I confess I don’t fully understand what sequencing the human genome means for us. Somewhere between the Secret Of Life and a tall story, it appears. molecular biology, which for 20 years has been on the A level syllabus, wasn’t discovered when I was in the sixth form. It was so simple then: there was Mendel and there were Crick and Watson, and they more or less explained everything.
Now we have mitochondrial DNA, not then known to school text books. We have junk DNA, more respectfully known as non-coding DNA, and now it is widely thought to have functions we don't yet understand. Since it comprises 98% of our genome, that’s a huge potential influence. Then there is epigenetics, which explains – in part – why identical twins reared together don’t always have the same illnesses, careers and taste in boyfriends. Add the enormous effect of environment and lifestyle, and for most of us most of the time what determines our lives has more to do with our phenotype and our environment than our genotype.
Members of the public are already having key genetic markers in their genome sequenced. Advertisements invite them to investigate their ancestry. Y chromosomes being very stable, men, for as little as $199 for 20 markers, can identify hitherto unknown relatives around the world, sharing information through a database. Or they may discover that someone they thought a blood relative isn’t, so this interesting hobby is not without a potential to harm. You can have a test to find out if you have genes from exotic races, but until more genomes have been sequenced you won’t know whether you are glamorously unusual in having, say, Neanderthal genes, or whether everyone else round the dinner party table has them too.
The most common clinical reason for finding out your genetic status is on behalf of someone else, someone as yet unborn or not yet conceived. Counselling and testing in communities at high risk of genetic disease has greatly reduced the incidence of Tay Sachs disease in Ashkenazi Jewish communities and thalassaemia in Cyprus. In India, parents are urged to match thalassaemia tests rather than horoscopes when considering their children’s marriage partners. But ‘blue sky’ testing of everyone for a wide range of genetic conditions would be costly and, as with any screening of low-risk populations, likely to create anxiety rather than avoid disease.
Genome sequencing will change cancer screening and treatment. Till now it has not been possible to predict whether men with prostate cancer will die with it or of it. Now we know that 16 single-nucleotide polymorphisms (SNPs) are associated with aggressive disease, so in future it will be easier to determine who needs aggressive treatment. And their SNPs will help to determine which 20% of women with a BRCA gene don’t develop breast cancer. Angelina Jolie may have reduced her risk by 95%, but major surgery is not without dangers, so determining these SNPs will provide valuable guidance.
Targeted cancer treatments – drugs designed for specific cancer abnormalities – may not be the magic bullet they first appeared to be, but as cancer genetics develops they are going to make a huge difference to the survival and quality of life of – let’s hope – many cancer patients.
There is some enthusiasm for identifying the alleles which influence warfarin metabolism so that warfarin dosage can be better tailored. Great claims are made for strokes and bleeds prevented. But if warfarin dosage is managed following well-established algorithms, the risk is in any case low. And by the time it is feasible to test all patients, warfarin will be last century’s drug.
Testing for specific gene sequences in particular clinical situations clearly has huge potential for good. Mass screening for a group of recessive conditions needs careful consideration of the benefits and costs, both to individuals and to the NHS. Whole genome sequencing is now available for those with a few thousand pounds to spend, and the price will drop. It’s good to know, people say, and doctors shouldn’t stand in the way of patients knowing about themselves. But commercial companies have an interest in people investing in gene sequencing. Some offer pre-test counselling, but many are quiet about the downsides and have no wish to pick up the pieces. The real cost is much more than the price of the test, and what you get is not knowledge but information.
A full genome sequence is like a very thick Russian novel with long chapters on obscure aspects of Russian history. And it’s in Russian. And I can’t help you interpret it since I don’t speak Russian. Even the genome scientists only know a few phrases.
We GPs already struggle to help patients manage the anxiety of not-quite-normal screening tests, and we worry about advising patients with slightly raised risks of ischaemic heart disease. When genome sequencing takes off there will be a lot of fretting. Genetic counselling is a specialised task and not something we are currently trained to do. And it takes a lot of time. Many people understand – more or less – single gene problems like haemophilia, but most conditions are influenced by multiple alleles and SNPs. Judging the clinical significance of these is still in its infancy. And, outside the betting shop, understanding risk is, as we know, very poor.
Gene sequencing provides huge opportunities for prevention and management of disease. And commerce is going to have a huge interest in our genes, to target sales, to weight our insurance, to decide whether we are too risky to employ. We have some time to absorb the implications and to work out how we live with them. Meanwhile, a family tree tells most of us a lot about how our genetic inheritance may influence our lives, and we GPs should bear in mind that, whatever their genetic inheritance, the best thing anyone can do for their health is to stop smoking.
Judith Harvey was a research scientist, ran the VSO programme in Papua New Guinea and taught in a Liverpool comprehensive school before going to medical school. She has been a partner, a salaried GP and a locum, an LMC chair and a long-time supporter NASGP. Her charity, Cuba Medical Link, enables medical students to go to Cuba for their electives.
Judith has now published all her articles from the NASGP website as a new book Perspectives: A GP reflects on medical practice and, well, just about everything…