I'm on one of the NIH grants to look at the impact of clinical genomic sequencing on patients, which includes a bioethics perspective. The hardest thing is definitely that our ability to measure greatly outpaces our ability provide meaningful interpretation. You get into all these discussions about what constitutes a medically significant finding. It's very hard to quantify when you start to grapple with it, and slippery slopes abound. Happy to answer specific questions on this in more detail if anyone wants.
A comment I left on a LessWrong post in July might help people understand why it is such a problem:
The genome is the ultimate spaghetti code. I would not be at all surprised if some genes code for the direct opposite characteristics in the presence of other genes. It is going to take more than just running relatively simple correlation studies to untangle the functions of most genes. We are going to have to understand what proteins the genes code for and how the proteins work.
Edited for clarity, eliminated a couple of ambiguous pronouns.
You're getting at the heart of the matter as far as the complexity, but just to put an even finer point on the it:
A single gene sequence can code for many different alternate versions of the same protein. These different variations can have pretty wildly different biochemical properties. Furthermore, the protein products of a given gene varies by environment, ethnicity, organ, tissue, cell type, and stage of life (development, infancy, puberty, etc...).
If that weren't daunting enough, many proteins have a secondary function of regulating their own production and the production of other (somehow related) proteins. This means that there are these highly complex interdependent feedback loops governing the activity and concentration of proteins.
The closest programming analogy might be spaghetti of LISP-like macros that are themselves spaghetti code that writes LISP-like macros.
But all that covers the basic research question of "how is this gene connected to human disease?". Even when you get past that, it's not so easy to know what results to supply back to patients. Do you tell the parents of an 8 year old who has had her genome sequenced that their daughter has a very high predisposition of getting cancer in her 40's? The daughter is too young to consent to hear that info. Now you're forcing the parents to make the choice for her. Not only that, even though the child is the one in for the test, the parents now (possibly without fully thinking it through) are recipients of information about themselves. All that because they wanted a genetic test to see why she's shorter than average.
While it's undoubtedly unpleasant to hear that you're more likely to get cancer than most people, that information could save your life. I'm not sure that I see a moral quandary here.
It's about what people choose to know. There are many people who don't want to know about things they can't always do something about. Many people would rather live a carefree life than know they can get a particular disease. This is a point of view I have trouble wrapping my head around personally, but it can't just be discounted. My example is also a little more clear cut than most. There are many cases where it's not so definitive. Some of the risk calculations result in increases over the baseline for the population of 10%. What does that even mean? It's all pretty poorly understood. Hence there is a real desire to only report back the really strong data. But that unfortunately results in eliminating useful, but highly speculative data.
In the off chance that it doesn't save their life, theres a great concern that it would significantly decrease her quality of life preceding a diagnosis. not just psychologically--theres insurance to worry about here too.
Baseline chance of cancer is what, half? Finding out you're likely to get a specific kind should barely affect quality of life. It'll just tell you where to scan.
Well there's a couple of things at work. For one, the key barrier to "clinical demand" is that clinicians (other than highly specialized ones) are not really prepared for dealing with genetic results. Most primary care doctors haven't thought about genetics since med school. I would also say that many of them question the utility of such data in clinical care. So I would describe the demand side as "tepid" except for the cases of specialities where it makes a big impact.
The above cultural issue is compounded by the fact that genetic testing is the only kind of test that transcends time. Your DNA sequence determined today could (and likely will) mean something different in the future as we learn more about the genome. But medicine historically has been very transactional: your doctor orders a test, the result comes back, you discuss results, make some lifestyle or treatment decisions and move on. With genetic tests, you could be "normal" today and tomorrow a paper lands in the New England Journal of Medicine that demonstrates with high certainty you're going to get early onset dementia or something. Well that's a problem in the current system (at least in the US). Whose job is it to go back and analyze people's genomes and update them with new info like this? Who do you bill for that? How do you notify someone? Some people don't want to know such things, can they opt out?
Targeted genetic testing has been used for years to identify specific diseases. But the tech to do huge swaths of the genome affordably is only a few years old. So even the diagnostic tech is still a bit "beta". That's the final piece limiting adoption. We're all collectively figuring out how to do this and how it fits in with existing regulatory requirements. All that "figuring stuff out" takes time.
Thanks for the response - really interesting stuff. I'd love to take a look anything that you/your collaborators have published in this space if anything's out yet.
Two weeks ago I went to go find a new primary care doctor, largely because I had received my results from a 23andme kit (but also because I didn't care much for my old doctor). The SNP matching told me a lot of things I should look out for later in my life, and it let me select someone who specialized in all the ways I was going to break.
Some people may be creeped out by a fully sequenced genetic code, but being able to sit down with a doctor and go through each match individually and talk about it was one of the coolest experiences I've had. I'm actually going in for a blood test tomorrow for the first of yearly checkups I'll have for a particular cancer that I'm at a high risk for, which I otherwise wouldn't have known about had I not done the genetic test.
Issues and concerns with the ethics of genes will inevitably arise, but the opportunities that it presents casts a shadow far greater than the problems.
I fail to see how your main citation supports your position. Just because an increased risk may be outweighed by environmental factors, or that an increased risk based on currently available information accounts for only a small percentage of the variation, does not mean that it would be unreasonable to take it into account when selecting a new healthcare provider.
It's sort of silly to say that 23andMe hasn't been "validated" to tell you things to look out for later in life. The article said that the quality of the SNP is highly accurate, with caveats about being aware of the population studied in the studies. If it tells you that you have a statistically higher chance of developing Alzheimer's (say, 2 or 3 times average), then you can prepare for that level of increased risk to the extent that it is rational to do so (maybe 3 times the risk shouldn't cause any behavior change), whether or not this has been approved by some sort of governmental or scientific agency.
Edit: To be more general, the category of "Bayesian evidence" is larger than the category of "scientific evidence." Acting based on Bayesian evidence is the Right Strategy.
>Some people may be creeped out by a fully sequenced genetic code
Just to be clear to others reading this. 23andMe SNP results are a far cry from being "fully sequenced". The technology to do full sequencing is out there, and it's way, way more detailed than what 23andMe is currently offering.
Also, as others have pointed out, their results should not be used for medical decision making without some confirmatory work in a fully certified medical diagnostic lab.
It's true that they aren't up to par with some of the other genetic tests out there, but they're the only one who offers anything at a reasonable price. Even if the results don't have the confidence level that other companies may provide, it's still better than, "you're Caucasian so you probably will develop X over your lifetime."
Being someone that has suffered health anxiety since early childhood, I'd like to applaud anyone thinking of taking one of these tests to think twice (Obviously if you have something that runs in the family etc then ignore me). Taking blood tests for the rest of your life for a condition you may develop is a fast road to hypochondria and believe me when I say it's no easy thing, living in fear.
Better to live every year like it's your last. Have no regrets, do what you love to do, and be with the ones you love.
Certainly though, things which have a good cure should be tested for regularly across the board. I don't want to know the day I'll die unless I could do something to prevent it.
Then you might miss out on the wonderful experience of working through a 10 year tunnel to accomplish something amazing. Like, say, a successful startup.
A friend of mine did this for a new pregnancy and it basically ruined their pregnancy. They now have a constant worry that the fetus may have "this and that" wrong with it. Very sad.
Would you abort your potentially perfect/potentially flawed baby? At what point? No thanks.
The 23andme results aren't an exact prediction, right? They tell you if you have the genes that could lead to a condition from what I remember. Also, how did you deal with the results on a personal level? I've thought about getting it since they opened, but always dreaded the bad reaction I could have. I vacillate between wanting to know and knowing I'll freak. :-)
Could a sort of escrow be setup to manage these kind of issues?
By this I mean that if the gene researcher finds something significant she can post it to a secure site with pre-established anonymized ID.
The anonymous donor can check this site with their special ID ... if they so choose so.
I'm sure there are flaws to this, but it seems like some sort of solution could be devised that allows sensitive information to be passed on to the anonymous donors without the researcher knowing who that donor is.
At most institutions, there already is such a system in place. Research subjects are typically anonymous to the research team, but there's a 3rd party "honest broker" who maintains the link. It's not a technical problem as much as a policy one.
The issue is that with most research studies the patients sign a consent that goes over the parameters of the research. Most consents in most institutions for years have had the clause that research results wouldn't be returned. Part of this is that research is, well, research. So you never know what you're going to find and it's usually very speculative, full of hand-wavey equivocations. Sometimes it's just not practical to re-contact people. Even in cases where it is, the research team is very often not in a position to offer primary medical care, so now you're burdening a doctor with test results they didn't ask for and might not be able to interpret. Finally, research usually doesn't employ the very strict guidelines that are in place for clinical diagnostics (since these limit how fast you can analyze data and push the envelope). Tubes can get mixed up, results can be just above the level of noise. All that is par for the course in research because you're supposed to be on the bleeding edge (well no excuse for tube mix-ups, but I digress...).
Returning results has the potential to add overhead to a research study, and for some, might make the entire study cost prohibitive (if genetic counselors and specialty care docs have to be on hand to interpret results for patients). Also, you run into the specter of "incidental findings" with genetic tests. For example, while health insurers can't discriminate on the basis of genetic tests, I'm pretty certain life insurers can. So a high predisposition to early onset Alzheimers might force a person to pay higher rates (or not be able to get life insurance at all). They will forever have to check the box next to "Have you ever been told by a doctor that...."
In places where insurance is required, how do genetic tests interact with preexisting/ongoing condition exemptions? Is a hereditary disease considered to have started at birth, or at the first (approved/licenced) diagnosis?
Would a patient receiving unsolicited results as mentioned in the article be under any obligation to inform their insurers?
BIG BIG slippery slope here and I'm glad you raised it. When it comes to insurance, "plausible deniability" is the best policy because they can deny coverage for so many petty reasons. I believe Obamacare is supposed to address some of these issues, but not certain. Nevertheless, insurance companies would certainly move for genetic sequencing prior to issuing a policy at some point in the future, it just makes too much business sense for them. Which is why health insurance should be non-profit - to take away the profit motive that corrupts health care.
No. The US Congress already passed a Genetic Information Non-discrimination Act in 2008 that makes it illegal for insurance companies to do this. They won't take your genetic data even if you offer it to them.
Even a non-profit insurance company would want to know about your genetic sequence; if nothing else, it would help them predict how much money they need in order to treat you over the course of your lifetime.
Parent probably meant to mean universal access, not nonprofit. Profit isn't really the issue. For profit insurance with universal access is totally workable
Well in the US 'mandatory' insurance under the AHA removed the ability to turn someone down based on 'pre-existing' conditions.
"Starting in 2014, insurers can no longer carve out needed benefits, charge higher premiums, set lifetime limits on benefits, or deny coverage due to a person’s pre-existing condition."
Well there is an interesting one - you have the gene that causes huntingdons. You are born with it. That's about as Pre-existing as it gets - ante natal. Now please give me my insurance at nominal rates. I will be collecting soon
what is Pre-existing. The symptoms? But symptoms are just a means to tell a disease exists. The gene for huntingdons - is that a symptom?
Interesting. I feel like secure parallel computing / Garbled Circuits would provide an possible solution for maintaining anonymity while allowing you to send back important notices to the source.
