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Bioethics & Medical Ethics
Informing People About Their Genetic Risks
Jan Deckers and Dominic Hall ask whether relatives of patients with a genetic disease should be told that they themselves are at an increased risk.
Sporadic Alzheimer’s Disease is the commonest cause of dementia, and one of the most prevalent diseases in those over 65. It must be distinguished from familial (early onset) Alzheimer’s disease, which accounts for less than 5% of Alzheimer’s, and which manifests itself earlier in life. Clinicians in relatively affluent countries can now take blood from patients suspected to be at risk of Sporadic Alzheimer’s Disease and send it over to the lab for genetic analysis. The gene most commonly associated with SAD is APOE. APOE provides instructions to make a protein that transports fats within the brain. Everyone has 2 copies of the APOE gene, of which there are 3 main variants (alleles), known as ε2, ε3, and ε4. Since APOE is a susceptibility gene, spotting it does not mean that the patient will necessarily develop the disease. However, the presence of the ε4 variant does significantly increase an individual’s chance of developing it.
Genes are paired at a particular place (locus) on a chromosome, and they are homozygous if the two genes at a given locus are identical, or heterozygous if they differ. Relative to someone with ε3/ε3, who might be said to have an average risk, being heterozygous for ε4 – having only one ε4 – increases one’s chance of developing Sporadic Alzheimer’s Disease by 2.6 or 3.2 times, depending on the genotype (ε2/ε4 and ε3/ε4, respectively). However, being homozygous for ε4 – that is, having two ε4 genotypes – increases an individual’s risk of developing the disease by 14.9 times (‘Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease, A Meta-Analysis’, L. Farrer et al., JAMA 16, 1997). A risk 14.9 times higher than the standard risk makes it highly likely that one will suffer from Sporadic Alzheimer’s Disease by the age of 80. Here we won’t address the question whether clinicians should help patients who seek information about their APOE gene status, but the more complex question of what the duties of clinicians might be in relation to their patient’s relatives who may carry the same genetic risks.
Four Ethical Principles
When analysing cases in health care, it is useful to apply the four ethical principles of autonomy, non-maleficence, beneficence and justice.
Firstly, clinicians are obliged to respect individuals’ autonomous wishes to make decisions about their own care. It is frequently assumed that this demands that patients are fully informed about any conditions that affect them when they ask for a genetic test. The problem in the situation we’re considering is when clinicians don’t know what the patient’s relatives want to know. They might either wish to receive some information, or they might prefer not to know their genetic risks, to safeguard their desire for an open future. How can clinicians know whether relatives may wish to know about the risk factors? Some clinicians may think that knowledge is power, as it might help one to plan for the future. Others, however, may think that ignorance is bliss. So how might clinicians decide which relatives to inform, if any?
Relatives can vary greatly from one another in terms of which genotypes they possess. However, consider estranged (genetically) identical twins where one is found to carry the ε4/ε4 pair. How is the clinician to know whether the twin sibling might like to know he has this too?
The suggestion that the doctor should ‘just ask them’ is fraught with problems. Imagine a doctor contacting someone out of the blue to ask them whether they might like to know whether or not they carry a genetic condition. Most would suspect that the sheer fact that they’re being approached in this way implies that they ought to know something and that they must be afflicted with some condition, thus compromising the voluntary nature of their decision.
The principle of non-maleficence – ‘do no harm’ – must also be considered here, as the duty to not cause harm is integral to the health care profession. Although being told about one’s genetic risk may cause no direct physical harm, knowledge of one’s genotype may cause psychological stress. How Sporadic Alzheimer’s Disease operates isn’t fully understood. However, a popular theory claims that an increase in reactive oxygen damages cells, leading to neurodegeneration. This oxygen release can be exacerbated by both physical and mental stress. Since knowledge of one’s genotype may induce stress, it therefore might not be prudent to inform patients of their genotype, as this could result in the prognosis of Sporadic Alzheimer’s Disease being a self-fulfilling prophecy. The same applies to being contacted out of the blue with the question whether one might like to know something about one’s genes.
One study which involved disclosing their APOE genotype to participants, showed that those who were ε4 negative (which indicates a decreased chance of the disease developing) showed reduced levels of distress compared to those who were ε4 positive; but even the increased distress found in the latter group was of a mild and transient nature. The authors concluded that “these data support the psychological safety of disclosing data … to screened adult children of patients with Alzheimer's disease who request such information” (‘Disclosure of APOE Genotype for Risk of Alzheimer’s Disease’, R. Green, J. Roberts, L. Cupples, et al., New England Journal of Medicine, 361, 2009, p.251.) But there is no reason to believe that this implies that those who do not solicit such information would also be likely to experience ‘little distress’ upon being told out of the blue that they might be susceptible to a disease that can neither be prevented nor cured.
The third principle, beneficence – ‘do good’ – demands that medical procedures should be performed with the intention of providing a beneficial result, when balanced against the risks. It might be argued that knowledge of possessing an ε4 genotype would be beneficial, since the individual would have time (and be motivated) to make lifestyle changes to reduce their risk of developing Sporadic Alzheimer’s Disease: they might take regular cardiovascular exercise, abstain from smoking, try to sleep well, keep their brain active, and eat healthily – all of which reduce the risk of cogitative decline. This argument appears to be borne out by one study, which reported that those “who learned they were ε4 positive were significantly more likely than ε4 negative participants to report Sporadic Alzheimer’s Disease-specific health behaviour change 1 year after disclosure” (‘Health Behavior Changes After Genetic Risk Assessment For Alzheimer Disease: The REVEAL Study’, S. Chao, J. Roberts, T. Marteau, et al., Alzheimer Disease and Associated Disorders, 22, 2008). One problem with this study is that we do not know if this effect will last, which is particularly relevant with a disease that may not manifest itself for a very long time. Another is that reported behaviour may not coincide with actual behaviour, particularly when people may experience social pressure to adopt particular lifestyle changes. The relevance of knowing one’s genetic profile may also be questioned in light of the fact that doctors should advocate healthy behaviours to everyone anyway, since this reduces the risk of developing countless other diseases. People may not need genetic incentives to live more healthily.
The final ethical principle is justice, which focuses on fairness in health care. Knowledge of one’s APOE genotype could definitely impact a person’s right to health care. In countries without universal health care where insurance is purchased from a non-governmental company, an ε4 genotype could have detrimental effects on one’s long-term insurance policy, increasing one’s premium and leaving one in a state of discrimination. However, in the USA specifically, Congress passed the Genetic Information Non-discrimination Act in 2008. This stops health insurers discriminating based on genetics. One problem with this law is that it does not cover all insurance, exempting for example life and long-term care insurance. Another problem is that genetic information allows insurees who are in the knowledge of their genetic status to make strategic decisions that favour their interests, perhaps to the detriment of those who do not know their status, and perhaps also increasing pressure on them to be tested. A study in the USA has already found that people who had at least one ε4 gene were more likely to buy long-term care insurance compared to others (‘Genetic Testing For Alzheimer’s And Long-Term Care Insurance’, D. Taylor, R. Cook-Deegan, S. Hiraki, et al., Health Affairs 29, 2010). Whereas knowledge of their status may have reduced their financial worries concerning their lon- term care, it also triggered them into paying for insurance schemes that are likely to become more expensive as increasing numbers of people act on newly acquired genetic knowledge. Moreover, whereas many other countries have taken similar steps to the USA to try to limit genetic discrimination, the protective shield provided by regulations is unlikely to be free from attack in a globalised world where insurance companies compete in the market.
To Inform or Not?
Whether or not it’s fair to inform an unsuspecting person that they might be at a relatively greater risk of contracting Sporadic Alzheimer’s Disease will therefore depend on a careful assessment of what the person in question might prefer, as well as of that person’s health and socioeconomic context. Where it is not possible to obtain this knowledge about them without significant intrusion on their private lives and without compromising their voluntary decision-making, clinicians will need to assess carefully whether informing relatives might be more beneficial than not doing so. To do this they will need to ensure that they keep abreast of any changes in the condition’s likelihood, preventability, and treatability, as well as of any anticipated changes in the socioeconomic context, for example in the law on insurance.
It is most disconcerting that some scholars have expressed the view that geneticists should turn a blind eye to any personal or contextual features, and instead inform family members of their own genetic risks as a matter of course (‘Genetic Information: A Joint Account?’, M. Parker, A. Lucassen, BMJ 329, 2004). The analogy used is that genetic information would be like the information held on a joint bank account, where all parties are informed by the bank about financial affairs as a matter of course, rather than the information being restricted to some of the account holders. But the analogy is ludicrous, since it supposes that a jointly-consented decision to share financial information can be meaningfully compared with a situation where consent to share genetic information has never been given. What is needed is rather a constant commitment to, so to speak, step into the shoes of relatives.
If all patients were routinely asked whether they might wish to be informed about a range of hypothetical genetic risks, it might be easier to approach people about a particular risk. However, problems would remain, including the need to provide adequate, and potentially expensive, genetic counselling, which would allow patients to imagine potential scenarios; as well as the need to be mindful of preferences shifting over time.
If relatively little can be done to stave off one’s risk other than to follow behavioural patterns that are generally recommended to maintain good health, it may not be appropriate to be told, without having asked for the information, that one’s risk of Sporadic Alzheimer’s Disease may be increased by about 15 times relative to the average person. So although genetic information might help a patient’s relatives to plan for their futures, a disclosure of Sporadic Alzheimer’s Disease risks to patients’ relatives should be the exception rather than the rule.
© Jan Deckers and Dominic Hall 2017
Jan Deckers is a Senior Lecturer in Health Care Ethics at Newcastle University, UK. Dominic Hall is in his third year of study reading Biomedical Sciences BSc at Newcastle University. The degree topics include laboratory research techniques, biological theory and bioethics.