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