0:00:00.637,0:00:02.092 I'm going to start with a little story. 0:00:02.092,0:00:05.204 So, I grew up in this neighborhood. When I was 15 years old, 0:00:05.204,0:00:09.755 I went from being what I think was a strapping young athlete, 0:00:09.755,0:00:13.716 over four months, slowly wasting away until 0:00:13.716,0:00:15.604 I was basically a famine victim 0:00:15.604,0:00:17.628 with an unquenchable thirst. 0:00:17.628,0:00:21.237 I had basically digested away my body. 0:00:21.237,0:00:25.531 And this all came to a head when I was on a backpacking trip, 0:00:25.531,0:00:27.576 my first one ever actually, on Old Rag Mountain 0:00:27.576,0:00:31.560 in West Virginia, and was putting my face into puddles 0:00:31.560,0:00:33.816 of water and drinking like a dog. 0:00:33.816,0:00:38.328 That night, I was taken into the emergency room 0:00:38.328,0:00:42.209 and diagnosed as a type 1 diabetic in full-blown ketoacidosis. 0:00:42.209,0:00:48.144 And I recovered, thanks to the miracles of modern medicine, 0:00:48.144,0:00:53.600 insulin and other things, and gained all my weight back and more. 0:00:53.600,0:00:59.111 And something festered inside me after this happened. 0:00:59.111,0:01:02.624 What I thought about was, what caused the diabetes? 0:01:02.624,0:01:04.477 You see, diabetes is an autoimmune disease 0:01:04.477,0:01:07.852 where your body fights itself, and at the time people thought 0:01:07.852,0:01:10.893 that somehow maybe exposure to a pathogen 0:01:10.893,0:01:15.365 had triggered my immune system to fight the pathogen 0:01:15.365,0:01:17.423 and then kill the cells that make insulin. 0:01:17.423,0:01:19.733 And this is what I thought for a long period of time, 0:01:19.733,0:01:23.781 and that's in fact what medicine and people have focused on quite a bit, 0:01:23.781,0:01:26.703 the microbes that do bad things. 0:01:26.703,0:01:29.771 And that's where I need my assistant here now. 0:01:29.771,0:01:32.209 You may recognize her. 0:01:32.209,0:01:37.889 So, I went yesterday, I apologize, I skipped a few of the talks, 0:01:37.889,0:01:40.130 and I went over to the National Academy of Sciences building, 0:01:40.130,0:01:45.577 and they sell toys, giant microbes. 0:01:45.577,0:01:48.962 And here we go! 0:01:48.962,0:01:53.717 So you have caught flesh-eating disease if you caught that one. 0:01:53.717,0:01:58.145 I gotta get back out my baseball ability here. 0:01:58.145,0:02:01.852 (Laughter) 0:02:01.852,0:02:08.233 So, unfortunately or not surprisingly, most of the microbes 0:02:08.233,0:02:11.576 they sell at the National Academy building are pathogens. 0:02:11.576,0:02:14.545 Everybody focuses on the things that kill us, 0:02:14.545,0:02:16.192 and that's what I was focusing on. 0:02:16.192,0:02:20.753 And it turns out that we are covered in a cloud of microbes, 0:02:20.753,0:02:25.273 and those microbes actually do us good much of the time, 0:02:25.273,0:02:26.393 rather than killing us. 0:02:26.393,0:02:29.584 And so, we've known about this for some period of time. 0:02:29.584,0:02:33.161 People have used microscopes to look at the microbes that cover us, 0:02:33.161,0:02:34.953 I know you're not paying attention to me, but ... 0:02:34.953,0:02:37.051 (Laughter) 0:02:37.051,0:02:38.993 The microbes that cover us. 0:02:38.993,0:02:42.153 And if you look at them in the microscope, 0:02:42.153,0:02:45.557 you can see that we actually have 10 times as many cells 0:02:45.557,0:02:49.025 of microbes on us as we have human cells. 0:02:49.025,0:02:53.776 There's more mass in the microbes than the mass of our brain. 0:02:53.776,0:02:58.097 We are literally a teeming ecosystem of microorganisms. 0:02:58.097,0:03:02.697 And unfortunately, if you want to learn about the microorganisms, 0:03:02.697,0:03:04.977 just looking at them in a microscope is not sufficient. 0:03:04.977,0:03:07.557 And so we just heard about the DNA sequencing. 0:03:07.557,0:03:10.085 It turns out that one of the best ways to look at microbes 0:03:10.085,0:03:12.621 and to understand them is to look at their DNA. 0:03:12.621,0:03:14.763 And that's what I've been doing for 20 years, 0:03:14.763,0:03:18.645 using DNA sequencing, collecting samples from various places, 0:03:18.645,0:03:21.549 including the human body, reading the DNA sequence 0:03:21.549,0:03:24.169 and then using that DNA sequencing to tell us about 0:03:24.169,0:03:26.335 the microbes that are in a particular place. 0:03:26.335,0:03:29.198 And what's amazing, when you use this technology, 0:03:29.198,0:03:32.358 for example, looking at humans, we're not just covered 0:03:32.358,0:03:33.494 in a sea of microbes. 0:03:33.494,0:03:38.605 There are thousands upon thousands of different kinds of microbes on us. 0:03:38.605,0:03:43.958 We have millions of genes of microbes in our human 0:03:43.958,0:03:45.605 microbiome covering us. 0:03:45.605,0:03:49.110 And so this microbial diversity differs between people, 0:03:49.110,0:03:52.246 and what people have been thinking about in the last 10, 0:03:52.246,0:03:55.366 maybe 15 years is, maybe these microbes, 0:03:55.366,0:03:57.414 this microbial cloud in and on us, 0:03:57.414,0:04:01.294 and the variation between us, may be responsible 0:04:01.294,0:04:04.864 for some of the health and illness differences between us. 0:04:04.864,0:04:07.987 And that comes back to the diabetes story I was telling you. 0:04:07.987,0:04:11.393 It turns out that people now think that one of the triggers 0:04:11.393,0:04:13.774 for type 1 diabetes is not fighting a pathogen, 0:04:13.774,0:04:18.165 but is in fact trying to -- miscommunicating with the microbes 0:04:18.165,0:04:19.662 that live in and on you. 0:04:19.662,0:04:22.366 And somehow maybe the microbial community that's 0:04:22.366,0:04:26.399 in and on me got off, and then this triggered some sort 0:04:26.399,0:04:28.638 of immune response and led to me killing the cells 0:04:28.638,0:04:30.859 that make insulin in my body. 0:04:30.859,0:04:33.955 And so what I want to tell you about for a few minutes is, 0:04:33.955,0:04:37.747 what people have learned using DNA sequencing techniques 0:04:37.747,0:04:41.406 in particular, to study the microbial cloud 0:04:41.406,0:04:42.980 that lives in and on us. 0:04:42.980,0:04:45.444 And I want to tell you a story about a personal project. 0:04:45.444,0:04:48.238 My first personal experience with studying the microbes 0:04:48.238,0:04:52.388 on the human body actually came from a talk that I gave, 0:04:52.388,0:04:54.188 right around the corner from here at Georgetown. 0:04:54.188,0:04:57.205 I gave a talk, and a family friend who happened to be 0:04:57.205,0:04:59.748 the Dean of Georgetown Medical School was at the talk, 0:04:59.748,0:05:02.238 and came up to me afterwards saying, they were doing 0:05:02.238,0:05:05.588 a study of ileal transplants in people. 0:05:05.588,0:05:09.564 And they wanted to look at the microbes after the transplants. 0:05:09.564,0:05:12.628 And so I started a collaboration with this person, 0:05:12.628,0:05:15.901 Michael Zasloff and Thomas Fishbein, to look at the microbes 0:05:15.901,0:05:20.374 that colonized these ilea after they were transplanted into a recipient. 0:05:20.374,0:05:23.516 And I can tell you all the details about the microbial study 0:05:23.516,0:05:25.766 that we did there, but the reason I want to tell you this story 0:05:25.766,0:05:28.990 is something really striking that they did at the beginning 0:05:28.990,0:05:30.013 of this project. 0:05:30.013,0:05:34.378 They take the donor ileum, which is filled with microbes from a donor 0:05:34.378,0:05:36.661 and they have a recipient who might have a problem 0:05:36.661,0:05:39.286 with their microbial community, say Crohn's disease, 0:05:39.286,0:05:42.846 and they sterilized the donor ileum. 0:05:42.846,0:05:47.141 Cleaned out all the microbes, and then put it in the recipient. 0:05:47.141,0:05:49.805 They did this because this was common practice 0:05:49.805,0:05:52.934 in medicine, even though it was obvious 0:05:52.934,0:05:55.072 that this was not a good idea. 0:05:55.072,0:05:58.077 And fortunately, in the course of this project, 0:05:58.077,0:06:00.640 the transplant surgeons and the other people 0:06:00.640,0:06:05.061 decided, forget common practice. We have to switch. 0:06:05.061,0:06:09.206 So they actually switched to leaving some of the microbial 0:06:09.206,0:06:13.206 community in the ileum. They leave the microbes with the donor, 0:06:13.206,0:06:16.782 and theoretically that might help the people who are 0:06:16.782,0:06:18.871 receiving this ileal transplant. 0:06:18.871,0:06:22.173 And so, people -- this is a study that I did now. 0:06:22.173,0:06:24.478 In the last few years there's been a great expansion 0:06:24.478,0:06:28.656 in using DNA technology to study the microbes in and on people. 0:06:28.656,0:06:30.464 There's something called the Human Microbiome Project 0:06:30.464,0:06:32.320 that's going on in the United States, 0:06:32.320,0:06:34.854 and MetaHIT going on in Europe, and a lot of other projects. 0:06:34.854,0:06:38.043 And when people have done a variety of studies, 0:06:38.043,0:06:41.675 they have learned things such as, when a baby is 0:06:41.675,0:06:44.659 born, during vaginal delivery you get colonized by the 0:06:44.659,0:06:45.851 microbes from your mother. 0:06:45.851,0:06:48.907 There are risk factors associated with cesarean sections, 0:06:48.907,0:06:52.938 some of those risk factors may be due to mis-colonization 0:06:52.938,0:06:55.330 when you carve a baby out of its mother 0:06:55.330,0:06:58.155 rather than being delivered through the birth canal. 0:06:58.155,0:07:01.604 And a variety of other studies have shown that the 0:07:01.604,0:07:03.411 microbial community that lives in and on us 0:07:03.411,0:07:05.674 helps in development of the immune system, 0:07:05.674,0:07:10.619 helps in fighting off pathogens, helps in our metabolism, 0:07:10.619,0:07:13.699 and determining our metabolic rate, probably 0:07:13.699,0:07:16.874 determines our odor, and may even shape our behavior 0:07:16.874,0:07:18.810 in a variety of ways. 0:07:18.810,0:07:21.866 And so, these studies have documented or suggested 0:07:21.866,0:07:26.153 out of a variety of important functions for the microbial community, 0:07:26.153,0:07:30.690 this cloud, the non-pathogens that live in and on us. 0:07:30.690,0:07:34.274 And one area that I think is very interesting, 0:07:34.274,0:07:36.940 which many of you may have now that we've thrown 0:07:36.940,0:07:40.870 microbes into the crowd, is something that I would call "germophobia." 0:07:40.870,0:07:43.829 So people are really into cleanliness, right? 0:07:43.829,0:07:45.808 We have antibiotics in our kitchen counters, 0:07:45.808,0:07:48.904 people are washing every part of them all of the time, 0:07:48.904,0:07:53.930 we pump antibiotics into our food, into our communities, 0:07:53.930,0:07:56.371 we take antibiotics excessively. 0:07:56.371,0:08:00.210 And killing pathogens is a good thing if you're sick, 0:08:00.210,0:08:03.474 but we should understand that when we pump chemicals 0:08:03.474,0:08:06.371 and antibiotics into our world, that we're also killing 0:08:06.371,0:08:08.666 the cloud of microbes that live in and on us. 0:08:08.666,0:08:11.666 And excessive use of antibiotics, in particular in children, 0:08:11.666,0:08:14.895 has been shown to be associated with, again, risk factors 0:08:14.895,0:08:19.151 for obesity, for autoimmune diseases, for a variety 0:08:19.151,0:08:21.055 of problems that are probably due to disruption 0:08:21.055,0:08:24.159 of the microbial community. 0:08:24.159,0:08:27.511 So the microbial community can go wrong 0:08:27.511,0:08:29.223 whether we want it to or not, 0:08:29.223,0:08:31.471 or we can kill it with antibiotics, 0:08:31.471,0:08:33.567 but what can we do to restore it? 0:08:33.567,0:08:36.679 I'm sure many people here have heard about probiotics. 0:08:36.679,0:08:39.687 Probiotics are one thing that you can try and do to restore 0:08:39.687,0:08:42.111 the microbial community that is in and on you. 0:08:42.111,0:08:45.583 And they definitely have been shown to be effective in some cases. 0:08:45.583,0:08:48.680 There's a project going on at UC Davis where people are using 0:08:48.680,0:08:51.575 probiotics to try and treat, prevent, 0:08:51.575,0:08:54.087 necrotizing enterocolitis in premature infants. 0:08:54.087,0:08:57.495 Premature infants have real problems with their microbial community. 0:08:57.495,0:09:00.015 And it may be that probiotics can help prevent 0:09:00.015,0:09:03.151 the development of this horrible necrotizing enterocolitis 0:09:03.151,0:09:04.816 in these premature infants. 0:09:04.816,0:09:08.807 But probiotics are sort of a very, very simple solution. 0:09:08.807,0:09:12.162 Most of the pills that you can take or the yogurts that you can eat 0:09:12.162,0:09:16.949 have one or two species in them, maybe five species in them, 0:09:16.949,0:09:20.615 and the human community is thousands upon thousands of species. 0:09:20.615,0:09:24.543 So what can we do to restore our microbial community 0:09:24.543,0:09:27.742 when we have thousands and thousands of species on us? 0:09:27.742,0:09:30.448 Well, one thing that animals seem to do is, 0:09:30.448,0:09:34.462 they eat poo -- coprophagia. 0:09:34.462,0:09:39.071 And it turns out that many veterinarians, 0:09:39.071,0:09:41.080 old school veterinarians in particular, 0:09:41.080,0:09:43.796 have been doing something called "poo tea," 0:09:43.796,0:09:49.601 not booty, but poo tea, to treat colic and other 0:09:49.601,0:09:53.224 ailments in horses and cows and things like that, 0:09:53.224,0:09:57.172 where you make tea from the poo from a healthy 0:09:57.172,0:10:00.321 individual animal and you feed it to a sick animal. 0:10:00.321,0:10:04.761 Although, unless you have a fistulated cow with a big hole in its side, 0:10:04.761,0:10:07.300 and you can put your hand into its rumen, 0:10:07.300,0:10:10.708 it's hard to imagine that the delivery of microbes 0:10:10.708,0:10:13.637 directly into the mouth and through the entire 0:10:13.637,0:10:17.285 top of the digestive tract is the best delivery system, 0:10:17.285,0:10:21.405 so you may have heard in people they are now doing 0:10:21.405,0:10:26.055 fecal transplants, where rather than delivering 0:10:26.055,0:10:28.487 a couple of probiotic microbes through the mouth, 0:10:28.487,0:10:31.940 they are delivering a community of probiotics, 0:10:31.940,0:10:34.420 a community of microbes from a healthy donor, 0:10:34.420,0:10:36.557 through the other end. 0:10:36.557,0:10:39.887 And this has turned out to be very effective in fighting 0:10:39.887,0:10:42.253 certain intransigent infectious diseases 0:10:42.253,0:10:46.092 like Clostridium difficile infections that can stay 0:10:46.092,0:10:48.189 with people for years and years and years. 0:10:48.189,0:10:53.052 Transplants of the feces, of the microbes from the feces, 0:10:53.052,0:10:55.917 from a healthy donor has actually been shown to cure 0:10:55.917,0:10:58.778 systemic C. dif infections in some people. 0:10:58.778,0:11:04.620 Now what these transplants, these fecal transplants, or 0:11:04.620,0:11:09.079 the poo tea suggest to me, and many other people 0:11:09.079,0:11:10.823 have come up with this same idea, is that 0:11:10.823,0:11:14.711 the microbial community in and on us, it's an organ. 0:11:14.711,0:11:19.718 We should view it as a functioning organ, part of ourselves. 0:11:19.718,0:11:23.709 We should treat it carefully and with respect, 0:11:23.709,0:11:27.689 and we do not want to mess with it, say by C-sections 0:11:27.689,0:11:32.597 or by antibiotics or excessive cleanliness, 0:11:32.597,0:11:35.814 without some real good justification. 0:11:35.814,0:11:39.454 And what the DNA sequencing technologies are allowing people to do now 0:11:39.454,0:11:46.406 is do detailed studies of, say, 100 patients who have Crohn's disease 0:11:46.406,0:11:48.941 and 100 people who don't have Crohn's disease. 0:11:48.941,0:11:52.774 Or 100 people who took antibiotics when they were little, 0:11:52.774,0:11:55.198 and 100 people who did not take antibiotics. 0:11:55.198,0:11:59.278 And we can now start to compare the community of microbes 0:11:59.278,0:12:02.581 and their genes and see if there are differences. 0:12:02.581,0:12:05.983 And eventually we may be able to understand if they're not 0:12:05.983,0:12:08.607 just correlative differences, but causative. 0:12:08.607,0:12:12.077 Studies in model systems like mouse and other animals 0:12:12.077,0:12:15.286 are also helping do this, but people are now using 0:12:15.286,0:12:17.590 these technologies because they've gotten very cheap, 0:12:17.590,0:12:21.504 to study the microbes in and on a variety of people. 0:12:21.504,0:12:26.094 So, in wrapping up, what I want to tell you about is, 0:12:26.094,0:12:29.301 I didn't tell you a part of the story of coming down with diabetes. 0:12:29.301,0:12:32.065 It turns out that my father was an M.D., 0:12:32.065,0:12:36.537 actually studied hormones. I told him many times 0:12:36.537,0:12:41.327 that I was tired, thirsty, not feeling very good. 0:12:41.327,0:12:44.206 And he shrugged it off, I think he either thought 0:12:44.206,0:12:47.485 I was just complaining a lot, or it was the typical 0:12:47.485,0:12:50.104 M.D. "nothing can be wrong with my children." 0:12:50.104,0:12:53.325 We even went to the International Society of Endocrinology 0:12:53.325,0:12:55.455 meeting as family in Quebec. 0:12:55.455,0:13:00.949 And I was getting up every five minutes to pee, 0:13:00.949,0:13:03.384 and drinking everybody's water at the table, 0:13:03.384,0:13:06.318 and I think they all thought I was a druggie. 0:13:06.318,0:13:08.038 (Laughter) 0:13:08.038,0:13:10.014 But the reason I'm telling you this is that 0:13:10.014,0:13:13.014 the medical community, my father as an example, 0:13:13.014,0:13:16.581 sometimes doesn't see what's right in front of their eyes. 0:13:16.581,0:13:20.566 The microbial cloud, it is right in front of us. 0:13:20.566,0:13:23.366 We can't see it most of the time. It's invisible. 0:13:23.366,0:13:24.837 They're microbes. They're tiny. 0:13:24.837,0:13:27.789 But we can see them through their DNA, 0:13:27.789,0:13:31.038 we can see them through the effects that they have on people. 0:13:31.038,0:13:32.656 And what we need now 0:13:32.656,0:13:36.325 is to start thinking about this microbial community in the context 0:13:36.325,0:13:38.838 of everything in human medicine. 0:13:38.838,0:13:41.905 It doesn't mean that it affects every part of us, 0:13:41.905,0:13:43.304 but it might. 0:13:43.304,0:13:47.229 What we need is a full field guide to the microbes 0:13:47.229,0:13:50.622 that live in and on people, so that we can understand 0:13:50.622,0:13:53.894 what they're doing to our lives. 0:13:53.894,0:13:56.965 We are them. They are us. 0:13:56.965,0:13:58.293 Thank you. 0:13:58.293,0:14:00.278 (Applause)