Navigenics is a company focusing on personalized genetics and it launched its service just weeks ago. Dr. Dietrich Stephan, a human geneticist at Navigenics, agreed to answer some of my questions. And many thanks to David Harley who helped me a lot to get this interview done.
- As a co-founder, why did you take part in constructing such a service?
My mother died of breast cancer when she was in her early 30’s due to a missed lump. This shaped my career and guided me toward developing effective early diagnostics and new knowledge-based therapies for human disease. I have been working in academia for the last 15 years to identify gene variants that cause human disease.
My group has been involved in identifying the genetic basis of a dozen monogenic diseases that now allows early genetic testing following the established principles of medical genetics and genetic counseling. While crucial to the families afflicted with these diseases, they remain rare on a population-wide basis.
Approximately 5 years ago I charged into the field of deciphering complex genetic disorders using ultra-high density SNP genotyping arrays and case-control study designs. We published the first paper using more than 500,000 SNPs (in Science), established new risk alleles for Alzheimer’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, and half have dozens more projects ongoing. I believe we are still the only group that makes our raw genotype data freely available on-line for any scientist to download and use .
These risk alleles that we have been finding have effect sizes that are on exactly the same order of magnitude scale as the environmental risk factors that we, as a community, accept as robust and communicate to members of our community on a daily basis (for example “you are obese so you are going to get a heart attack”, or “you smoke so you are going to get lung cancer”). The risk communication for environmental risk factors does not require a testing lab because we can see or sense the exposures in most cases, and the method of communication is quick and crude in that we do not communicate effect sizes or interactive models between risk factors.
As my group continued to define allelic imbalances that are predisposed to human disease, I looked for a place where we could genotype individuals to assess their risk. There were no monogenic testing facilities that we felt comfortable performing the genotyping tests and interpreting the results. Additionally, there were no genetic counselors or physicians who felt comfortable in using genetic risk information to work with their patients proactively to prevent disease based on a holistic understanding of their risk. It is critical to remember that all human disease has a genetic component.
I started Navigenics with my partner David Agus, who is a clinical oncologist, to build the appropriate infrastructure to allow widespread assessment of genetic risks so that we, as a global community, could have a chance at effective prevention strategies to stave off a global health-care crisis in the next 50 years. The concept revolved around encouraging focused prevention, early screening, and early intervention to compress the burden of morbidity to the end of like and balance it with lifespan.
- Will you perform SNP analysis or whole-genome sequencing on patient samples?
We will perform both – starting with genotyping for common variants for common diseases and ending with whole-genome resequencing. You will see an exciting product line evolution over the coming year.
- Based only on SNPs, how can we tell patients about their disease-specific risks? Even if I have some SNPs that indicate a serious risk for coronary heart disease, there can be other SNPs, we don’t know yet, which lower my risk. So can you really tell the patient about their risks?
The SNPs we are reporting on are valid associations (based on thorough validation) and are independent risk factors in population-wide studies. Most of our interpretations are based on studies for which a whole-genome scan has been performed and we know that there are no other large effect size SNPs lurking in the genome. We are making the assumption that independent risk factors when present do not cancel each other out, rather they compound risk. We have seen no validated exceptions to this assumption in the literature. As we become aware of exceptions to this assumption we can modify our reporting. We are providing the current state-of-the-art associations and informing members that their risks may refine themselves over time. Take the example again of environmental risk factors – the more you have the higher your likelihood of disease – but we know that we can’t predict with certainty an outcome.
- What kind of role will web 2.0, the new generation of web, play in your service?
Web2.0 features will be employed primarily to ensure data privacy, but also to assist in visualizing very complex data sets and results so they are understandable to members and physicians.
- Why will people choose Navigenics instead of the other genetic companies?
Quality. Data will be complete with all risk genotypes being called. Genotypes will be generated in a CLIA-certified diagnostic environment. On staff genetic counselors assist in interpreting this information any time of the day or night. We will not give risk information on associations that are wrong. Our ethics, policy, clinical, scientific, and business advisory boards are experienced and made up of individuals who want to ensure this type of sensitive information is used correctly and accurately. For example we are sponsoring an industry standard-setting meeting in conjunction with the personalized medicine coalition this fall. When making health decisions you need to be able to trust the quality of the information you base those decisions on.
- What do you expect to see in the field of personalized genetics in the next few years?
Full resequencing of the genome, copy number analysis, and methylation status assessment where all of that data is run through the Navigenics interpretation engine to provide a rank-ordered list of health risks so that a focused prevention plan can be devised along with the physician, and a focused biomarker monitoring program for early detection is implemented. Early intervention equals better outcomes.