CDCV is Dead! – Long Live CDCV!

Tim Hunkapiller has always warned me against expecting instant gratification from genetic data. His reasoning is that if Common Diseases were caused by Common genetic Variants they would have been selected out of the population long ago. So while there are some significant heritable diseases, we should not overestimate the clinical utility of common variants.

With this in mind, the insights that you can gain from standard genotyping panels today are limited because they are based upon common variants. Since many of the current personal genomics companies built their business on Genome Wide Association Studies of common variants they have been limited to informational services sometimes derided as “genomic tourism”. The  layoffs at 23andMe or the bankruptcy of deCODE are symptoms of the fact that there is a limited market for products that have limited actionability. We are beginning to see Gartner’s technology hype cycle in action with the personal genomics industry rapidly descending into the “Trough of Disillusionment”.

This was highlighted this week at a roundtable discussion Personal Genomes: Promise or Hype? at the University of Washington. Sydney Brenner thoroughly enjoyed his role as curmudgeon in residence by thoroughly  ridiculing the nascent personal genomics industry. He compared genomics to astronomy explaining that astronomy had split into astrophysics and astrology. The non-subtle point was that the PG industry was more akin to “genology” than to genetics.

For me his dismissive attitude was somewhat surreal considering that he was sitting next to Mary-Claire King. As he was speaking I recalled the account in James Watson’s DNA that described a woman with a frightening family history of breast cancer who avoided a prophylactic bilateral mastectomy because of insight from Dr. King’s research. In fact later in the week 23andMe and Navigenics responded to a critique in Nature by pointing out that even though the BRCA mutations explain only a small fraction of the population risk for cancer, those people who have dangerous variants have significantly increased individual risk.

I also recalled a pharmacogenetics presentation by Dr. Gualberto Ruaño to physicians at a mental health hospital. The premise of PGx is that a relatively small set of genes metabolize a large number of drugs. Variants that are very common in the population cause either a lack of efficacy for drugs or synthetic disease in the form of adverse drug reactions. Psychoactive drugs are notoriously difficult to prescribe and those doctors were pretty energized about the possibility of reducing failures that could be predicted.

Nobody seriously doubts whether genetics can inform medicine, but the key question is how personal genomics will evolve from novelty to necessity. The limitations of CDCV preclude an all-purpose clinical assay but but there are a few focused scenarios where common variants cause a predictable change in outcome. When you consider pharmacogenetics alone there are an estimated 100,000 deaths in the US per year and a remarkably high number of people have some variation in their genes that effects the way they process medications.

From a technology standpoint, focusing on these scenarios and delivering end-to-end solutions from instrument to iPhone seems like the best way to accelerate the use of personalized medicine.