Genetic markers: The dilemmas of discovering destiny
The advantages of this technology are manifold; not only will it allow those identified as being high-risk to modify their lifestyles, tackling those behaviours such as drinking and smoking which would further elevate their chances of developing the diseases, and be closely monitored for early symptoms, it could also lead to the development of new drugs for hard-to-tackle cancers.
It is hoped the tests, which have come about as the result of four years’ research by more than 1,000 scientists, will also reduce the need for mass breast screening, a controversial initiative which, while saving lives, also leads to unnecessary diagnosis and surgery, as mammograms cannot distinguish between those who have a potentially fatal form of the disease and those who may never develop any symptoms.
With 80 new inherited regions of the genetic code which increase an individual’s chances of breast, prostate and ovarian cancer now identified, doctors believe it will be possible to single out and monitor the one man in 100 who has a 50 per cent chance of developing prostate cancer and the one woman in 100 with a 30 per cent chance of developing breast cancer. Tests for breast and prostate cancer are likely to be trialled within 18 months, with a test for ovarian cancer taking slightly longer to develop. No wonder scientists, including Professor Alan Ashworth, chief executive of the Institute of Cancer Research, are describing the discoveries as “a game-changer”.
Yet, like every development in genetics, news of the saliva test brings with it a fresh wave of ethical, psychological and philosophical dilemmas centred on the potential impact of being able to glimpse one’s medical destiny. Ever since the Human Genome Project (the attempt to chart the sum total of the hereditary information in a human being), began in 1990, the same question has reared its head repeatedly. While highlighting cancer risks may have benefits for society as a whole, reducing the financial burden on the NHS, is it always good for us as individuals to be told what health problems may lie ahead?
The question is particularly potent when you consider how complicated a science genetics is. Important though they are, the latest discoveries account for only 40 per cent of the risk factors associated with the three cancers. Since most diseases are caused by an inextricable mix of genetic and environmental components how accurate can any test be?
Then there is the issue of access to the information itself; although there is currently a voluntary moratorium on insurance companies seeking the results of genetic testing (other than for Huntington’s Disease), how long will it be before they start demanding such information and hiking up premiums for those with an increased risk?
But there are also deeper philosophical questions raised by the vagaries of the human condition. For example, how well-equipped are any of us to deal with information about risk? “Understanding actual risk is not something any of us are very good at. If we were, we wouldn’t do the lottery or put our money on a horse, so even in our ordinary daily lives we do things which are really not based on the actual risk at all, but on the perception of risk,” says Sheila McLean, professor of law and ethics at Glasgow University. “Having a higher risk of getting a disease does not mean you will get it and having a lower one does not mean you won’t. And having a 5 per cent increased risk of contracting a disease does not mean you have a 5 per cent chance of getting it.”
McLean says that whether or not a patient’s response is proportionate to the actual risk depends on their ability to understand and absorb the information they are being given. “I question whether such tests should be carried out in a GP’s surgery because, with all respect to them, they are not experts in genetics – will they be able to explain what the results mean and to provide the appropriate level of counselling?” she asks.
Since most of us will have an elevated risk of contracting one disease or another, there is a danger that extensive testing will lead to surgeries packed with the worried well – patients who regard every twinge as evidence they have fallen victim to their own DNA. Furthermore, couldn’t testing for a predisposition to some conditions become a self-fulfilling prophecy? If you knew, for example, that you had a gene linked to depression mightn’t that heighten your chances of becoming depressed?
Greater knowledge of our genetic make-up could influence the way we choose to live our lives. Yes, on the plus side, it could encourage us to adopt healthier habits, but wouldn’t our happiness be diminished if every time we lifted a glass of wine or a bar of chocolate, we started fretting about how it would play on our genes? Also, since human beings can be quite perverse, isn’t there a chance it would make us more reckless in a kind of “We’re screwed anyway, we might as well live it up” kind of a way?
On a more extreme end of the scale, there is a risk that knowledge of our genetic flaws might prove self-limiting. Already, some women with the BRAC1 and BRAC2 gene mutations have double mastectomies. It is not difficult to see how learning more about your genetic make-up might lead you to marry young, pursue a “safe” career or not have children.
“Parents are not recommended to have children tested for genes relating to conditions which won’t manifest themselves until adulthood precisely because it might deny them ‘an open future,’ ” says McLean. “Immediately everyone would treat them differently, they would be alerted to being different, more at risk in some way.”
Some of the ethical dilemmas surrounding genetic testing first materialised in relation to Huntington’s Disease, a neurodegenerative disorder leading to cognitive decline and psychiatric problems, which begins to manifest itself in middle age and is caused by an inherited defect in a single gene. Those who have Huntington’s have a 50 per cent chance of passing that defective gene on to their children.
Genetic tests for Huntington’s have existed since 1993; unlike the saliva tests which merely predict risk, the discovery of the Huntington’s gene is conclusive – all those who have it will go on to develop the disease in later life. Furthermore, with Huntington’s, there is no cure or effective treatment.
Knowing you have the defective gene, or even that you are at risk of having it, can alter your attitude towards life and your perception of your own abilities. In her book Mapping Fate – a memoir of a family affected by Huntington’s – Alice Wexler describes how a ballerina started experiencing difficulties learning dance routines long before she had any actual symptoms. “Living at risk undermines confidence, for there is no way of separating the ordinary difficulties and setbacks of life from the early symptoms of the illness,” she writes.
With this in mind, it is perhaps unsurprising that fewer than 15 per cent of those from affected families opt to take the genetic test; that is their right just as it is the right of those who do want to know to find out. But where some members of a Huntington-affected family do want to know and others don’t, it can cause a real ethical conundrum. Take the example of a young woman who wants to find out if she has the gene because she is thinking about starting a family; at the same time her mother long ago decided she would prefer to live in ignorance. If the daughter finds out she has the gene, then it follows her mother has it too. Either she carries the weight of that information alone or her mother is forced to confront the truth about her own genes against her will.
With cancer testing, the patient has some control; if he or she is at higher risk then a degree of preventative action can be taken, but there can still be an enormous burden on those who decide to investigate their genetic make-up. “Let’s say I have been observing my family history and I notice that one or two female relatives have died of breast cancer over the years so I go and get the test done and it turns out I have the BRACA 1 and BRACA 2 gene, the question then is: ‘What obligation does that put on me to tell my sister or mother or daughter that they too might have a greater risk?’ ” says McLean. “The complication of that is two-fold. First, most people regard their own medical information as being confidential and they may not want to disclose a potential problem to third parties. However, they may feel they have an moral obligation to share this information. But what if they tell family members and they are absolutely devastated because they too may have observed the same pattern and decided against testing?”
Finding out you have a gene related to a particular condition, also throws up dilemmas over reproduction. Those who have the Huntington’s gene may want to go down the route of having pre-natal diagnosis through amniocentesis (with termination an option in affected pregnancies) or IVF and pre-implantation genetic diagnosis (PGD), a trickier process in which only embryos without the gene mutations are selected and implanted.
Advances are also being made in gene therapy – the replacement of a mutant gene with a functional one. And last week the Human Fertilisation and Embryology Authority gave the go-ahead for research into the production of the so-called three-parent baby – where an embryo created through IVF is transferred into a donor egg to prevent faulty mitochondrial DNA from being passed on. But at what point should we call a halt? Should we screen embryos for genes which carry a risk factor for a disease which, if it develops at all, is unlikely to do so until middle age or beyond? And what about the discovery of genes which carry a predisposition to conditions such as alcoholism, depression, aggression or developmental disorders? Most people would disapprove of genetic intervention to improve stature or intelligence, but where exactly do we draw the line between gene therapy and gene enhancement (which carries with it the spectre of eugenics)?
These issues notwithstanding, most medical experts are excited by the saliva tests and the potential they offer for improved treatment. Dr George Fernie, president of the Royal College of Physicians’ Faculty of Forensic and Legal Medicine, believes they represent a real step forward. “I’m very much in favour of patient autonomy, which is one of the basic ethical precepts. You want patients to make as informed choices as they can in terms of their health and this would enable them to do that, but I think it’s sensible it should be done in conjunction with the family doctor so that, if you’re imparting knowledge, your patients understand what is proposed, the likely consequences and the possible outcomes,” he says.
Even so, the balance between being informed about your genetic make-up and becoming obsessed by it can be a difficult one to strike. Every time we are handed another piece of our genetic jigsaw, we have to decide how to handle it. And the burden that places on us is only likely to increase as scientists find the genetic code to an ever wider range of diseases and conditions. Even as we welcome new discoveries as launchpads to a better, healthier future, it may be wise to bear in mind the rights, responsibilities and the possible pitfalls that come with knowing our genetic destiny – and having the power to alter it.