Professor Kay Davies - Professor of Human Anatomy and Genetics at the University of Oxford. Professor Davies is researching the genetics of muscular dystrophy and is developing solutions for gene therapy in this area.

How is knowledge of the human genome relevant to disease?
What you can do is use the genetic information to look at the disease process, because it gives you the tools and the information to ask the question 'what is the difference between the genes here in a particular disease cell versus a normal cell?'. And that tells you where to target treatment, because it tells you what the important differences are, and what the destructive differences are for a particular disorder.

How will this help for treatment of disease, for example from your own experience of research into muscular dystrophy?
Muscular dystrophy is a disease caused by a single gene deficiency. The most common forms of muscular dystrophy affects mainly boys - boys go into a wheelchair at 12 and usually die in their late teens or early 20s. The sort of treatment we're looking for is trying to replace the gene that's missing or trying to find ways of compensating for it. Replacing the gene itself requires a technique called gene therapy, where you disable a virus like the cold virus, you take the bits out that harm you when you have a normal cold and replace those with the human gene that's missing. Because viruses can infect muscle cells very easily you can then inject that virus into the muscle, the virus then produces the protein that's missing which then produces a good functional muscle. The difficulty is that you will have an immune response to the virus, just as you have an immune response to the cold virus and we have to find ways to suppress that immune reaction. In addition, because you have a lot of muscle in your body and all of your muscles are affected, we need to target all that muscle, both the heart muscle as well as the skeletal muscles in your arms and your legs. So it's still a big challenge, but there are a lot of developments in the field at the moment.

What do you think the overall impact of the human genome project will be?
The impact of the human genome project in medicine is really going to be diagnosis, prediction and treatment. The first thing is diagnosis - for example, you go into your GP surgery and you have a lump in your breast and the first thing for the diagnosis is to be able to take a sample of that tumour and identify exactly what sub-type it is of breast cancer. That will determine what sort of treatment you will have, what chemotherapy you might be put on or, more likely, which gene therapy protocol you will be exposed to: if your particular gene profile for your tumour is over-expression of gene A, they will try and down-regulate - make your cancer produce less of that - to make the tumour regress; if it's B, it will be a different gene therapy. The other thing that you could do within the clinic is determine whether you already have a predisposition to the disease. There are people in the population that are more susceptible to breast cancer than others, and that is partly genetic.

So you could do a genetic screen to determine which particular individuals had a susceptible allele - a marker in their genes - which made them more susceptible to an environmental insult. If you have a genetic predisposition then you can have continual screening. Now, that won't be an absolute answer, it will be 70%, 80% risk, but it gives you the opportunity of modifying your lifestyle, your diet, the way you live or being given drugs which might modify the clinical port. If you don't have a genetic predisposition, then you don't have to do that. This testing is particularly important for things like colon cancer - already there are individuals in families which have susceptibility to colon cancer that previously have had to go back to the clinic on a biannual basis and have an invasive investigation. Now they can have a gene test and half of those people can be told they're not at risk and therefore don't have to go through that process. That not only is good news for the family, it's good news for the NHS, because those resources can be used for something else.

Another advantage of gene therapy is that you can work very closely with the surgeons, and they're getting very much more skilled at directing things to very small areas of the body. So for example in heart disease it may be that the heart surgeon in collaboration with the gene therapist may be able to deliver a little capsule, which has got a gene factory in it, to a particular artery which would keep that artery clear. I think all sorts of applications of a combination of surgery and gene therapy are possible in the future.

Is the recent media coverage too much hype?
The media, I think, have improved in their presentations of the human genome project, but there is a fair amount of hype, there's an expectation that the treatments will be just round the corner. I think you have to remember that the first gene, which was for a blood disorder, was cloned in 1972 and we still can't cure that disease. Having said that, there are preliminary clinical trials for a particular type of treatment for that which does work spectacularly in two or three patients, which tells you we've made one step in a very important progress.

I think the impact of the human genome project on medicine is likely to be enormous, it's just that it'll take a little bit of time to get the results from the lab into the clinic. Even getting a diagnosis into every GP surgery is going to be expensive, it's going to require a lot of automated equipment, it's going to require a lot education of GPs, nurses and so on. So the impact on the 50 year scale is huge, in the 5-10 scale, simply because we have to implement it, is probably going to be relatively small. I think the media just have to get the time scale right, because otherwise people will think that it's going to happen tomorrow and it's not.

Couldn't genetic testing present problems, for example if people are put under pressure to find out if they have a predisposition for a disease?
There is an ethical problem in the human genome project being applied to diagnosis: some people will obviously want to know, they feel very proactive about their health and want to do all sorts of things; there will be others who don't want to know. I suspect personally that if it's something like diabetes most people will want to know because it is fairly simple and straightforward to make a lot of difference.

But if you had a very severe disorder, like Huntingdon's disease, which is an incurable neurodegenerative disorder, then you probably might not want to know. There's got to be very careful counselling here so that you're not forced to want to know. The danger then is that the insurance companies will demand to know and I think we have to educate these companies that those with incurable diseases are a small proportion of the population and we ought to be able to spread the load across that whole population. As long as if you refuse a test you're not allowed to take a million pounds insurance policy, it should work out alright.

What are the potential strains genetic testing could put on the NHS?
Genetic testing and bringing it in to the NHS is a major challenge, because you not only have got to deliver the test, you've got to be able to explain the answer of the test to the patient. I think what we have to remember with genetic testing is that it isn't something you can only go to your GP for. There will be companies, and there are already companies out there, internationally, that will put on their website 'we offer a test for breast cancer, Alzheimer's, and cystic fybrosis'. If you put a mouth swab, put a little cotton bud around your mouth, put it in this little tube, post it to us, we will give you back your genetic profile'.

I think the challenge for the NHS will be those people that decide they do want to know what their genetic make up is, and of course they're always optimistic so they'll put their sample in the post and they won't expect a negative answer back. If they get a negative answer they will be going to their GP and saying, 'Look, I've got an 80% risk of Alzheimer's, what are you going to do about it?'. So I think it's not just delivering what's already available in the NHS now, which is already a challenge, it's how are we going to meet the challenge of that sort of demand as well.

What is your opinion about pharmacogenetics and its potential in treatment of disease?
Pharmacogenetics is where you profile a particular patient group so that you understand better what sort of disease they have. For example, Alzheimer's disease is caused by several different faults, and you need to know exactly which type of Alzheimer's someone has in order to be able to get the treatment exactly tailored for that particular patient. Pharmacogenetics screens the patients first and determines whether they're group 1, 2 or 3 and then you can tailor the treatment. Now, the argument for pharmacogenetics is that if you target the right treatment to the right patient sub-group, then you're much more likely to see efficacy of that particular drug. But these sub-groups will have to be collected very carefully, because they're going to have to have high enough numbers in them to be statistically significant. You're also going to have to develop 3 drugs which potentially are going to be much more expensive to bring to the clinic - all of the optimisation which normally goes on in the drug companies is going to have to be done for each one of those, and the clinical trials are going to be carried out just as rigorously for each. So that is a note of caution of the sheer expense of introducing something like pharmacogenetics.

  < previous   next > Page 3 of 7