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When Ron van Schaik visits his local pharmacy in Rotterdam, he always has two pieces of plastic in his wallet: a credit card to pay for his medicines, and a second card, similar in size and shape, bearing information that will ensure the drugs cure rather than harm him.
The professor of pharmacogenetics at Erasmus Medical Centre, one of the country’s most prestigious hospitals, is one of tens of thousands of Dutch citizens who carry with them the results of genetic tests which show the speed at which 10 different enzymes in their bodies can metabolise drugs.
“You can go to any pharmacist in any small village [in the Netherlands], show the ‘DNA medication passport’ and tell them which drug you need,” says Van Schaik, “and they will know how to adjust the dose based on your DNA information”.
The “passports” are a record of so-called “pharmacogenetic” tests that are ordered by a GP or specialist when a Dutch patient is prescribed drugs for which the information would be clinically meaningful. The costs are covered by health insurance.
The Netherlands is unusually advanced in its approach, but all over the world health systems are becoming aware of the need to take patients’ individual genetic make up into account when prescribing drugs.
As an example, Van Schaik cites Metoprolol, a beta blocker. “If you have ultrafast metabolism for one particular enzyme . . . then you will metabolise [the drug] so quickly that it will have hardly any effect.” An alternative drug would then be considered preferable.
“My estimate is that 80 per cent of the population will, in their lifetime, be prescribed a drug for which the information of just six enzymes on such a card is already relevant [and there is a need] to adjust the dose based on your personal DNA,” he adds.
The drive towards individualised prescribing has been made more urgent by an explosion in the number of approved medicines.
Dr Adrián Llerena, director of the Extremadura University Biosanitary Research Institute INUBE, likens it to the way in which a rise in the number of cars on the road automatically increases the risk of an accident.
“The number of people that die from adverse drug reactions has tripled in the last decade,” he says. “We are facing a worldwide epidemic.”
The problem receives too little attention from politicians and the public, Llerena suggests. Research that he led in his home region of Extremadura found that as many as 28 per cent of people had suffered at some point in their lives from an adverse drug reaction. “It’s a very important healthcare issue that people in general are not very much aware of.”
In June, 2023, the Spanish government agreed that genetic testing must be provided free for patients when a doctor decides to prescribe any one of a group of 65 drugs — and additional drugs were now being added to that list, he said.
One question with which Llerena and other researchers are grappling, however, is how to ensure that the genetic tests do not exclude and disadvantage those of non-white ethnicity.
Researchers want to widen the range of gene variants used in tests © unaihuiziphotography/Getty Images
At the University of Liverpool’s Institute of Systems, Molecular and Integrative Biology in the UK, Professor Sir Munir Pirmohamed is working to ensure that patients who are given a widely-used group of anti-cancer drugs called fluoropyrimidines do not suffer adverse effects due to their genetic make-up.
Some people have a genetic deficiency of dihydropyrimidine dehydrogenase, an enzyme needed to break the medicine down, so a conventional dose “can . . . cause serious toxicity in the body”, he says.
In up to 1 per cent of people “it can actually lead to death because of the side effects,” he adds.
In October 2020 came a breakthrough: the NHS agreed to genotype all people who were due to receive the drug. Since then, about 45,000 people a year have been tested. “If they’ve got one of these changes in their DNA, they get a lower dose”, he says.
However, although the DNA changes affect all ethnic groups, “the four variants [of the gene linked to the function of the enzyme] that we test for at the moment are largely derived from white populations. So we’re not testing for all the other different variants that may occur in other populations”, he adds.
Through work funded by the NHS Race and Health Observatory, which has a mission to ensure racial equality in healthcare, Pirmohamed and fellow researchers have identified one DNA change which was only seen in people of African background.
“We’ve made an application to the NHS that this particular change . . . should be introduced into the panel . . . so that we don’t disadvantage [them],” he says, pointing to census data showing that in the UK about 2.4 per cent of the population is of African ancestry.
Pirmohamed says the argument in favour of the work he and his colleagues are doing is both economic and human. By reducing hospital admissions caused by adverse reactions, the genetic testing programme was “saving money” for a cash-strapped NHS.
But a far greater prize has already been achieved: “I have no doubt that it has saved lives.”