Monday, November 5, 2012

Area Doctor Shatters Area Girl's Dream of Being Taller Than She Is. (A personal genomics parable)

March 15, 1993. Oviedo, FL - A sophomore at OHS who injured the soft tissue in her knee in a freak accident while warming up for the 4 x 100 meter relay at an area track meet on Friday night was told, by her doctor, that she is done growing.

X-rays of Holly Dunsworth's knee--part of routine injury diagnosis and plans for repair--showed that the growth plates in her proximal tibia and distal femur are fused. This indicated to the doctor that Dunsworth has completed growth and has reached her full stature, so he passed this information along to her.

"He said it so cavalierly, too," said Dunsworth. "I spent my whole life wondering how tall I'd grow to be, hoping and wishing I'd grow to be tall enough to really dominate on the basketball court. And my doctor didn't even warn me that he was about to deliver this dream-killing news, and he definitely didn't ask me if I even wanted to hear it in the first place."
x-ray of human knee showing unfused growth plate of still-growing tibia (lower right bone). Source
The news was "even more devastating," said Dunsworth, than learning that her knee injury would most likely require surgical ACL (anterior cruciate ligament) reconstruction, meaning several months of recovery and probably a missed junior year of basketball.

"Sitting out a varsity basketball season just as I'm starting to be noticed by college recruiters is one thing," said Dunsworth, "but learning that I'll probably never be tall enough to play in the NBA or the Olympics is another. What should I dream now? What can I look forward to? I will never dunk. It's over. I wish the doctor would have kept my growth plates to himself."

When asked whether she expected to be much taller than her present 5'7" because she'd seen other girls continue to grow taller at her age, or whether it was because of her freakishly tall parents, Dunsworth said, "Oh no. Girls are pretty much full-sized by sophomore year. And my dad's 5'11" and my mom's 5'8". But I guess I just hoped I'd luck out. And now all that hope is gone, long gone. A big part of me is dead and I don't know how I'll fill this hole with anything good. I just don't know how I'll do it."

True story. Fake quotes. Thanks, The Onion, for the inspiring framework. Note that I did not work the word "cavalierly" into my verbal capacity until many many years later. (Fine, it was today.)  

Here's a look at one of the dreams that died that day:

If you follow this blog then you know that we talk about personal genomics quite a bit. My parable's not a perfect comparison for many reasons.  Obviously the cessation of growth is not equivalent to the cessation of life (death sentences, being how people can interpret genomic data) or even to the deterioration of health, as with the onset of disease. Further, my complete growth plate fusion was not probabilistic news, like so many of the genetic interpretations that companies like 23andMe provide.

But I thought it was important to share this sort of story where my identity and dreams were wrapped up in my biology and where a doctor delivered news of incidental findings about that biology (which deeply affected my identity and my dreams) without my consent or without even considering my feelings.

I had some rather ignorant notions about biology if I thought I could still grow taller past 16 years of age, especially given my parents' heights, but does it matter if you consider how fundamental those assumptions, however misguided, were to forming my identity? I never even stopped to consider whether I was done growing. It was always a hopeful mystery. Learning from a scientific authority that it was all over was harsh. It's culture, people, and it's not always rational but it's what we do. It's who we are.

On the other hand, culture changes with education. Humans will always have dreams, and I will always have dreams, but maybe my dreams would have been different in high school had I learned to ditch magical thinking in favor of the real evidence staring me in the face. Thanks to family history and to growth patterns of my classmates, it was obvious that I was done growing. I shouldn't have needed the doctor to tell me that! But I did. I needed the education. I needed to be enlightened.

I've been thinking about this story of mine because of what I've been reading about personal genomics and probability lately:
  1. What Your Doctor Isn't Telling You About Your DNA. (Time Magazine)
  2. John Hawks's recent reflections on things like the Time piece.
  3. Razib Khan's reaction to the Time piece
  4. Genetics textbook author Ricki Lewis doesn't want to see her genome
  5. If you're taking gene-based probabilities as certainties--the hullabaloo over Nate Silver's estimates  demonstrated that many do!--then there's potential for harm from participating in personal genomics.
Sure, a big part of the personal genomics dilemma is whether to make people worry about something they cannot prevent at our present level of knowledge (e.g. Huntington's, which 23andMe does not report).

But another big part of the personal genomics dilemma is whether to make people worry over nothing at all (e.g. higher estimated gene-based risk but the condition never ends up presenting).  This is the paradox of probabilistic medical data.  There was no such uncertainty or estimation about my fused growth plates, and since the news wasn't about how I could get sick or die, that's presumably why my doctor did not have to seek my consent to tell me this incidental finding of the radiography.

That I'm done growing is fact. That I have increased risk of breast cancer is fact-ish. It's a fact that I have certain SNPs or alleles or mutations associated with a specific type of breast cancer. That's certain.  Whether those alleles are meaningfully associated with breast cancer isn't. And what having those alleles means for me, Holly Dunsworth, isn't either. My risk for breast cancer might not be as high as 23andMe estimated (or it could be even higher, or it could be  lower). That estimate's not based on any data from my lifestyle and environment. It's only based on my genes in my spit--and only the genes that were genotyped. My report of increased breast cancer risk has got the potential to worry me over nothing. But it could also make me more vigilant so I can catch it early if it does occur.

I'm one of the many out there who wants to know everything about my genome that I can, even if interpreting much of it requires fancy brains to program fancy computers to estimate probabilities. I unlocked my Alzheimer's and Parkinson's reports on 23andMe and if they genotyped for Huntington's I'd have unlocked that too. I'd like to have all the information I can have. I hope risk estimates will improve over time. I'm optimistic like that, but (a) I understand very well that there is so much of our health, our lives, etc that we will never be able to predict no matter how much science learns about the genome and (b)  I have no idea how high a reported disease risk has to be to significantly worry me. Something is bound to kill me. If it's not all the confounders of old age, then hopefully it's molten lava or a black hole or chocolate. What's the big deal? We all die. I'm also pretty comfortable with some level of genetic determinism since genes figure greatly in how bodies work. It's not scary. It is what it is. Actually, it's brilliant. And it's even more amazing that it's a terribly difficult and sometimes impossible system to understand. If it wasn't so complex, all our little variations wouldn't have the wiggle room and the workarounds to function and to function well!

That earth-shattering news about my growth plates? I got over it. And pretty quickly. That hole inside my melodramatic, Holden Caufield-loving teenage heart? It was filled up with other dreams.

I wonder about all those people with life-threatening conditions and a shortened life expectancy. My grandfather was one of them, living some 40 years past his expiration date. I recently met an enchanting 70 year-old woman with a heart condition and an expiration date of 25 years old. She claims that it was her doctor's diagnosis (some might call it a death sentence) that gave her such a wonderful life, inciting her to cherish every moment and seek pleasure in ways that others do not or cannot.

But while deciding whether to see your genome and to receive the disease risk estimates calculated from it, how does anyone know they'll react like my joie-de-vivre'd friend? How does anyone know whether probabilities of disease-risk will be at least not misery-inducing and at best life-enhancing? Could there be a SNP for this charmed outlook on life/death that we could test for before we agree to learn what our disease genes say?


And as for the new dreams that filled the empty hole in my soul where all the basketball dreams had died:  Maybe those new dreams were better dreams! I can certainly choose to describe my life in hindsight that way. And I do. They really were much better dreams. Similarly, I can choose to see my increased risk for breast cancer, psoriasis, age-related macular degeneration, rheumatoid arthritis, restless leg syndrome, exfoliation glaucoma, melanoma, esophageal squamous cell carcinoma, and stomach cancer (so says 23andMe) anyway that I choose.

For starters, ever met anyone afflicted with all those problems during their life? Right. That's really telling isn't it? And, of course, understanding even in theory how those risk estimates are made helps a great deal. And so does knowing that most of those conditions are already documented in my family history. And so does knowing that for some known conditions I could have new mutations that are hard to detect, or may never be detected. And so does knowing that those risk estimates don't incorporate my phenotype, lifestyle, or environment. And so does knowing that, just by being alive, my risks for obesity, coronary heart disease, and type 2 diabetes are still higher than my relatively increased risk for any of those aforementioned conditions.

Exercise, eat well, live right. My genes are my genes. And it is what it is. It's what I've got and it's good. Amen, awomen, amonkey.

And if this post wasn't a slam dunk, surely I'll have another shot. Because of how I'm built, I have no choice but to believe that I will.


Anne Buchanan said...

Point beautifully made, Holly, as always. And nicely nuanced, which is absolutely as it should be. But given that this is MT, and that we've been debating this issue for some time now, I still do have to weigh in with my view which, in keeping with the theme of your post, is that I think these DTC companies are basically playing games.

People with frank Mendelian disorders in their families don't need them, and I'm guessing are unlikely to turn to them, because they've got an informed medical system to turn to -- genetic counselors and physicians. Which is not to say that the system is infallible for these people at all, but at least estimates are based on actual family data.

And, these companies can tell people with rare sporadic disorders nothing -- indeed, even whole genome sequencing is unlikely to identify causative mutations in such cases. So who are we left with to play ball with these companies? I don't know this, but I'm guessing it's essentially healthy people curious about what today's risk estimates can tell them about tomorrow's risk. Which even if today's estimates are rock solid, which they are not, is necessarily going to be limited, given that we don't know about tomorrow's environmental risk factors, or how our life style will in fact affect our risk. And given this, what does this say about what they are actually selling us?

I agree with you, obviously, that these issues are nuanced, and there's more to understanding risk than knowing our alleles -- or on the other side of the coin, our environmental/life style risk factors and exposures. Epidemiologists, after all, are as bad at prediction as anyone. But I disagree that these companies are selling much if anything that it's truly helpful to know. Ok, yes, some specific information about carrier status for a limited set of diseases, but since that generally comes packaged with all the rest of the hype, I think it's not enough to justify the oversell.

Ken Weiss said...

I'll add to Anne's comment, that I know from personal experience one reason for the turn to genetics, besides the sexy technology, money, and resurgent belief that we can peer into peoples' genuine inherency (or worth?):

The reason is that epidemiology was failing to understand the diseases now so fervently approached as if they were 'genetic'--even when we know, and knew, that most cases are not predictable by genes _and_ that environmental factors predominate in determining risk.

The major secular trends in incidence of most of the non-'Mendelian' diseases shows this clearly.

But we are a technophilic society and have the belief that technology and hard 'science' will solve almost any problem. That belief may or may not prove to be justified, but it is certainly deeply engrained in our current culture.

Holly Dunsworth said...

Yes, for some technophiles genetics is their version of homeopathy!

Holly Dunsworth said...

Anne said, " But I disagree that these companies are selling much if anything that it's truly helpful to know."

This is maybe true if you mean about "me" but what I'm seeing with 23andMe is it's teaching about BIOLOGY and GENETICS... the larger picture. You're engaged and all of a sudden, now you're going to learn these things. The educational side effects to naval gazing are, to me, a huge plus.

Ellen said...

I'm Anne and Ken's daughter and I'll just spill the beans on a recent development in our lives. I've had a lifelong illness, an ion channelopathy called hypokalemic periodic paralysis. Some of the mutations that cause the disorder have been identified. Mine hasn't been, yet, but the three of us have just joined a study seeking the causative mutations for various rare Mendelian diseases. They will do whole exome sequencing on myself and my parents.

I've made the opposite decision that you have. I don't want to know anything at all about my genome except what is directly related to my illness. I have already spent most of my lifetime deeply compromised by my health. I already know that I have something, I already know what it's like to cope with the reality of permanent disability, and I personally have no desire to spend the rest of my life worrying about any other possible or absolute susceptibilities to other diseases especially since, as you said, it's hard to know how helpful that information is at all. I want to hang onto the freedom of whatever obliviousness I have left.

Ellen said...

(No offense intended towards your own perspective on the issue, by the way. Like you said, we each have to read our own ability to handle the type of information(ish stuff) that is provided by knowing one's genome.)

Holly Dunsworth said...

Hi Ellen. Thanks for sharing your experience and point of view with us. Very very best wishes and warmest thoughts as you undergo your study.

MOCKBA said...

Genetic testing as a dream killer? In most cases I remember, it was a nightmare-killer, when a terrible disease runs in a family and the people feel doomed, but then the testing tells them that they didn't inherit the familial mutation - or that they did, and there is such and such way to mitigate the risk...

MOCKBA said...
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Holly Dunsworth said...

My post brings up many issues and topics for conversation without going into much detail for any particular one. I knew this would potentially cause trouble for some readers in connecting the dots, e.g. comments above that sum things up as "genetic testing as dream killer." C'est la vie.

MOCKBA said...
This comment has been removed by the author.
Holly Dunsworth said...

I sense prickliness that I don't understand so I'll just thank you for reading and for sharing your thoughts.