It takes guts: Lawrence David explains unconventional research on microbiome

<p>Lawrence David is currently&nbsp;an assistant professor in the Duke Center for Genomic and Computational Biology.</p>

Lawrence David is currently an assistant professor in the Duke Center for Genomic and Computational Biology.

For a research study published in 2014, Lawrence David, now an assistant professor in the Duke Center for Genomic and Computational Biology, collected his own saliva and feces every day for a year, in order to study his personal microbiome. The Chronicle sat down with David to discuss his unusual approach to research and his path to Duke.

The Chronicle: Could you give an overview of your research?

Lawrence David: What we do is we work on trying to come up with tools and theory for controlling microbial communities.

Everywhere on Earth there are bacteria—there are very few places on the surface of the planet that are sterile. In particular, inside of people there are some of the world’s densest microbial communities. You’ve got something like 10 billion bacteria per gram of your gut contents.

Scientists have had some inkling for decades about the composition of bacteria in the gut, and that their activity can cause diseases and infection. So what my lab is specifically interested in is this question of, “If we can figure out which bacteria might be good for you, as well as which ones are harmful, how do we come up with ways to make sure there are more of the helpful ones and fewer of the harmful ones?” Right now we actually don’t have that many answers for this.

We have things like antibiotics, but they’re not very precise. They come in and will usually lead to the death of most bacteria in the gut, so you lose the harmful, but you also lose the helpful ones. In fact, it's kind of ironic that after antibiotic exposure, a lot of the bacteria that grow the fastest tend not to be normally associated with health. So I think what it means is that we need tools to get better if we are going to be a little bit more precise.

TC: Can you tell us about your path to Duke?

LD: In college, I did undergraduate research with an applied mathematician named Chris Wiggins at Columbia. And I really loved that experience, so I decided to go to graduate school to pursue science.

During my time in graduate school, there was an energy crisis happening, so what I decided to look into was biofuels research. But the kink in this plan was that no one at the institution was actually doing biofuels research, and what I did instead was I ended up doing research in a lab where the lab was studying the evolution of bacterial metabolism. I did my Ph.D. on how bacterial genomes evolve over time scales of billions of years, so it didn’t have a lot to do with the human microbiome.

A couple of things happened during my Ph.D.—one was that I realized that I wanted to be working with systems that operated on slightly faster timescales than billions of years so that we could do experiments to test hypotheses. And the other thing that happened was that I did this experiment with my old graduate advisor where we, having heard about the microbiome and being intrigued by it, we decided to study our own microbiomes every day for a year.

We did this long-term time series experiment where we wrote down everything we did, everywhere we went, what we ate, how much we slept, how much we exercised—basically everything you could think of quantifying. Then we combined that with building time series of how bacterial communities inside of us changed over time.

That experience was just exhilarating. It felt like I was getting involved with a field that was rapidly expanding and really brought interest to a lot of people. So after I finished my Ph.D., I decided to keep doing microbiome research.

I hung out as something called a junior fellow at Harvard, which is a position that is not tenured, so not meant to be permanent, but they make you an investigator, so you’re somewhat independent. There I worked with an awesome scientist named Peter Turnbaugh, who was a fellow at the time. We did more microbiome research, and he also got me interested in infections.

It was possible through some really lovely collaborations I was able to get involved with in Boston that we looked at people before and after they got sick with cholera. So with my research interests in microbial communities and infection, it just so happened that Duke was trying to recruit someone interested in bacteria and pathogens. So I applied to this department, and it was a really nice fit.

TC: Separating fact from fiction, is some of the online information regarding the gut microbiome untrue?

LD: First off, a lot of the studies that are coming out today are in animals, specifically in mice. So we are kind of far off on a lot of the work surrounding causality. We do not know if certain bacteria cause disease or prevent disease in humans. But a lot of these experiments are too hard to do in people, so that is an important caveat that isn’t fully appreciated.

Interesting things that have come out of our research, which even surprised me when I saw the results, were that bacterial communities inhabiting our intestines are surprisingly stable. Meaning that the bacterial species that you see on any given day seem to be the same, day in and day out, despite the fact that people live pretty varied lives.

You eat different things every day, you go different places, but for the most part, the bacteria inside of you are independent of lifestyle choice. That might be in contrast to what you read a lot, about how the microbiome is involved in so many things. I think it creates the perception that it might be really delicate or highly variable—constantly changing in response to how you live your life. That is not true.

TC: You've been described in other publications as a “quirky” scientist. What is your take on this?

LD: You know, that’s a hard question, but I bet that my wife wouldn’t argue with that.

TC: When you studied your own microbiome, did you know that the idea was going to be groundbreaking, or did you just think it was interesting and go for it?

LD: A little bit of both. On the former, it turned out that we had competition—someone was doing it at exactly the same time and actually published before us, which was a little bit of a bummer. But there have only been two such studies.

But to the second part of the question, I thought it was a really good idea for a couple of reasons. The data sets are pretty rare, and there are some interesting analyses you can do with them. We could ask some questions that had never been asked before. We were able to compare bacteria using models that people use to analyze the stock market.

What was also really good about it, I thought, was that we at the time wanted to know what was reasonable to ask people to do in terms of a microbiome study. How many samples could you expect them to reasonably collect? And to what degree could you expect someone to collect data about how they were living their lives?

I gained a lot of really valuable information regarding those questions by doing it myself. As a result, when we have done studies looking at other people, it has made me more considerate and sensitive about what we asked people to do because I had experienced the burden of participating in these experiments. Engineers call it “eating your own dog food"—you have to know what your product is like.

TC: What advice might you have for other students who want to approach scientific research from a new angle?

LD: My personal philosophy in science is that I think it’s really helpful to come at problems from a different angle, and one of the more obvious ways to do that is to try and be open to getting as diverse of a set of scientific research experiences as possible.

I think it's often a very linear path to pursuing one’s own training, but any given field might have two or three related fields. So what one could do is to get really good at those two or three related fields and spend a lot of time focusing in those domains of knowledge and research.

One thing I’ve tried to be conscious and somewhat deliberate is doing my best to expose myself to a lot of different kinds of fields—for me, because it's just really fun and you get to learn about a lot of subjects. But then that way too, you get to borrow ideas that other really smart people had somewhere else, but haven’t been applied to the field that you are working in.

That is something that I think is central to how I find the research that gets done in our lab goes. We try to borrow ideas or techniques not just from biology, but also engineering, ecology, math and computer science. It takes a certain openness and willingness to know that you are going to look dumb a lot. When you try to wade into another field, there is so much to learn, and you make a lot of mistakes, but what is important is that you do not worry about that. Just make sure that you learn something and appreciate how much you don’t know. 


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