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- 5 December 2013 11:26 am , Vol. 342 , #6163
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Examining His Own Body, Stanford Geneticist Stops Diabetes in Its Tracks
16 March 2012 3:28 pm
Michael Snyder has taken "know thyself" to the next level—and helped heal thyself.
Over a 14-month period, the molecular geneticist at Stanford University in Palo Alto, California, analyzed his blood 20 different times to pluck out a wide variety of biochemical data depicting the status of his body's immune system, metabolism, and gene activity. In today's issue of Cell, Snyder and a team of 40 other researchers present the results of this extraordinarily detailed look at his body, which they call an integrative personal omics profile (iPOP) because it combines cutting-edge scientific fields such as genomics (study of one's DNA), metabolomics (study of metabolism), and proteomics (study of proteins). Instead of seeing a snapshot of the body taken during the typical visit to a doctor's office, iPOP effectively offers an IMAX movie, which in Snyder's case had the added drama of charting his response to two viral infections and the emergence of type 2 diabetes.
Clinicians at the front of the movement to personalize medicine see Snyder's self-analysis as a landmark. Cardiologist Eric Topol, who runs the Scripps Translational Science Institute in San Diego, California, calls the work a "tour de force 'N of 1' report with remarkably comprehensive state-of-the-art omics from one individual." Topol recently published a book, The Creative Destruction of Medicine, that spells out how he believes the technologies Snyder tapped will create better health care. "The way the field is moving in such an accelerated fashion," Topol writes in an e-mail, "this type of 'pan-ar-omic' study of individuals is now not only feasible but in select individuals with medical conditions, particularly useful clinically."
Scientists in Snyder's field similarly praise him and his team for collecting and attempting to find the links at different time points between the 3.2 billion nucleotides of DNA in his genome and more than 3 billion fluctuations in his blood molecules such as proteins, metabolites, microRNAs, cytokines, antibodies, glucose, and gene transcripts. "It's a visionary kind of approach," says Jan Korbel, a molecular virologist and cancer researcher at the European Molecular Biology Laboratory in Heidelberg, Germany. Daniel MacArthur, a genomics researcher at Massachusetts General Hospital in Boston, says the "fascinating study" is much more informative than simply looking at someone's static genome sequence. (Snyder's group decoded his at the beginning of the project.) "The nice feature of this study is that it profiles many of the dynamic molecular changes that our body experiences in response to environmental stresses."
Snyder, now 56, says he began the study 2 years ago because of a slew of technological advances that make it feasible to view the working of the body more intimately than ever before. "The way we're practicing medicine now seems woefully inadequate," he says. "When you go to the doctor's office and they do a blood test, they typically measure no more than 20 things. With the technology out there now, we feel you should be able to measure thousands if not tens of thousands if not ultimately millions of things. That would be a much clearer picture of what's going on."
Snyder selected himself as the subject of this study for the most practical of reasons. He says he wanted someone local who could frequently give blood samples, and he also needed to make sure the person would not turn on his research group if devastating information surfaced. "I wasn't going to sue myself," he says.
Snyder had a cold at the first blood draw, which allowed the researchers to track how a rhinovirus infection alters the human body in perhaps more detail than ever before. The initial sequencing of his genome had also showed that he had an increased risk for type 2 diabetes, but he initially paid that little heed because he did not know anyone in his family who had had the disease and he himself was not overweight. Still he and his team decided to closely monitor biomarkers associated with the diabetes, including insulin and glucose pathways. The scientist later became infected with respiratory syncytial virus, and his group saw that a sharp rise in glucose levels followed almost immediately. "We weren't expecting that," Snyder says. "I went to get a very fancy glucose metabolism test at Stanford and the woman looked at me and said, 'There's no way you have diabetes.' I said, 'I know that's true, but my genome says something funny here.' "
A physician later diagnosed Snyder with type 2 diabetes, leading him to change his diet and increase his exercise. It took 6 months for his glucose levels to return to normal. "My interpretation of this, which is not unreasonable, is that my genome has me predisposed to diabetes and the viral infection triggered it," says Snyder, who acknowledges that no known link currently exists between type 2 diabetes and infection. He has become so convinced that this type of analysis is the future of medicine that last summer he co-founded a company in Palo Alto, Personalis, which aims to help clinicians make sense of genomic information.
George Church, who has pioneered DNA sequencing technology and runs the Personal Genome Project* at Harvard Medical School in Boston that enrolls people willing to share genomic and medical information similar to what's presented in the Cell report, says some might critique Snyder's self-exam as merely anecdotal. "But one response is that it is the perfect counterpoint to correlative studies which lump together thousands of cases versus controls with relatively much less attention to individual idiosyncrasies," Church says. "I think that N=1 causal analyses will be increasingly important."
*Disclosure: The author, Jon Cohen, recently joined the Personal Genome Project.