Friday, October 17, 2014

Comparing uBiome data through time

Like I said previously, the data (and tools) at the uBiome site are fantastic, and it’s taking me a long time to understand what meaningful conclusions I can make. But first, one basic question I had is how stable the results are. If the microbiota changes all the time, then maybe you can’t really conclude much unless you track long-term trends.

In an excellent study published over the summer, Lawrence David at Duke University followed two subjects, measuring their microbiota and zillions of other variables every day for a year. His team concluded that although illness or travel can dramatically change microbiota composition in a single day, and different foods cause levels to fluctuate by up to 15% per day, generally things stay pretty stable.

So what happens if I send two samples, taken a few weeks apart, to uBiome? That’s what I tried, keeping close track of exactly what I ate and did in the meantime.

Here are the results for the first sample (the one I posted before)


Here’s the newer sample, taken three weeks later:


Hmmm. As you can see, these results seem quite different – far more than the 15% daily fluctuation from the Lawrence study.

No special travel or other unusual activity during those three weeks. Nothing unusual in my diet. I’m still analyzing what I ate, but for example here’s the amount of fiber per day, starting the week before the first test.


Nothing super unusual there. Note that I am a completely healthy male, normal/stable weight, no history of anything. Last antibiotic use was a long time ago.

Incidentally, Tina Saey (@thsaey) sent the same sample to two labs (uBiome plus American Gut Project), and got dramatically different results. uBiome wrote a detailed response – my takeway was that the differences can be mostly explained by how each lab handles the samples but that you can correct for that (mostly).

Still more analysis ahead of me. Meanwhile, I’ve sent them a third sample to compare further.

Thursday, October 16, 2014

[book] Missing Microbes

Another fantastic book, by Martin Blaser, professor of microbiology at NYU: Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues.

Microbes, a word that refers to microscopic lifeforms like bacteria, archaea, and viruses have been around way longer than anything else, and show far more variety than any visible life. If you imagine a circular clock face representing the degrees of microbiological difference between various life forms, humans and corn plants would be separated by only a single degree — the rest of the clock is an unimaginable variety of life, so different from us and inhabiting every nook and cranny on earth, from the radioactive sludge inside a dark nuclear plant to high in the atmosphere. Life is everywhere, and almost all of it is microbial. But as ubiquitous and resilient as these microbes are, many of those that matter most to humans have been under attack for the past century because of antibiotics, and the resulting changes may be the root cause of many modern afflictions, from obesity to autism to diabetes to cancer.

Here are just a few of the facts you’ll learn in this book:
  • Specialized lab mice that are raised germ-free may appear outwardly normal, but their blood contains only 52 out of the 4200 compounds found in normal mice. The implication is that microbes in the gut and skin generate many thousands of chemicals — vitamins, hormones, and more-- that are important for life.
  • Gut microbes produce a native compound similar to valium, normally cleared out by the liver. End-stage cancer patients often slip into a valium-induced coma when their livers fail.
  • Veridans streptococci usually live harmlessly in the mouth and serve to prevent Step A infections by simply crowding out other bacteria. But when they get into the heart, they are the major cause of heart valve infections.
  • The FDA doesn’t require labeling for products (like milk or organic apples) that contain less than 50mg of tetracycline. That seems like a trivial amount, with no possible affect on your health, but the dosages add up: drink milk every day and you have ingested a noticeable amount after a week.
  • Your gut bacteria produce 80% of the seratonin your brain uses to remain calm and promote good sleep. There are certainly many other examples of important hormones produced, not by the body, but by microbes.
Many, many more facts and ideas, well worth reading.  Highly recommended.

Wednesday, October 15, 2014

What's in my microbiome?

Although I was an early customer of 23andme, I found the results unsatisfying because there is so little that is actionable. I mean, you don't need a test to tell you that you have green eyes or that you're lactose intolerant. And if you have some weird disease in your future, the main advice -- eat well, get exercise, buy life insurance -- applies to everyone whether you know you're at risk or not. Although I think it's fun and interesting for its own sake, I frankly understand why normal people wouldn't bother.

That's why I'm now so intrigued with the microbiome, that collection of hundreds of species of bacteria and other microbes that live all over you, inside and out. In total, they weigh about as much as your brain; it's as if your body has a whole other organ that you can't see. Massive improvements in genetic sequencing technology over the past decade have suddenly brought the ability to view and measure this micro-world, and important new discoveries are happening every day.

The best part? you can change your microbes! It can be difficult, because once these things have found a foothold somewhere in your body, they don't want to let go, but at least it's possible, whether through eating different foods or supplements (fermented products, probiotics, fiber) or by avoiding antibiotics (including germ-killing hand sanitizers), your actions have an affect your microbiome. So if you don't like something, you can (at least in theory) change it.

To find out what's in my microbiome now, I bought a $400 kit from the San Francisco company uBiome. For that, I received swabs for my mouth, gut, genitals, nose, and skin. The most interesting one is the gut, which you can buy for $89, and is the one I'd most recommend. After you collect the samples (warning for the squeamish: it involves soiled toilet paper), send them back and they give you results like this:

The microbiome is so complicated -- we're dealing with hundreds of different species, each with its own genome -- that it's hard to summarize in a single, quick takeaway. The web site lets you dive deeper into the various strains of bacteria, looking at the results organized by phylum/class/order/family/genus, digging into more detail at each level. Since each user fills out a detailed questionnaire when returning the sample, you can compare your results to self-described vegans, paleo dieters, and several other categories to see how you stack up to people who have been gaining or losing weight recently, for example.

The tools on the site are fantastic, and they are obviously putting more effort into improving them (they've become noticeably better just in the past few weeks). Better yet, you can download all of your results in XML format to keep forever, or analyze anyway you like.

My only complaint was the amount of time it took to get results: a full three months for this sample. Their customer support staff is very responsive -- I always got a helpful response within a few hours, even on weekends -- but I do wish it didn't take so long.

But frankly that complaint rings hollow when I consider how long it will take me to understand the plethora of fascinating torrent of data I got back. You can see from the chart above that I have more of certain types of bacteria than their average customer. Is that good? bad? neutral? Who knows?

This is not uBiome's fault. Science just hasn't figured out these answers yet. In my case, I'm a healthy, fit, normal-weight omnivore, so I assume that the percentage differences with "Average" are perfectly fine, but I could imagine how somebody with weight or other problems might be concerned if they saw something significantly different from average. The good news is that, in theory, you can change your results, but the bad news is that science really has little clue exactly how to do that, or even what constitutes "good".

Because the technology is so new, you may find that your snapshot looks different each time you take the test. Sometimes people report different results from different locations on the same sample. So it's best not to read much into of any findings yet. Still, it's the ability to change your microbiome that makes all the difference and I expect to learn much more as the science progresses.

Thursday, October 02, 2014

Why review dentists?

Open Ah!
Searching for a new family dentist I checked the normal reviews on Yelp and Google,  searched a bit on the internet, transferred my records from the previous dentist, and finally this morning went in for my first exam. During the two-hour initial appointment, I spent less than 10 minutes with the dentist, who seems as nice and competent as all the reviews suggested.

But most of my time was spent with the hygienist, who talked with me, reviewed my history, gave me advice, and of course spent the better part of an hour chiseling away one on my mouth one tooth at a time. As long as my teeth and gums remain healthy, (which hopefully will be forever), I expect today’s experience to be typical. I will spend far, far more of my time with the hygienist than with the dentist.

So why do I care about the dentist reviews? Wouldn’t I be better off looking for the best hygienist? In fact, this person who cleaned my teeth, I know only her first name. She’s listed on their office web site, but only briefly under a section on “staff” and they don’t even list her last name. How long has she been there? Will she be there next time? Is she the best one in the office? Who knows?

Isn’t it odd that the person who is truly responsible for my experience is so invisible to the review process?

Wednesday, September 10, 2014

Apple Watch: the first wearable good enough to criticize

The Apple Watch launch event was so popular that the livestreamed version I saw kept breaking down, but I saw enough to be impressed.  My overall takeaway, to paraphrase what Alan Kay said about the first Macintosh: it’s the first wearable good enough to criticize.

As expected, Apple did it mostly right: a gorgeous high-quality design with plenty of personalization and rock-solid at its core time-keeping function. The first iPhone had brilliant, very clear positioning that helped excite people and make it easy to understand what was in fact a new product category.  Broken into three easy-to-understand pieces, Steve Jobs announced it was (1) a widescreen iPod  (2) great phone (3) the internet in your pocket.  Apple's Watch message isn’t quite that simple (or, frankly for many people, compelling) but here it is:
  1. incredibly precise timepiece,
  2. immediate, intimate way to connect,
  3. intelligent health and fitness companion
The first one is strong, though I might have said something about the fashion rather than the precision time-keeping. Do normal people really care that it’s within 50ms of the correct time?  On the other hand, a mass-market watch had better look nice — and personalized for me — or you’ll have a hard time getting people to wear it. With its mens/womens sizing, the plethora of band choices, and three versions (including the real gold “edition” ), Apple clearly raises the bar for all wearables. Competitors can no longer release crappy chunks of plastic now that Apple is here.

The second message, an intimate way to connect, is the weakest piece of the story. I get the “intimate” part — it’s something you put on your wrist, it’s part of your daily appearance — but why do I want to “connect”? If it’s a Dick Tracy-style phone on my wrist (it has a built-in microphone and speaker, so it’s possible), why not just say that? The goofy “share a heart beat” with your friends sounds hard to get working, and few people will probably bother.

It will be nice to receive text updates on my wrist rather than having to pull my phone from my pocket, but I can’t see Maps being very important — certainly not enough to justify the time spent in the keynote demo. It’ll be nice to have the haptic feedback — a slight “buzz” when it’s time to turn corners — but for serious navigation wouldn’t I just want to use my phone? You’ll need your iPhone nearby to use the internet features like maps, so I just don’t understand the advantage of having it on my wrist.

But the third message — health and fitness — is immediately understandable and appealing. Apple’s new Activity app, with its easy-to-use three rings to show progress, and the Workout app for more serious exercising, look like the most well-thought and strongest features of the Watch. With sensors sensitive enough to tell when you’re walking up a stairs or rowing a boat, this will be one of the best wrist trackers ever.

That said, I have a few concerns. To get an accurate heart beat from the wrist, other wearables (e.g. Basis) rely on a tight fit (which would be uncomfortable after a while) or you have to explicitly request a reading by tapping a button — a real pain. Has Apple found a way to get real-time, continuous heart beat monitoring with a loose-fitting band?  It’s not impossible, so if they’ve done that, I’m impressed.

Also, if you need to recharge it regularly (nightly?), then unfortunately you can’t track sleep. There are apparently no other new sensors — for example, I had been hoping for galvanic skin resistance, or maybe even skin temperature, so really this is about activity tracking and not much else.

For now. The important feature Apple brings to the wearables market is legitimacy as an accessory. Now that we have something that looks and feels good, packaged on a platform that’s extensible for new uses (bluetooth/wifi and NFC are built in), it’s finally possible to begin making great personal wearable apps.

We can go on and on about what’s missing from the Watch, but it’s nice, at last, to have a stake in the ground — something good enough to criticize, and build upon.

Monday, September 01, 2014

Notes on Seth Roberts Memorial Symposium

I had a long-planned family reunion in Maine the week of the Ancestral Health Symposium in Berkeley this month, so it was just not possible for me to attend the Seth Roberts Memorial Symposium, but thanks to Tess McEnulty there are videos of the public talks. The talks are well worth watching, but if you don’t have the time, here is my brief summary of the highlights:

Nassim Taleb explained how Seth’s philosophy (n=1) is the exact opposite of what you see in today’s fascination with Big Data. No matter how many data points you accumulate, a new theory can be disproven with a single counter example; and sometimes you can build a true theory based on a single example. (“OJ Simpson only killed once; does that mean you can’t prove he’s a murderer?”). In fact, the more variables you add to a model, the more likely you are to find spurious correlations, as he shows in this slide:Nassim Taleb: Tragedy of Big Data

Tim Ferris (Four Hour Work Week) credited much of his book The Four Hour Body to ideas he got from Seth, who taught him five things:
  • Extremes inform the means. New products and ideas rarely come from “normal” use cases. If you want to find something interesting, search for odd examples.
  • Choose fast results over big data. Look for quick-and-dirty experiments, not big-huge-complicated ones.
  • Track yourself regularly: don’t try to judge a soccer match from a single ultra-hi res photo; it’s much better to have multiple, low-res photos, so track what you can however you can. Seth tracked most stuff with pencil and paper.
  • Remember the “Minimum Effective Dose”: for example, he gets fantastic sleep by taking raw honey and a single tablespoon of apple cider vinegar before bed. No more.
  • Care about normal people: Seth didn’t care who you are or your background. You can learn something from anybody.
Gary Taubes says Seth was one of the only people he ever talked with (they hiked regularly in Berkeley). His talk started with an overview from 19th century doctor Claude Bernard, whose 1865 book Intro to the Study of Experimental Medicine "should be required reading for every med student”.  Key quote: "All human knowledge is limited to working back from observed effects to their cause”. The rest of the talk was a summary of the limitations of various approaches to scientific research (observational studies, randomized control trials, etc.). There are no really good solutions, other than the open-minded and humble approach of people like Seth.

There were several other speakers, like best-selling “fratire" author Tucker Max (who met Seth by randomly emailing him), Paleo author John Durant (who appreciates Seth’s example that you don’t need fancy equipment to do science), experimental psychologist Aaron Blaisdell (who founded the health crowdsourcing site thanks to collaborations with Seth), and many others.

So many great memories of Seth’s ideas, by people who knew him well. I wish I could have attended in person.

Sunday, August 31, 2014

Keep this in mind when viewing the news

An excellent piece by a former AP reporter, discussing how news organizations report about Israel, but I find this point to be true about nearly all news reporting:

The world is not responding to events in this country, but rather to the description of these events by news organizations. The key to understanding the strange nature of the response is thus to be found in the practice of journalism

I don’t know President Obama or Sarah Palin, or for that matter people like Steve Ballmer or Steve Jobs (public figures I’ve met in person).  I only know the description provided to me by other people. Same thing goes for big organizations, even countries, the only (partial) exception being the ones where I have personally worked or lived. When I do have some first-hand experience, I almost always find that outside reporting, even when factually correct, puts emphasis differently than I would.

Robin Hanson’s Overcoming Bias blog is another source of wisdom on the overall subject of how to avoid being fooled by what you read or think you know.