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Do we have the right to ignorance?

So, you've just been sequenced.  The test did not figure out why you have chronic hypertension, but it did find a mutation in a gene that may cause your brain to degenerate rapidly in your late 50s.  Didn't see that coming, did you?  Do you wish that no one had told you? 
 
Recently, the ACMG (a board that release guidelines for clinical sequencing)  suggested that you do not have the right to not know about potentially disease causing mutations in a particular set of genes even if you were not interested in diseases associated with those genes (so called incidental or secondary findings).    This recommendation was controversial, because the genomics/genetics community has generally supported the idea of your right to "not know".
 
I had a very pleasant lunch last week with one of the authors of the ACMG recommendations and asked him why he thought people didn't have the right to "not know" and he explained his reasoning to me thusly (which I hope I am presenting fully and accurately):
1) In no other field of medicine do they give patients the right to opt-out of the results of testing.  Even in fields where secondary findings are common, for example, imaging, where, for example, you may discover early on-set lung cancer when you were actually just imaging the heart.  Further, it was argued that if the patient didn't want any secondary findings that she could opt out of the test entirely and this was an acceptable way for the patient to control what they learned about their genome.
2) The "secondary finding" gene list only includes genes where it is possible to influence the out-come of the genetic finding (i.e. it does not include genes for which the disease is inevitable and non-treatable).  Thus, by knowing you may actually be able to do something about the genetic defect.
 
The first point is an argument against "genetic exceptionalism" -- that is, medical genetics is a field of medicine just like every other field of medicine and should be treated as such.  the alternative is that every medical test which is likely to find incidental results (such as imaging) allow people to opt out of those results.  I was told, however, that this alternative was not likely to happen as it would create too much work for the doctor. 
 
Genome wide sequencing, however, IS different from these other tests in a few important ways:
a) You sequence the whole genome and thus you are much more likely to find something you weren't looking for.  This is roughly equivalent to only being able to get an MRI of your whole body, no matter what organ the MDs thought might be involved.  The only problems with this analogy is that we have approximately a score of organs but ~8,000 genes associated with disease and thus must be much more likely to find a disease causing mutation by accident.
 
b) When you get sequenced you're also sequencing everyone who is related to you.  IF you have your child sequenced, you are sequencing yourself, your spouse, your parents, your siblings and any other children you might have.  When you are given incidental findings about yourself, you're potentially delivering those same results to your family.  Whether they wanted to know or not, they, too are being tested.
 
c) In genetics, we are much worse at knowing whether a particular genetic observation is necessarily indicative of disease than we are in other fields.  In particular, it is not always possible to know whether a mutation in a gene can lead to disease, and even if it can, whether it will in a particular case.  many mutations (if we know at all) only have an associated increase in risk for a particular disease and in no way guarantee that you will get ill.  This is markedly different from incidentally observing an early (potentially cancerous) lesion in that the disease is already manifest, there are further tests that can be performed on the lesion to ensure it is diseased tissue, and treatment is readily available (and indeed, ideally started) for the cancerous lesion.
 

It is this last point that seems critical to me: if there is little that can be done to help the genetic problem or little that we can know with certainty, then it's not clear that the information has much value to the patient other than "for it's own sake".  Thus, if the patient doesn't want to know this information, it will do more harm than good, and fundamentally, the practice of medicine must be to maximize benefit and minimize harm for the patient.

Matthew Bainbridge's picture
About the author

Matthew Bainbridge is President and CEO of Codified Genomics, analyst, and sometimes scientist