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Scott Shreeve, MD

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I'm the CEO of Crossover Health, a patient-centered, membership-based medical group that is redesigning the practice, delivery, and experience of health care. We offer urgent, primary, and online care to our members who can access our technology platform, practice model, and provider network from anywhere and anytime to optimize their health. Email Me



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Genomics vs. Proteonomics: Accessorizing Your Genes

Accessorize (ăk-sĕs’ə-rīz) v.


1. To furnish with accessories: accessorized my outfit with a matching watch.
2. To wear or select accessories:
accessorizes according to the latest fashions.

I had the occasion this past weekend to be out with my wife doing some shopping. Apparently, I have been too busy of late to notice that my wardrobe had been in some decline. My wife therefore drug me out on grey Saturday (which follows Black Friday) to hit the local Nordstrom Rack. I was shamed into trying on jeans formerly priced at over $200 (who pay sthis kind of money for a pair of jeans?), gigolo bling-bling shoes (are pointy toes really appropriate for male shoes?) , and a variety of belts and watches (how does wearing a watch “change” my outfit) required to properly “accessorize” my look. We ultimately settled out on some funky 7 Diamonds and Roar surfer shirts to match the now half priced jeans. More on the shoes later.

The experience of “accessorizing” reminded me of a recent post by Matthew Holt regarding Personal Genome Management over on the new Health 2.0 Blog. Matthew reviews some of the recent buzz surrounding 23andMe, highlights longtime player DNA Direct, and then puts out some thoughts as to where the market is and can go over the next several years (there is some interesting banter within the comments section as well). He concludes with this consideration:

“The genetic test market is very small, and the management services that these companies offer around it are going to only be a share of the testing market itself. So the fact that Navigenics has already raised money at a substantial valuation means that some very astute people are thinking that genetic testing will turn from an occasional activity for a small minority of patients (usually those going into pregnancy with some type of risk factor) into a consumer norm that most patients will have as part of the standard testing they get done and that management of that genetic information will be part of the new flow of consumer and clinician activity.”

Matthew hints at something that I believe most people have failed to grasp when considering the genetic market. I actually see three distinct limitations:

1. One and Done. Genetic profiling is a one time event – a single snapshot that once completed really does not need to be repeated. There is no repeat customers, no transactional nature, and no subscription model to the DNA testing market. So while I share the optimism in the potential market, I also recognize that it is transactionally bound by the singular nature of a single sales event.

2. Genotype vs. Phenotype. In addition, once the blueprint has been identified, then the analytic software goes to work to attempt to divine the ACGT combinations in to a series of probabilities and risk for acquisition of all types of disease states. As anyone familiar with cellular biology knows, having the genetic sequence of a known gene (genotype) does not equate to having the disease state (phenotype) represented by that gene. It requires specific cellular triggers, and specialized cellular machinary, to literally “translate” the code into the work horse of the cellular world – proteins.

3. Cellular Accessories. Furthermore, not only do we have still have a very limited understanding of human genes, there are very few pathological conditions represented by single genes. Most diseases are a confounding confluence of cascading brownian events beyond our current scientific understanding. The inherent complexity, and all the cellular accessory events that occur to create these microscopic “perfect storms“, should dispel any illusion that health and disease fits neatly into discrete genetic units.

As a result, while genomics provides a methodology to understand the sheet music of life, I am much more interested in the proteomic symphony that results by literally bringing the dead notes to life. Since the actual performance of the sheet music can vary based on the whims of the composer are the individual variation or free lancing of the orchestral performers. As a consequence of these unique variations, I am murch more interested in the potential and the promise of emerging predictive proteomic companies like Biophysical than I am of a Kleiner Perkins backed genomic startup like Navigenic (or a Google-powered 23andMe).

Biophysical is an Austin-based spinoff that commercializes the biomarkers discovered by sister company Rules-Based Medicine. RBM is a biomarker testing laboratory comapany that has developed multiplexed immunoassay capabilities. This is seen in their Multi-Analyte Profiles (MAP’s) that can measure up to hundreds of proteins in a very small samples and sample types. The novel utilization of MAPs provides for comprehensive and cost-effective evaluation of the protein expression patterns critical for understanding drug safety and efficacy, disease diagnosis, and predictive disease modeling.

Once RBM has discovered and tested a new biomarker for clinical or disease relevance, it is commercialized by Biophysical into a predictive disease diagnosis/modeling tool. While the traditional Chem 20 group of analytes has provided workmanlike information, the Biophysical 250 provides exquisite detail on the biopresence of bioactive biomarkers. In essensce, Biophysical has the capacity to detect active pathology at the protein level long before enough cells have aggregated to be detected by traditional diagnostic testing methods. The power of the Biophysical model is to literally be in the accoustic chamber actively listening to the symphonic soliloquoy.

From a business perspective, Biophysical is also a subscription model. Essentially, they are selling “ongoing” biosurveillance. The value of their service increases over time as more tests are run, as baselines levels are followed over time, and as an aggregate picture of individual biohealth emerges. This concept has recently been picked up by Dr. Mehmet Oz, the current leading guru of longevity and real-age health. Biophysical recently launched a modified version of the Biophysical 250 (called Biophysical YOU) with Dr. Oz on the internationally syndicated Oprah Winfrey show. The response, as you may have predicted, has been overwhelming.

So while the sheet music is absolutely essential to even contemplate a symphonic performance, no one goes to listen to the sheet music. It is the individual performances, the living-breathing- audible-panoramic-splendid-view of the whole chamber coming to life that ultimately stirs the soul. In an analogous fashion, the proteins are the cellular accessories that literally add life to an other wise staid genetic makeup. Infinitely more variable, infinitely more possibilities, and as a result, infinitely more interesting.

And as far as fashion accessories, those pointy Steve Madden’s actually look pretty dang good with those funky designer jeans.

* DISCLAIMER: I have been a consultant to Biophysical since early November 2007

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