Why Is It So Difficult to Translate Genetic Breakthroughs into Clinical Benefits?


The enormous, even exponential, advance in the understanding of human genetics over the past three decades has so far yielded much less improvement in clinical results than was once hoped. It has proved more difficult than anticipated to translate biological knowledge into clinical benefit.


This is not, of course, to say that there have been no benefits at all from the advances in genetic understanding, particularly in such fields as prenatal counselling. Another superficially promising field is that of pharmacogenetics, that is to say the prediction of responses to medicaments according to the patients’ genetic type. This is very important, for hitherto it has proved difficult to predict whether a patient will respond positively or negatively to a given treatment, and whether he or she needs a higher or a lower dose to produce a desired effect.

The latter is particularly important in the case of treatment with anticoagulants (blood-thinners) because a therapeutic dose is usually so close to a dangerous dose. If we could predict who needs what dose rather than, as at present, proceed essentially by trial and error, it would be of great advantage to patients who need anticoagulation.  They would receive the benefit of anticoagulation – fewer heart attacks and strokes – without the risks of complications such as cerebral and other bleeds.

Three trials of attempts to tailor doses of anticoagulants according to the patients’ genetic type have been published in a recent edition of the New England Journal of Medicine. The authors compared prescription of anticoagulants by the normal methods with determination by genetic type. The results of the three trials were contradictory.



The main aim in all three trials was to ensure that the patients’ tendency to form clots, as measured by something called the INR, came within the internationally agreed desirable range for patients who need anticoagulation because of their increased risk of thrombosis leading to stroke or heart attack. One of the trials found that prescription by knowledge of the patients’ genetic predisposition to respond to anticoagulants in a certain way improved the doctors’ prescriptions and two others that it did not. In any case, the effect was comparatively small.

However, in all three trials there were fewer cases of haemorrhage or untoward bleeding among those who were treated according to their genetic predisposition than among those who were treated in the normal hit and miss fashion. This is important because the major danger of anticoagulant therapy is that the patient will bleed to death. The results of the trials, then, are not the end of a road, but the beginning of the end of a road.

Whenever doctors in ordinary clinical practice read of such experimental results they are apt to ask whether they have much, or indeed any, bearing on their daily work. The answer for the moment must be “No.” Anticoagulation is a small aspect of most doctors’ clinical existence, but while anticoagulation is peculiarly susceptible in theory to improvement by analysis of genetic predisposition of the patients who need it, one could not say that these trials are so compelling that they will alter how most doctors proceed in the matter of anticoagulation. In principle, however, it would be desirable for doctors to be able to predict the response of their patients to the drugs that they prescribe.


The value of pharmacogenetic analysis is in any case limited because genetic predisposition is only one of the factors that affects how a patient react to the drugs his doctor has prescribed for him. In practice such factors as weight, sex and compliance – the degree to which he carries out his doctor’s instructions – are very much more important.


images courtesy shutterstock /  vitstudio / Sebastian Kaulitzki


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