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Most of you probably know that Congress, aided and abetted by the Government Accountability Office, came down on consumer genomics companies like a ton of bricks yesterday. I am still sifting through the rubble, but here are some thoughts, questions, Friday morning quarterbacking, and a few provocations:

• Standards. In the course of writing my book, I learned that, for a time, 23andMe, deCODEme and Navigenics (aka The Big Three) were having discussions in an effort to hammer out standards for their services. For whatever reason, those talks fell apart. They are paying the price for that today. The publication of David Ewing Duncan’s genome scan results and the Ng paper, both of which described discrepancies among the companies’ interpretations, were two huge red flags and should have led to 1) a meeting of the minds with a big tent full of experts to try to reach a consensus on interpretation for things like prostate cancer and hypertension; 2) removal of those conditions from their services in favor of, say, clearly useful and less contested things like carrier screening and pharmacogenomics; or 3) a serious downgrade of those results to “provisional” or “preliminary” status. The companies have no one to blame but themselves for these discrepancies, which, in my view, are the most damning aspect of the report and could have been avoided. I would urge them to pursue at least one of the three aforementioned options and get their ducks in a row. Come on y’all: if the oil companies can do it, so can you.
• Ethnicity. Most human genetics research has been done on persons of European ancestry. Genomes of African origin, for example, tend to be more diverse. Thus, with fewer markers typed, consumer genomics test results are apt to be of less value to persons not of European descent. I reckon the companies might have mitigated this criticism by more prominent disclosure of this limitation. Over the longer term, however, the companies are in a position to address this problem–and it is a problem, especially with respect to health disparities–by filling the data gap. We know they can do research, so instead of going to Davos, why not go to Oakland or Tijuana?
• Who are these companies? Dear GAO, if the goal is transparency, I don’t understand why you cannot name names (pdf).  Why be coy? FWIW, here are my guesses: “Company 1″ = 23andMe; “Company 2″ = deCODEme; “Company 3″ = Pathway Genomics; Company 4 = Navigenics. I won’t bore you with my reasoning and I could be wrong, but again, why make us guess? (UPDATE: 23andMe confirms my guesses.)
• Surreptitious testing. Companies: don’t do it. You can sell the spit kit, but no surprise parties.
• The word “diagnostic.” Companies: don’t use it unless you mean it and can prove it. Otherwise you will give Jim Evans a coronary and that would make me sad.
• “You’d be in the high risk of pretty much getting it,” is how a representative responded when our fictitious consumer asked if results indicating she was at above average risk for breast cancer meant she’s definitely getting the disease (see video). If a Navigenics counselor said this when discussing a woman’s risk for non-BRCA1 or BRCA2 breast cancer, then yeah, that’s “horrifying.” But for the sake of completeness, I would like to know the full context of the conversation. What was the quoted risk percentage on the fictitious customer’s profile that would have led her to such a conclusion? I bring this up for two reasons: 1) we’ve seen recently exactly how important such context is with respect to audio-visual evidence, especially when one’s accuser has an axe to grind; and 2) when I had my counseling session with Navigenics, the counselor and I spent much of the time discussing my family history of breast cancer and the possibility I carry a BRCA1 or BRCA2 mutation, despite the fact that Navi doesn’t test for those mutations. But just because the company doesn’t test for it doesn’t mean we can’t talk about it.  These mutations are highly penetrant, i.e., they confer high risk to carriers. Could it be that the counselor was discussing familial breast cancer and not the Navigenics assay? Maybe not, but I would like to hear more of the phone conversation rather than just a brief video with leading statements in the titles.
• Baby meet bathwater. “The test results we received are misleading and of little or no practical use to consumers.” The GAO is entitled to its opinion. Clearly there are issues with these tests. But I found that learning my carrier status for a number of diseases, risk for late-onset Alzheimer’s, and genetic responses to a number of drugs to be useful. I found the ancestry information to be interesting and entertaining. Would I have paid $1000? No. $99? Yes. More than that? It depends on what I’d be getting. That’s why the GAO’s failure to distinguish among the companies, their pricing structures and their offerings is so unfortunate. The net result does not allow for any nuance whatsoever. Rather, if one accepts the GAO’s conclusions, there seems to be room for only one response: “Off with their heads.” If that’s the case, then consumer genomics will be driven underground and/or overseas. In my view, that would be a shame.

We saw a very similar hearing — with the same undercover M.O. and public perp walk — in 2006. Were/are some companies behaving badly? Absolutely. And they should be called on the carpet. But let’s not kid ourselves: this dog and pony show was as much an opportunity for chest beating and righteous indignation as it was for “protecting the public health.” It was an opportunity for politicians to scream “snake oil” and fret about the possibility of their constituents “jumping off a building” as much as it was an attempt to bring about constructive change to a nascent industry’s practices. Why is that? Why is the demand for data never made of the alarmists? Why do the companies not get to see the GAO’s report ahead of time? Why did the FDA exhibit a genuine spirit of open inquiry and invite a broad range of stakeholders to its meeting while Congress could not be bothered to do the same? Why does the outcome of such hearings always seem to be a foregone conclusion?

Representative Stupak says he and his colleagues are on top of their game.

What game is that exactly?

Some days it still feels like September 12, 2001:

Millions of Americans arrested for but not convicted of crimes will likely have their DNA forcibly extracted and added to a national database, according to a bill approved by the U.S. House of Representatives on Tuesday.

By a 357 to 32 vote, the House approved legislation that will pay state governments to require DNA samples, which could mean drawing blood with a needle, from adults “arrested for” certain serious crimes. Not one Democrat voted against the database measure, which would hand out about $75 million to states that agree to make such testing mandatory.

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House Speaker Nancy Pelosi and the Democratic leadership scheduled Tuesday’s debate on the bill–called the Katie Sepich Enhanced DNA Collection Act of 2010–using a procedure known as the “suspension calendar” intended to be reserved for non-controversial legislation.

“Suspension of the rules is supposed to be for praising the winner of the NCAA championship or renaming Post Offices,” Harper says. “Things like collecting Americans’ DNA are supposed to be fully debated in Congress.”

(hat tip: Jenny Reardon)

Jerome Groopman offers a withering assessment of comparative effectiveness research:

There is a growing awareness among researchers, including advocates of quality measures, that past efforts to standardize and broadly mandate “best practices” were scientifically misconceived. Dr. Carolyn Clancy of the Agency for Healthcare Research and Quality, the federal body that establishes quality measures, acknowledged that clinical trials yield averages that often do not reflect the “real world” of individual patients, particularly those with multiple medical conditions. Nor do current findings on best practices take into account changes in an illness as it evolves over time. Tight control of blood sugar may help some diabetics, but not others. Such control may be prudent at one stage of the malady and not at a later stage. For years, the standards for treatment of the disease were blind to this clinical reality.^[7]

Orszag’s mandates not only ignore such conceptual concerns but also raise ethical dilemmas. Should physicians and hospitals receive refunds after they have suffered financial penalties for deviating from mistaken quality measures? Should public apologies be made for incorrect reports from government sources informing the public that certain doctors or hospitals were not providing “quality care” when they actually were? Should a physician who is skeptical about a mandated “best practice” inform the patient of his opinion? To aggressively implement a presumed but still unproven “best practice” is essentially a clinical experiment. Should the patient sign an informed consent document before he receives the treatment? Should every patient who is treated by a questionable “best practice” be told that there are credible experts who disagree with the guideline?

Amen, Jerry. CER may be well on its way to becoming the “No Child Left Behind” of health care. “Let’s create some immutable standards, wield them like a sledgehammer, and then declare victory!”

Doctors are pooh-poohing personal genomics. Yet they would put their faith in behavioral economics? Talk about going “off label”…

Stephen Asma:

Feeling unworthy is still a large part of Western religious culture, but many people, especially in multicultural urban centers, are less religious. There are still those who believe that God is watching them and judging them, so their feelings of guilt and moral indignation are couched in the traditional theological furniture. But increasing numbers in the middle and upper classes identify themselves as being secular or perhaps “spiritual” rather than religious.

Now the secular world still has to make sense out of its own invisible, psychological drama—in particular, its feelings of guilt and indignation. Environmentalism, as a substitute for religion, has come to the rescue. Nietzsche’s argument about an ideal God and guilt can be replicated in a new form: We need a belief in a pristine environment because we need to be cruel to ourselves as inferior beings, and we need that because we have these aggressive instincts that cannot be let out.

The Presidential Commission for the Study of Bioethical Issues is back and better than ever…we hope:

The commission’s wider scope will also force some tough choices in deciding priorities, says [George] Annas. “Doctors’ [involvement in] force-feeding prisoners at Guantanamo, doctors and torture, and international human-research rules are pressing issues of our day which demand our attention,” he says. Among the other issues he thinks the commission should juggle are new reproductive technologies, an overhaul of informed-consent procedures and — perhaps most immediate — fairer ways to apportion health care. 

To that modest list I’d add achieving peace in the Middle East, ending world hunger, eliminating poverty, curing cancer, and repairing the global economy. I can think of two guys I’d appoint immediately…at least, I think they’re two different guys.

Jenny Reardon on those who choose to opt out:

Only significant effort will achieve the participation of the broader and more diverse range of human beings required for [genomic] research. Understanding why some people participate, and many do not, will demand understanding the specific ways in which genomic ideas and practices form from and re-form social practices of racism and inequality–issues that remain with us despite the last decade of proclamations about the anti-racist and equalitarian features of genomics.

At Nature News, there is something of a eulogy/finger-pointing festival for deCODE and indeed, for personal genomics in general:

…Some other researchers, however, say that deCODE’s scientific approach is to blame. The company worked to mine genetic data for common variations linked to disease through genome-wide association studies (GWAS), and some experts note that these studies have turned up only a small fraction of the variation that causes disease. “The translation to commercial value is just not very direct,” says [Duke’s David] Goldstein, “in part because it is now clear that GWAS is not the tool of choice for unlocking the genetics of most common diseases.”

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…companies that focus exclusively on personal genomics services, such as the one sold by deCODE as deCODEme, might find themselves in more trouble, [Leerink Swann’s Isaac] Ro says. The services are not seen as a medical necessity, diminishing their appeal, particularly in difficult economic times. This year the personal-genomics company 23andMe, based in Mountain View, California, announced two rounds of lay-offs, lost one of its two co-founders and announced a series of product and price restructurings.

“There’s no clinical trial supporting the value of these results, so it’s really recreational genomics,” Ro says. Large academic centres, not consumers, will find value in the rich genetic databases; 23andMe has tried to move into the research market, but because its data come from a self-selected customer population their value is limited, he says.

Here we go, still trotting out the same tired tropes. I agree: GWAS is of limited value and this probably contributed to deCODE’s demise. But whatever deCODE’s fate, if whole human genomes can be sequenced for < $2000, isn’t it about time we stopped kicking GWAS’s ever-stiffening corpse?  Second, just because something is not a medical necessity, does it follow that it is worthless? Ask the participants in the REVEAL study or anyone else who’s received an APOE genotype because she WANTED to know. Ask the people who learned something about their hereditary breast cancer risk from 23andMe. Is that recreation? What about abacavir hypersensitivity? And finally:  yes, DTC genomics customers are self-selected. So are the 50,000 PatientsLikeMe participants. So are the 10,000 in the Coriell Personalized Medicine Collaborative. So are the 15,000 on the Personal Genome Project waiting list. So are the 400,000 in the UK Biobank. Maybe we should just toss out all of that data, too.

From a compelling story in the New York Times Magazine:

In an age of DNA, when biological relationships can be identified with certainty, it can seem absurd to hew so closely to a centuries-old idea of paternity. And yet basing paternity decisions solely on genetics places the nonbiological father’s welfare above the child’s. Phil Reilly, a lawyer who is also a clinical geneticist, has been wrestling with the policy implications of DNA testing for years, and even he is stumped about how society should manage the problem that men like Mike face. “We’re at a point in our society where the DNA molecule is ascendant, and it’s very much in the public’s consciousness that this is a powerful way to identify relationships,” Reilly says. “Yet at the same time, more people than ever are adopting children, showing that parents can very much love a child who is not their own. The difference here for many men is the combination of hurt and rage over the deceit, the fact that they’re twice beaten. I can see both sides of this argument. As a nation, we’re still in search of what the most ethical policy should be. Every solution is imperfect.”

The Personal Genome Project includes disclosure of nonpaternity as one of the explicit risks of participation. That said, having been warned is probably not much consolation to people who discover certain surprising things about their families.

Elsewhere in this volume she talks about creationism, saying she “didn’t believe in the theory that human beings — thinking, loving beings — originated from fish that sprouted legs and crawled out of the sea” or from “monkeys who eventually swung down from the trees.”

An Italian court has cut the sentence given to a convicted murderer by a year because he has genes linked to violent behaviour—the first time that behavioural genetics has affected a sentence passed by a European court. But researchers contacted by Nature have questioned whether the decision was based on sound science.

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“90% of all murders are committed by people with a Y chromosome—males. Should we always give males a shorter sentence?” says Steve Jones, a geneticist at University College London. “I have low MAOA activity but I don’t go around attacking people.”

Farahany points out that prosecutors could use the same genetic evidence to argue for tougher sentences by suggesting people with such genes are inherently ‘bad’.

“The question is where do you stop,” Jones adds.