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Interview Sir David Sir David Weatherall PERSPECTIVE Drug Discovery Today Volume 11, Numbers 13/14 July 2006 interview Sir David Sir David Weatherall Weatherall reflects David Weatherall qualified at Liverpool University, UK in 1956 and, after a period of National Service in Malaya, spent on genetics and four years at John Hopkins Hospital, Baltimore, USA. He returned to Liverpool in 1965, where he was appointed personalized Professor of Haematology in 1971. In 1974 he moved to medicine Oxford, UK, where he was Nuffield Professor of Clinical Medicine until 1992. In 1992 he was appointed Regius Professor of Medicine at Oxford. In 1979 he became Honorary Director of the MRC Interviewed by Ulrike Knies-Bamforth Molecular Haematology Unit, and in 1989 he established the Institute of Molecular Medicine at Oxford (later named Weatherall Institute of Molecular Medicine), of Perspective which he was Honorary Director. His major research contributions, resulting in some 700 publications, have been in the elucidation of the clinical and molecular Tell us a bit about yourself and your basis for the thalassaemias and the application of this information for the control INTERVIEW career so far and prevention of these diseases in developing countries. He was knighted in For the last thirty years, I’ve been in Oxford, first 1987, elected FRS in 1977 and became a Foreign Associate of the National as the Nuffield Professor of Clinical Medicine, Academy of Sciences, USA, in 1990. In 1992 he was President of the British then Regius Professor of Medicine. In 1989 I Association for the Advancement of Science. He became Emeritus Regius Professor founded the Institute of Molecular Medicine here of Medicine in September 2000 upon his retirement, and was appointed in Oxford. Since retirement I’ve been spending a Chancellor of Keele University in 2002. lot of time in the developing countries and did a report on the application of genomics for global health for the World Health Organization and I’ve which people who have talked about persona- diseases and it has already been possible to been interested in trying to apply some of the lized medicine have centred their argument. We target treatment more logically. technology of molecular genetics for problems concluded that a better understanding of We were more cautious as to how the of the third world. genetics and drug metabolism is likely to knowledge of an individual’s genetic make-up improve the efficiency of drug development by would be applied broadly in clinical practice. ‘We concluded that a better under- the pharmaceutical industry. We were a lot more There is this idea that in 20 years time a general standing of genetics and drug meta- cautious about the immediate application of practitioner would have a printout of your bolism is likely to improve the personalized medicine in the clinic. We felt that genome on the desk, and if you came in with a efficiency of drug development by one of the major possibilities in the medium- headache he’d press a button and tell you if the pharmaceutical industry.’ term would be that the genetic analysis of you’re a one- or two-aspirin person. This could be common diseases could well show that what we a long way off – if ever! Take, for example, a You recently chaired the Royal Society now think is a single disease has multiple dif- commonly used drug like warfarin, which we’ve report on personalized medicine. For ferent causes, which would undoubtedly pro- known (for 40 years) has genetic variation in its the benefit of our readers, could you duce more focused and targeted medicines. We metabolism, and we now know that there are at briefly sum up the conclusions of this already have a very good example in the cancer least two genes involved. But nobody has yet report? field, where what we used to think of as one type done a large community study to ask whether it The report revolves largely around pharmaco- of cancer, for example lung or breast cancer, now is cost effective and clinically effective for the gentics because it is one of the major areas in turns out to be a group of several different patient to know their genetic make-up before 576 www.drugdiscoverytoday.com 1359-6446/06/$ - see front matter doi:10.1016/j.drudis.2006.05.007 Drug Discovery Today Volume 11, Numbers 13/14 July 2006 PERSPECTIVE they start the drug. In other words, is the genetic of examples of rarer forms in childhood, where mous level of cost to healthcare. If you could approach to treatment better than what is being defining the precise cause has made rational keep a large number of people out of hospital done at this time, which is simply the monitoring therapy possible. It’s highly possible that certain because you avoid side-effects of drugs it of dose against effect and careful monitoring for diseases of the nervous system are also suitable would probably be cost effective, but until side-effects? for personalized medicine. Because, according to you’ve tested a few drugs in this way we just So we were much more cautious about the WHO, we’re all going to be depressed, and by the don’t know. If you ask me that question in five practical use of pharmacogenetics in the com- year 2020 bipolar depressive illness is going to or ten years time when we know that it is munity. And then, finally, we discussed the be the major cause of ill health, we’d want to be effective for management, as well as in terms organizational and ethical issues: who is going to able to treat it more logically. There has been ofcost,todosimplegenetictestsforoneor hold this genetic information, who is going to do some progress looking at the genetics of two commonly used drugs then you can the genetic testing, who is going to advise the drugs that are used to treat depression and, I answer that question. At the moment, patient? Is it the hospital, primary care doctor, believe, large community trials similar to those we don’t have any idea. Curiously, some epi- nurse or pharmacist? for warfarin have started, so I can see gradual demiologists are advocating that all of us take snipping away at progress in those two common a ‘wonder pill’ to control our blood pressure, ‘A lot of progress has been made in diseases. cholesterol and more – from middle-age defining the genetic variability to onwards. Even this de-personalized medicine drugs, and many drugs are probably Is there anything that can be done to will be very costly. Will we then have to have metabolized by more than one gene.’ accelerate the process of bringing several different wonder pills based on our personalized medicine into the clinic? genetic make-up? Could you briefly explain why, although To my mind, perhaps a slight change in attitude a lot of progress has been made in in the research community and, as usual, more ‘...the day of the blockbuster might personalized medicine, particularly in funding. Although there is some beautiful work be over and [pharmaceutical compa- the field of cancer, you still think that going on in this field, the really difficult stage is nies] will have to reorientate their real progress is 20 to 30 years away? when you take your basic information that a way of thinking.’ We’re just starting to see targeted therapy for drug does have a strong genetic component in this common disease. It’s still too early to say its metabolism and move on to do the boring Would pharmacogenomics, if it was how effective it’s going to be, and to what extent but vital studies in the community, as I was feasible, not just cut up the market and new mutations in cancer cells will lead to explaining for warfarin. make this concept completely resistance to targeted drugs. So I think the full You’ve got to take a large number of people in unattractive to big pharma – who don’t picture is not yet clear. Other disorders, such as the community and either treat them knowing seem to have financial models for drugs heart disease and diabetes for example, are their genetic make-up ahead of time or in the other than the blockbusters? probably heterogeneous as well. There’s a large present way, that is careful monitoring. The aim Yes, there is that danger and the pharmaceutical INTERVIEW environmental component and there are prob- is to find out whether knowing the genetic industry is well aware of it. In the cancer field you ably many different genes that can make you component is cost effective and also patient now find that a drug is, perhaps, only effective in more or less susceptible. A lot of progress has effective. And that’s got to be done drug by drug; a small percentage of patients. This will have to been made in defining the genetic variability to there are no short cuts. be watched very carefully. Governments and Perspective drugs, and many drugs are probably metabo- health agencies will have to come to grips with lized by more than one gene. So, as I explained In the long-term, do you think that the possibility that they might have to come to for warfarin, moving from the research labora- personalized medicine will change the financial arrangements with companies. In fact tory to something that is going to be of day-to- face of medicine and that prophylactic the representatives of pharmaceutical compa- day clinical value is a long time ahead. Because of medicines will become more popular? nies that we talked to admitted that, probably, all the hype since the genome project was Can we actually afford to treat everyone the day of the blockbuster might be over and successfully completed, particularly about its prophylactically and how likely is it that they will have to reorientate their way of clinical value, we needed to get a hold on the this is going to be successful? thinking.
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