I often liken the human genome to a savings bond. When we get it, we overpay. Eventually– barring an economic meltdown (or genomic bubble)—it matures. For most of us the return on investment will be low. But for a few of us, the return on investment will be substantial.
– Misha Angrist, Personalized Medicine 2011 8(6), pg 654
Most people who have met with a financial advisor have probably used some sort of Risk Tolerance Calculator at some point in time. These calculation tools are meant to help give you and the advisor an accurate sense of the types of investments and portfolios that are likely to be right for you. My husband and I went through this exercise again recently and it was interesting for me to see how different our risk tolerances are. I started thinking that this type of risk tolerance tool could be applied in a genetic counselling context, especially with respect to whole genome sequencing.
Last week John Lauerman published an article describing his experience with whole genome sequencing (through the Personal Genome Project) and his struggle to come to terms with his results: learning he carries a potentially life-threatening gene mutation. He reviews his results with Aubrey Milunksy, a Harvard geneticist who expressed concern over the reporter’s decision to participate in the genome sequencing research project. Their conversation highlights the two very different ways to look at the same information:
“You know it’s there, but you don’t know what it means,” [Milunksy] said. “You’re smack in the territory of inviting anxiety into your life. And this may have no meaning whatsoever in your entire life.” I disagreed. The results had actually taken some uncertainty out of my life, I told Milunsky… I have a rare mutation linked to rare conditions, most cases of which can be treated. Wouldn’t it make sense for me to undergo a blood test regularly to see whether my blood counts had changed?
In my role at Medcan, I counsel healthy people who are undergoing SNP-based genomic testing for preventative health reasons. Our current testing panel is centered on: 1) common diseases 2) SNPs that have the highest level of validation and 3) health conditions where ‘actionable’ preventative recommendations can be given. Clients have the option to opt-out of receiving certain results (for late-onset Alzheimer’s disease, for example), although anecdotally very few patients actively opt-out of receiving information. Conversely, clients routinely ask about the possibility to know ‘everything.’ These individuals aren’t concerned that there is no preventative recommendations related to particular health condition, they are just interested and curious to access as much info as they can. Just like John Lauerman, these are the type of people who would participate in the Personal Genome Project, if it were available to them in Canada.
A new genetic counselling challenge
Whole genome sequencing (WGS) presents a new challenge for the field of genetic counselling. It is impossible for genetic counsellors not to think about how different our role will be in the context of clinical results of an entire genome. In my opinion, it is not necessarily the ambiguity of the results that poses the biggest challenge (most of us already deal with ambiguous results on a daily basis), but rather the sheer volume of data that seems insurmountable. Most genetic counsellors will spend about 30-45 minutes with a client discussing genetic testing for a single gene. Using our current model, it seems incomprehensible to review results of a whole genome sequence.
To date, this issue has mostly been discussed in the context of returning WGS results to research participants. In his 2011 article in Personalized Medicine, Misha Angrist argues that the ‘feasibility issue’ shouldn’t be used as a reason not to return research results. Similarly, I agree that lack of feasibility should not be a reason to keep WGS out of the clinic. There are new models of care and new technological tools that can be developed to address the feasibility issue.
Genetic counselling ’risk tolerance’ tool
So, how do you manage to provide comprehensive genetic counselling in the context of piles and piles of data? I think the key is to find a way to distinguish between what people can know and what people want to know. The obvious idea (and similar to what we currently use at Medcan in counselling about the SNP-based genome testing) would be to create a comprehensive checklist of health conditions that people would like to opt-out of receiving. For understandable reasons this would be overly cumbersome and incredibly time consuming.
A more interesting thought would be to develop a ‘risk tolerance’ tool to help identify the type of information that an individual is comfortable receiving. This, when used in the context of pre- and post-test genetic counselling, could be a way to have patients start to think about the potential implications of various types of results and whether or not this is information that they’d like to know. Personalized reports could then be generated based on categorizing findings according to (for example):
- Clinical validity (known disease associated vs. variants of unknown significance)
- Actionability (definitive clinical recommendations, some clinical recommendations, or no recommendations)
There are various ways to design this type of tool and personalized report. But a built-in mechanism to provide updated reports to reflect changes in categories or changes in patient decision-making (which may shift based on age, circumstance, health status) would be important.
As far as I know, I don’t think this sort of tool is being used currently, although I’d love to hear from genetic counsellors working in WGS research settings or in those clinics that are offering whole exome sequencing for complex cases. I do think this type of tool should be trialed in a research context, so when it comes time for clinical applications we are prepared to deal with the deluge of data.
While there are clearly differences between the financial application of a Risk Tolerance tool and one that is applied to health, disease prevention and diagnostics, I think this is an important concept to consider. The same justification that can be used to argue against a one-size-fits-all approach to medicine can be used when it comes to whole genome sequencing. As patients increasingly become more involved in their healthcare, it is important that we are armed with the tools to enable individuals to decide the type of information that they want to know.
This blog post was originally published on www.theGenoScape.com