of CNRS, France鈥檚 national research agency, in Marseille, diseases are
almost never caused by genes going wrong. 鈥淭he overall goal of deciphering
genomic information is not to see which genes are 鈥榳rong鈥� and to cure disease by
gene therapy. It is to understand how normal people with normal genes function,
so we can plan how and where to intervene.鈥�
About 10 per cent of human genes might correspond to potential drug targets,
Claverie estimates. With only 30,000 genes, that would make only 3000 drug
targets, or 30 each for the top 100 pharmaceuticals companies.
That may force companies to think up different ways to develop new
treatments. This pressure, Claverie predicts, could drive the move towards
personalised medicine, in which treatments will be tailored to suit individual
lifestyles and genetic background.
Venter sees things differently. He believes the relatively small number of
genes suggests that the way our cells use genetic information is far more
complex than most researchers thought. 鈥淭here are probably orders of magnitude
more ways for pharmaceutical companies to intervene in cancer and other diseases
[than if we had more genes].鈥�
The big problem now for geneticists is how to unravel such complexities.
Sequencing the genomes of creatures such as mice, pufferfish and rats could
reveal many of the answers. For example, Joseph Nadeau at the Case Western
Reserve University School of Medicine in Cleveland, Ohio, is leading a project
called the International Mouse Mutagenesis Consortium. This aims to mutate every
one of the 30,000 or so mouse genes to see what they do, and then transfer that
knowledge to humans.
And by 鈥渇ingerprinting鈥� the fragments of genes expressed in different tissues
and organs, it should be possible to catalogue splice variants, says Eric
Lander, director of the Whitehead Institute Center for Biomedical Research in
Boston. This would show which variants do what in which organs.
