The cure is in your genes

IMAGINE it. You suffer from high cholesterol, and your GP wants to put you on a drug to bring down your cholesterol levels. But which drug? There are lots from which to choose - and because we are all different, we all respond to them differently. What works for one person won't necessarily work for you.

Your doctor isn't worried. He wants to prescribe you a statin - a commonly-used drug with few side effects that works by blocking production of cholesterol in the liver.

The trouble is, research has shown that for some people with a certain genetic makeup, statins don't work very well.

So he hits a key on his computer pad and - ping! - the screen brings up a read-out of your genetic code. It tells him that according to your gene profile prescribing you a statin will be a waste of time. He puts you on another drug instead - one that the computer says will be more effective - and within a short while, your cholesterol levels are back under control.

It is a concept known as 'personalised medicine' - the idea of tailor-making medical treatment for each of us depending on our own, individual genetic fingerprint.

Sounds like science fiction?

Maybe. "But many scientists feel that personalised medicines will revolutionise medical care in the future, leading to doctors prescribing the right drug, for the right patient, at the right dose," says Dr Graham Lewis of the Science and Technology Studies Unit (SATSU) at York University.

You don't need to be a brainbox to realise we're all different. A quick look around you will do the trick. From the colour of our eyes, hair and skin to the shape of our face and even our size - tall, short, fat or thin - no two of us are alike. It's one of the things that makes us so endlessly fascinating - to ourselves, at least.

It's our genes that make us different. Imprinted on to the tiny strands of our genetic material (our DNA) is the wealth of information that, from the moment we are conceived, forms the blueprint for the person we grow up to be.

It is tiny differences in our DNA that makes us all turn out so differently from each other - including the way we react to medicines. Because of our different genes, a drug which works for one person will be absolutely useless with someone else - and might even cause a nasty side-effect.

It's a bigger problem than many people realise. "Six per cent of all hospital admissions are adverse reactions to drugs," says Dr Lewis.

Which is where personalised medicine - or 'pharmacogenetics', to give it its technical name - could come in. If we could 'read' a patient's own genetic code, goes the theory, we could check out what their reaction to a drug will be before it is even prescribed.

"There may be a condition where a drug has a serious side effect for a small proportion of the population, so we need to identify which part of the population the patient falls in," says Dr Lewis. "It may be possible to do that by doing a genetics test."

If it is possible, the benefits could be huge: both in terms of patients' health (if doctors knew beforehand how you'd react to a drug, there would be no risk of giving you one that won't work or, worse, one that will land you in hospital) and cost savings for the NHS. Personalised medicine could even make it cheaper to develop new drugs, Dr Lewis says.

The problem is that so far we don't know enough about how specific genes are linked to the way we react to drugs.

That may be about to change. A team of York researchers is taking part in an £850,000 study that may be the first big step towards identifying genes that cause harmful responses to drugs.

Over the next three years, 2,400 patients in Liverpool and Birmingham will be monitored for the way they react to warfarin - a drug commonly used to prevent blood-clots among people thought to be at risk of the condition - and the results will be 'mapped' against the patients' individual DNA profiles.

About 600,000 people in the UK take warfarin. It's an anti-coagulant, which means that it helps stop clots forming.

Getting the balance right is vital. Too little warfarin, and it won't work. Too much, and you could bleed to death inside.

The problem is that because we are all genetically different, our response to the drug is different, too.

"Warfarin is a very useful drug," says Dr Lewis. "But a small proportion of patients suffer serious side-effects, which may be life threatening, and which we may be able to prevent by identifying patients' genetic make-up before warfarin is prescribed."

Dr Lewis says the aim of the study is to try to put patients into categories depending on whether they react well or less well to warfarin - and to see whether these reactions correspond to differences in their genetic profiles. If the researchers can identify a particular kind of genetic profile that causes a bad reaction to warfarin, it could transform the way the drug is used in future.

If the technique works for warfarin, there is no reason why it shouldn't work for other medicines.

Ultimately, it may be possible to identify a number of genetic profiles that are linked to bad reactions to a whole range of drugs - so that if a patient was given a DNA test before being prescribed any of them, doctors could see in advance whether the drug would be effective or possibly harmful.

Just how seriously the government is taking it is proved by the fact that in a white paper published last year - Our Inheritance, Our Future: Realising The Potential Of Genetics In The NHS - £4 million was made available for research into pharmacogenetics.

The York researchers are part of a large team of scientists from across the UK involved in the three-year warfarin project, which is using some of that government money.

Their role will be vital. The use of people's genetic profiles in medical treatment raises all kinds of ethical issues, Dr Lewis says - not least about the taking of DNA samples from patients and the use of these samples to 'read' their individual genetic code.

The job of the York SATSU team, all members of the university's sociology department, will be to interview patients and medical staff taking part in the study, to find out how they feel about the taking of DNA samples and to assess how publicly acceptable such an approach to medicine may be.

"The introduction of genetic testing into routine medical practice raises many questions," says Dr Lewis, "such as appropriate informed consent, confidentiality, and the possible impact of genetic information on other family members.

"So it is important to understand patients' feelings and reactions to this new development.

"For example, will patients see it like any other medical test doctors carry out, or will they attach special significance to the tests because they involve genetic information?

"Pharmacogenetics can provide major benefits for health care by reducing the incidence of adverse drug reactions and helping develop more effective drugs.

"But it's important to find out how both patients and clinical staff react to the introduction of genetic testing into routine clinical practice.

"Hopefully, we can improve the prescribing of warfarin and at the same time learn more about any concerns patients may have about genetic testing and personalised medicine."

Even if personalised medicine is theoretically possible and even if people are willing to accept the idea of their DNA being used to decide what drugs they should be given, it could still be some way off, warns Dr Lewis.

There are all sorts of technical problems to be overcome: not least, the short period of time a GP has to spend with each patient.

Would it really be practicable to carry out a genetic test in that time? Where would the DNA sample be taken? And where would it be analysed?

There is a long way to go yet before your DNA starts doing the prescribing for you.

Updated: 12:19 Wednesday, July 14, 2004