Don't hold your breath over genetics

Has genetics failed to live up to its expectations?

IS IT just me, or has modern genetics failed to live up to expectations? Listening to, and reading about Dr Craig Venter’s latest claims regarding Synthia, the synthetic cell he created and which he claims means life can now be started straight from a blueprint on a computer, my initial reaction was: pull the other one.

A past master at media manipulation, Venter says the technology could be used to modify organisms to make them produce useful medicines or provide a source of energy. He says his research group was working on ways to speed up vaccine production, and his method could make new chemicals or food ingredients.

So a brave new chapter of genetic cures and new compounds is about to be written. Well, don’t hold your breath, because many of the promises made 10 years ago when the first draft of the human genome project was published have not been realised. Although that breakthrough allows us to identify the mutations responsible for a large number of disorders, progress in genetic manipulation as a preventive therapy has been very slow.

Writing in the British Medical Journal recently, Dr James Le Fanu says the realistic prospect of preventing disease through antenatal screening remains limited to the thalassaemias and Tay-Sachs disease. “The ingenious techniques of biotechnology may have given us human insulin, antiretroviral drugs [for Aids], herceptin [to treat breast cancer], infliximab and similar valuable compounds, but they remain the exception,” he says.

But Prof DJ Weatherall believes benefits are already emerging. “One of the first applications was for the analysis of the molecular basis for monogenic disease. Though many of these conditions are rare, it is estimated that 300,000-400,000 babies are born each year with a serious inherited disorder of haemoglobin. The discovery of their molecular basis provided invaluable information about abnormal gene action and led rapidly to their more accurate diagnosis and prenatal detection, greatly reducing births of affected babies in many countries.”

A review of genetics and cardiovascular risk by Kunal Patel and Ross Murphy of the TCD Institute of Molecular Medicine, published in Cardiodiabetes, refers to a number of false dawns in the area. Noting the presence of a range of subtle genetic factors that play a role in cardiac disease, the authors ask: “Can we categorically say that one particular gene or functional molecule leads to increased cardiovascular risk? Not yet, and this is essentially because the technological advances of the past 10 years have rather outstripped their clinical applicability.”

This is certainly my experience at the coalface of everyday practice. Talk of progress in personalised medicine, whereby medication would be developed according to a particular genetic profile, has been well wide of the mark. Having different versions of common drugs, tweaked to reflect individual suitability, seems to have sunk quietly beneath the waves.

Le Fanu goes as far as to suggest modern genetics may be a blind alley. He argues that natural selection means genetics is not a particularly important or modifiable factor in human disease. Rejecting an entirely reductionist approach to human disease, he asks doubters to look at the recent findings of the Genome-Wide Association Studies, whose investigations show that genetics account for less than

5 per cent of the heritability of obesity, diabetes, Crohn’s disease and other conditions.

This may be a criticism too far, especially in the context of clinical geneticists being able to offer more effective genetic counselling based on better information. It allows patients a more informed choice in how to manage their genetic conditions, such as breast cancer associated with BRCA genes or Huntington’s disease.

Maybe we could look to aviation for a useful analogy. It took a long time from Lindbergh’s first Atlantic crossing for trans-Atlantic flights to become routine. It’s a comparison that could usefully be absorbed by showmen like Venter and their unquestioning media acolytes.

mhouston@irishtimes.com