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Q&A: Mike Snyder on Data-Driven Personalized Medicine for All, Stanford's iPOP Study

Michael Snyder

NEW YORK (GenomeWeb) – Mike Snyder, chair of the Department of Genetics at Stanford University School of Medicine, has been a pioneer of omics-driven personalized medicine.

In 2012, his lab made headlines when it published an "integrative personal omics profile" (iPOP) of Snyder that included an analysis of his genome sequence along with transcriptome, proteome, metabolome, and autoantibody profiles that were taken over a period of one to two years.

Among other things, the "Snyderome" revealed that he had an elevated genetic risk for type 2 diabetes, which helped him catch a spike in his blood glucose levels early. 

Following the proof-of-concept study, Stanford has scaled up iPOP to 100 individuals whose data are currently being analyzed, and interesting results are already coming in.

In addition, Snyder, who is also the director of the Stanford Center for Genomics and Personalized Medicine, is aiming to take genomic medicine to the masses: his new book "Genomics and Personalized Medicine" is scheduled for release by Oxford University Press next month.

Subtitled "What Everyone Needs to Know," the 160-page publication serves as a primer for patients and doctors, covering the basics of DNA analysis and inheritance, cancer genetics and tailored treatments, rare disease diagnostics, complex genetic diseases, pharmacogenomics, prenatal genetic testing, epigenetics, metabolomics, the microbiome, infectious disease diagnostics, genetics of aging, and wearable health devices. It also touches on the challenges of big data in medicine, ownership and privacy of genetic data, genetic discrimination, physician education, and the cost of preventive medicine.   

GenomeWeb spoke with Snyder this week about his ongoing work and the upcoming book. Below is an edited version of the interview.

What motivated you to write this book, and who is it addressed to? Who do you hope will read it?

This is an area that, quite frankly, everyone needs to know about, and people really want to learn this information. I give a fair number of public talks every year; usually, they are very well attended, and people always come up at the end and say, 'How do I learn more about this stuff?' I think that was the primary motivation — I haven't seen anything geared towards the lay person yet.  

I think doctors will probably like it, too. On the one hand, they are professionals, on the other hand, they don't really know this area, either, and they are very reluctant to prescribe anything they don't understand. You would be amazed at how few MDs understand the value of genome sequencing in cancer, what are its strengths and what are its limitations. Also, I have a section about immunotherapy in there, for example. That's really something a specialist would know, but I would argue most doctors don't even know about that.

It's meant to be a super easy read. It's meant to be short and simple. I hope that even doctors would read it and get an even better appreciation of what's going on.

What's going on at Stanford these days, following your 2012 iPOP study?

We are going through data from 100 people who we are following like me in this iPOP study. We are not done fully analyzing everyone's genome, but even in that smallish cohort, we find plenty of people with incredibly useful information.

As an example, one person has a mutation that suggests she is at high risk for a certain kind of cancer called paraganglioma. There is no way she would have known that had we not done that, and there is a simple urine test she should take to watch out for this cancer occurring. There is another individual whose father just had a heart attack and there is a mutation in his DNA that suggests he is at high risk for the same thing. He can watch out for that and look for heart issues, and he would not have done that had we not sequenced his DNA. It's a very rare mutation in one of many genes you would look at for heart issues, but it's not on the ACMG [American College of Medical Genetics and Genomics] gene list, for example.

I think we're going to see many examples of this sort of thing. It's only going to get better as we understand the genome better, and how to interpret it.

The book is generally quite upbeat about genomic medicine, but how many people do you think will benefit from it? In cancer, for example, it holds a lot of promise, but the NCI MATCH trial recently took a break for an interim analysis and found that it could only match a few patients to treatments.

If you ask people, they'll say 'This has not been proven; even in cancer, the trials have yet to show that this genome sequencing benefits people.' But you ask the exact same person, 'If someone in your family had cancer, would you sequence their genome?' and without hesitation, every single one of them says 'Absolutely.' So although you can criticize that its value has not been shown, nobody wants to be among the few percent who did not get their genome sequenced that could have suggested a therapy that would have helped them. I actually think the numbers are going to be better.

Certainly in our own experience, for every person we sequenced, the information we get is either 'Yes, they are on the right treatment' or 'Here is something else they should consider.' And it's true the latter might be less common, but it does happen. I have watched it personally: my mother in law benefited from a genetic test which suggested a phase III drug which did in fact help her. So if you are one of those people, you are certainly glad that you had those tests done.

How much will screening healthy people with omics technologies improve their health? How much disease will we actually be able to prevent, or significantly alter in its course, rather than just knowing that it might come someday?

That's a good question and probably the biggest challenge. A lot of what you learn from your genome might say 'Exercise more and lose weight.' That's what you tell people anyway, and they don't do it. What I can say is that it hits you a little harder when you see it in your DNA. I think the heart situation that I mentioned is a very different kind of thing, somebody is actually watching out for symptoms based on the kind of heart issue he has, and I don't think he would have done that normally. I think you will be doing, in some cases, different kinds of monitoring. And I think knowing that you are at risk for something, like your family history, probably will help you catch it earlier.

Wearable devices will be very powerful in this area, as well. I think we will see more and more wearable devices measuring different kinds of things. You may have seen this recent paper in Nature from Ron Davis' lab, where they are sensing molecules from sweat. I think you are going to see more of these biochemical assays being performed on people in a much more frequent fashion, ideally in a continuous measurement, but some of them as periodic measurements. That's one area that's booming a lot at Stanford, this whole wearable space; we are doing a lot, as are other groups.

I did not put this in the book because I think it's even more futuristic, but I also do see a world where people's diet, and in particular supplements, are recommended based on their genomic and other omic measurements and lifestyle. Because one thing people are good at doing is taking supplements. I think you could actually manipulate people's microbiomes, and other things. And I do think that will have some benefit. It does have to be kind of painless, or people won't do it.

Who will pay for omics-based preventive medicine? As you say in the book, insurance carriers, at least in the US, are currently reluctant to pay for it because it's a long-term investment, and people might switch insurance.

As the cost gets so cheap, it will pay the healthcare provider to offer this because it helps people manage their health better, and then the cost-benefit goes up. Right now, it's pretty expensive to do this stuff, and people do switch their plans.

Some people are getting it done in conjunction with research projects. I think it's valuable because the research projects demonstrate utility, and that, in turn, leads to more adoption from the rest of society and makes providers think twice. I think a lot of providers would like to offer it, but they don't know how to do it. Geisinger is one that seems to be out in front; they partnered with Regeneron [to sequence the exomes of 250,000 Geisinger patients]. That's a win-win situation, where people get their genomes sequenced and they learn some useful stuff, and the companies probably get some economic value out of it.  

Books about genomics are invariably outdated the day they come out. What's happened in personalized medicine that did not make it into the book?

Immunotherapy has increased relative to what it was since I wrote the book. It was done in August of last year, and then I was able to sneak in a few more recent numbers as it went to the proofs.

And CRISPR/Cas9, which you see alluded to in the book, is probably the biggest thing that's undervalued. I did not want to put things in there that seemed like false promises at the time — I did not want people to go 'How do I do CRISPR/Cas9 on my kids.' We're not ready for that, but a lot closer than we were six months ago; that area has moved a big step forward.

What's the most important thing you have learned from your own genome, and from tracking your omics data over many years now?

I have learned a lot. First was the diabetes risk, which I caught early and managed, although my high sugar has come back and it's something I do have to deal with. Recently, through tracking myself, I caught Lyme disease fairly early when it occurred. That came out of the tracking and the wearables, not so much the biochemical measurements. I see all kinds of other interesting markers, some of which will be parts of future studies — I'll leave it at that for now.

The thing that is incredibly cool about this is, as we follow people individually, every single person is interesting. That is to say, you'll learn interesting information, either from their DNA or from their omics profile, that is both scientifically interesting and often has personal value towards their health. I think it's safe to say, 'Everyone is interesting, not just to their mother.'