Dr Alun McCarthy is the European Head of Drug Development Genetics at GlaxoSmithKline. Dr McCarthy is part of a team working on 'pharmacogenetics', a new kind of drug development in which drugs are tailored to individuals' genetic make-up, to reduce side effects.

What is pharmacogenetics?
Pharmacogenetics is looking at how genetic variation affects people's response to medicines. For example, if you take a hundred people with elevated blood pressure and give them the same medicine, some of them will respond very well and some won't. We now realise that quite a lot of that variability is due to the differences of the genetics of the proteins that are involved in controlling the blood pressure and in theory you can apply the science to any disease area. So what we're trying to do is understand what is the variation that affects that response and then get physicians to use that information to help them make therapeutic choices.

What are the implications for future drugs? If you think about how medicines are used at the moment, using the example of blood pressure, a physician will try probably a diuretic first, if that doesn't work they'll try maybe a betablocker or an ace inhibitor, the different classes that are available. With this better understanding, we can actually take the patient in front of the physician and say, well actually they are most likely to respond to this class. Instead of a patient having to go back to a doctor 3, 4 times, they just go a fewer number of times and get effective treatment sooner. So the drugs will still work to lower blood pressure, but we can get to effective treatment sooner. In addition, it's almost inevitable when you give a completely new chemical to people that there will be a percentage of people that will have side-effects. Again, there's quite a good understanding that some of the basis of these adverse reactions could be genetic variation - with pharmacogenetics we can also exclude a specific genetic group from treatment with a particular class of drug that would be likely to cause them side-effects.

What work are you doing at the moment in terms of pharmacogentics?
Here at GlaxoSmithKline we have one example which we're working on quite actively at the moment, particularly around adverse reactions. It's to do with treatments for HIV, many of which have side-effects associated with them. In fact, recently the treatment guidelines for HIV have shifted so that in fact people will be treated later on in the disease rather than earlier, because of the instance of adverse reactions. We're setting up quite a major study to see if we can understand the genetic basis for these adverse reactions, so we can perhaps understand what's going on: for some people who are not going to get those adverse reactions we can then bring the treatment forward in time; for people who are likely to suffer we now get to understand what's the basis of these adverse reactions and we can now design new treatments that won't have these problems. So that's an active programme, but like all these things it doesn't happen overnight, so it'll be a number of years before the populations are found, the study is carried out and the findings are made available. But we're starting now.

How do you respond the people who are sceptical of the significance of the human genome project?
Will the human genome project transform medicine? I think mapping of the genome is bound to revolutionise medicine. It will give us such huge insights and such tremendous tools for research that the impact will be absolutely enormous, I'm convinced of that. But it won't be very quickly, we won't see in 2 years time medicine completely transformed. The time frame for bringing pharmacogenetic changes to healthcare will be around 5 years and for 5 years onwards. In terms of the insights into new medicines, that will take longer because of the research, then the clinical testing, etc, that's actually more than 10 years from having a bright idea to having a medicine. So if we were having this discussion in 20 years time, we would look back and say, yes the genome project has completely transformed medicine. I think there are expectations for immediate translations into benefits and I think that's where people feel it hasn't delivered or it won't deliver.

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