Dr Ian Dunham is a scientist working at the Sanger Centre, the UK wing of the Human Genome Project. Dr Dunham heads the team which sequenced Chromosome 22.

What work is done at the Sanger Centre?
The human genome project is a global 15 year initiative to discover essentially the complete set of genes that make up man. So what that means in practice is that we've tried to determine the order of our genetic material, the chemical bases A, T, C and G, along our chromosomes. What we've done at the Sanger Centre is to sequence those bases for about one third of the human genome, the rest of it is being done in an international consortium of labs around the world, the majority of which is actually in the US, but there's always contributions from labs in Germany, France, Japan and even China. The kind of techniques that we're using are we take human DNA, we put it into bacterial cells and then use a series of biochemical reactions to determine the sequence of the bases.

What are the results so far?
First of all, it's important to realise that we haven't completed the sequence yet, what we've done is to make what we call a "rough draft". That means that really we can be sure of about 99.9% of the sequence, but there are still gaps. What we can tell from that rough draft is that there's approximately 30,000 genes in the human genome. There may be slightly more, there may be slightly less, because when we get to the final stages we'll be able to see where we've made errors in the sequence, where we can join genes into one structure, or what was one gene was maybe 2 structures. So we've got a pretty good idea but not a complete accurate figure of the number of genes in the genome.

Fewer genes have been found than was originally predicted. Does this mean genetics is less important than is claimed?
The number of genes in the genome being estimated as around 30,000 was not that much of a surprise to people in the field - over the last 2 or 3 years it had become increasingly obvious that that was going to be around the right kind of number. When people talk say, "Does that mean that we're 'less genetic', or there is less genetic influence on our make up, well the number of genes doesn't actually matter that much - we know that we're genetic because if you look at traits that are passed through from generation to generation it's clear that you're receiving those traits from your mothers and father. What we need to do is explain how those 30,000 genes interact with each other to make up the complexity of the human body - there's obviously a lot of complexity there.

Is disease genetic?
There's a range of influences on human disease, from the diseases that are clearly entirely genetic - so for instance muscular dystrophy, cystic fibrosis - to diseases which are caused by infection - it would seem obvious that things like influenza, malaria, even AIDS are caused by infectious agents. Then somewhere in the middle there are a range of diseases that have influence from genes and from the environment. But it's clear that genes do play a role, so if we look at, say, juvenile onset diabetes, at least 50% of your contribution to getting diabetes actually comes from your genetic inheritance. I'd go on and say even something like the HIV infection has a genetic component as well, because there are certain people who have certain sets of genes who are less likely to become infected with the HIV agent than other people who don't have those sets of genes. So there's a clear range of possibilities between genetics and the environment.

What impact has the work sequencing the genome had on medicine?
I think knowing a complete set of genes that makes up a human being is extremely important for medicine in a number of different ways. Firstly it gives us the power to use DNA technology in diagnosis: diagnosis can be for genetic disease, it can also be for disease that involves genetic material, like cancer, so one can envisage that we will be able to look at sets of tumours and diagnose which ones are the best to have a particular type of treatment, using DNA technology.

Secondly, DNA technology is going to be important in discovering new drugs. We know that there's only about 480 targets for the drugs that are currently used in the pharmaceutical industry - clearly there are a lot more genes that we could target in the genome to try to develop drugs. That's going to be one of the major effects in the next 10 to 20 years. We can also look at how people are susceptible to particular diseases, so in diseases where a considerable component comes from genetics, like diabetes, like heart disease, we can look to see which genes are playing a role in giving that susceptibility and try to assess the risk that individuals have to particular diseases.

Finally, one thing that having the complete set of building blocks does is that it gives an incredible tool to study the biochemistry of disease, to study how disease works - whether it's genetic or whether it's infectious - and to try to pinpoint what molecules are involved to treat the disease, to develop new therapies, to develop new drugs. Knowing the complete set of genes is useful, but on a research level, because it provides with the set of instructions we need to go and study those more complex problems.

An example I've heard used is that you wouldn't go to a garage and expect somebody to start tinkering with your car without knowing what's going on inside. Having got this set of DNA instructions means that we actually have the information there to go on and study how humans work as a whole, and that's the level it's important. And you might not see the effect of that for some years down the road, so it might be a few years before you go into your GP and they start using genetic information directly at the GP surgery but I'm sure it will happen.

What do you think of the idea that the study of genetics might eclipse clinical research?
I think that although genetics is getting a lot of publicity at the moment there is a good reason for that, and that is because it provides you with these basic tools. These tools are going to be used everywhere - they are going to be used in clinical biochemistry, in clinical trials, they are going to be used in all sorts of clinical application when you want to know what is the base level of information in the individuals that you are looking at. So, for example, if you have a clinical trial of a particular drug you are going to want to know what is the genetic makeup of all the people who are involved in that clinical trial, because that will give you fundamental information as to how that trial is working. One thing that is important to mention is that the funding, both in the UK and in the US where the major amount of the genome project was done, was actually on top of what was already provided for biomedical research and clinical research as well. So it wasn't a question of taking away from pot, it was actually adding more money that really has benefited all areas of research.

What is your opinion of the recent media hype about the human genome project?
I actually think that that has been quite good, because it has brought genetics and the kind of information that is being produced by the genome project to public awareness. And if we are to use, as a society, that information in a positive way we need to discuss it as a society, and people have to be aware of what's going on. Even if there are some confusions that are caused by coverage in the media, it's better that those things come to light than that the issue is never raised. So I think media attention has always been good for the genome project.

  < previous   next > Page 5 of 7