Waiting for the genetic revolution
Authors: Douglas Kamerow
Journal: BMJ (2008)

The sequencing of the human genome was completed in 2003. Since then we’ve been told that we’re living in the “genomic era”—the biggest revolution in human health since antibiotics, some say, and the beginning of scientific, personalised medicine. In the United States we’ve spent about $4bn (£2bn; €2.8bn) since 2000 to fund the National Human Genome Research Institute, so it seems fair to ask what we’ve got for our money.

Certainly there have been dramatic improvements in the efficiency of DNA sequencing and other related technologies. Polymerase chain reaction and other amplification techniques have made what was exotic and painstaking work commonplace and quick. And I guess that some indirect applications of genomics can be found in the doctor’s surgery. Human papillomavirus DNA testing, rapid tests for some infectious diseases by polymerase chain reaction, HIV analyses, and other diagnostic laboratory tests have found their way into general practice.

Genomic tools have been used to develop some drugs that specialists use, and more are being evaluated all the time. But most that I’ve heard of are the province of oncologists or ophthalmologists. Given that we baby boomers are all getting older, I suppose I should be happy that new drugs are available for age related macular degeneration, arthritis, and various cancers, but I’m not sure how big a difference they’ve made on a population basis.

Pharmacogenomic testing may be able to help us target specific drugs at the people most likely to benefit from them, telling us who should get trastuzumab (if they can afford it), who is likely to be hypersensitive to which antiretroviral, or which chemotherapy regimen is likely to be most effective. But again this is consultant level stuff.

What about the common, everyday diagnoses—heart disease, diabetes, and other multigene disorders? I hope that there is some new information out about them. Generally when I hear experts addressing GPs on genomics they offer the same stock examples: the woman with breast and cervical cancer in her family history who is referred with her daughters for testing; the man with colorectal cancer at a young age who turns out to have a hereditary syndrome. But we knew about these kinds of things a long time ago—we just didn’t have the exact gene. It comes down to taking a good family history.

Maybe the future lies in the flashy new genetic testing websites that have sprung up, all planning to start collecting our money and DNA this year. Just pay your $995 to $2500, spit into a tube or scrape your cheek, and in four to six weeks you can see your genetic destiny on a special secure website. Apparently the smart money is betting on these companies, to judge from the venture capitalists they have behind them, including Google founder Sergey Brin and Silicon Valley guru Esther Dyson.

These “personal genomic services” allow you to “unlock the secrets of your own DNA.” They can tell you your risk of developing lots of common and less common diseases, in comparison with the rest of the population. The rub, of course, is what to do with these data. All the sites take pains to point out that they aren’t giving medical advice. And most of them don’t report any single gene disorders that are the daily work of clinical geneticists and genetic counsellors. What are you supposed to do with the knowledge that you have a 30% increased risk of Alzheimer’s disease or a 40% less likelihood of developing atrial fibrillation? Change your behaviour? How?

There is precious little evidence that simple knowledge about anything changes people’s health related behaviours. And even less is known about how people’s knowledge of their genetic risks will affect them. The US Centers for Disease Control and Prevention convened a panel of experts in 2004 to assess genetic tests and technologies for their appropriateness in practice. After three years of work setting up a systematic, evidence based process they have just issued their first recommendation. They evaluated pharmacogenomic testing for cytochrome P450 in depressed patients to predict how well selective serotonin reuptake inhibitors would work. Their conclusion: the evidence to recommend for or against such testing is insufficient (Genetics in Medicine 2007;7:819-25).

And what about all the legal and ethical challenges involved in genetic testing, especially the broad genetic surveys? It’s probably not an accident that these new websites steer clear of conventional medical care. What will happen if (or when) insurance companies get hold of our genetic profiles? Legislation that would prohibit discrimination on the basis of genetic risks has been pending at the US Congress for a number of years but never seems to pass. It is no surprise that the US National Human Genome Research Institute has a whole programme devoted to research and policies on what they call “ELSI,” the ethical, legal, and social issues involved in genomics.

This is not to say that progress hasn’t been made or that these discoveries won’t some day revolutionise health care. But the day when the genome is a regular part of the medical record, when personalised medicine is a reality rather than a catchphrase, seems a long way off.

Precious little is known about how people’s knowledge of their genetic risks will affect their behaviour