Wednesday, September 3, 2008

The end of the 'all-white' pill

Sep 3, 2008

By Chang Ai-Lien, Science Correspondent

PILLS may come in many colours, but they remain stubbornly white inside.

Until recently, drugs were tested mainly on Caucasian populations, although they are used by patients of every skin colour. Doctors now know that racial differences and their underlying genetic variants can play a critical role in how, or even if, medicines work.

Studies have found, for example, that African-Americans respond poorly to some of the main drugs used to treat heart conditions like beta blockers and angiotensin-converting enzyme inhibitors.

In Singapore, researchers at the National University Hospital (NUH) have found that Indians need different doses of the blood-thinning drug warfarin compared to Chinese and Malays.

The dominance of the all-white pill began to erode about a decade ago. In tandem with the rise of China and India, drug companies turned to trials involving ethnically-diverse populations.

Singapore is playing a pivotal role in this particular transformation of medicine. The NUH study was the first definitive data from non-white patients on the relevance of genetics to warfarin response.

Based partly on that work, the United States Food and Drug Administration made it compulsory to state on warfarin labels that genetic variations could influence how people responded to the drug.

But race as such is old hat. The field of pharmacogenomics goes beyond race. NUH, for instance, is now testing out a formula which calculates precisely how much warfarin patients might need, depending on their genetic make-up, weight and age. Ethnicity is just one factor in the equation.

If it succeeds, this research will have an immediate impact on health care worldwide. It would be a great leap in medicine when treatment can be customised precisely to the individual.

Ethnic diversity, it turns out, provides just a glimpse into a medical future that will rely on the three billion chemical letters that spell out the unique recipe for each individual. The results of a comparison between the genomes of two white men bear this out.

On Aug 19, Nobel laureate James Watson - the co-discoverer of the DNA's structure - and the equally famous Craig Venter who spurred the race to decode the human genome, had their own genomes decoded.

The result: out of six genes known to play key roles in metabolising medicine, Watson and Venter had three which were identical and three which showed variations that could result in different reactions to several common drugs. Their genomes disclosed information that a cursory look at their physical appearance - skin colour - could not.

Professor Watson, for instance, had a mutation in a drug-metabolising gene rare for a Caucasian; it was more likely to be found in an Asian. The mutation meant that pain relievers such as codeine would not work as well on him as on Dr Venter, nor would antipsychotic drugs and certain antidepressants.

Such personalised information will one day render tests based on ethnicity obsolete. But since mapping a genome currently costs about $500,000, race will have to do for now.

Still, the gauntlet has been thrown down: map a person's genome within a week, for less than US$1,000 (S$1,430); develop a test that would be fast and cheap and available to most people. Researchers from the Genome Institute of Singapore, the Institute of Microelectronics and Singapore Institute of Manufacturing Technology have joined an international race to do just that.

When it happens - and experts are predicting it will within a decade - medical treatment based on such information will come with its own set of ethical issues, not least the problems of safeguarding personal genetic information.

But when it happens, hundreds of thousands of lives will be saved just by calibrating the dosage levels of various medication to take account of genetic variations. And as the science advances, people will be pooled according to how their genes would react to, say, a type of heart medication or a specific cancer drug.

Then, race truly won't matter.

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