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I'm going to start with a little story.

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So, I grew up in this neighborhood. When I was 15 years old,

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I went from being what I think was a strapping young athlete,

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over four months, slowly wasting away until

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I was basically a famine victim

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with an unquenchable thirst.

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I had basically digested away my body.

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And this all came to a head when I was on a backpacking trip,

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my first one ever actually, on Old Rag Mountain

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in West Virginia, and was putting my face into puddles

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of water and drinking like a dog.

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That night, I was taken into the emergency room

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and diagnosed as a type 1 diabetic in full-blown ketoacidosis.

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And I recovered, thanks to the miracles of modern medicine,

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insulin and other things, and gained all my weight back and more.

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And something festered inside me after this happened.

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What I thought about was, what caused the diabetes?

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You see, diabetes is an autoimmune disease

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where your body fights itself, and at the time people thought

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that somehow maybe exposure to a pathogen

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had triggered my immune system to fight the pathogen

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and then kill the cells that make insulin.

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And this is what I thought for a long period of time,

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and that's in fact what medicine and people have focused on quite a bit,

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the microbes that do bad things.

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And that's where I need my assistant here now.

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You may recognize her.

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So, I went yesterday, I apologize, I skipped a few of the talks,

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and I went over to the National Academy of Sciences building,

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and they sell toys, giant microbes.

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And here we go!

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So you have caught flesh-eating disease if you caught that one.

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I gotta get back out my baseball ability here.

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(Laughter)

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So, unfortunately or not surprisingly, most of the microbes

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they sell at the National Academy building are pathogens.

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Everybody focuses on the things that kill us,

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and that's what I was focusing on.

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And it turns out that we are covered in a cloud of microbes,

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and those microbes actually do us good much of the time,

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rather than killing us.

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And so, we've known about this for some period of time.

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People have used microscopes to look at the microbes that cover us,

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I know you're not paying attention to me, but ...

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(Laughter)

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The microbes that cover us.

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And if you look at them in the microscope,

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you can see that we actually have 10 times as many cells

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of microbes on us as we have human cells.

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There's more mass in the microbes than the mass of our brain.

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We are literally a teeming ecosystem of microorganisms.

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And unfortunately, if you want to learn about the microorganisms,

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just looking at them in a microscope is not sufficient.

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And so we just heard about the DNA sequencing.

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It turns out that one of the best ways to look at microbes

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and to understand them is to look at their DNA.

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And that's what I've been doing for 20 years,

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using DNA sequencing, collecting samples from various places,

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including the human body, reading the DNA sequence

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and then using that DNA sequencing to tell us about

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the microbes that are in a particular place.

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And what's amazing, when you use this technology,

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for example, looking at humans, we're not just covered

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in a sea of microbes.

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There are thousands upon thousands of different kinds of microbes on us.

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We have millions of genes of microbes in our human

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microbiome covering us.

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And so this microbial diversity differs between people,

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and what people have been thinking about in the last 10,

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maybe 15 years is, maybe these microbes,

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this microbial cloud in and on us,

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and the variation between us, may be responsible

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for some of the health and illness differences between us.

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And that comes back to the diabetes story I was telling you.

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It turns out that people now think that one of the triggers

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for type 1 diabetes is not fighting a pathogen,

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but is in fact trying to -- miscommunicating with the microbes

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that live in and on you.

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And somehow maybe the microbial community that's

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in and on me got off, and then this triggered some sort

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of immune response and led to me killing the cells

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that make insulin in my body.

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And so what I want to tell you about for a few minutes is,

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what people have learned using DNA sequencing techniques

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in particular, to study the microbial cloud

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that lives in and on us.

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And I want to tell you a story about a personal project.

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My first personal experience with studying the microbes

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on the human body actually came from a talk that I gave,

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right around the corner from here at Georgetown.

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I gave a talk, and a family friend who happened to be

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the Dean of Georgetown Medical School was at the talk,

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and came up to me afterwards saying, they were doing

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a study of ileal transplants in people.

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And they wanted to look at the microbes after the transplants.

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And so I started a collaboration with this person,

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Michael Zasloff and Thomas Fishbein, to look at the microbes

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that colonized these ilea after they were transplanted into a recipient.

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And I can tell you all the details about the microbial study

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that we did there, but the reason I want to tell you this story

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is something really striking that they did at the beginning

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of this project.

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They take the donor ileum, which is filled with microbes from a donor

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and they have a recipient who might have a problem

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with their microbial community, say Crohn's disease,

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and they sterilized the donor ileum.

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Cleaned out all the microbes, and then put it in the recipient.

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They did this because this was common practice

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in medicine, even though it was obvious

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that this was not a good idea.

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And fortunately, in the course of this project,

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the transplant surgeons and the other people

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decided, forget common practice. We have to switch.

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So they actually switched to leaving some of the microbial

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community in the ileum. They leave the microbes with the donor,

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and theoretically that might help the people who are

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receiving this ileal transplant.

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And so, people -- this is a study that I did now.

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In the last few years there's been a great expansion

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in using DNA technology to study the microbes in and on people.

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There's something called the Human Microbiome Project

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that's going on in the United States,

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and MetaHIT going on in Europe, and a lot of other projects.

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And when people have done a variety of studies,

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they have learned things such as, when a baby is

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born, during vaginal delivery you get colonized by the

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microbes from your mother.

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There are risk factors associated with cesarean sections,

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some of those risk factors may be due to mis-colonization

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when you carve a baby out of its mother

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rather than being delivered through the birth canal.

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And a variety of other studies have shown that the

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microbial community that lives in and on us

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helps in development of the immune system,

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helps in fighting off pathogens, helps in our metabolism,

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and determining our metabolic rate, probably

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determines our odor, and may even shape our behavior

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in a variety of ways.

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And so, these studies have documented or suggested

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out of a variety of important functions for the microbial community,

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this cloud, the non-pathogens that live in and on us.

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And one area that I think is very interesting,

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which many of you may have now that we've thrown

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microbes into the crowd, is something that I would call "germophobia."

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So people are really into cleanliness, right?

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We have antibiotics in our kitchen counters,

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people are washing every part of them all of the time,

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we pump antibiotics into our food, into our communities,

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we take antibiotics excessively.

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And killing pathogens is a good thing if you're sick,

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but we should understand that when we pump chemicals

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and antibiotics into our world, that we're also killing

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the cloud of microbes that live in and on us.

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And excessive use of antibiotics, in particular in children,

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has been shown to be associated with, again, risk factors

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for obesity, for autoimmune diseases, for a variety

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of problems that are probably due to disruption

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of the microbial community.

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So the microbial community can go wrong

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whether we want it to or not,

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or we can kill it with antibiotics,

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but what can we do to restore it?

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I'm sure many people here have heard about probiotics.

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Probiotics are one thing that you can try and do to restore

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the microbial community that is in and on you.

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And they definitely have been shown to be effective in some cases.

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There's a project going on at UC Davis where people are using

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probiotics to try and treat, prevent,

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necrotizing enterocolitis in premature infants.

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Premature infants have real problems with their microbial community.

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And it may be that probiotics can help prevent

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the development of this horrible necrotizing enterocolitis

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in these premature infants.

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But probiotics are sort of a very, very simple solution.

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Most of the pills that you can take or the yogurts that you can eat

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have one or two species in them, maybe five species in them,

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and the human community is thousands upon thousands of species.

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So what can we do to restore our microbial community

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when we have thousands and thousands of species on us?

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Well, one thing that animals seem to do is,

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they eat poo -- coprophagia.

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And it turns out that many veterinarians,

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old school veterinarians in particular,

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have been doing something called "poo tea,"

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not booty, but poo tea, to treat colic and other

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ailments in horses and cows and things like that,

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where you make tea from the poo from a healthy

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individual animal and you feed it to a sick animal.

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Although, unless you have a fistulated cow with a big hole in its side,

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and you can put your hand into its rumen,

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it's hard to imagine that the delivery of microbes

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directly into the mouth and through the entire

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top of the digestive tract is the best delivery system,

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so you may have heard in people they are now doing

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fecal transplants, where rather than delivering

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a couple of probiotic microbes through the mouth,

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they are delivering a community of probiotics,

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a community of microbes from a healthy donor,

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through the other end.

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And this has turned out to be very effective in fighting

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certain intransigent infectious diseases

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like Clostridium difficile infections that can stay

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with people for years and years and years.

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Transplants of the feces, of the microbes from the feces,

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from a healthy donor has actually been shown to cure

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systemic C. dif infections in some people.

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Now what these transplants, these fecal transplants, or

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the poo tea suggest to me, and many other people

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have come up with this same idea, is that

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the microbial community in and on us, it's an organ.

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We should view it as a functioning organ, part of ourselves.

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We should treat it carefully and with respect,

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and we do not want to mess with it, say by C-sections

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or by antibiotics or excessive cleanliness,

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without some real good justification.

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And what the DNA sequencing technologies are allowing people to do now

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is do detailed studies of, say, 100 patients who have Crohn's disease

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and 100 people who don't have Crohn's disease.

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Or 100 people who took antibiotics when they were little,

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and 100 people who did not take antibiotics.

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And we can now start to compare the community of microbes

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and their genes and see if there are differences.

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And eventually we may be able to understand if they're not

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just correlative differences, but causative.

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Studies in model systems like mouse and other animals

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are also helping do this, but people are now using

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these technologies because they've gotten very cheap,

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to study the microbes in and on a variety of people.

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So, in wrapping up, what I want to tell you about is,

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I didn't tell you a part of the story of coming down with diabetes.

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It turns out that my father was an M.D.,

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actually studied hormones. I told him many times

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that I was tired, thirsty, not feeling very good.

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And he shrugged it off, I think he either thought

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I was just complaining a lot, or it was the typical

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M.D. "nothing can be wrong with my children."

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We even went to the International Society of Endocrinology

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meeting as family in Quebec.

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And I was getting up every five minutes to pee,

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and drinking everybody's water at the table,

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and I think they all thought I was a druggie.

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(Laughter)

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But the reason I'm telling you this is that

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the medical community, my father as an example,

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sometimes doesn't see what's right in front of their eyes.

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The microbial cloud, it is right in front of us.

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We can't see it most of the time. It's invisible.

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They're microbes. They're tiny.

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But we can see them through their DNA,

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we can see them through the effects that they have on people.

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And what we need now

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is to start thinking about this microbial community in the context

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of everything in human medicine.

254
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It doesn't mean that it affects every part of us,

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but it might.

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What we need is a full field guide to the microbes

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that live in and on people, so that we can understand

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what they're doing to our lives.

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We are them. They are us.

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Thank you.

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(Applause)