By Max Cowan
This article was originally published in The Oxford Scientist Michaelmas Term 2021 edition, Change.
In 2000, the first draft of the human genome was published. It was an unprecedented multibillion dollar project that saw extensive international cooperation, and was heralded as the next frontier in medicine. In the NHS, Genomics England, a private company owned by the UK Government, is responsible for the provision of hundreds of diagnostic genetic tests, the genetic study of infectious diseases, and the provision of genetic information necessary to stratify and to guide subgroups of cancer therapies. For many, this research has been life changing or life-saving. For others, the identification of different diagnoses, although incurable, has aided the counselling and management of people’s lives. Much of this is performed similarly to how a pathology service might operate – as it is needed. It aims to be predictive, preventative, personalised, and participatory. Recently, Genomics England has conducted public consultations on the Whole Genome Sequencing of newborns in order to screen for genetic predictors of disease, and to identify the ‘normal’ parameters of genetic variation. Further, genome sequencing is now commercially available, and the techniques used rival those in current clinical practise. As genomic information becomes increasingly common, it must be asked: do we really know what we are doing?
In the years that followed the publication of the draft genome, many single gene causes of disease were identified, but also, the unanticipated complexity of the human genome became obvious. Correlations between a person’s genotype (what was in their genes) and their phenotype (how they appear) became more opaque as more and more information at increasingly higher resolution became available. Further, interesting studies correlated genome sequence with geography, demonstrating that a person’s ethnicity could be determined by looking at their genome and that different ethnic groups tolerated different types of variation. The amount of diseases mediated by a variation at a single location in the genome represented only a fraction of what was expected, and further research projects revealed that the genome is up to 50% ‘junk’ and that only 1-2% of the genome codes the proteins essential to life. Generally, it is extremely difficult to predict how a person’s genotype would affect their phenotype over their whole life. It was famously said: “The more we learn about the human genome, the more there is to explore”.
In the years that followed the publication of the draft genome, many single gene causes of disease were identified, but also, the unanticipated complexity of the human genome became obvious.
There are some famous genetic tests that are able to predict whether an individual will suffer from a genetic disease: the test for Duchenne muscular dystrophy has a 100% predictive power, and the test for early onset Huntington’s disease is 95%. These are diseases mediated by monogenic causes; compare this to the onset of diseases such as Type 2 Diabetes, which are polygenic (meaning many genes are affected together) and therefore much harder to predict. Notwithstanding, monogenic disease studies have their limitations too: while tests such as the Huntington’s Disease and Duchenne Muscular Dystrophy can confirm that a disease will occur, they tell us nothing about the severity or timing of onset. This is often referred to as the ‘penetrance’ of the disease, and it is difficult to discern. Further, once a diagnosis is confirmed, there is often no curative intervention that can be made – the diseases are managed symptomatically. Thus, the question must be asked, how useful is this information? Would you as an individual want to know? What would it change? As a doctor, how would you be able to use this information to improve the patient’s quality of life?
Currently, in adults and children, even where extensive genetic testing is conducted, it is often difficult to interpret and communicate the results simply due to the fact we are constantly observing new variants, often with unknown significance. Even with extensive genetic databases such as the 100,000 genomes project, new variants are continually being identified. A key limitation of these projects is that they mostly include Caucasian Europeans, and thus provide the most benefit to this ethnic group, creating a potential health care inequality that is being hastily corrected by further studies. Ultimately, the consequences of ‘normal’ and ‘abnormal’ genome variance will only be fully understood with the collection of massive amounts of data across all the continents.
Thus, the question must be asked, how useful is this information? Would you as an individual want to know? What would it change? As a doctor, how would you be able to use this information to improve the patient’s quality of life?
This presents a unique challenge: the collection and storage of phenomenal amounts of data of which very little is interpretable. The Chief Medical Officer’s 2017 Annual Report describes that genomics presents key therapeutic potential while simultaneously carrying incalculable risk. Recent public consultations conducted by Genomics England regarding newborn Whole Genome Sequencing revealed concerns about the project, but that the sample ultimately supported the project. I find the public relationship with Genomics England very interesting to observe. The NHS is service operated by the Government and has a social contract with the constituents of the UK to provide free health care at the point of delivery on the basis of clinical need. Alternatively, Genomics England is a private company that is wholly owned by the UK government and lead by a former McKinsey partner that provides services to the NHS, just as many other private companies do. Consequently, the social contract between Genomics England and the public is very different, and yet this company is tasked with storing the most valuable and most sensitive personal information about us: our DNA. Gaille, Horn and the UK-FR GENE consortia (2021) write about the social values of genomic services in the UK and France, and note that there are still no laws governing the processing of genetic data, particularly in relation to managing privacy. The proposal for newborn sequencing contains provisions that permit both research and clinical action – this blurred boundary and ambiguity around the specific reasons for data retention. Currently, the genomic sequencing results are stored for 20 years, so one must ask how a newborn, who will eventually become an adult with their own autonomous views, could possibly consent to the retention of this highly sensitive data. Further, what would happen if this information was accessed by an unauthorised or even hostile entity? Perhaps even a malicious nation state? In an age where biological weapons present the next frontier of weapons of mass destruction, how can we trust a private company to retain and manage this data? Even the NHS itself has been subjected to large scale data breaches, as have powerful private companies in which trust so much personal information to, such as the Facebook group, which lack transparency with their management of our data whilst simultaneously violating their social contract with us as users repeatedly.
Currently, the genomic sequencing results are stored for 20 years, so one must ask how a newborn, who will eventually become an adult with their own autonomous views, could possibly consent to the retention of this highly sensitive data.
To compound the concerns regarding genomics and private companies, many companies currently claim to offer genetic tests to the public. Genomic sequencing technology is rapidly advancing and consequently private test providers offer superior technology than that available through the NHS and Genomics England. Just as there were waves of controversies when it was revealed that many corporations made money by selling customer’s data, one must critically ask what these corporations are doing with the data they collect, and the security with which they store and dispose of it. Further, this advances a new concern, that private tests are currently more accurate than many whole genome or whole exome genetic studies in the NHS. So what is a doctor to do when they are presenting with patients who are concerned about genetic tests they have conducted in private when they are asymptomatic? It is also plausible that NHS and private tests may achieve conflicting results, how confident can we be in the current diagnostic power NHS tests return?
This is not to say that Genomics England should not be trusted, nor is it to suggest that the services they offer are not clinically relevant: they absolutely are and they change lives. The overwhelming sentiment of these concerns is that this is a field in its infancy, and it is a field that wields incredible potential for both positive and negative repercussions. Biology will be the next technological revolution. Just as synthetic chemistry changed the world in the 20th century, further studies in genomics and synthetic biology will, beyond any reasonable doubt, change the world. As we continue to design the genomics architecture in England, and as the UK continues to lead global initiatives in this field, it is essential that we do so responsibly.