We’re not ready for do it yourself genetic analysis

You may be wondering why Stanford Medical School’s new genetic interpretation class – the one that offers medical students the opportunity to study their own genes – has made the news. After all, what better genes are there to study than your own? And if you were a medical student, wouldn’t you want to have your medical school subsidize 80% of an $800 test as part of your curriculum – isn’t that kind of like a “free” healthcare kickback?

But people whose work includes genetic counseling, or people who themselves have undergone genetic testing for a serious disorder, will likely beg to differ. And usually in very strong terms. The fact is, looking at your own genes is not at all like that Bio 101 lab we all remember where we got to look at our own cellular spit under a microscope. Do-it-yourself genetic analysis – especially the kind that methodically sifts through the dusty archeology of all known hideous human disorders – is a whole world of hurt, just waiting to happen.

Genes have become our modern day molecular gods and goddesses. Uncoil the wrong one of these tiny strands of nucleosides and you can inadvertently unleash enough tragedy and omnipotence to be worthy of a Greek myth.

A lot of genetic-counseling experts will tell you that sure, it can be done safely. But only with the proper understanding and respect for what you may awaken. And you have to keep in mind that it’s vitally important to have the tools to deal with the fallout when the unexpected is unleashed. Especially if what you find is a nasty gene, slumbering amid all the mummified others in your airless chromosomal Pantheon.

Here’s one example of the kind of fallout I’m talking about. Say a member of a family needs a transplant. Maybe it’s a close-knit family with kids in their twenties and parents who’ve stuck by each other as lives have changed and careers have risen and fallen and now, when life should be a source of teasing and holidays in crowded kitchens snorted laughs in response to old jokes. But, instead, tragedy has struck and life has become one endless series of hospital rooms and misery and wasting. Everyone wants to help, to be a donor. Siblings, parents, even cousins, aunts and uncles will all show up to get tested for a genetic match. It is not that uncommon for the testing to reveal that one of the men who volunteers as a potential donor is not, after all, the biologic father of one of his (often adult) children. But that’s not what was asked, and instead of delving into what is called “ancillary” findings, the family is only told there “isn’t a match.”

Now, since the Stanford Medical School class isn’t looking at family-member gene comparisons (yet), no one is likely to step on that particular landmine. But minefields await, some of them even more self-destructive. Because here’s the sneaky thing about genes: Even if you know, intellectually, that genes don’t determine everything, there’s still some part of your brain that does believe that they do decide everything. Filtering flawed information through the bias of self-interest has always been know to be bad medicine (“the doctor who doctors himself has a fool for a physician”). Much of the predictive value of genetic testing still falls into the category of (at best) bad science, or (at worst) profiteering snake oil.

But what makes the situation even worse is the fact that hidden within this murky labyrinth of cracked pots are some omnipotent nasties you wouldn’t ever want to unleash on the unsuspecting. Some genes are, clinically, as all-powerful as our subconscious fears.

At least one of the genes for early dementia, for example, is “dominant with 100% penetrance.” That’s dry medico-jargon for the fact that if you have this gene, you will indeed be stricken with severe dementia – usually in your forties. It remains a disease for which there is no treatment. As scientists dryly report “such knowledge has been reported by patients to significantly alter life decisions and relationships.” Reasonable people might argue that knowing such a fate in advance could be worse than living the experience later.

The number of genetic diseases that manage to hit the sweet spot of being altogether a) reliably detectable, plus b) reliably predictive of disease, and c) very treatable, are almost non-existent in the adult clinical world. The story is different for children, where the classic example of effective genetic testing is that of newborn-testing for phenylketonuria (PKU) – a disease whose potentially tragic outcome can be completely avoided by knowing you have the gene and changing your diet. But in adult medicine, genome mapping has unearthed, as of yet, almost no PKU treasures.

Yet.

With few exceptions, we are still, for the most part, a wonderfully messy combination of what we are born with, and what we make of it. And, for almost all medical conditions, how good our care is.

For years I resisted getting genetic testing for breast cancer – my primary fear being that I would become a healthcare pariah. If a positive test was in my record, I’d be one of those people whose lives and careers are determined by the coverage they can get (or keep). As a doctor, I knew that a decent physician would know my risks purely by taking a good history – and that the test itself shouldn’t change things that much. I chose to get the genetic tests when I had a biopsy done, reasoning that the biopsy alone raised so many red flags that the difference in getting tested would be relatively trivial. The fact was, I realized I wanted to know for my daughters – that I didn’t want to have genetic testing on their medical records if it could now be on mine. And, frankly, if my test showed that I was positive for one of the more nasty genes, I’d be at peace with making evidence-based decisions about all the risk-reducing options, including the more drastic surgical ones. I had one priority – I wanted to survive for my kids.

It all seemed so clinically logical. So financially prudent. So cleanly prioritized.

So I was woefully unprepared for the emotions that testing churned up. I went through the counseling, mentally ticking through the checklist of data to see if my counselor covered it all (she did), while my emotions veered and scrambled and careened. I sleep badly and called my mother to ask who died of what (“hard to say, ‘female troubles,’ that’s all we were told”). I put my family into boxes and X-d out the dead. I’d thought we were healthy, farm-folk who were tough and persevered. Apparently we died like flies. I balked at asking for my family’s medical records, merely shaking my head at my counselor’s lack of understanding about the South, and the natural modesty and privacy of people. Besides, I knew the request, veiled as a normal part of the process, was purely for research purposes and would not benefit my personal medical care at all – not unless we, as a family, wanted to become the subject of someone’s doctoral project.

I didn’t sleep the night before my appointment time. I tossed and turned and had fevered discussions with my long-ago passed away, wasted-of-pancreatic-cancer grandmother as she suffered and moaned despite getting enough morphine to kill a horse.

I arrived early at UCSF, and, being a medical insider, I knew when my counselor called my cell to tell me she was running late for our appointment, what my result test would be. No one runs late to give bad news.

So I had a negative test result, but I was told, earnestly, that I mustn’t let my guard down – that I’m now labeled as being part of a “cancer cluster.”

Probably they just don’t have a genetic test yet for what my family has.

Genetic testing stirs up all the silt in your life, even when the result is good, even when there’s something you can do about the result. A wry, insightful physician-colleague of mine (another internist), after extensive heart problems, got genetic testing done and found that he had the kind of gene that can make people drop dead. From his Castro home, he felt compelled to pack his bags and head to Memphis, driving down two-lane roads to find far-flung family that he hadn’t spoken to in decades, and had sometimes only heard out in that way we Southerners drape our family trees to orient a conversation (“you remember Ethyl’s kid – the one with the limp? – his youngest, the one that married Myrtie’s second littlest after they met at the Revival? – well, his third cousin, Rayford’s buddy, got a job down at the plant…”).

He told me about his days of standing in blistering Tennessee heat as he explained to virtual strangers genetic details about the very fabric of their cells, and how they should be tested, and that if they had the gene a resuscitation box could be stuck under the skin of their chest – here, like this, see, it’s only as big as a pack of cigarettes – and that this box could shock a heart back to life if a person tried to suddenly die (“swoon, you mean? My great aunt did that all the time, and we don’t have health insurance…and besides, how is it I’m supposed to explain this to a doc?”).

To me, the frustrations, and explosive emotions, and changing life-paths all provoked by this one genetic test represent what many would call, ironically, a best-case scenario outcome. After all, testing for a sudden death gene is not exactly like testing for aggressive, early dementia – having a defibrillator implanted, while not at all trivial, is a one-off treatment option.

And if the task is to filter through your body’s entire genome, surprising discoveries can happen to anyone. People whose family histories do not seem full of health problems can find unexpected genetic results – after all, recent studies reveal that we’re all, basically, mutants. So how is a relatively young, inexperienced, probably ill-informed and un-counseled medical student going to deal with an explosive genetic result? Stanford has taken steps, but is it enough? Even for my experienced, well-informed physician colleague, who thoughtfully requested his own specific testing, the experience was intense.

One day during his trip to Tennessee, feeling demoralized, overwhelmed, his life derailed completely, he found himself stuck on a two-lane road in his rental car, traffic rapidly backing up behind him. The way forward was blocked by a mutt, an unwashed ribs-showing dog that had suddenly wandered onto the center line. The dog was two-headed – literally. My physician friend said it was the kind of thing you only seem to see on very rural roads. There the two-headed dog stood, swaying, and the poor thing appeared stuck, unable to decide, it seemed, which way to go next.

It was, he said, symbolic of the whole experience.

Jan Gurley is an internal medicine physician who blogs at Doc Gurley.

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  • http://wordsforhirellc.com/blog Karen Swim

    Thank you for writing this wonderful, insightful post. I spent a great deal of my corporate healthcare career working for clinical labs that did genetic testing and have always been fervently against self-testing. There are too many variables, emotions, and potentially life altering decisions that come with being “armed with information.” I have seen the impact from the healthcare side and the personal side as I endured BRCA testing with a best friend (also in healthcare). Knowing your genetic history even in the company of trained professionals can be an emotional journey. While testing helps, it should never be treated lightly and definitely not attempted without a village of support.

  • SarahW

    Can’t agree. It’s always better to know – you might succumb, you might be saved, or save yourself. Your best opportunity is earliest knowledge. Your best opportunity to manage your future is an ability to predict what might happen, an you gain whatever control there is to be had over the situation.

    How you save, dress, eat, marry, work live – all your choices, informed by the risk you’ve discovered. And assuming people aren’t in isolation, larger identified at-risk populations could be a boon for research and maybe even prevention, cure, delay or management to minimize decline is possible.

    • pj

      “… predict what might happen” sounds like an oxymoron. Anything “might” happen.

      Be careful re “always better to know.” Ask all the older gentlemen who become impotent and incontinent after a high PSA level led to prostate surgery and it turns out they didnt have cancer or had a non aggressive type, one that would’nt have killed them. Or chronic back pain patients who became worse after an MRI found a bulging disc because once scar tissue is created in the spine (from surgery), it can NEVER be undone.

      Try googling, “incidentalomas”. Also, NPR had a good piece on the (bad) advice people are given who bought DIY gene testing kits that showed abnormalities.

      Not nearly enough patients and Docs ask, “How is this test going to change the treatment?”

  • Suzy Q

    I can’t agree either. I recently found out my first cousin’s son was diagnosed with hereditary hemochromatosis and is undergoing regular phlebotomy in order to prevent complications. If he hadn’t needed a complete physical to obtain life insurance in his mid-thirties he would not have known until too late. By deductive inference, I then realized this is what my father’s two brothers had died of in their early sixties. I had myself tested for the two possible genes that I could cause this fatal illness. This was partly to protect myself and partly to protect my son, who wouldn’t have to be tested if I were “clean.”

    P.S. I don’t have any copy of either gene. That’s good to know. If I had a gene or genes I would not have panicked or initiated treatment without further tests to see if I had actually developed the disease the genes control.

  • Christina

    This isn’t a comment about this article, which I throughly enjoyed by the way, but about the writting style of the doctor. She has a definite gift and I wonder if she has ever written non medical books? I would love to read stories about her growing up in the south.

  • http://mad.printf.net Madeleine Ball

    PKU is not tested genetically. It’s a biochemical test.

    There’s a lot of different genetic mutations that impact the PAH enzyme and it’s unclear how well one could predict PKU knowing the genotype. For an example of an attempt to classify these, see: http://www.ncbi.nlm.nih.gov/pubmed/9634518

    I find it troubling how often I see PKU held up as an example of successful genetic testing. This sort of mistake seems to reflect a lot of ignorance on the part of commentators, in line with Dan Vorhaus’s observation: “a disturbing trend: developments in the area of personal genomics that deserve serious public debate are shaped from the outset by commentators, policymakers and lawmakers more concerned with making a point than with advancing the conversation.”

    Regarding genetic testing impacting health insurance: why didn’t you mention GINA? The Genetic Information Nondiscrimination Act of 2008 is supposed to prohibit health insurance companies from discriminating on the basis of genetic results. Either you were aware of it but chose not to inform readers of it, or you didn’t know about it (if so, I hope hearing about it helps your experience feel a bit less negative).

    I appreciate that you have a negative experience to relate, but many individuals have positive experiences with genetic testing. I don’t think anecdotes and hypothetical risks advance the conversation very well. Remember that personal autonomy is highly valued in our society (we take risks when we drive, when we overeat, etc.). I think we should be careful about restricting it, especially if that restriction inhibits the moral/philosophical desire for self knowledge.