genomeboy.com

Me: I’m hoping you’ll sign my book.

JCV: You wrote a book?

Me: Not yet, but you did. Will you sign it?

JCV: It’s not out for another month. How did you get it?

Me (sheepish, eyes cast downward): Um…eBay?

JCV: (grumbles about eBay, signs book, hands it to me). Here. Now it’s worth a whole bunch of money. (As elevator doors are closing) Did you read it?

A friend asked me about my decision to enroll in the PGP and the effect it might have on my two kids. By releasing my genome, he wanted to know, am I potentially limiting my children’s claim to privacy?

The short answer is yes. “Personal” implies it’s only about you, the sequencee. But you don’t have to be Gregor Freaking Mendel to know that it ain’t just about you. In the near term, familial disclosure may be the biggest elephant in the room for personal genomics.

If you want an idea of how this will play out again and again, read the front-page article in last Sunday’s NY Times about the 33-year-old medical resident, Deborah Lindner, her positive test for a mutation in the breast cancer gene BRCA1, her reaction, and the effect it had on her family.

Within the Lindner family, you see two types of folks, which Jason Bobe presciently summarized: the infovores and the ignotarians. The former see knowledge as power. The fact that their relative was found to carry a mutation was a call to action. They got tested for the mutation and, if they were positive too, they either continued to monitor themselves closely through mammography or else elected to have prophylactic surgery. The others, the ignotarians, did not get tested and in some cases derided Deborah’s decision to have a mastectomy–”Why is she mutilating her body?” they wondered. I suspect their objections were as much about being forced to confront and perhaps lose their ignotarian status as it was about anything else.

Despite my participation in the PGP, I am very sympathetic to the ignotarian position. Just because I have a toothache doesn’t mean I want to rush off to the dentist. My first course of action will be to ignore it and hope it goes away. I reckon that most of us have aspects of our lives in which we choose to be ignotarians.

I pray that nothing in my genome will cause my daughters anxiety. I can’t change their genomes, but as they get older I can counsel them about the evils of genetic determinism, I can tell them that what’s known about my genome is only probabilistic as far as they’re concerned. In other words, I can try to help them interpret what the information in my genome and/or theirs might mean. The option of choosing to remain a card-carrying ignotarian, however, will only get harder as time passes, and for them it may well be impossible.

I’m guessing that in the end it won’t matter–they will probably both have blogs and Facebook profiles and all the rest by the time they’re adolescents, just as they can’t get enough of that goddamn Webkinz right now. And I imagine by that time, posting one’s genome online will be no more taboo than posting one’s CV, or at worst, one’s slightly drunken Flickr photos.

But I could be wrong.

Berci comments:

“Personally, I wouldn’t like to know about my ApoE status as long as there are no treatments…”

Well, this is the thing. Correct me if I’m wrong, my board-certified brothers and sisters, but my sense is that for most highly heritable conditions there are few meaningful treatments. Even if that’s no longer the case for Alzheimer’s (and I’m no neurologist, but I have serious doubts), I don’t think anyone would dispute the broader notion that we’re generally much better at diagnosing and characterizing diseases than we are at treating them. One hopes that that equation will continue to change as it has for, say, HIV (at least in the developed world), albeit on a much faster trajectory and without the same terrible cost in human lives and human suffering.

Until then, we clearly have the technology to blind ourselves to the parts of our genomes we don’t want to know about. My questions are more about the source of that reticence and whether it will last: how much grim self-knowledge can we live with and will the ready availability of genomic information alone raise the threshold of what we can tolerate? “I got sequenced because I could. And oh yeah, by the way, it turns out I am at 100-fold increased risk for Fatal, Incurable Disease X.”

And if we’re willing to find out for ourselves, are we willing to share it with others? For those of us signing up to be public genomes, even though we’ve been given the option to redact whatever we want, have we somehow signaled an implicit willingness to let it all hang out, no matter how ominous the data?

I also should have realized that Peter Pauling would feel a filial duty to send my manuscript to his father. After reading it, Linus fired off an angry letter to [editor] Tom Wilson calling Base Pairs “a disgraceful example of malevolence and egocentricity.” He wrote demanding that I remove the lines “Linus’s screwy chemistry” and “Linus looking like an ass.” These were phrases I knew good taste would lead me to delete before the manuscript went to the printer. But since they were true, I was loath to remove them before absolutely necessary.

- from Watson’s forthcoming memoir, Avoid Boring People

I went back to my mother
I said, “I’m crazy, Ma, help me”
She said, “I know how it feels, son,
‘Cause it runs in the family…”

- Pete Townshend, “The Real Me“

This remarkable piece in the LA Times about legal scholar Elyn Saks, her battle with schizophrenia, and her decision to write a book about it, is a must-read:

Saks knew she might pay a price for her candor. Would her hard-earned career come crashing down if people knew the real workings of her mind?

A colleague suggested that Saks write under a pseudonym. But that would send the wrong message, Saks explained.

“Elyn,” her colleague reasoned, “do you want to be known as a schizophrenic with a job?”

The fact that Saks waited until she was 51 (!) before “coming out” as a schizophrenic says something to me about the biggest potential stigmas attached to personal genomics. As uptight as we Americans are about sex, we seem to be even more hung up on brains. Jim Watson (whose own son, incidentally, has schizophrenia), is prepared to disclose his entire genome except for a single gene, the Alzheimer’s disease susceptibility locus APOE. When I interviewed him at Cold Spring Harbor in May and asked him why, he shrugged and said his maternal grandmother died of Alzheimer’s at eighty-three. “I don’t want to worry that every lapse in memory is the start of something,” he told me. (Of course, I’m thinking, “Dude. You’re almost eighty!“) And recently, a prominent genetic policy scholar surprised me by writing in an email that he wouldn’t want the world to know if he were homozygous for APOE4 or if he had a mutation in another Alzheimer’s susceptibility gene, PS1.

One of my fellow PGPers suggested that genes like APOE that affect brain function may be considered more important by those of us who are “knowledge workers.” And yeah, I suppose if I knew there was a good chance I’d wind up eating dinner through a straw, forgetting my closest friends and family, and wearing diapers for the rest of my adult life, I probably wouldn’t want to advertise it to the world.

But must I feel that way? What does it mean when Nobel laureates, to say nothing of garden-variety dorks like me, are so uncomfortable with even the possibilities of their own biology that they feel compelled to hide them, even from themselves? Aren’t we knowledge workers supposed to be the enlightened ones?

This morning I was on my back counting dots in the ceiling tile while a pleasant woman repeatedly asked me to turn my head toward her and Sheryl Crow quietly insisted that a change would do me good. (Ach, Honey, don’t I know it.) Alas, it’s not what you’re thinking. As the pleasant woman poked and prodded my fork-tender gums with what I swear is the same device we used to eviscerate fetal pigs back in freshman biology lab, I tried not to flinch or, at the very least, tried to ignore the tears running down my cheeks.

Our species may have undergone a spectacular makeover since its knuckle-dragging origins, and our phenotypes may change dramatically during our brief time on this mortal coil*, but I swear to Jesus Haploid Christ that I hate going to the dentist just as much as I did in 1972.

As the feeling left my lower extremities and the pleasant woman continued violating the Geneva Convention in 11 ways, stopping only to Hoover the blood and saliva from the recesses of my mouth, I tried to console myself with the idea that next month (right, George?), when George Church presents me with my genome sequence, I will somehow be vindicated. There amongst my motley collection of A’s, T’s, G’s and C’s will be evidence that the disaster that is my mouth is not my fault. The gum disease, the infections that have led to periodic root canals and implants, the chips and cracks that make my oral cavity indistinguishable from that of a Dickensian orphan–all will be revealed to have a genetic basis. I mean, it stands to reason that I must have a humoral immune defect or mutations affecting my periodontal tissues. Or some other pernicious host factor that renders me susceptible to tooth decay or worse. Must be, right? The PGP may not get much from my spartan medical records, I thought, but at the risk of immodesty, I am a dental genomicist’s dream: my paper trail of oral surgery, orthodontia and good old-fashioned fillings and crowns is a mile long. (Not that I’ll let any research-minded dentists anywhere near me…)

When the bi-annual ordeal finally ended and I extricated myself from the chair, I went across the street for what I thought was a richly deserved coffee and chocolate chip scone. It was then, bathed in warm glucose, that the voice of the genome du jour entered my head. “…you cannot define a life or any life based on DNA alone,” he writes in his forthcoming book. “An organism’s environment is ultimately as unique as its genetic code.”

Or, as my mother would say, “Don’t forget to floss.”

UPDATE: As usual, I am behind the curve. (thanks, Keith)

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*O Prostate, why hast Thou forsaken me?

So PLoS Biology is publishing a paper on Craig Venter’s genome tomorrow, Tuesday September 4. Apparently there was a press conference this morning at 10AM Eastern to discuss it. I’m very confused: this is “the first diploid human genome” and it’s unveiled with barely a heads-up on Labor Day morning?

Who are you people and what have you done with Craig Venter?

UPDATE: Um, never mind…

Genomicron offers a recipe for how to write a bad science story and pretty much nails it. I plan on sharing this with my students next semester.