Mike Snyder – Why Study Diabetes?

Stanford Geneticist Mike Snyder

In March 2012, Stanford scientist Mike Snyder published a groundbreaking study in Cell that showed the most detailed biological profile of a person ever done.  It includes two years of monthly data, meaning Snyder’s DNA, plus measurements of the constantly changing rise and fall among proteins created by his genes, many of his metabolic byproducts, special immune system cells that point to infection or autoimmune disease, and more.   And in the middle of all this monitoring, Snyder developed Type 2 diabetes, allowing researchers to track the molecular changes connected to it.  The good news, he caught the condition early, and changed his lifestyle so that not only did the researchers get to track his “markers” as his blood sugars shot up and he became a diabetic.  They also got to track his markers as his blood sugars gradually went down over time and he “un” became a diabetic.


Here’s part 1 of a 2-part conversation with Stanford geneticist Michael Snyder. .  It begins with Mike getting yet another blood draw in the name of science . . .  Shelley – Meandmydiabetes

LISTEN (about 45 Minutes)

MIKE SNYDER
It turns out . . . so they want to, um.  They want me to give some blood.     Is that going to gross you out?

Oh, this is great.  Do you want your blood taken in audio?

SCIENTISTS
Unless he starts screaming.

So you’re rolling up your sleeve . . . this is only audio, so you’re going to have to narrate.

MIKE SNYDER
Okay.  Very good.  I’m rolling up my sleeve.  We’re doing another blood draw this morning so that we can do another sample of one of my Omics profiles.

And what’s you’re name?

MIKE SNYDER
My name is Michael Snyder.  I’m Chair of the Department of Genetics and I’m also the Director of the Center for Genomics and Personalized medicine.

It looks like you’ve done this so many times, you don’t even mind doing it anymore.

MIKE SNYDER
Well, that’s right.  Not a problem.

My goodness it looks like you have out about 2000 tubes to put the blood in.  How many are there?

SCIENTIST
Tennish.  About ten tubes.

And who are you?

SHIN LIN
I’m Shin Lin.  I’m a cardiology fellow at Stanford.

RUI CHEN
My name’s Rui Chen.  I’m a postdoc in Dr. Snyder’s lab.  We co-authored the Cell Paper.

How many times have you poked this guy?

CHEN
I’ve never poked this guy because I’m not a medical doctor but he’s been poked many many many times.  This is the 41st time now.

In the last two years?

CHEN
This is the  41st time now

MIKE SNYDER
I had lost track!  So what we’re looking for is a very detailed molecular profile of what’s in my blood and the idea is that we’ll be able to follow health states much much better this way than if we simply measure a few things as is currently done.  So right now when you get a blood test about 15 things are measured.  What we would like to see happen in the future is that you’re measuring thousands of things.   We are measuring in fact 40,000 things, different components every time.

And when you measure, what are you measuring.  Standard stuff?  Proteins.  DNA?  What are you measuring?

MIKE SNYDER
We are measuring RNA, which is what gets made from the genes.  We measure proteins and we measure metabolites.  We also measure antibodies to see if I’m making antibodies against anything that might suggest something’s wrong.

Meaning antibodies against something you want your body to fight, or antibodies against things you really don’t want your body to fight, because it’s fighting you!

MIKE SNYDER
Mostly, we’re looking for the latter, antibodies that are recognizing things we don’t want to see.

LIN
Allright. ready?   One, two, three.

You even look at the needle as you’re getting poked.

MIKE SNYDER
Yeah, I follow what’s going on.

So it looks like 8 tubes.

MIKE SNYDER
I think it’s 10 total.  The different tubes are for different things.  There’s one tube used for the antibodies and then another that’s used for standard medical tests and then a series of eight other tubes for the measure of all the components I mentioned to you before.

And you’re using your own technology for measuring the RNA?

MIKE SNYDER
That’s right, RNA sequencing… it lets us measure literally the expression of every single gene in the body

That’s what?    20,000 proteins?

MIKE SNYDER
It’s 20,000 genes but interestingly each gene makes more than one protein on average so you can get different RNAs made from the same gene.

To measure these, are you using the high-tech device called a mass spec machine?

MIKE SNYDER
We use mass spec to follow about 4,000 proteins at each time point, and then we use very special tests for some very interesting proteins called cytokines which are quite biologically interesting.  They don’t get detected by mass spec, and they’re not very common in the blood so you have to use special methods for that.

Are you using aptamer technology?

MIKE SNYDER
No.  We’re using pretty much standard antibody assays but set up in a high throughput fashion

Standard assays.  So could Quest Lab do this for anybody, or are you special?

MIKE SNYDER
Right now they can’t.  But we think in the future this can be optimized so anyone can do it.

But right now, even the fact that you, personally, got to see what’s in your own blood and your own DNA plus your own proteins is very special.   Nobody gets to do that.

MIKE SNYDER
That’s right.   Nobody certainly has looked at things at this level before, so that’s what makes this study unique.

Did you have to get special permissions to look at your own blood this closely?

MIKE SNYDER
You do.  You have to  enroll in the study, so I had to consent myself, essentially, to become part of this study, although I actually enrolled with a close collaborator Kari Nadeau, and so she’s in fact the one who consented me, but we do hope to enlarge the study.  We’re now are applying for approval to be able to look at lots of different people.

Did I read the study correctly that you also looked at your mom’s blood?

MIKE SNYDER
Yes, well, we certainly sequestered her DNA and we’ve done a limited analysis on her blood.  She was a very willing participant in the study.  She’s a very curious person by nature and so she wanted to take part in this.

So you had a somewhat normal person and I’m assuming she’s not a scientist?

MIKE SNYDER
She’s retired schoolteacher.

And she was okay finding out all kind of things about what’s in her blood?

MIKE SNYDER
We haven’t found anything so problematical for her yet –  she’s 83 years old and going strong so we’re not expecting . . . anything we find out her case is likely to be good news.

Just so our listeners know, we’re doing this conversation as tube after tube of blood is being drawn from your arm.

MIKE SNYDER
That’s right.

No big deal

MIKE SNYDER
No big deal.

Now as part of this you found out that you are not only prone to diabetes but that you are indeed, a diabetic.  What was that like to find out?

MIKE SNYDER
So we discovered that early in the study, when we sequenced my DNA and it suggested I was at high risk for diabetes.  That was a bit of a surprise because I was not aware of that running in my family

Now, you’re a slim person and you look athletic.  Were you his way when you found out that you are prone to diabetes?

MIKE SNYDER
I might’ve been slightly heavier — 15 pounds heavier, but generally I do not fit the profiles of someone who has diabetes.

How old are you now?

MIKE SNYDER
I’m now 56, and we started the study when I was 54 so I guess I got the first news that I was prone at 54.

How did you decide that you weren’t just at risk for diabetes but you might have it?

MIKE SNYDER
I had been tracking all the things as you see now.  We are currently tracking by blood components.

So right now, you’re holding the little piece of gauze in the crook of your arm to keep the blood from continuing to flow because you’re done now?

LIN
Well, actually, we’re going to have to poke you again because the flow got too slow.  Is that okay with you?

MIKE SNYDER
That’s fine.

LIN
Okay

So this is all part of it

MIKE SNYDER
That’s right.   You’re seeing real life.  And . . . I lost my train of thought.

At some point you wondered if you actually were a diabetic instead of just a potential one.

MIKE SNYDER
Yeah, so what we’ve been doing is following my blood complements all along, and in fact, they had been running normal.  But because of my genome sequence . . .

You mean your blood sugars?  What were you monitoring that was your clue?

MIKE SNYDER
Well we were following everything, but blood sugar, in particular, because of the diabetes concern.

That’s a test that anyone can do.

MIKE SNYDER
It is, and in fact, it had been done routinely as well as by the methods we were using.  But the key was when we went to a specialist who looks at glucose metabolism and went for very fancy tests.  This was in Gerry Reaven’s group, here at Stanford.  And she looked at me and certainly didn’t think I was at risk for diabetes nor did I at the time.  But when we did that first measurement it turns out my glucose level was high even before we started the test.

How high was high.

MIKE SNYDER
It was 127

And that was fasting — that was going in without eating anything

MIKE SNYDER
It was fasting and we repeated the test and it was still high.   And it went up even higher after that first one during the test — up to 150 and probably more important is that there’s another test, called hemoglobin A1C, that was also high. The  first measurement was 6.4 and then later 6.7

LIN
1-2-3

Look at this, you’re smiling as you get poked again.

MIKE SNYDER
I’ve had this done before.

Now, the first hemoglobin A1 you had before you even started this test, would have defined you as a diabetic.

MIKE SNYDER
Well,  we did not do an early hemoglobin A1C because there was no reason to think I was diabetic and also because my glucose levels were quite low early on in the test.

And what were they?

MIKE SNYDER
They were in the 90 to 100 range, depending on whether I was fasting or not.

So they started out in the 90s and 100s which was sort of normal and then at some point they went up further, and then you said, hmm, maybe we should go check with Gerry Reaven’s group?

MIKE SNYDER
No, actually, they went up the first time I went to see Gerry Reaven’s group.  So I just happened to go there for the fancy, this glucose metabolism test, and at that first measurement my blood sugar and A1C were high, and the reason they was high, we think, is because I went to do it after this viral infection.

Well, that’s right, you’ve written that you were doing fine in terms of blood sugars, and then you caught the flu, or something like that.

MIKE SNYDER
It was respiratory syncytial virus infection which is a fairly common cold but not as common as some others.  Anyway, it pretty nasty version.  I was out of work for several days and shortly afterward, I happened to go for this test, and that’s when my blood sugars skyrocketed and they were up for several months before I changed my diet and I changed my exercise habits and such,  It took a while but my levels of glucose gradually did come down to normal.  So it was temporary in the sense that it lasted several months before we started and then took some time to come down.

LIN
Thanks.

MIKE SNYDER
We’re done.

LIN
Good bye now.

MIKE SNYDER
They need to run off to process the samples.

The action is always good.   Getting back to your story, you got diabetes and then you “un” got diabetes without taking medication.   So what did you change in how you ate and exercised?

MIKE SNYDER
Yes.  I changed both my eating and exercise habits and I also took baby aspirin every day although I don’t think the latter was what made the difference.

So you don’t think the baby aspirin was making a big difference, but what did you change about the way you ate?  What did you change about what you ate for breakfast?

MIKE SNYDER
Before this was diagnosed, I was probably the world’s worst eater.  I ate lots of sweets and desserts, cakes, whatever, candy bars etc. And so April 13 last year I completely cut all that out, and I haven’t had desserts since except in the form of fruits and things like that.

Alright then, what did you have for breakfast today?

MIKE SNYDER
Well today I didn’t eat breakfast because I was going to give blood this morning!  That was a fasting sample.

What did you have for breakfast yesterday when you did not give blood.

MIKE SNYDER
I guess I had Cheerios with blueberries..

And  for lunch?

MIKE SNYDER
I usually have either a salad with chicken, or sometimes they have some sushi here, or sometimes I have some chicken on rice sort of thing.  I don’t eat much pasta anymore.  I used to eat a lot of pasta before all this was diagnosed and as a consequence I would say, with my eating habits changing as well as my increase exercise . . .  I pretty much always ride my bike to work. though today I didn’t because I have to take someone somewhere, but as a rule I ride my bike to work.  When I increased my exercise I would probably ride even more places and things like that so I doubled the amount of biking.  I started running again which I used to do but haven’t been doing up to the point I was diagnosed.

You are exercising more, you cut back on the total amount of carbohydrates, especially sugars.  Do you have a sense of what your ratio is of fat to protein to carbohydrate?

MIKE SNYDER
It is known in detail, but I don’t know off the top of my head

Do you eat more fat.  Do you eat fewer carbohydrates?

MIKE SNYDER
I definitely eat fewer carbohydrates overall, I eat more probably more protein and more salads and things like that.

You’re still keeping your fats pretty low,  you’re not a fat eating person?

MIKE SNYDER
Well I guess I eat some.  I have high cholesterol and high triglycerides and I do take simvastatin which is a statin.  That has been very effective at lowering my cholesterol and triglycerides, but you know I also do watch a little bit on that end, so I guess I eat some fat

Here we are getting to talk about the intimate details of what is inside your blood that are supposed to be private for most people, unless they want to share it, and you’re sharing it all with the world.  What are you finding out about your triglycerides and cholesterol, now that you’ve changed to a diet with less carbs for the sake of your diabetes?

MIKE SNYDER
Well, the cholesterol and triglycerides have probably mostly come down because of the statins, so I’m a good responder.  We know that because they came down even before I change my diet.

Have they come down further now?

MIKE SNYDER
I think they’re running around the same, to be honest, so what’s come down the most with my change of diet and exercise has been the sugar levels.

So to bring your sugars down, you didn’t need to make a huge radical change of what you ate.  You cut out the deserts and you exercised more.  Some diabetics have to cut out almost all the carbs and  you didn’t have to do that.

MIKE SNYDER
Well I would say I’ve changed my diet pretty dramatically.  I used to eat lots of pasta and lots of sweets.  And all that has pretty much gone.  So it really has changed quite a bit.

Now, tell me this, since we’ve talked about how you eat now and how you exercise, let’s go back to Gerry Reaven’s lab.  What kind of test did they do?  Did they did check not only your blood sugars but your insulin levels and some other hormones.  Did they do the test, over time, as you were eating food to see how your bloodwork responded to the food?

MIKE SNYDER
Mostly they monitored glucose metabolism using various agents that block uptake and things like that, so they’re following the details of how you metabolize glucose.

So they injected glucose into your blood and they injected insulin to see how those two interact?

MIKE SNYDER
Yes, they’re following exactly how you metabolize glucose.

Did they find out that your body was needing to use a lot more insulin to make things happen, or was your pancreas putzing out and not having enough insulin

MIKE SNYDER
Well the nice thing is I was still classified as insulin sensitive, that is, I wasn’t insulin resistant, which is often associated with diabetes.  In my case I was still, at least I appeared to be, insulin sensitive, and we think that’s because I caught this early because I’ve been following myself all along, so I could see when this first increase occurred.  Now we did do more testing before I changed my diet and probably more than a month went by, but ultimately, once I was diagnosed, and it was very clear after repeated tests that I did have high glucose, we did change my diet and  because I caught it early I think that’s why I was so insulin sensitive and I could do something about it.  That’s a  general issue with disease.  If you catch it early, you can usually control it by simple means, But if you catch it too late, there is usually damage done and it’s really problematic:.  Had I waited a longer time before changing my diet and exercise, it’s possible I would have needed drugs.

You were lucky!   Most people catch diabetes  years after they started having the problem.

MIKE SNYDER
Under normal circumstances as a healthy person I would normally go to the doctor maybe once every three years. That means I would not have caught this high glucose right away, and so probably a year or two after it happened, or something like that and by then there could have been significant damage.  So the nice thing is it was caught early, and I was able to manage it and I’ve changed my lifestyle and to be honest, I feel better because of it.

Well, if you were insulin sensitive and your blood sugars were still going up, does that mean your pancreas was stressed and not able to produce as much insulin as you needed?

MIKE SNYDER
We don’t know for certain why this occurred.  My insulin production seems okay.  We’ve measured that over various time points.  But it may be more the way my body’s utilizing and responding to the insulin that’s the change.

There’s some  talk about how insulin is important for allocating and managing what is happening with your immune system, and if you’re sick your insulin needs to say, ‘I need to go work with the white blood cells and make them work better.’

MIKE SNYDER
The relationship between insulin and getting sick through infection and various things is still an area where things are not very well understood.  Certainly what people can say is that stress responses are very much associated with type II diabetes.  Viral responses have not been shown, with the exception of some of the chronic cases, but I think what’s particularly surprising about our study is that it’s very clear that this appeared after that nasty viral infection, so we did make a connection though it may just be that the viral infection caused general stress, which in turn led to the increase in sugar and this type II diabetes onset.  These are some of the things we hope to understand better as we do more experiments and follow up with more people.

It sounds like you would be a believer of people saying that “It was after I had surgery,” or “It was after my father died and I had a divorce, that all of a sudden I had diabetes.

MIKE SNYDER
We do think that’s a likely scenario.  That after these situations people are at risk for a having this happen, and I think it would make a lot of sense for people to go and get checked out on a more frequent basis after life stresses shall we say.

Thank you for explaining the details of your story and how you got better, and congratulations on feeling better. It was also interesting in your published article for The Cell, in reading the discussions about the potential for this research, and thinking about  just how you caught this problem, it sounds as though it didn’t take anything fancy to catch your early diabetes.

MIKE SNYDER
We have the tools right now to discover whether somebody has early diabetes, just by following glucose.  I think what was special my case is that l I don’t have any of the obvious features that people expect with diabetics and I also didn’t have obvious family history.

Did you have symptoms that made you go, hmmm.  Was your vision getting a little blurry, or were you thirsty more often or using the bathroom more often.

MIKE SNYDER
None of that so much and certainly not before all this kicked in and we did measure my vision and stuff after my glucose level shot up, and after that, we were checking for glaucoma and checking my retina, and everything looked fine. So again we think we caught this right after it happened

So you weren’t showing any symptoms, and you didn’t notice a change in how you felt.  It was just the blood sugar on a glucometer and also your hemoglobin A1C.  Just your average blood sugars over three months plus finger pricks to see what your blood sugar is in the moment.

MIKE SNYDER
That’s right.

But you did all this fancy DNA stuff and protein stuff.  You didn’t need those to diagnose it, but as a scientist you’re looking at all the data and saying, there are some other markers here that are fascinating?

MIKE SNYDER
Yes, if I knew I was going to get diabetes I could’ve just measured glucose.  But we didn’t know that going into the studies.  So we are trying to follow everything that’s going on for any potential disease that comes up so that we might be able see what early markers are there in general and the other thing I would say is that diabetes is probably clearly not one disease,  It’s  probably hundreds of diseases and if you look at it everybody is a little different.   I don’t fit the classic case of someone getting diabetes.  Diabetics generally have much a higher body mass index is, so what we think, and others think as well, is that diabetes is 100 diseases so we think by following all these different markers we hope to be able to see how many different kinds there are.

Well before we go on, just so people know, how tall are you and how much do you weigh?

MIKE SNYDER
I’m always five foot nine, but at the start of the study I was 162 pounds and now 147 pounds.

Probably your body mass index is putting you  below average, for body, and in the fit category

MIKE SNYDER
I like to think so.

Right now as we talk about diabetes as a disease, I wonder whether you’re thinking of diabetes as several diseases or if there’s a new way to think about disease.  For instance, did you find out during this time period that your inflammatory markers went up?

MIKE SNYDER
We did, because I went through these viral infections — I  have been through four viral infections now, two initially since we published this study and it’s  pretty clear that during each of these infections you see a lot of inflammation going on and inflammatory markers going up.  Interestingly, after this RSV infection that I mentioned earlier, there was a big inflammatory response at the time of infection, and there was also a spike one or two weeks later which may or may not have something to do with the onset of my blood sugars shooting up.

Many researchers say that what’s happening with chronic inflammatory markers is a clue to all kinds of disease states.  Are these the markers that you were most intrigued with in terms of how they changed or was there something else?

MIKE SNYDER
We’re following everything.  We don’t know what it all means yet to be honest.  We’re still analyzing the data.  We do see some very interesting pathways and things changing, markers that are showing up in these complex pathways and we’re still trying to understand what all means.

Can you tell me about it, or does it need to stay a secret now — all of these millions and millions of markers that you’ve been collecting?

MIKE SNYDER
There’s nothing secret about the data, and anyone can download the data and re-analyze it for themselves.   All I can say right now is that we are following these 40,000 components and we see things are going up and down.  The inflammation responses are a no-brainer.  We see that happening during these infectious times and just before the onset of diabetes.  Going back to your earlier question, the inflammation has been associated with lots of different diseases.  That might be a downstream effect of the disease, like inflammation has been associated with cancer and other sorts of diseases as well and so some of this may be downstream events.  And that’s fine.  We do want to see them, but we also want to see the earliest events because those are the things that are probably triggering the disease.  If we can catch those markers early and find markers for those and catch those early enough and then also try and understand exactly what’s going on that might give us a better handle on how to treat the disease in its earliest possible state- catch and treat –  I should say.

And also you’re indicating that in your case you didn’t have to have to add any  diabetes medications and you  didn’t have to start injecting insulin.  Instead, you changed your lifestyle.  Was it  motivating to see in your bloodwork what was happening to you?  Did seeing the information help you realize you had a health issue ahead and maybe you don’t want to eat all that ice cream?

MIKE SNYDER
It was clear I had a health issue, and so I dealt with it.  But to be honest with you the only  thing I really do miss out of changing my diet as is the ice cream.  But that’s a small price to pay for maintaining your health.

There’s a potential that this kind of information might motivate more people to take care of their health, as you mention in The Cell article, in your discussion section.  But right now the FDA does not allow people to know all of this cool stuff about what’s happening in their blood.  Right now we don’t have affordable ways that people can regularly check their hemoglobin A1C’s and their insulin levels, let alone these more complex tests,  That’s out of the  price range of most people.  So we have both the fact that we don’t have the information available — it’s barred from most people to find out all that you found out.  Plus, it’s expensive.

MIKE SNYDER
Well,  I don’t know how much it is truly barred, in the sense that you can’t access it, so much as it’s not affordable.  For these latest technologies we’re using a million-dollar mass spectrometer — that’s for measuring the proteins, and we’re using an $600,000 mass spectrometer for measuring metabolites.  And the whole sequence, so that the setup cost for this was enormous.   But now we can analyze the samples for around $2500 apiece although we’re analyzing them in exquisite detail

$2500 a piece, give or take a little bit of research and development costs up front!

MIKE SNYDER
A lot of research and development up front.   The point is, I think what will happen is like everything in science — it’s very expensive to do it now, and it’s not accessible because this is a research project.  It truly is.  It has to be, because we’re still trying to understand the data and what it means for all the issues associated with this.  But I’d like to see in the future this become quite inexpensive, so it could be done as a home test.  Quite frankly, so instead of pricking your finger and measuring one simple thing which is glucose, you can measure 5000 things and actually get a much clearer picture what’s going on.

A much clearer picture about what’s going on is important to you and I’m thinking about what’s going to happen with the people that are in your next test. you mentioned that you’re going to try to do this with a broader range of people — not scientists?

MIKE SNYDER
That’s right.  We’d certainly like to make sure everyone we talk to who we enroll in the study understands what it’s all about and what to do and so they need some level of sophistication to be able to comprehend what we want to do.

Most studies are done in a double-blinded placebo style, meaning that you don’t get to know each person individually  as much as you have them be a data point.   And the test subjects don’t get to know what the data says about them.   They just get to know the fact that they were part of a general study.   In your personal case, it was motivating for you to hear what your information was.   Are you planning to do this study in the double blinded way, or are you planning to do it in a way where you can inform people about what their blood says about them as you go along?

MIKE SNYDER
Well, I personally would like to inform them about what their blood says as we go along simply because I think it can help them, rather than hurt them, if their glucose shoots up or something.   But to back up a little bit, the study will be focused primarily on pre-diabetics, meaning people at risk for diabetes who are starting to show some high levels of glucose and we also  know already just from statistics that about a third of them will become diabetics, so we are going to be following an at-risk population, and we will follow them in time, and presumably, like me, some of them, we will see their glucose shoot up and we will see what’s happening in those earliest events.  What kind of life stresses that’s associated with, if any, and that sort of thing.

So you want to see what’s happening in their lives individually so you can tie that back with what you see.  Now are you just going to tell them about the markers that they could get by going to a doctor to hear about their blood sugars and maybe their insulin levels and A1Cs or will you also tell them about this wide world of inflammatory markers and say here’s what we’ve seen here with your inflammatory markers too?

MIKE SNYDER
Well, we’ll tell them  what we understand.  I’m not sure there’s a point in telling them what we don’t understand.  If there is a strong inflammation response and we see that it’s associated with a health risk I guess we probably would tell them.  I assume that if  there’s a strong inflammation response it is associated with something and so we’d want to figure out what that something is.

Now you want to see this happen for two reasons.  1.  For sake of the people to see if it will motivate them to get more information, 2.   You’re going to get research information from it.  But the FDA gets concerned if they think someone’s getting information about something that’s a non-approved medical device, and some of the data that you’re getting is not approved and reference checked by the FDA.  How do you work with that?

MIKE SNYDER
We would only return results through the physician, that is to say . . . let me back up a little bit.  You are absolutely correct that this really is a research project and the primary goal is to study what’s going on in the blood of these individuals and associate it with any other other sorts of changes that are going on in their life — viruses, life stresses, things like that.  So that really is the primary objective.  But we think it’s valuable, and  you are allowed to, if you find things that occur during the course of the study that affect someone’s health, you can relay that to the physician who in turn can relay it to the patient.  That’s how we would handle this data.  In this study, we’re not trying to circumvent any rules about this sort of thing.  The goal would really be to return any research findings that might help the health of an individual during the study.

It’s going to be a fascinating study.  So you’ll give to the patient, through their physician, information to help their health.   Does that mean a Stanford physician who’s in charge of the project or does that mean the patient’s regular, personal physician?

MIKE SNYDER
We have a physician already identified to be part of this and so I think they would be the one to return this information, as needed and as desired.  Some patients may not want to know anything.  That’s fine.  We will just go on as we go on, but if they do want to know some things that are related to their health I think we can certainly tell them.  That that would be the plan.

So that means that the 30,000 or so measures you take take each time for yourself, during this study, you researchers will look at every single one of those markers, for each research subject.  You won’t share all those with the patient. But for the markers that make sense to share, and which have more history behind them, so that the physician can explain to the patient, it depends.  If those “known” markers relate to that person’s health, the physician can tell the patient what’s useful to that person.

MIKE SNYDER
That’s right and in the case of the people we’re talking about since they’re prediabetics, the number one thing we would look out for would be their glucose levels.   And so we can certainly see their glucose levels go up, the physician can then suggest that the patient go to additional tests such as hemoglobin A-1-C. or what have you.  And they can do an official clinical test to see whether anything we discovered in the research project is in fact real and they can use that information.

In The Cell article, you were very eloquent in explaining what you think the potential is for this test and for a future where people find things out early enough, and they get good enough information, so that the health professionals and the person can be motivated to take the right kind of care for that person.

MIKE SNYDER
That’s right.  I think that most complex diseases are, as the name sounds, complex, and diabetes is one of those, schizophrenia, there are many diseases like this and they’re probably not one simple disease and probably again lots of different diseases and so if we can understand  them  better how many different diseases there are, we can treat each appropriately and in the case of diabetes for example some people do respond well to anti-inflammatory drugs and so those do incredibly well with that but then there is another group that’s been unresponsive to this and likewise there’s a group that responds to the drug called metformin and there’s another group that doesn’t respond so it seems like everybody’s a little different, and if we can just figure out how many different diseases there are we would know which ones to treat which way and that could be very valuable then in very rapidly deciding the right treatment for the right person

I can envision a time where instead of telling someone, “You have schizophrenia,” or “You have diabetes,” your health professional could say, “You have a disease that tends to really affect inflammatory pathways and the signaling that goes to your hippocampus, and if we can settle that down and get more normal signaling you’re probably going to feel better.”

MIKE SNYDER
We hope it would turn out as simple as that.   It would be a great outcome of all of this.  Can’t guarantee that this would be the case, but that’s what we hope.

And that’s kind of how you’re thinking, regarding how these markers change and how sometimes they target one organ or one system. You’re looking at the markers as the way to identify health states or disease states, instead of just using our current diagnostic labels for disease . . . and treatment.    Looking at this more comprehensive series of markers would be a different way of looking at a person.

MIKE SNYDER
It’s really to understand what’s going on in an incredible molecular detail.  It’s zooming at a resolution that’s never been done  before.

Thank you for being the first proof of concept person that’s ever done this publicly.  Do you think many people are doing this behind-the-scenes right now?

MIKE SNYDER
Not at this level because it requires a certain level sophistication,  Most people can’t analyze DNA, RNA, proteins and metabolites at the same level our particular group can and our collaborators.  We have some really terrific collaborators with Euan Ashley , Russ Altman, Atul Butte, Mark Gerstein, Kari Nadeau.  It’s really a very unique team that’s been able to come together to do the study.  You really need the right expertise to be able put all this together.   But I hope that someday it will become a lot more standard so that it can be done routinely for everyone.

How soon is someday?

MIKE SNYDER
It’s difficult to predict how long it takes to get from the lab to the clinic.  Usually it takes a lot longer than people think — often 15 or 20 years.   I think some form of the test could come out in in much less time, but not analyzing 40,000 components, and maybe we don’t need to analyze 40,000 components.  Maybe we only need to analyze 2,000 critical ones that can tell everything that’s going on in a so-called health state, so with that kind of information it can be a lot simpler to design a test for the future that specifically looks at those 2,000 things.  And again I don’t know how long.  You’d have to figure out how to do it exactly and then you’d have to have it approved by the FDA and such.  And that would take some time.  But if there’s a demand for these things they tend to move pretty quickly.  Right now a lot of people are getting their genome sequenced which you never would even have thought of 10 years ago

But genome sequencing isn’t as exciting as what you’ve done.  Because once you know what your genes are, they’re not going to be changing very much for the rest of your life.  But our proteins and our metabolites, our hormones, the fatty acids in  our bodies, they change based on what you do and what comes your way and hits you.  Those are changing all the time as opposed to DNA which is holding steady.

MIKE SNYDER

That’s right.  But I think your genome, getting your genome sequenced is an important part of this because it lays the groundwork for what you might look out for But you’re absolutley right.  It’s  only part of the equation, and a bigger part is trying to follow all the other stuff.

How often would you like to see people measure this stuff?

MIKE SNYDER
One possible scenario that would like to see, but not everyone would agree, is that there would be as simple a test as doing  your glucose where, instead of pricking yourself and measuring one thing — glucose — you prick yourself and measure 5,000 things.  You need a very robust test and you need to handle it in an appropriate fashion, so people don’t mislead themselves to think, oh, I’m following myself and that’s good enough.  But it could help you imagine a scenario where you do this once a month or once every two months.  Suddenly you could catch things much much earlier then  if you go every two or three years like most healthy people do, and the convenience would make it quite attractive.   In my mind this would be a great outcome if people can self monitor and catch a lot of stuff early.  It wouldn’t replace them going to the doctor for their annual physical or a biannual physical, what have you.  But it could supplement that and add a lot more information that could greatly help them monitor their health.  If they see something funny they could to go to the doctor much earlier and then get it confirmed.  Catching disease early is really the key.

Someday you’d like to see a test that people can do it themselves, once a month, a test that catches 5,000 different things at once, and if they sign-up for $1000 plan, they can do this once a month and get all that information.

MIKE SNYDER
Something like that would be quite attractive.  I think a lot of people would want to do that.