Until very recently genetic testing was largely limited to the sequencing of single genes. However, advances in technology mean that whole genome sequencing, which enables scientists to determine the complete DNA sequence of an individual’s genome and to identify variants that may contribute to ill-health, is quickly becoming a clinical reality.
There is a veritable buzz about the potential of whole genome testing. This is partly because the reduction in the cost of sequencing (from many billions of dollars to less than US$1,000) means that the technology can now be used routinely. It is also because our understanding of the clinical relevance of genetic variants is improving rapidly.
It is important not to surrender to the hype around genomics – we are a long way from identifying all the genetic variants that are of clinical relevance and even further away from understanding the way in which these variants interact with environmental factors to create a state of ill-health. Nevertheless, it does have the potential to revolutionise medical practice in the near future by vastly increasing our ability to prevent, diagnose, and treat diseases that are partially caused by genetic factors. It might also herald the era of a truly personalised medicine.
My interest in genomics was recently piqued when I was asked to discuss some of the ethical conundrums raised by the revolution in whole genome sequencing during the creation of a new MOOC. Three issues seemed highly pertinent: incidental findings, confidentiality, and responsibility.
Incidental genetic findings
The widespread use of whole genome sequencing will lead to a substantial increase in the prevalence of incidental genetic findings, unexpected results that are unrelated to the reason for a test, but which may be clinically relevant. Incidental genetic findings are especially difficult to deal with because the clinical relevance of these findings are often hard to determine.
The ethical debate around incidental genetic findings has focused on whether the people who are being tested have a right to be informed about any relevant genetic findings that are made. The answer to this question depends in part on whether the incidental finding occurs during the course of research or whether it occurs in the context of clinical practice.
The clinical importance of the incidental finding is also a key factor. If the gene variant detected is likely to cause a serious disease and if an early diagnosis will retard the development (or reduce the severity) of the disease then it is hard to justify nondisclosure. On the other hand, if the clinical relevance of a gene variant is unclear and if there is limited evidence about the predictive value of the variant it is less clear whether such information should be given to a patient.
Withholding health data, even if it is uncertain and unclear, smacks of old-school paternalism. It could be argued that 21st-century patients have the right to access their health records – including the results of any test performed on them. However, although failing to provide such information may be construed as a violation of patient autonomy, where there is genuine uncertainty about the risks posed by certain findings a small dose of paternalism may be judicious.
Ethical questions about confidentiality have been well rehearsed in relation to genetic testing. But if a patient’s whole genome is sequenced and a number of clinically actionable variants are discovered, should this information be passed on to third parties who might also be affected? If the patient consents to this disclosure the ethical argument is often compelling but if the patient wants the information to be kept confidential what should be done? Is there an obligation to breach confidentiality in such circumstances?
Clearly, the rights of third parties to be warned of the risks that they face must be weighed against privacy rights but because genes are “shared” between (biological) family members, clinically relevant genetic test results could be said to “belong” to all affected parties. I have some sympathy with this idea, but there is a distinct risk that patients will refuse testing altogether if they know that their privacy will violated in this way. As such, geneticists should be very wary of adopting a policy of automatic disclosure.
The impact that genome wide sequencing has on the concept of responsibility for health has hardly been analysed at all – although a small number of academics have started to sink their teeth into the issue.
Traditionally, genetic diseases have been regarded as quintessential examples of diseases for which the sufferer is neither causally nor morally responsible. In the parlance of political philosophers, being born with a genetic disorder is the clearest example of bad “brute luck”.
However, whole genome sequencing might partially upend this idea because people will find out that they have genetic variants that increase their susceptibility to a range of diseases. For example, some people will discover that they have a relatively high risk of developing breast cancer or diabetes. Once in possession of this information patients might be able to reduce their overall risk via prophylactic “treatment” or by modifying their lifestyle. Of course, being born with a genetic disorder will still be a matter of bad luck. However, if adults armed with genetic information can modify their particular risk factors, the health outcomes, if not the initial genetic risk, will not be entirely a matter of luck.
The revolution in genome wide sequencing might also impact heavily on what might be called “reproductive responsibility”. In the not too distant future prospective parents might choose to have their whole genomes sequenced in order to determine their likelihood of transmitting problematic gene variants to their children. Couples who find that they are “at risk” may then make use of a combination of pre-implantation genetic diagnosis and whole genome sequencing to ensure that only genetically “healthy” embryos are implanted. Parents who refuse such tests and decide to conceive naturally may even be expected to pay a premium if a child is born with a genetic disorder that could have been identified by such methods.
Whole genome sequencing is still in its infancy. Like with all technology there are potential risks as well as benefits. On the up side we may be able to significantly reduce the negative impact that genes have on our health. On the down side we may be one step closer to realising the kind of dystopia encountered in Niccol’s GATTACA and Huxley’s Brave New World. In order to ensure an ethically acceptable future there is little choice but to delve deep into the problems of genethics as a matter of considerable urgency.
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Author: Carwyn Hooper is Senior Lecturer in Medical Ethics and Law at St George’s, University of London.
Image: A DNA double helix is seen in an undated artist’s illustration released by the National Human Genome Research Institute to Reuters. REUTERS/National Human Genome Research Institute/Handout