Rapid deployment of new sequencing technologies in clinical practice lead to discovery of new disease-causing variants that have significant implications for patients and sometimes provide life-saving insights. However these revolutionary technologies will exacerbate constant ethical dilemmas for geneticists and counselors: what type of disease prediction should be disclosed to the patient?
In general ethics guidelines for geneticists state that only medically relevant and currently “actionable” disease predispositions, i.e. diseases for which treatment is available, should be conveyed to clients. This means that if a patient is a carrier of a mutation that predisposes to a “curable” or “preventable” disease she/he will be informed about it so preventative treatments could be initiated. Contrastingly, patients that are at very high risk to develop currently untreatable disease will be left in the dark. In extremely rare situations, the genetic counselors would actually ask client whether she/he wants to know about the risk of incurable disease, and they well be asked to sign an informed consent and the disclosure policy, so the hypochondriacs can opt for the “leave me in the dark” option.
But should you really know what is going on with you, even if this information might be scary?
To answer this question we have to refute the popular view that genetics is deterministic and whatever is “written in your genes” will for sure happen. As en experienced geneticist I can assure that this is not true!
First of all, genetics is a statistical science – all disease risks are not absolute and have their probabilities! There are only a handful of cases where you know for sure that a disease will certainly manifest itself because of a specific genetic variant such as the Down syndrome and other severe genetic abnormalities, but even in such cases there is a wide range of clinical severity. Most of the classical genetic diseases can range from fatal to asymptomatic due to the additional effects of the modifier genes and environment. Therefore, I would argue that it is better to know all genetic risks even for the currently incurable diseases.
“But why should I know that I will loose my mind in early forties and die early?”
Let’s analyze the Huntington’s disease (HD) as a worst-case scenario. Huntington’s is a dominant (i.e. even one disease causing allele is sufficient for disease manifestation) progressive neurodegenerative disorder. The Huntingtons disease is caused by the aggregation of mutated protein in neurons; when these aggregates become too big, neurons die and manifests at 35-45. Currently HD is incurable and demented patients die of complications. For everybody it is a devastating to receive a positive diagnosis, but the main reason given for choosing testing for HD is to aid in career and family decisions. For example young patients should avoid lengthy career pursuits, but rather focus on something that they enjoy in their short active lifespan. But for families with high risk of HD genetic diagnostic can reduce the risk of having kids with HD through IVF and pre-impanation testing.
However, over 95% of individuals at risk of inheriting HD do not proceed with testing, mostly because there is no treatment. But psychological impact even without genetic testing to the individual at risk is enormous: the fear and anxiety of not knowing whether he/she will eventually develop HD, can lead to severe depression or suicide. The impact of stress is comparable to the impact of a positive test result. So should you know or not???
As I said earlier, it may be better to know. Although HD is currently incurable, may scientists across the world are trying to find a cure. Yes, it might take decades to get even a drug approved, but the HD carrier can register for clinical trials for new experimental medications. Let’s say the new drug does not cure the disease, but it is able to delay the onset of disease by couple of years. By enrolling into clinical trial patient has a 50:50 chance to get either drug or placebo, so statistically speaking patient has an opportunity to gain a full year of active life. Plus given that in the vast majority of the trials placebo group frequently also shows a positive effect due to better medical care, these patients can gain something as well. How much this year is worth for you? Base on cancer we can say that is a year of quality life is generally valued over $150,000, which is by far less then cost of genetic testing….
For all degenerative diseases such as HD and Alzheimer’s, from the therapeutics perspective, it is important to know your genetic risk is useful before the symptoms occur in order to benefit from treatments. Recent trials in Alzheimer’s with new treatments designed to block amyloid plaque formation do not work in symptomatic patients, probably due to extensive brain damage. However, as for any other disease it is much easier to prevent than to cure! The same logic applies to wet macular degeneration and other eye diseases – early treatment, even in the pre-symptomatic stage yield better results.
As Terry Goodkind said: “Knowledge is a weapon. I intend to be formidably armed”.
Though genetic testing is certainly is not a cure for any disease, this knowledge is essential for the well-being of an entire family. Having one affected partner is devastating, but I strongly feel that ignorance is a bad excuse for “reproductive negligence” – there way too many cases when one affected patient is not using genetic testing before procreating and bring to life more children that unfortunately share the same disabilities and destined to suffer their entire lives. I remember a CBC “heroic” story, where one Canadian woman with congenital heart abnormality that required heart transplant had two daughters, both of which also required heart transplants in childhood. I do not believe that it was very wise to ignore the fact that genetic testing is available and gamble with children’s health.
Why not to use genetics before making children? I know that it is impossible to predict how the child will turn out to be because for every couple there are billions of different gene combinations, resulting in having absolutely unique babies. But in some cases there is an opportunity to use some of the information to greatly reduce a risk of having severely affected kids – most of genetic diseases are “preventable” by pre-implantation diagnostics.
Back to Huntington’s disease – The Dutch government has now mandated that Prenatal Genetic Diagnostics (PGD) for HD will be performed only on couples that underwent genetic testing themselves. This is very smart decision for several reasons: it reduces the risks of embryo loss due to unnecessary PDG and also reduces the costs of PGD screening, but more importantly extensive genetic screenings of prospective parents for multiple diseases can potentially give valuable insights on health of their future progeny.
Again, there are many thorny ethical points such as insurance and disclosure. The non-discrimination legislation passed in the USA and Europe, but ironically not yet in Canada, bars discrimination based on genetics, so it could be used to protect patients against hikes in insurance premiums. Disclosure to partner about the HD carrier status is still a hot ethics issue, but it can be simply resolved when the person at risk and the partner are not told whether any embryos were found to have the HD mutation, and only informed that embryos with the normal copy of the gene were implanted.
P.S. American College of Medical Geneticists published new recommendations on disclosure of genetic test results, emphasizing the importance of finding genetic predispositions to preventable diseases. Recommend to read a very nice summary published by Genomes Unzipped.