Genetics in the 21st Century: Implications for patients, consumers and citizens

People as patients

The UK has been an early implementer of genomics in a healthcare setting. In 2014, the Deciphering Developmental Disorders Study reported the first results from the sequencing of 12,000 children with developmental disorders². At the same time, work began on a project to sequence 100,000 genomes of 70,000 NHS patients³. Outside of the UK, sequencing in healthcare settings is also expanding. For example, the National Institutes of Health Precision Medicine Initiative in the US offers 1 million people some level of genomic sequencing⁴ and the Australian Genomics Health Alliance is currently creating the infrastructure to integrate genomic medicine into healthcare nationally. Possibly the most striking example comes form Qatar where the government has plans to offer genome sequencing to their entire population (www.qatargenome.org.qa/).

A commitment to significant and ongoing investment in genomics on an international scale is demonstrated by the ‘Million European Genomes Project’, where genomic and health data will be linked from 1 million European patients⁵ and The Global Alliance for Genomics and Health (www.ga4gh.org) that represents more than 500+ organisations globally all with the shared endeavour of implementing and enabling genomic data sharing to be applied in research and clinical practice.

Genomic technology is now being utilised globally in a wide range of contexts to provide diagnostic, prognostic and treatment information for patients in a way that is predicted to transform healthcare¹. Genetic testing is currently used in a range of hospital settings, including the diagnosis of rare disease in paediatrics, prenatal care, ophthalmology, dermatology, ENT, etc. Such testing will continue to be used in these settings. However, as genetic testing (single genes) shifts to genomic testing (many genes) and the ability to test becomes faster and cheaper, a key change that will occur is a dramatic increase in the amount of information generated. As an example, as recently as 5 years ago, a breast cancer patient who also has family history of young onset breast cancer would likely be tested in a healthcare setting for two genes (BRCA1 and BRCA2). Alterations in these genes are known to lead an increased risk for certain types of cancer, most notably breast and ovarian cancer. Whereas now, such a patient may have a ‘panel test’ where over 20 genes associated with breast cancer are explored⁶. Each of these genes will have different links to cancer, thus increasing the complexity of the results that emerge. In addition to using genomic technology to understand the genetic basis of an existing condition such as breast cancer, it can also be used to uncover a new diagnosis for a previously undescribed rare condition⁷. Again, here the key change is the volume of information that will be generated. Instead of testing just a few genes, a child with an unknown developmental disorder may now have 20,000+ genes sequenced and then filtered bioinformatically to explore all of the genes linked to intellectual disability, autism and developmental conditions. This may reveal new diagnostic or prognostic information. Whilst it is unrealistic to suggest that all 20,000 genes will be analysed and reported as a whole⁸, the resource is at least available to be interrogated as and when required. As genomic medicine is increasingly available across healthcare systems, we are moving closer to genetics becoming ‘mainstreamed’^7,9. Thus, patients have more exposure than ever before to the volume and complexity of genetic information.

While there are many ways in which genomics is improving healthcare, it is important to note that there is evidence that genomic medicine does not always simplify or improve care. For example Adam Hedgecoe¹⁰ questions the utility of genetic testing, which can increase diagnostic uncertainty and Sophie Day et al.,¹¹ identify the ways in which genomic medicine further complicates treatment pathways for breast cancer. Arribas-Ayllon¹² reviews the literature to show that applications of genetic testing in healthcare are uneven and partial.

An increase in the scale of testing available inevitably also means an increase in the range of results returned – many of which, in the current climate, can only be interpreted as ambiguous or uncertain (due to the embryonic nature of our knowledge of this field)¹³. Such ’Variants of Uncertain Significance’ are results where the meaning is unclear and are more likely to be discovered when multiple genes are tested for at once¹⁴. In addition to the management of uncertainty, patients will be faced with more information options and so it becomes ever more pertinent to ask ‘how much do you really want to know?’¹⁵.

Given the ability to look at multiple genes within one test, genomic technologies deliver an opportunity to serendipitously explore genes unrelated to the health condition being explored. This means that when a patient has their cancer genes looked at it would also be possible, at the same time, to explore their genes linked to heart disease. Such results might be referred to as ‘additional looked for findings’³, ‘secondary or incidental findings’ or an ‘opportunistic screen’¹⁵. Indeed, within the NHS’s 100,000 Genomes Project parents of a child who is having genome sequencing can have the opportunity to be tested for ‘additional looked for findings’ related to their own risk of future disease, unrelated to their child’s condition¹⁶.

As patients are exposed to increasingly complex and uncertain genetic information, debates have emerged as to the best way to manage this. Middleton et al.,¹⁵ demonstrate that while many people are enthusiastic about receiving genetic information healthcare professions (especially those who work in genetics) are more cautious. Joon-Ho et al.,¹⁷ suggest that genetic information should be framed as a ‘dynamic resource’ with uncertainty managed by viewing this information as a resource that should be revisited over the lifetime of an individual. There is as yet no consensus regarding the best way to manage the increasing volume of complexity and uncertainty generated by genomic sequencing. In the ongoing discussion we argue it is crucial that debates are informed by wide range of voices.

Genomic testing is also increasingly being used to guide treatment options and provide more individualised risk assessments, often called ‘precision’ or ‘personalised’ medicine¹⁸. This allows clinicians and genetic counsellors to explore predispositions to developing future disease, thereby enabling steps for prevention, screening and/or management to be taken. Furthermore, this may be linked to pharmacogenomics – genetic testing used to guide drug use in medicine. For example, before prescribing, patients may be tested first to see if they are likely to be able to metabolise certain drugs¹⁹. This is also being used in oncology, where chemotherapies are targeted towards people with certain genetic profiles²⁰.

Genomic information is different to other sorts of medical information, in that it is shared between biological relatives. So, even if a person is not using healthcare services themselves, they may be related to someone else who is; thus, the reach of the results moves outside of the clinical encounter and into the wider family. Whilst most of us will not currently be a patient in a healthcare setting, we may still be related to someone who is having testing and the questions they have answered may be very relevant to us too. Therefore, the impact of genomic information naturally extends beyond a healthcare encounter–through conversation it travels from the patient, out to their extended family and to people who are not yet patients. Such people could be considered a type of ‘patient in waiting’²¹; we don’t yet know where and how they seek out information and meaning, but it is likely they look to the media²², popular culture²³ and the Internet²⁴ for insight. It is important when assessing how people respond to genetic information to ensure that ’the public’ is not envisioned as a singular, unified entity. Scholarship, especially from genetic counselling, demonstrates that the different ways people understand and make sense of genetic information is complex, varied and often idiosyncratic.^25–28. An important ethical issue, especially in the context of continuing enthusiasm for genomics, is how to respect the wishes of those who dissent, turning down personal genomic knowledge²⁸.

The complex ways that genetics – and now genomics – will affect patients, means that the provision of genetic counselling is of increasing significance. Patients have voiced the opinion that the provision of genetic counselling is important when having genome sequencing²⁹. Researchers and clinicians have also highlighted the importance of drawing on the expertise of genetic counsellors in order to ensure new technologies are integrated appropriately into healthcare³⁰.

People as consumers

Having discussed some of the implications of genetics for patients we will now explore some of the ways that genomics will affect people as ‘consumers.’ One way is via ‘direct to consumer’ (DTC) genetic testing. This is a growing industry with private companies marketing and selling a wide range of tests through the Internet. Consumers are able to send off a DNA sample (normally a saliva sample) and a few weeks later receive their test results. There are a wide range of DTC genetic tests both health related and non-health related. Health related tests include identifying predispositions to common and complex disorders, such as cancer and cardiovascular disease, tests for carrier status that could guide reproductive decisions, and nutrigenomics and pharmacogenomics that could potentially guide treatment and lifestyle choices³¹. Non health-related tests include testing for paternity, ancestry, athletic ability, as well as traits such as earwax characteristics and caffeine metabolism³¹. DTC genetic testing is rising in prominence. In 2008, 23andMe’s retail DNA testing kit was named invention of the year by Time magazine. In 2016, genomics was named by Forbes as one of the three ‘Big Technologies to Watch’ over the subsequent decade, together with nanotechnology and robotics, predicted to have the biggest impact on society³².

The potential risks and benefits of DTC genetic testing have been widely debated. Proponents argue that they empower consumers to take responsibility for their health³³ and improve the quality of their life³⁴. However, researchers and health professionals have raised concerns about the clinical validity of DTC genetic tests, particularly in relation to susceptibility testing for complex disease, such as diabetes or dementia^35,36. Specifically, researchers have argued that these tests fail to take into account non-genetic factors that can contribute to complex disease³³. For Mendelian conditions, where a single gene is causative of disease, concerns have been voiced regarding the negative and positive predictive value of DTC genetics tests³⁷. Researchers have also expressed concerns that when testing for serious, potentially life-threatening conditions, there is the possibility for unanticipated emotional reactions that cannot easily be addressed immediately via an Internet based service³⁸. Despite the professional bodies who represent genetic health professionals (e.g. European Society Human Genetics and American College of Medical Genetics and Genomics) recommending that genetic counselling should be provided by DTC genetic testing companies, a review of such services indicated that the support services on offer are often severely lacking³⁹.

DTC genetic testing is a growth market and as genetic testing becomes cheaper an increasing number of online genetic services will be available to members of the public⁴⁰. With purported plans to incorporate genomic testing into the Apple watch⁴¹, as well as fitness monitoring market⁴², we as consumers will be faced with more opportunities to engage with genomic technology and the implications for our health and wellbeing.

In making purchasing decisions consumers will increasingly have to draw on their scientific understanding as well as cultural beliefs in order to make purchasing decisions. Abrams and colleagues conclude:

People as citizens

So far, we have explored the implications of genetics for us as patients and consumers. Finally, by focussing on some of the novel ethical dilemmas that will arise from technological advancements, we are able to explore some of the broader societal implications of genomics for us as citizens.

Scholars have drawn attention to the ways in which commercial companies are exploiting new genomic technologies⁴⁴ with genomic and post-genomic (e.g. stem-cell) science seen as a crucial aspect of many state economic strategies⁴⁵. Indeed one of the primary functions of the 100,000 Genomes Project, the NHS genomic sequencing project, is: “Stimulating and enhancing UK industry and investment”¹⁶.

The commercialisation of genomics is inevitable; indeed, to accelerate future drug development, it is imperative. However, with the for-profit industry comes an ethical tension in relation to the raw assets – genomes – that form the resource of data used in genomic research. Empirical research has shown us that whilst publics are willing to donate their DNA and medical information for use in research, they are more suspicious of donating their data for use by for-profit companies⁴⁶; with concerns that unaffordable medicines would be developed as well as profits made for shareholders that they would not benefit from. We are encouraged as citizens to be altruistic with the donation of our data for the greater good and yet at the same time many will benefit, in a monetary sense, from this altruism. This tension is subject to increasing debate^47,48.

Genomic data is commonly stored electronically online; it is exchanged, shared and traded over the Internet every second of the day, as clinicians and researchers and pharmaceutical companies alike explore what a specific variant means. In order to interpret the significance of an individual finding, researchers need to see how this finding has expressed itself previously, by comparing it to datasets from thousands of other people³⁹. The importance of sharing data is outlined by Lucassen and Montgomery (2017) who say:

Thus, for us as citizens there are now emerging ethical dilemmas in relation to data security and privacy. If the only way to fully realise the potential of genomics is to collect large volumes of genomic data from millions of people (to be accessed by clinicians, non-profit and for-profit researchers in the endeavour to better understand the link between genes and disease), then this means that such data needs to be stored online, shared, and protected against unauthorised use. Together with medical data, the storage of DNA information forms one of the key issues for international policy creation – with the pivotal issue being how to make online data storage safe and secure⁵⁰.

One very significant dataset of genomic information is contained within the UK’s National DNA Database. Here, DNA information is stored from people who are convicted, cautioned or recently arrested of a crime and can be matched to DNA collected from crime scenes. Scholars have raised concerns about how DNA should be utilised in criminal law, with DNA databases having a disproportionally high number of people of ethnic minority status⁵¹. It was this fact that Lord Justice Stephen Sedley used when arguing for expansion of the National DNA Database. Sedley countered civil liberty concerns arguing that a universal database would be less discriminatory if it was representative of the national population⁵¹.

Concerns about discrimination have also been raised in other policy areas regarding genetics. Scholars writing from a disability rights perspective have argued that genetic screening programs can reify a view of disability as purely a medical issue, ignoring social barriers that marginalise people in society. As such, implicit judgments are made about what is a worthwhile life, with genetic screening programmes having the potential to increase discrimination of people with disabilities⁵².