genomeboy.com

Years ago when I was a callow genetic counseling student doing a fellowship in a then-newfangled human genetics lab, I met a guy–a psychiatrist, no less!–who claimed to have obtained a minus-80-degree freezer, a PCR machine, a centrifuge, some pipettors and some gel boxes and installed them in his barn out in the woods. It struck me as both funny and outrageous. Why did he do it? “There are experiments I wanna do that I just can’t do at work,” he said with a straight face.

I confess I don’t know what became of my acquaintance, the Jeremiah Johnson of Molecular Biology, but no one’s laughing now. Because this is exactly what Hugh Rienhoff did (presumably minus the woods) in order to try to track down a mutation that might explain his young daughter’s rare congenital syndrome and her consequent failure to thrive: he bought a used PCR machine, a microcentrifuge, some pipettes, and a gel box. (My only question: did he get them from eBay?) I know I’m a week late on this piece in Nature (subscription only–sorry!–but summarized nicely here), but I’m only just now getting my head around it. In any case, it is an extraordinary story well worth your time and I hope Brendan Maher winds up in Best American Science Writing because of it.

Some thoughts:

• “…we’re still left with maybe a third of patients who come in with morphological abnormalities for whom we’re unable to make a diagnosis.”
  

I find this to be terribly depressing. One in three clinical genetics patients can’t get a diagnosis, let alone a treatment? The incidentalome and all the other bottlenecks notwithstanding, is there a better argument than this grim statistic for starting to imagine what it would take to make re-sequencing a meaningful and routine part of medical genetics workups?

• …With help from George Church, a Harvard Medical School professor with an extensive track record in new technologies for sequencing and synthesizing DNA, Rienhoff developed a sort of ‘phenotype spreadsheet’ on which to record his daughter’s clinical history.

Ah yes, George Church…Hmmm. Isn’t this guy supposed to be one of those “elitist celebrity genomes?”

• …Rienhoff gave his daughter’s doctors permission to speak to me, and not all of them agreed that he was doing the right thing…in deference to [Hal] Dietz he has removed from his website a folder called ‘How to sequence DNA’ that he had never filled.

This seems to be a pervasive argument–which I’ve heard directly from some folks at the NIH and elsewhere–the essence of which is, “We’re professionals. Don’t try this at home.” As if to sequence one’s own DNA might be akin to building–or disarming–an atomic bomb, a terrifying and awesome responsibility that we won’t be ready for until some governmental or academic body says that we are. Next thing you know desperate people will start trying to cure their own terminal cancers.

Somehow it all feels so familiar…

Well, they had to do something, right?

Someone close to the American Society of Human Genetics tells me that when urged to take a stand on Watson’s remarks, the Society responded with a tepid, “He’s not one of our members.”

I propose establishing a Genome Commons, a public knowledgebase of human genetic variation and its effect, culled from databases, diagnostic laboratories, and the scientific literature. Ultimately, such a repository of our common human inheritance would be a vast resource for research, medicine and understanding ourselves.

I visited a lab several months ago and was given a tour of the sequencing operation. At the end I asked, “Then what happens? Is there some off-the-shelf tool to collate and interpret human genomic data?” There was some shuffling of feet and some mumbling about 23andMe. The short answer was “No.”

Well, leave it to a microbial biologist. Steven Brenner puts forth a potential solution that is obvious, easy to understand and would fill a rapidly growing need. And involving the private sector without ceding control to any one company or the government seems like a promising approach. It’s clear we have a long way to go, especially with respect to phenotypic information. But if it’s done right this could be the Library of Congress for human genomic variation.

Jim Watson has stepped in it again:

One of the world’s most eminent scientists was embroiled in an extraordinary row last night after he claimed that black people were less intelligent than white people and the idea that “equal powers of reason” were shared across racial groups was a delusion.

Is anyone really surprised by these comments coming from Watson? Dude will say anything. I mean, did you watch the Baylor press conference?

This David Ewing Duncan piece sheds a bit of light on various issues du jour in commercial personal genomics, including:

• The mysterious 23andMe business model

The company is considering a feature that would allow people to…link their personalized pages to those of others who share their DNA—fellow sprinters, say, or people at risk for Alzheimer’s—just as you can now link to college chums on Facebook. 23andMe has not discussed pricing, but competitors are talking about charging upwards of $2,000 a person.

• Potential market size: $12.5 billion

“I’m convinced there is an early-adopter market here,” says Sue Siegel, former president of Affymetrix and now a venture capitalist at Mohr Davidow. “Millions of people are used to getting health-care information online.”

• Navigenics‘ “know as you go” strategy

…But Navigenics’ site won’t release all of the data collected by the chip, only the designated panel of gene tests. The company plans to offer information and telephone support from genetic counselors, and a subscription to its service will last a year. “Your DNA will be on file, and we’ll test it against new findings,” says Amy DuRoss, Navigenics’ head of policy and business affairs.

• The imminent entry into the market of yet another 800-lb transgenic gorilla

DeCODE C.E.O. Kári Stefánsson says that the company plans to launch a direct-to-consumer site next spring. “We have the original data and they don’t,” says Stefánsson about his I.T. competitors.

• A welcome note of skepticism

“…by and large, the information is not useful to the individual,” says Doug Fambrough of Oxford Bioscience Partners, a biotech venture capital firm headquartered in Boston. “First of all, the information is hard to understand for anyone who is not a trained molecular biologist. It has to be boiled down. Also, the science has not yet arrived. We can tell a single trait here and there, but what people really want to know is how this affects their life. We can’t yet make accurate predictions about this.”

George sends me this note:

…Dana brought to my attention your mug shot blog.

It’s common practice to also show a profile view and booking number.

So here’s the full photo from the archives of the Coriell maximum security repository (where the “cells” are kept at inhuman temperatures with no lighting; and where a life-term of over 150 years is more than a legal technicality):

…Thanks,

–George

If there’s a point to be made here (beyond the collection of further evidence of George’s well developed sense of humor), it’s that researchers will soon be able to order both cells and DNA from the PGP 10 via Coriell. The advantage, we hope, is that those samples will come with unusually detailed phenotypic and genotypic information (to say nothing of flattering snapshots). The question is: assuming someone else will pick up the tab (not a trivial assumption, I don’t think) how many of the next 99,990 exomes will be willing to make their cells and DNA available to anyone with “institutional approval?”

QUASI-RELATED UPDATE: George makes the list of The Ten Hottest Nerds (thanks Dana!)

I’m at GME 2007, taking it all in and even comprehending some of it. The best moment so far came during the Q&A after Venter sequencing maven Sam Levy finished his remarkable talk on the Craigome:

Q: Several years ago we studied the dog genome and found a variety of SNPs and indels. Have you thought about comparing Craig’s genome to his dog’s genome?

Sam Levy (with impeccable comic timing): Well, when we saw that half of his indels were also found in the chimp we stopped right there.

They asked us to put a tape ruler on our foreheads before they took 3D images of our faces in order to have a baseline measurement of our facial features. And to, you know, make it easier for law enforcement…