Personal genethics

Posted on March 7, 2010 by Cath@VWXYNot?

A long time ago, on a blog platform far, far away, Richard Grant blogged about his delirious experience with some hard-core drugs given to him by ~~some shady Dutch-Canadian drug dealer~~ Eva Amsen. In the comments, Austin Elliott suggested that Richard may be one of the 10% of Caucasians with deficient CYP2D6 enzyme activity, leading to long lived high levels of dextromethorphan that may result in the transformation of an innocent cough and cold remedy into a dissociative psychedelic drug. Network-wide genetic testing was suggested.
This episode reminded me of a dilemma experienced by a Former Colleague (FC). FC had just read a paper¹ reporting that a promoter length polymorphism in the 5-HTT gene is associated with the development of depression in response to stressful situations. FC had developed depression during a time of stress some years before, and wondered whether this polymorphism might be to blame. Finding their thoughts returning again and again to this question, FC considered whether it was a) possible and b) advisable to run a surreptitious test on their own DNA.
Possible? Sure. FC’s lab did lots of DNA extractions and even more PCR. No-one checked the primer sequences FC ordered to ensure that they matched project-related sequences. Adding an extracurricular extraction, amplification and electrophoresis gel lane would in all likelihood have gone completely unnoticed.
Advisable?
Well, let’s leave aside the obviously, objectively, unethical use of grant-funded lab supplies and equipment for personal genetic tests. Yes, it would have been wrong, but the unethical spending would have represented an essentially negligible fraction of the lab’s overall budget… and anyway, other aspects of the dilemma are much more interesting.
What really gave FC pause was the psychological effect of knowing their genotype, even though they understood full well that the association between the variant 5-HTT allele and stress-triggered depression is not absolute, and some uncertainty would remain. Would it change the way they thought about their depression to know that it was quite possibly caused by a single polymorphism? Might it help to mitigate the stigma of poor mental health, and possibly even relieve some of the symptoms? Conversely, if the PCR results ruled out the polymorphism, might FC’s depression worsen? How might the result affect their future deliberations about whether to have children?
In the end, after much thought and discussion among friends, FC decided not to run the test. Not for nothing do genetic counsellors undergo so much training, and going it alone just felt like too much of a minefield.
With the advent of next generation sequencing, more and more of these genotype-phenotype correlations will become apparent. And in labs around the world, anyone with access to a PCR machine could find themselves wondering if the latest finding might just apply to them. Without the usual checks and balances in place that regulate the translation of genetic tests into clinical practice, students, postdocs, and other lab staff are vulnerable to the temptation to tack one extra lane onto their next experiment in order to delve into their own genome.
Would it really matter if lab workers could test themselves to confirm that NeoCitran makes them delirious because of a CYP2D6 deficiency? Well, only if they intend to use that knowledge to obtain a cheap, over-the-counter high. But when the results might change the way someone thinks about their mental health, the stakes are raised and we have a very real dilemma on our hands.
The other issue is that personal genetic testing performed in secret by lab workers potentially leaves the lab open to litigation and other costs. My undergrad department used to get students to extract and stain their own chromosomes in a second year cytogenetics lab, but stopped a couple of years before I started the course when one student was found to have a balanced translocation that suddenly shed light on her sister’s recent miscarriage. The university department ended up paying for her entire family’s genetic counselling costs. I could also imagine a scenario in which someone in a similar situation to FC uses their lab’s equipment and supplies to run a test on their own DNA, is distressed by the results, and sues because they were never told that this is something that you shouldn’t do…
Have any readers ever tested their own DNA, either with or without their superiors’ knowledge and permission? Has anyone received any formal training or advice on this issue? I think it’s going to be a growing problem, and I wouldn’t be surprised to see it appearing in some research institutes’ employee handbooks and training / orientation sessions in the near future.
1) Caspi et al, “Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene”. Science 2003, 301:386-9

About Cath@VWXYNot?

"one of the sillier science bloggers [...] I thought I should give a warning to the more staid members of the community." - Bob O'Hara, December 2010

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21 Responses to Personal genethics

Frank Norman says:

March 8, 2010 at 2:11 pm

One of the questions to ask is “How will this help?” Will knowing you have a particular genotype point you to particular remedies, or suggest substances/behaviours to avoid?
Cath Ennis says:

March 8, 2010 at 2:51 pm

Yes, good point Frank – there will be examples where the benefits of running the test outweigh the risks, depending on which polymorphism you’re looking for. Those are probably the tests that’ll make it into mainstream medicine the most quickly; I was thinking more of people reading primary research papers years or even decades before the research findings start to impact clinical practice, if they ever do. And there’s still the question of whether an untrained person surreptitiously running a test in their own lab will be able to cope with the implications for their decision whether to have kids, even if the result is unambiguously beneficial to them themself.
In the depression-associated polymorphism case I used as an example, there would be no clear therapeutic benefit to knowing your own genotype.
Eva Amsen says:

March 8, 2010 at 4:57 pm

Three years ago, I spent several months visiting a number of doctors who all thought – based on my symptoms and age – that I had hepatitis and did a gazillion blood tests. I didn’t have hepatitis, got better on a diet, and got sick again as soon as I started eating anything unhealthy again. When I ended up in the ER after eating chips/fries, I saw a young doctor, who had heard of such a thing called “genetics”, and it was he who – without any additional tests – had the presence of mind to ask me “Has anyone in your family ever had gallstones?”. “Yes, my cousin, and my aunt (her mom – my mom’s sister)” I explained.
And yes, that was the answer. I apparently (although it was never verified with a DNA test) suffered from a hereditary form of gallbladder disease, that none of the other doctors picked up on, because they (a.) assumed only fat women over forty get that, (b.) did not think that there even was a hereditary form and (c.) lost my diagnostic ultrasound, which didn’t seem relevant at the time, among the multitude of tests they subjected me to.
So, yes, I would have liked to know beforehand that eating chips and cheese would put me in the hospital before I turned thirty. That would have been nice. I don’t actually know if it has been pinpointed to a specific gene yet, but if it is, I would want to know these things. This was a disease that could have easily been prevented with a change in diet, if only I had known that I was at risk.
On the other hand, I would not want to know if I was susceptible to anything that can’t be cured or prevented within my lifetime. I think there’ll be a treatment or cure for Alzheimer’s before I turn 80, so I’m not too worried about that, but I wouldn’t want to know if I was at risk for any cancers that aren’t treatable.
So, maybe there could be levels of genetic tests: testing to see what can be prevented or treated, vs. testing whether or not you’re DOOMED.
Erika Cule says:

March 8, 2010 at 5:40 pm

I was going to post a relevant comment, honestly. But I am just so delighted at being able to log in and comment that I have completely forgotten what I was going to say.
Nice post, though, Cath. I like it! Now, to get a blog post posted on this newfangled thingy…
Cath Ennis says:

March 8, 2010 at 6:11 pm

Eva, that does sound horribly frustrating. I’m glad you got it sorted out in the end though!
I wonder if institutes that decide to implement a policy on personal genetic testing might consider allowing some tests, but not others? It’s a legal and ethical minefield, though, and I would imagine that those institutes that consider the issue at all would be more likely to go for a blanket ban. Either that or a “don’t ask, don’t tell” policy, aka the ostrich approach.
Erika, welcome back! Good luck with the first blog post. I almost feel guilty for having such a smooth ride after so many other people experienced problems – I tried for the first time yesterday, and got straight in with no issues at all. I guess I’m not part of the elite power-user clique 🙂
Elizabeth Moritz says:

March 8, 2010 at 8:15 pm

I checked around with the 1st graduate students in our lab who have just completed their mandatory ethics course if such a situation was covered at all. They all said no but agreed that it would have been a useful thing to talk about.
The only ethical issues they discussed that came close was improper use of lab resources and not using your own cells in cell culture experiments due to the danger of introducing viruses/etc (that you maybe didn’t know you had) into your lab.
I think that if you really wanted to do PCR-based genetic tests on yourself, you’d be best off ordering the machinery cheap from lab resale sites and reagents on your own.
Sonja Babovic says:

March 8, 2010 at 9:37 pm

I wonder sometimes how many people at the BCCA have sequenced their BRCA1 and 2 alleles!
Stephen Curry says:

March 8, 2010 at 10:14 pm

A very interesting post Cath – I would agree that FC made the right choice. Since our knowledge of genetics runs so far ahead of available therapies (and of our understanding of the links between genotype and phenotype for many conditions), these are difficult issues. I know at least one person who was interested in paying up for one of those 23andme (?) genetic tests which reports on many different facets of the genotype but it has never appealed to me.
Cath Ennis says:

March 8, 2010 at 10:17 pm

Elizabeth, thanks for checking!
I wonder how easy it would be for a private citizen to order PCR reagents, primers etc. from their home address without attracting attention from the government?! ‘cos having my own lab in the garage does sound like fun (although I’d probably find something more interesting than my own genes to study).
The other issue with culturing your own cells is that you run the risk of generating a transformed, oncogenic cell line that your immune system will not reject as foreign*. I remember that my old institute had a cell line in storage derived from one of the neighbouring lab’s technicians, and we weren’t allowed to open the entire storage unit (except to add fresh liquid nitrogen) while she still worked in the building. The rules had changed a wee bit since they generated the line!
Sonja, I would imagine that it’s been done, but I don’t imagine you’d find anyone who would own up to it! That’s actually a great example of a gene where knowing your own genotype could be hugely advantageous (i.e. going for mammograms earlier and more frequently than the general population), but also one where I wouldn’t want to find out I had a mutation without some kind of professional support – there are very serious consequences to that mutation, potentially including prophylactic double mastectomy and ovarectomy. Not one to be taken lightly.
*conversely, a friend had an extreme (localised) immune reaction when he accidentally injected a bunch of HeLa cells into his hand. He found this rather more reassuring than I might have done if it had happened to me…
Cath Ennis says:

March 8, 2010 at 10:28 pm

Sorry, Stephen, our posts crossed. There’s a bigger lag here than I’m used to!
I agree that doing something like 23andme doesn’t really appeal to me. I’m reasonably confident in my family’s genetic origins (we’re a boringly common Irish-Scottish-English mix), and I have no symptoms or family history that suggest the test would turn up any clinically important findings. Not at our current level of knowledge, anyway. However if there was a specific test for something like Eva’s gallstone thing, and a clear therapeutic benefit to knowing the answer, I would definitely want to know. In the latter case though, one would hope that the test would be available from a doctor, rather than having to run and interpret it yourself, and deal with the consequences…
Åsa Karlström says:

March 8, 2010 at 10:57 pm

Cath> We had a similar question in discussion when I took a GeneticCouncelling class at UBC 00 (looong time ago) 😉
Then it was more to remind everyone that the idea of taking a test of BRCA1/2 does pose a bunch of questions afterwards. “Would you tell your sister/mother/family” and “would they like to know in case you told them?”.
I think you/FC nailed it with the comment: Would it change the way they thought about their depression to know that it was quite possibly caused by a single polymorphism? Would it make anything ‘better’ knowing “it’s all in my genes”? Wouldn’t one want to treat the depressive thoughts and behaviour regardless?
I was very tempted for a while to send things to 23andme, apart from my paranoia and not knowing what they will do with the results. The main reason I would be tempted running a test on my own in the lab and then destroy the records so they don’t accendental end up in a register somewhere…. [it’s not really paranoia if they are out to get you 😉 ]
Cath Ennis says:

March 9, 2010 at 6:29 pm

Åsa, I hadn’t even considered the “should I tell my relatives” aspect of this. That would be a very tricky one, especially in cases where the genotype-phenotype link isn’t clear cut. Hmmm. In the case of BRCA mutations I would definitely tell my relatives, but for other tests it would depend on whether the result could affect their choice of lifestyle prevention measures or treatment options.
Richard Wintle says:

March 9, 2010 at 6:37 pm

Interesting, and timely since Navigenics, 23andMe, and others now retail “personalized” health risk profiles (largely based on public-domain association data and off-the-shelf SNP genotyping arrays). I think DeCode used to sell something similar, and there are many, many companies that will sell you genetic tests for cosmetic choice, weight loss, or other completely baseless applications.
I’ve had many, many opportunities over the years to include my own DNA as a control in various experiments, ranging from mutation detection in disease genes to benign polymorphism assays. Generally, I’ve never bothered, as it didn’t seem that finding any of this out would be very important (for example, what good does it do me to know I have an allele of some gene that gives me a 1.5-fold risk of a disease that has a prevalence of 1 in 10,000?).
Personalized genomic medicine has great potential, I’m convinced of that – once you get past the concept that 99.9% of your genome sequence is not going to tell you anything useful (this might decrease to 99% over the next ten years or so I suppose).
Cath Ennis says:

March 9, 2010 at 7:58 pm

I’m a “normal” DNA control for a tumour tissue bank, but that’s all anonymised. And I donated quite a bit of blood at my last job; the R&D and QC departments used employees’ blood to test new products, while the sales staff used it for bizarre satanic rituals(allegedly, she adds hurriedly). They paid $10 a tube, which was mostly used to buy nice lunches and cookies. No idea whether that was truly anonymous or not; it would be interesting to see what might happen if a technician found something abnormal.
Åsa Karlström says:

March 9, 2010 at 8:41 pm

Cath I hadn’t even considered the “should I tell my relatives” aspect of this.
That was one of the main questions to think about in the class we did this “thinking about genetic councelling and why it’s not as easy as it seems” . Partly because there might be difference within a family who wants to know and who doesn’t etc.. partly one of those things that usually aren’t addressed on the “comapny website of all these ‘do it yourself kits'”.
You’re right about the tricky part, especially when the linkage geno-pheno isn’t superclear. As it turned out, when we did case studies, it is hard even with the BRCA scenario. Especially with female relatives under the age of 40 – when you have to address questions like “remove ovaries as well as breasts, only breasts etc” when one relative has found a mutation in her genes. Who contacts the relatives for example? (It’s all easier to address from the other end, prior to the testing. although some people feel that they get nervous “for no reason” then. tricky is the word.)
Sonja Babovic says:

March 9, 2010 at 8:53 pm

I find donating blood for immunology research (especially in-house) super sketchy…. can you imagine if someone’s blood ended up being used to test, say, a CD4 T cell enrichment kit, and it was found that their count was abnormally low? Oh the speculation!
Cath Ennis says:

March 11, 2010 at 2:21 pm

Yeah, it was never actually clear to me how anonymous that blood donation system was! I’d never thought of the CD4 T cell count aspect, although we did once discuss how nice it was to get a regular, free, leukaemia screening test…
Richard Wintle says:

March 11, 2010 at 2:29 pm

This discussion of blood (vs. DNA) reminds me I used to donate blood for neutrophil research – in exchange for money. I was a graduate student, what can I say? I think it was only $10 a time though. And years ago I was one of many who donated blood in order to provide human serum to grow hematopoeitic stem cells in a famous local lab here. I only did it once, because it required fasting (i.e. being spiked before breakfast). The wooziness was a bit too much for me. Later in the day, I’m fine for full-scale Red Cross-style blood donations, but early in the morning with no food – not so much…
Cath Ennis says:

March 11, 2010 at 2:42 pm

yeah, fasting blood draws are nasty (especially if you bike everywhere, usually after breakfast, and don’t do too well when pedalling up hills on an empty stomach). My old company only ever required 3 or 4 tubes at a time, though, and luckily not fasting. They’d have had to pay me much more for fasting blood!
Nicolas Fanget says:

March 11, 2010 at 2:58 pm

Going back to FC’s dilemma, wouldn’t knowing you are susceptible to depression be anxiogenic to start with? So genetic testing for e.g. metabolic disorders could be do-it-at-home OK, a bit like pregnancy tests, but for anything that involves counselling stiffer safeguards would have to be put in place.
Cath Ennis says:

March 11, 2010 at 3:30 pm

FC was already depressed, though.
I agree that there are some genetic tests that will require counselling, and some that won’t, but I don’t think it’s as clear cut as metabolic vs. other, and I think it will be different for different people. e.g. for some people, knowing that their symptoms are caused by a genetic disease would be a relief (“it’s not my fault?!”), while for others the exact same result might be distressing (“there’s something wrong with me / my children”)…
For some people, at-home pregnancy tests might be in the “needs counselling” category 🙂