The Root.com - A New Media Site, Plus Genetic Testing (Huh?)

I just heard about The Root, a "Slate for black readers," according to founder Henry Louis Gates Jr. Since Slate is one of my favorite sites, this is a cool development. So what's that got to do with public health or genetics or medicine? Well, right there smack on the prime front page real estate is an unexpected service - a link to Gates' AfricanDNA.com, Gates' effort to bring some substance to the DNA ancestry market. There is a disclaimer that notes AfricanDNA.com is a separate company, but the link is otherwise seamless - here's what it looks like on the home page (the DNA is on the right side, under "Roots"): I have no criticism here - I'm not saying there's a conflict. I find it noteworthy simply because it's the first explicit combination of journalism and genetic services I've seen. These don't seem like obvious complimentary partners, but with a little thought it actually makes sense. 23andme, for instance, is very much a content company - they've put a great effort in writing up their Gene Journals to help customers understand their genetic backgrounds and information. My hunch is that the utility of genetics as a consumer service will depend on the ability of companies to translate what this abstract science actually means for you. Sure, there are early adopters who get it and will sign up for the raw data.

But it's really those companies that can put genetics in a relevant context - and companies that do so in a trustworthy way - that will really allow genetics and personal genomics to become a conventional bit of information. Since Gates has already said that this is pretty much his stated purpose in creating Africandna.com, I think it'll be interesting to see how the Root and AfricanDNA continue to substantiate each other.

George Church on Personal Genomics

Got a note from Harvard/MIT's George Church re: my story on personal genomics and 23andMe (he's on the 23andMe scientific advisory board and is quoted in the story).

Nice job on the article. Many of my colleagues agree. However some (including me) are concerned that the message about “limitations” of linkage-based chips is not coming through (despite the basic forthrightness of the first three Personal Genomics companies). The limitations are significant for research -- and even more so for diagnostics. Common diseases are not necessarily caused by common DNA variants – but also by DNA variants individually rare but collectively common. Associations can be statistically significant in a research population but have unacceptably high false positives and negatives in the individuals of that population. A good example is one of the oldest success stories in personal genomics -- BRCA1 & 2 which Myriad Genetics offers. Could those gene tests be done with any of the 3 new personal genomics chip assays? Probably not, since the causative alleles are “new” (i.e. less than 100,000 years old) and numerous. The causative alleles are not in linkage disequilibrium with the common alleles on the chips and hence require actual sequencing at Myriad. Despite the various limitations, early adopters may be richly rewarded by their insider-view if/when personal genomics takes off like personal computers. Thanks, --George

I agree absolutely with George about the risk of hype here, that the perception could easily emerge that a limited genotype might be taken as somehow an exhaustive total sequence, and that there's a gap between the general science of associations and the utility of these studies for any one individual. In my story, I tried to state as much (though frankly and obviously I don't have the grasp of the science and technology here that Church has).

And I know that 23andMe, in particular, is wary of leading customers to believe that there's any diagnostic utility in their service - they quite vociferously insist (again, as I point out in the article) that their service is just a starting point, and that for actual diagnosis of risk or propensity for disease, you'll have to go to a company like Myriad.

It'll be interesting to see how this plays out - will the FDA or another regulator decide that, caveats from the company aside, that consumers are under mistaken impression about these services and thus in need of some kind of increased regulatory protection? For my part, I hope not - I think we need to let this play out some before instituting new regulations on a fledgling industry.

(ps - "many of my colleagues agree." hmmm, I wonder who hated it?)

Your DNA, Decoded: 23andMe and Predictive Medicine

The December issue of Wired, on newsstands next week, has a story I've written on the debut of genomic medicine, via 23andMe, the much-anticipated startup. The story is now up here on Wired.com. I was fortunate enough to get an up close look at the inner workings of 23andMe, shadowing company founders Linda Avey and Anne Wojcicki (shown here) off and on over the course of the past few months. The story, though, isn't just about the company as another Silicon Valley startup. I was especially interested in the challenge they face in turning the very raw science of genetic discovery into a consumer friendly, retail service. Given that research into genetic associations is still quite early, and given that the medical establishment is just barely on the case, it's an especially compelling story about how individuals will be responsible for learning a huge amount in order to make sense of - and take advantage of - the genetic information 23andMe offers.

Readers of this blog will know that I was especially interested in how the company plans to use the pool of genetic data from its customers. While maintaining all privacy, 23andMe will be tapping the data for further genetic research, particularly towards orphaned diseases that are not presently the subject of much research.

There were, alas, some things I had to leave out of the story, particularly a discussion of George Church's Personal Genome Project (which I plan to return to in a later story), or a discussion of GINA and privacy regulations. Wired.com has a nice update to that story in a sidebar here. Wired.com also has a clip from an interview Linda and Anne did with Wired Science, our TV show with KCET on PBS. That episode airs this coming Wednesday.

There are a couple gems in the story - a tidbit about how the company plans to move into whole genome sequencing, and other details. There's also an easter egg of sorts in how the story is laid out in the physical magazine, that's not evident in the online version. I'm very curious to see if anybody spots it.

The debut of 23andMe and its competitors, DeCodeMe and Navigenics (and surely there are more out there about to pop up) marks a very significant inflection point in our society. Predictive medicine is now not just a theoretical possibility that we should prepare for; it is very much a reality, available for just $999 (or, a bit more crassly, for DeCodeMe's "introductory promotional price" of $985).

There is a lot we still need to do - more science, certainly, but also more introspection, as a society, for what's around the corner, and more planning, in the health industries, for how this should be handled. But on the whole, I have to say I think it's a very good thing.

Please let me know what you think of the piece - either here or in comments at the story.

Your Failed Blockbuster Drug Is My Nichebuster Therapy

More on pharmacogenomics from the Personalized Medicine Meeting at UCSF

In the opening panel this am, David Parkinson from Nodality offered a choice: Put yourself in a pharmaceutical company's shoes: Would you rather have a drug that’s 10% effective for 100,000 or 100% effective for 10,000?

It's a trick question. Turns out Parkinson is describing the same drug – Gleevec. When your talking about using Gleevec to treat leukemia, it's effective in just 10 percent of patients. But use Gleevec to treat Chronic Myeloid Leukemia (CML), and you suddenly have something that's 100 percent effective.

The difference, Parkinson notes, is that Gleevec works in CML by blocking a tumor protein caused by the so-called Philadelphia chromosome, a chromosomal abnormality. Approved by the FDA in 2001, Gleevec represents a huge shift in cancer treatment - instead of using blunt instruments like chemotherapy or bone marrow transplants, which caused broad physiological effects, physicians now can offer a precise treatment that goes after the cancer itself. It is, in other words, the sort of drug we expect we'll be using all the time, once personalized medicine flourishes.

Gleevec is a lesson in how pharmacogenomics isn't just going to involve creating new drug molecules; it will also require ew tools applied to old drugs, tools that can separate signal from noise and turn failures into success. In pharma, they call this “drug rescue” – finding drugs that may’ve been shelved for side-effect or efficacy reasons, but through better targeting could be revived. Again, it hearkens to my notion of dark data – the stuff that’s been filed for whatever reasons but now, in new context, might have new value. In some ways, this sounds totally easy: Drug companies just have to start leveraging their back catalog, and start targeting the niche. In other words, this is simply the arrival of the long tail model to pharma (I’ve been waiting for this for a couple years, having spoken often to my boss, Chris Anderson about how pharma was a looming non-entertainment industry example of an indusry ripe for long tail economics). But it's been slow to happen - or at least seemingly so, from my outsider perspective. Good to hear, as in this morning's panel, that the idea is starting to catch on. As panel member Andy Williams from Pfizer acknowledged: The old blockbuster model is changing.

Personalized Medicine: Against the Odds

I dropped in today on the Personalized Medicine Meeting, an annual conference put together by Burrill & Co, a health care/technology consultancy. Amid all the hype over personalized medicine, I was glad to hear lots of attention paid to early stage interventions - meaning predictive and preventative strategies, rather than pharmacogenomics, which is the traditional face of personalized medicine. Indeed, there was a fairly manifest distinction drawn throughout the day between the pharmaceutical industry's approach to medicine and biotech's - and Steve Burrill set the tone when he called pharma's business model all but dead.

We'll see about that - but there were three telling stats that came up during the day. Together, they make quite the case for personalized medicine.

1) Half of all prescriptions don't work for the patients. Most drugs have an efficacy between 20 and 80 percent, averaging around 50 percent. Meaning that they only have their intended effect half the time. That might be awesome in baseball, but it's hardly reassuring in medicine.

2) Chemotherapy is effective - defined as remission - in just 5 to 10 percent of breast and colon cancer cases. This is likewise startling (the stat comes from Randall Scott of Genomic Health). And factor in the fact that chemo costs about $30,000 per patient per year, and there's a massively ineffecient treatment module out there.

3) Six weeks - that's how long it takes, give or take, for a physician to determine whether a given antidepressant is working for a patient. And given that only half of drugs work, that's a rather long time for a patient to go effectively without a treatment for their depression or mental illness. (This from Wolfgang Sadee, chair of the pharmacology department at Ohio State).

And one more observation that's not, technically, a statistic: The prognosis of a given patient is always a guess. Physicians know almost nothing about how a specific treatment will work for a specific patient. When a physician says a treatment works in 50 percent of cases (or 75 percent or 20 percent), they're always using population terms. There's no way to quantify how well those averages might or might not apply to any given patient (this observation comes from the Mayo Clinic's Franklyn Prendergast). It may be an obvious statement - but think about it from the patient's POV - there's no way medicine can accurately predict whether a treatment will work for them. That's, again, remarkable.

Together, these factors make a pretty damning case against current therapeutics. Basically, medicine today is a blunt instrument – too blunt for a 21st century science.

Dark Data in Action

More proof that dark data can be unexpectedly illuminating: researchers at Stanford re-analyzed 49 experiments and found statistical evidence of an association between two genes and obesity. This story is a little vague on details - which genes? what's the strength of the association? But it's fascinating to me that the studies used a variety of animals, from humans to rats to worms.

What's the Science Behind Watson's Racism?

A nice analysis in the Guardian dissects what, if any, basis in fact might lay behind James Watson's recent remarks about race. (Note: the juice is in a podcast, link here).

The World Toilet Summit

Apologies for the, uh, toilet humor, but couldn't resist this little news item on the first World Toilet Summit, bought to you by the World Toilet Organization.

Yes, it sounds like a joke. But it turns out its bonafide. Seems that one third of the world's population lacks proper sanitation, i.e. proper toilets, and that contributes to disease and environmental harm. It's helpful to remember here that while in developed world diarrhea is a joke, in the developing world it is an illness, indeed the leading killer of children.

Not such a joke after all.

Genetic Medicine: How Does it Play In South Dakota?

Forget Peoria. Sioux Falls is the new arbiter of American values. Especially when it comes to the portent of genetics on public health. A very telling story in the Sioux Falls, SD, Argus Leader about the implications of genetic medicine. It is a 500 word story (ie, short), and it's a great indication of where the perception of genetic medicine is in the greater US (I say this as a Minnesotan; I have no prejudice against South Dakotans, on the contrary. Wisconsinites, on the other hand...). The story hinges on the visit of a speech by Eugene Hoyme, a geneticist and "Dell Rapids native who recently became chief pediatric medical officer for Sanford USD Medical Center," according to the Argus Leader. (USD is University of South Dakota).

So what's the perception of genetic medicine in South Dakota? Here's where things stand:

Doctors now can perform genetic testing to determine how predisposed a person is to certain diseases or conditions. But that same advantage also can have potential downfalls, Hoyme said, as people could be labeled or stigmatized by their genetic makeup and likelihood for disease. There also are questions of how people react to diagnoses of genetic conditions, Hoyme said.

Seems pretty straightforward, right? Indeed, kinda stuff we knew about five or ten years ago? Well, to me, this is a very serious corrective on the excitement (hype?) about personalized medicine. I don't doubt that Hoyme knows his stuff. But it turns out that genetic medicine, as practiced in SD, is pretty much straight monogenic testing, the sort of stuff that has been clear and sound practice for a years. The frontier of genetic medicine - SNP based stuff, etc. - hasn't hit Sioux Falls. Indeed, it seems a dozen years away from Sioux Falls.

I note this not to condescend to South Dakota, which is a great state and has smart scientists. In fact, some of my best friends are from South Dakota. Really. I'll name them if I have to.

But the story, and the recounted state of genetic medicine, is a nice corrective for the genomic-frontier crowd on where the perception, and perhaps the actual applicability of genetics, actually stands.

We in California or New York or the forefront of genomic medicine anywhere might perceive the staus quo as a world where we discern all sorts of truths from our genes - or rather, may we may be about to discern such truths. In fact, back in Sioux Falls, they're not so ready to swear themselves to genetics. They get it - there are things to be learned - but its not the be all/end all.

Me? I think the Argus Leader may be kinda right.

The Fish Dilemma: Omega 3 or Mercury?

I have to say, of all public-health/food-safety issues out there, whether or not to eat fish is one of the most confusing. Seems like every week someone's asking me about fish - usually a woman friend of child-bearing inclination - and seems like every week, there's a study that either says, in Column A: Eat Fish: It's Good For You! or in Column B: Beware of Fish: It's Bad For You!

Column A is informed by the notion that Omega 3 fatty acids are incredibly beneficial to health, and have been associated with lower cholesterol and other positive health attributes. Also, it's a great way to get good protein. Column B is informed by the fact that the larger a fish is, the higher it will be in mercury content (thanks to the interaction of the food chain and the human creation of heavy metals). So Fish Is Good because it helps women's health and the development of healthy fetuses. But Fish Is Bad because its mercury content can cause birth defects and developmental problems.

It is indeed a dilemma (English major geek-out tangent: I'm using "dilemma" incorrectly here. The true definition of the word is a choice between two bad things, neither of which is advantageous. Obviously, Column A is preferable, so this is more a quandry - a vexing question - than a true dilemma). And it's a great example of the problem public health has in regard to public education. The general public is not wrong in thinking that it is constantly hearing two different completely contradictory things. So what's a considerate mother-to-be to do?

Well, a coalition of health experts - a really big coaltion, from the US Agricultural Department to the American College of Obstetricians and Gynecologists - has come out with a declaration: Eat Fish While Pregant.

The consensus verdict of the coalition is that, basically, the benefits outweigh the risks.

Great. Case closed.

Really?

Well...

Turns out the group received $60,000 from a seafood trade group to do the research. And their verdict is basically a lit-search review, not any new science. In other words, there's no new information on a retrospective study on fish consumption and birth defects or autism or anything. So it's a consensus opinion based on existing research. The same research that has been, up till now, inconclusive. So, basically, it's an opinion.

The upshot: while it's a great headline, I guess I'd still say the same thing to my possibly pregnant friends: Sure, have some fish. But go with the trout and the tilapia - low mercury, environmentally neutral farmed fish - and skip the shark, the tuna, or the swordfish.

Besides, none of my chef friends will eat swordfish anyway. Not for health reasons, though. They have their own reasons. Ewww.