The diversification of consumer genomics

Following the dramatic appearance of the field of personal genomics just over a year ago the major players in the field have worked hard to distinguish themselves from their competition: 23andMe has emphasised the intellectual joy of learning about genetics, and also attempted to actively engage its customers in the company's research projects; deCODEme has leaned heavily on the impressive academic credentials of its parent company, deCODE Genetics; Navigenics has committed itself utterly to an image of sober, responsible reflection on the medical information present in its customers' genomes; and Knome is a boutique affair, offering the ultimate in personal genomic luxury (a near-complete genome sequence) at a price well beyond the typical consumer's price range (around US$100,000).

At the same time, there has been considerable (and often heated) discussion about the blurred boundary between the services provided by these companies and the realm of medical diagnostics. Navigenics has deliberately leaned closest to the medical arena, while the others have generally done their best to delineate their own activities from "clinical diagnostics" (an effort that is at its most comically transparent in the quotes from Knome CEO Jorge Conde in this post).

There's good reason for this careful demarcation: as well as a desire to avoid the ire of regulators, these companies are well aware that the predictive utility of their disease genes is generally extremely low, resulting in risk estimates that are unimpressive and often inconsistent. Indeed, bloggers and journalists who have taken personal genomics tests have often seemed more perplexed than enlightened by the weak disease risk predictions (not that this is a bad thing, of course), while expressing fascination with the non-disease angles (such as ancestry and tracking of familial relatedness). In the same vein, the company that has attracted by far the most public interest is the competitor with by far the least "clinical" feel - 23andMe. 23andMe are the indisputable leaders in non-disease areas such as ancestry - Navigenics refuses to even offer ancestry testing, while deCODEme's effort is a fairly peremptory affair - thus putting them in prime position on what are currently the strongest features of personal genomic testing.

Still, this is one business where nothing stands still. One of the more intriguing pieces of new information from Steven Pinker's uniformly interesting NY Times piece (also noted yesterday by razib) was his unveiling of an enigmatic newcomer to the consumer genomics space, with a brand new angle:

The genes analyzed by a new company called Counsyl are more actionable, as they say in the trade. Their "universal carrier screen" is meant to tell prospective parents whether they carry genes that put their potential children at risk for more than a hundred serious diseases like cystic fibrosis and alpha thalassemia. If both parents have a copy of a recessive disease gene, there is a one-in-four chance that any child they conceive will develop the disease. With this knowledge they can choose to adopt a child instead or to undergo in-vitro fertilization and screen the embryos for the dangerous genes. It's a scaled-up version of the Tay-Sachs test that Ashkenazi Jews have undergone for decades.

There's virtually no information out there in the public domain about Counsyl beyond a basic teaser site, but Pinker's description would suggest a new participant in the consumer genomics arena that falls heavily at the "medical" end of the spectrum.

The variants that Pinker is talking about here are light-years away from the variants analysed by current personal genomics companies. While 23andMe et al. examine common variants, each generally with a tiny, probabilistic impact on disease risk, Counsyl's targets appear to be primarily rare variants with a potentially massive effect on health. In most cases individuals who carry a single copy of these variants (called "carriers") are healthy - but if they are unlucky enough to partner with someone who carries a similar variant in the same gene, each of their children will have a 25% chance of inheriting two "defective" copies of the gene and developing serious disease. We're talking nasty, early-onset, and often rapidly terminal conditions.

Numerous companies currently offer carrier screening for various inherited diseases either as single tests or small panels, but to the best of my knowledge Counsyl would be the first company to offer a single carrier screen targeting such an extensive range of rare disease-causing variants.

However, it's worth noting that 23andMe has already entered the carrier screening game in a much more limited fashion: the company currently offers its customers information about their carrier status for six conditions that are on the more common side of rare (such as cystic fibrosis and sickle cell anaemia). In each case the company screens for a single, relatively common variant associated with the disease - for cystic fibrosis, for instance, the carrier frequency in European populations is as high as 1 in 25.

It's unclear whether 23andMe intends to move more heavily into carrier testing by expanding its range of conditions and associated variants to lower and lower frequencies. However, it seems to me there are good reasons to avoid such a move: doing so would seriously undermine the company's ability to characterise its service as non-clinical in nature, substantially increase the risk of litigation for false results, and potentially catalyse unpleasant regulatory consequences both for the company and for the field as a whole. In addition, it's unclear to me whether extensive carrier screening would sit well with the overall image of the company - there's just not much that's fun about the possibility of discovering potential child-killing horrors lurking in your genome. Large-scale carrier testing is a product that would no doubt appeal to many prospective parents, but it would feel pretty jarring sitting next to cartoon movies about human evolution in 23andMe's repertoire.

So, will the diversification of the personal genomics companies continue in 2009, each carving out a unique niche? How will new players like Counsyl position themselves? Will 23andMe cross the line into outright medical genomics, with all of the regulatory obstacles and stylistic contradictions that this would entail? We'll find out soon...

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