

Genes Now Tell Doctors Secrets They Can’t Utter  - danso
http://www.nytimes.com/2012/08/26/health/research/with-rise-of-gene-sequencing-ethical-puzzles.html?src=me&ref=general

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JunkDNA
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.

~~~
billswift
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.

~~~
JunkDNA
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.

~~~
actsasbuffoon
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.

~~~
aggronn
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.

~~~
Dylan16807
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.

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jjcm
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.

~~~
tokenadult
_The SNP matching told me a lot of things I should look out for later in my
life_

The SNP matching by 23andme has not yet been validated for that purpose.

[http://www.genomicslawreport.com/wp-
content/uploads/2011/06/...](http://www.genomicslawreport.com/wp-
content/uploads/2011/06/asco-dtc-abstract.pdf)

Background reading:

[http://www.ashg.org/pdf/Lynn%20Jordes%202011%20Presidential%...](http://www.ashg.org/pdf/Lynn%20Jordes%202011%20Presidential%20Address_AJHG.pdf)

[http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjo...](http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001009)

[http://onlinelibrary.wiley.com/doi/10.1111/j.1467-8624.2012....](http://onlinelibrary.wiley.com/doi/10.1111/j.1467-8624.2012.01757.x/full)

~~~
xanados
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.

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rlvesco7
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.

~~~
JunkDNA
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...."

~~~
001sky
while health insurers can't discriminate on the basis of genetic tests, I'm
pretty certain life insurers can.

\- good to know

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shabble
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?

~~~
Quizz
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.

~~~
PotatoEngineer
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.

~~~
Evbn
Parent probably meant to mean universal access, not nonprofit. Profit isn't
really the issue. For profit insurance with universal access is totally
workable

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keithnoizu
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.

