Personalized genomics inflection point

One of the world’s fastest accelerating technologies is that of genomic sequencing. The first whole human genome (6 billion base pairs) was sequenced at a cost of $3b and was completed in 2003. The current cost is $20,000 for researchers (Complete Genomics) and $48,000 for consumers (with Illumina’s EveryGenome program). Leading third-generation sequencing company Pacific Biosciences affirmed at the Cold Spring Harbor Laboratory Personal Genomes meeting September 14-17, 2009 that the company has 12 prototype instruments in operation and continues to be on track for ~$100 (“the cost of a nice dinner”) whole human genome sequencing to be commercially available in the second half of 2010. NimbleGen indicated that they may have a $2,000 exome sequencer available in 2010.

In a challenging venture capital climate, Pacific Biosciences was able to close an additional $68m round in financing on August 12, 2009. Leading commercial sequencer Complete Genomics was also notable in closing a $45m D round on August 24, 2009. The company has sequenced 14 whole human genomes to date, and hopes to sequence exponentially more, 10,000, in 2010 at a minimum cost of $5,000 per genome.

Viability of DTC genomics sector
Where the genomics technology sector has rosy prognostications, the direct-to-consumer personalized genomics market has volatility. Events in the last several months have led to questions of the sector’s viability with upheavals at the three leading companies, 23andme (“Avey Leaves 23andMe to Start Alzheimer's Research Foundation Using DTC Genomics Firm's Platform"), deCODEme (“deCODE close to broke” – Augusty 11, 2009) and Navigenics (“Navigenics Names Jonathan Lord, MD to Serve as President and Chief Executive Officer” April 7, 2009). Absent innovation, DTC genomics companies are a “window business” in the sense that the window for their current offerings may only be open for a short time with the advent of whole human genome sequencing and standardized public multi-SNP condition interpretation tools.

Figure 1. Direct-to-Consumer Genomics Offerings: ongoing price declines (Chart PDF)

As depicted in Figure 1, there are three types of Direct-to-Consumer (DTC) genomics offerings currently available directly to individuals: one-off SNP (single nucleotide polymorphism) tests for specific conditions and paternity tests, multi-SNP risk assessment tests mapping several SNPs to dozens of disease conditions and whole human genome sequencing assessing hundreds of disease risks. The five companies offering multi-SNP risk assessments are: 23andme ($399 for 111 conditions), deCODEme (42 conditions for $985), Navigenics (28 conditions for $999), Gene Essence (84 conditions for $1,195) and Pathway Genomics (77 conditions for $249). 23andme, deCODEme and Navigenics are the most transparent, disclosing the specific SNPs, research references and risk assessment methodologies for their tests, Gene Essence discloses SNPs and Pathway Genomics does not disclose anything. A detailed condition and SNP analysis is here.

Slow DTC genomics adoption
DTC genomics has had slow adoption so far for several reasons, first, there has been very little marketing, few consumers know of the availability and value proposition of DTC genomics services. Second, since automated tools are not yet available, many people are not interested in preventively managing their health, and may still perceive it to be in the responsibility and domain of health care professionals. Third, the conventional but incorrect view is that genetic information is already known (from family history), negative and deterministic. Fourth, as initially pointed out by ExperimentalMan David Ewing Duncan, there are conflicting interpretations from DTC services for the same conditions such as heart attack. This is because the scientific community has little knowledge and agreement yet regarding multi-SNP conditions. DTC companies are looking at different SNPs, assigning different quantitative risk values and employing differing estimates of overall population averages which all contribute to heterogeneous interpretations of risk for the same condition.

DNA - the real Identity 2.0

Right now is an exciting time with at least eleven advancing technologies that could have an even bigger impact than the Internet in the next fifty years. More than any other area, biotechnology is showing potential for revolutionary change with interesting recent developments in personal genome services, synthetic biology and online health portals.

Personal genome services
Genetically, humans are 99.9% the same. The variations can be referred to as SNPs, single nucleotide polymorphisms. Medical tests have existed to look for specific SNPs and there are now recently launched general tests, $1,000 personal DNA services from 23andme and deCODEme, to scan for up to 1 million known possible SNPs on an individual’s genome checking for 18 diseases such as cancer, diabetes and Parkinson's. Dr. Hsien-Hsien Lei writes an excellent blog tracking advances in DNA.

As with any new technology, reactions are myriad and stratified by age. Middle-aged and older people are far more reticent than younger people to try it. There are many open questions such as are we ready for the information? Will the information be substantive? What use is the information if it is not readily actionable? Given the high similarity of DNA amongst family members, is it most ethically appropriate to discuss the situation with relatives ahead of time? In any case, this is the first time the consumer can be in the driver's seat with their medical information in a powerful new way and

the appetite for personal genetic data may prove insatiable.

Of course it is always prudent and fun to consider the darker uses for new technology and one can imagine Identity Theft 2.0, when someone's DNA is stolen and a newly synthesized mix injected as a replacement, waking up and really not feeling like yourself...or worse, being injected with genes that cause all of your cells to de-differentiate back into stem cells!

Synthetic biology
Until last week, synthetic biologists had only been able to create small DNA segments from scratch using computer synthesizers but then genomic pioneer Craig Venter announced that his lab had synthesized the full genome of the smallest known bacterium. It contains 485 genes and has 582,970 base pairs making it roughly 2% the size of the human genome. So far, it has been difficult to synthesize full genomes because long strands of manufactured DNA have tended to break but this new method utilizes the DNA repair mechanism of yeast to stitch the full genome together. It also includes a watermark to tag the bacteria and a gene so that it won’t infect humans or animals.

There is considerable controversy about the future implications of the technology, somewhat similar to those at the advent of genetically-modified food. The desired endgame of Venter's synthetic biology and this advance is to create synthetic biofuels and organisms that could combat global warming by absorbing carbon emissions and other related high impact solutions to open challenges.

The potential applications could be wide-ranging as biological machines automatically persevere once set to task; clean water, nuclear and hazardous waste cleanup and food generation may also be within their purview, not to mention building repair and cleansing, human and animal grooming and nutrient and drug delivery, potentially rivaling the as yet not arrived nanotech mites in a multiplicity of tasks...

Online health portal
Microsoft launched its online health portal, HealthVault in October 2007, allowing people to centralize and store personal medical records and prescription history, manage records, upload data from medical devices such as blood pressure monitors, and analyze and manage the data. A similar offering from Google is expected sometime in 2008 and Adam Bosworth, formerly leading the Google health effort now how his own startup in the personal health services space, Keas.

These Web 2.0 information portals help people to aggregate and proactively manage their health information and will probably continue to add valuable services, especially mobile-device based; at a glance: news, stock tickers, blood pressure and caloric expenditure...