Whole genome sequencing can provide an incredible amount of useful genetic and personal health information, however, there are a number of ethical concerns and practical dilemmas that need to be considered prior to fully integrating this technology into the clinical practice.
We live in a genomic age, where our genes - collections of DNA that code for proteins and are passed down to our offspring - are perceived to be the foundation of who we are. They determine everything, from our eye color, blood type and earlobe shape to our likelihood of developing certain ailments. Together, all of our genes make up our individual genomes. The National Health Service (NHS) in the United Kingdom (UK) has recently put forward plans to incorporate whole genome sequencing as a part of routine healthcare at birth. This has raised ethical concerns surrounding consent for the procedure, who is privy to the information obtained, and the true utility of the test. Nevertheless, the knowledge provided by whole genome sequencing both at the level of the individual and the population would be indispensable in helping prevent or treat diseases down the line. The highly specific and complex picture that whole genome sequencing can paint suggests that its implementation into routine care should be anything but black and white. It should not simply be that individuals can either opt-in or opt-out in its entirety. Rather, individuals should be given a multiform spectrum of options for use and disclosure of whole genome sequencing that can be tailored to each individual's desires.
The ability to read all of our genes
Our genes are made up of DNA and so to sequence a whole genome is to determine the order of all of the DNA in a given organism. For scale, humans have approximately 20500 genes, comprised of around 3 billion nucleotides, the building blocks of DNA. Given the sheer amount of information about an organism this can provide, scientists have been attempting to sequence components of the genome for quite some time. The original methodology to do so, pioneered by Frederick Sanger in 1977, was time consuming and extremely costly. As a result, it was typically only used to sequence small, specific fragments of an organism's DNA. However, major technological advancements beginning in the 1980's have allowed for significant increases in the speed and volume of information that can be captured by sequencing techniques. These breakthroughs allowed scientists to complete the Human Genome Project in April of 2003. This thirteen year project compiled genetic information from a number of volunteers and pieced all of the information together to successfully build a database of the entire human genome. Since this incredible achievement, further advances have paved the way for next generation sequencing technology which carries the ability to sequence an entire human genome in the span of 24 hours. Although a test of this nature could cost up to $1000 a few years ago, a leading genome sequencing company Veritas has reduced this cost down to $600 in 2019 and plans to further lower the price to $100-200 per test. This, paired with the recent decision by the United Kingdom, suggests that this technology may soon be as commonplace in clinical practice as a blood test.
It is important to note that the information provided by whole genome sequencing is not foolproof. Just because the genetic makeup may appear to predispose an individual to a certain disease, there is no guarantee that this will be the case. Indeed, some genetic mutations are fully penetrant, and their existence corresponds directly with disease onset. However, for the vast majority of illnesses, our environment and other factors such as geography, socioeconomic status and climate also contribute to a significant degree. Nevertheless, even if the predictions provided are not carved in stone, the scope of whole genome sequencing is unmatched. It greatly differs from DNA analysis done with popular at-home genetics kits from consumer genetic testing companies such as 23andMe or AncestryDNA. These tests use a method called genotyping to look for and identify the presence of small sequences of DNA that are known to be linked to particular diseases, and only capture around 1% of genetic information. Similarly, the routine heel prick test of newborn infants, implemented in health care around the world, only screens for a small number of known disease-causing genetic mutations. Whole genome sequencing, on the other hand, elucidates all variants of the individuals DNA regardless of whether there is a known genetic link to a disease or not.
Benefits to both individual and society
The extraordinary amount of data from a single genome wide sequencing test can benefit those who are screened both in times of disease and prior to onset. Many new therapies center around the idea of personalized medicine, whereby a treatment is specific or tailored to the individual based on different traits they may have. If individuals underwent whole genome screens, it may be known immediately what medication or treatment route might be best to undertake. A 2017 study published in the Annals of Internal Medicine assessed the feasibility and outcomes of routine genome screening when compared to simply asking participants about their medical history. To their surprise, they found that 20% of healthy individuals had unknown genetic mutations associated with rare or serious diseases. For example, after Renee Duchainey-Farkes was screened, she was made aware of a list of certain drugs that would exacerbate her rare skin condition she was previously unaware of. Furthermore, they also uncovered unknown genetic risk for more prevalent diseases. As a result of whole genome sequencing, individuals would now have the opportunity to implement proactive lifestyle changes to prevent onset altogether, or begin treatment measures early, if they know that they are particularly susceptible. For instance, as a result of participating in the above-mentioned study, Irena Vodenska was able to proactively schedule cardiology tests and make lifestyle changes when she was made aware of her genetic predisposition to cardiac problems. As discussed by Chris Lo, diagnosis of rare or complex diseases is often a long and tedious process, a delay that could end up impacting the individuals outcome. By screening the entire genome at birth, these situations could be avoided.
In addition to the benefits for the screened individual, routine whole genome sequencing plays a significant role in the progression of research and the potential clinical options available for future generations. Having large pools of genetic information can allow for scientists to uncover new genetic links or predictors of disease. Even if a certain disease may not have a known genetic cause to date, retrospective analysis of genomic data from individuals who end up getting the disorder could provide insight on novel disease markers and contribute to the development of better screening methods and predictive tests. Knowing a causal link to the disease would also allow for more focused research, rather than learning by trial and error.
An issue of confidentiality
Even with the clear clinical potential of genome wide sequencing, the sheer amount of identifiable and sensitive information collected will require strict measures in place to regulate who has access to this information and to prevent harm and discrimination. First and foremost, the patients should have access to their personal genetic information if they desire. Although knowing their predisposition to certain diseases may cause distress to some patients, previous research on the psychological implications of genetic testing for conditions that could potentially be prevented or managed with lifestyle changes, such as cardiovascular disease or breast cancer, has demonstrated no significant increases in psychological or emotional distress. Conversely, the study also showed that the psychological burden of knowing that you will definitely be diagnosed with an incurable disease in the future impacts many aspects of someone's life. Notably, many individuals with well known familial risks for progressive genetic diseases such as Huntington's, a fatal neurodegenerative disease that occurs in adults, often choose not to be screened to confirm whether or not they carry the detrimental gene. These findings suggest that when undergoing whole genome sequencing individuals should be given the option as to which, if any, findings they would like to be told. This spectrum could range from receiving the full set of genetic variations, being told only those with feasible treatment options, or disclosure of only those that pose significant and immediate risk to the individual's health.
The plan proposed by the UK would have this screening occur at birth. This would mean that parents would be the ones to consent to this procedure on behalf of the child. However, would this also entail them to be informed of the results? It is clear that parents and children do not always hold the same ideologies and although a parent may be comfortable with the screen, the child may not want any knowledge of this information or even its existence. To ask a parent to withhold information of this magnitude for the remainder of their lifetime would be unrealistic. It has been suggested that, to avoid this situation, whole genome sequencing ought to only be offered at 18 years of age. Yet, there is undoubtedly a number of juvenile diseases that could occur in that time frame. To best mitigate these situations, consent for this procedure should be twofold. For example, parents may consent for their child at birth and, if they desire, receive information pertaining to any ailments that would occur prior to the age of 18. Upon 18 years of age, individuals would have the option to re-consent and be informed to whatever degree they so desire, or choose to have their results wiped from their record.
Once completed, the results of the whole genome sequencing screen would have to be stored somewhere. This significantly increases the risk of accidental dissemination and unwanted sharing of personal genetic data. As Chloe Kent points out, employers in the UK could take steps to access their employees medical records and the existence of stored personal genomic information could open the door to potential hiring or workplace discrimination. For example, individuals who have been identified as being predisposed to certain conditions, such as anxiety, could be unjustly denied positions based solely on preconceptions surrounding mental health. Similarly, bioethicist Mark Rothstein has stated that third parties, such as life insurance companies and long-term care facilities, could request access to this information, resulting in biased fees or refusals to individuals based on predictions rather than actual diagnoses. Perhaps the most troublesome component is the susceptibility of online databases to hacking. Just last year, a security breach at LifeLabs, a Canadian diagnostic laboratory testing company, resulted in hackers obtaining information regarding the test results of 85 000 patients. Given these valid concerns, the medical community and policymakers must ensure that regulations and proper infrastructure are in place to be able to safely and securely manage the volume and sensitive nature of genetic information, prior to the implementation of whole genome sequencing as a routine health care option.
Whole genome sequencing provides both a person and society with an incredible amount of information. However, the extent to which this information is relevant, wanted and protected must be carefully considered before fully implementing this technology. Clearly, if this becomes routine, patients' decisions will not be as simple as a 'yes' or 'no'. Individuals must be given a variety of options for consent, storage and dissemination of information that aligns with their values and level of comfort. Furthermore, strict regulations must be in place to avoid misuse and discrimination arising as a result of having one's entire genome sequenced and known. Already, Canada has shown their commitment to preventing genetic discrimination with the upholding of the Genetic Non Discrimination Act by the Supreme Court this July. This law prevents insurance companies from requiring genetic testing of applicants or forced disclosure of existing genetic testing results. The extension of this law to employment or long term care admission procedures may be beneficial if whole genome sequencing is to become routine. As much as each person is unique, so too should be their choice in whole genome sequencing.