At the beginning of 2013, I wrote a bioethics-assignment report about a planned scheme to create a genetic database of cancer (and “rare disease”) patients’ DNA in the UK, announced in 2012 by the BBC news and Cancer Research media. It is a topic laced with ethical and practical issues, which has subsequently captured my ongoing interest. Whilst in my discussion I focused on the cancer-treatment aspect of the topic, the ultimate aim of the project is to allow personalised treatment of patients with rare diseases as well as cancers.
At the time of writing, the available details about the proposed plans were scarce, however in July 2013 a government press release confirmed further details of this planned project (https://www.gov.uk/government/news/dna-mapping-to-better-understand-cancer-rare-diseases-and-infectious-diseases). Allegedly, whole genome screening has not yet begun; as of 20th Dec 2013, blood samples from five “rare-disease” patients have been screened, but the plan is to map thousands of genomes over the next five years. A new Department of Health organisation, Genomics England (http://www.genomicsengland.co.uk/), has been established for regulating this project, and can be followed on Twitter: https://twitter.com/GenomicsEngland.
obstacles and opportunities of mass-mapping Cancer.
Author: Rebecca Hock (February 2013)
BBC news clip: “DNA mapping for thousands of cancer patients”: http://www.bbc.co.uk/news/health-20666736
For the first time, a large-scale project aiming to sequence the entire genomes of patients with cancer and other rare diseases has been planned in England. The results should generate genetic databases that will allow researchers to identify patterns in the genetic mutations associated with the diseases. This will potentially accelerate and expand on the production of personalised therapies targeted at individual patients. The scheme aims to sequence the DNA of up to 100,000 volunteers, but when the project will begin is not yet confirmed. Although sequencing has already identified a few gene mutations that could be specifically targeted for therapy, due to the falling expense of DNA mapping, this will be the first project in the world that involves cancer-sequencing of patients’ entire genomes on mass-scale. With a cost of £5000 to £10,000 per genome at the time of planning, the British government is investing £100 million in this research (see fig. 1).
The main ethical and practical concerns revolve around the usefulness and privacy protection of the genetic data that will be generated from this study. Other issues arise from the practicality and feasibility of making personalised medicine an accessible treatment option for patients.
Proponents of the project state that being able to compare the genetic profiles of a huge number of patients, lead to greater understanding of the disease, and will allow more efficient treatment that targets the particular needs of the individual patient (Walsh, 2012; Kalia, 2013). Personalised therapies would be tailored to the particular genetic profile of an individual with a particular type of cancer. However, the development of such therapies is still a distant objective; while the sequencing project itself will take an undefined number of years, the subsequent research into therapies using the generated data is expected to produce tangible therapeutic results in a few decades’ time, benefitting at the earliest the next generation of cancer sufferers (Walsh, 2012). This may therefore cause concerns that the current generation of cancer patients, including the participants of study, will not personally benefit from it.
Coupled with this is that, due to the sensitive nature of collecting genetic information, the scheme will rely on obtaining enough volunteers to supply their DNA (Walsh, 2012). That of course will have practical implications. Furthermore, successfully collecting enough participants will depend upon the critical issue of privacy. Recent discussions have been made about whether traditional medical confidentiality can be applied in this new area of genomic-healthcare research, given that the very nature of DNA allows an individual to be identified from their genome alone (Lunshof et al, 2008). Genetic information is considered highly sensitive compared to other medical information, as it reveals a person’s predisposition to various traits (Beauchamp and Childress, 2009). Therefore a common concern with collecting such information is that, if not kept in strictest confidence, it could be used by, for example, insurance companies to discriminate against participants and their relatives (Walsh, 2012); in this case particularly, given the hereditary links in many types of cancer. A related ethical concern is that of respecting the individual’s autonomy; their control over the use of their personal data (Beauchamp and Childress, 2009). This concern is reduced by using only volunteers’ information, thus obtaining participants’ informed consent for the use of their DNA. Nevertheless, such concerns can be enough to discourage potential volunteers (NHGRH, 1998). To gain enough volunteers, significant changes to public perception of these issues will need to be encouraged (Bell, 2012).
Figure 1- “Plummeting” cost of whole genome sequencing (National Human Genome Research Institute, [online at www.genome.gov ] updated Oct 29, 2013)
Another potential issue may be that of the justice of personalised therapies; that, once developed, they will only be available to those patients who have enough financial funds to buy them. However, as with the concern that the project will cost a lot of money, it can be argued that the decreasing cost of genetic screening will be hopefully associated with cheaper drug development, with the aim of making personalised treatments affordable to everybody (Ruiz et al, 2012). In the UK, this would require such treatments being made available on the NHS. Reforms to the NHS would be required to prepare it for “taking the lead” in the genetic healthcare “revolution” (Gallagher, 2012). As a healthcare system, this would therefore require improvements to the NHS’s infrastructure to incorporate large-scale genomic healthcare, for instance by retraining healthcare providers like GPs and nurses in genetic therapeutics (Bell, 2012; Robertson, 2003).
At the moment much of this is still futuristic, and will require time and money, however moves are already being made to prepare the NHS in training and infrastructure; for instance with the establishment of the UK Genetic Testing Network to support the NHS in delivering small scale genetic tests (UKGTN, 2013).
There is much potential for genetic screening to greatly improve current understanding of the vast variety of cancers via revealing the specific mutations associated with each disease; as demonstrated recently by a study that sequenced tumours from over 2000 women and discovered that breast cancer may be classified as at least 10 diseases based on differing genotypes (Curtis et al, 2012). Results from this particular study will take 3 years to become useful in the clinical setting (Walsh, 2012), but at least the opportunity exists for genomic analysis of the generated data that would aid in more accurate diagnosis, prognosis and pharmacogenomics (Kalia, 2013; Ruiz et al, 2012). Genomic analysis is by now considered an important contributor to personalised oncology, supporting the growing approach of using biomarkers to predict drug sensitivity of tumours, and hence allowing accurate treatment (Kalia, 2013).
Despite the longitudinal nature of the research, and the associated adjustments to the healthcare and legal system that will be required, ultimately one can make the point that the long term benefits of the results, once generated, could by far outweigh the time and financial cost of the project; it will take time but, arguably, the sooner such a scheme is started, the better.
Beauchamp T L, Childress JF (2009) Principles of Biomedical Ethics 6th Ed. New York, Oxford University Press Inc.
Bell J (2012) Building on our inheritance; Genomic technology in healthcare A report by the Human Genomics Strategy Group. January 2012 [http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_132382.pdf]
Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yinin Y, Gräf S, Ha G, Haffari G, Bashashati A, Russle R, McKinney S et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 486; 346-352Volume:Pages:
Gallagher J (2012) Genetic testing: NHS “must back revolution”; http://www.bbc.co.uk/news/health-16725032 Accessed 23rd Feb 2013.
Kalia M (2013) Personalized oncology: Recent advances and future challenges. Metabolism. 62, S11-S14.
Lunshof J, Chadwick R, Vorhaus D, Church G (2008) From Genetic Privacy to Open Consent. Nature Reviews Genetics 9, 406-411, doi:10.1038/nrg2360
National Human Genome Research Institute (2013) DNA Sequencing Costs; Data from the NHGRI Genome Sequencing Program (GSP); http://www.genome.gov/sequencingcosts/ – accessed 23 Feb 2013
Robertson, J (2003) The $1000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals. The American Journal of Bioethics 3: W35-W42.
Ruiz C, Tolnay M, Bubendorf L (2012) Application of personalised medicine to solid tumours: opportunities and challenges. Swiss Med Wkly. 142:w13587
UK Genetic Testing Network, UKGTN (2013): www.ukgtn.nhs.uk accessed 20 Feb 2013.
Walsh F (2012) DNA mapping for Cancer patients; http://www.bbc.co.uk/news/health-20663090 Accessed 20th Feb 2013).