 So, over and over again, science has revolutionized how we see our place in the universe. The Copernican Revolution, for example, made us realize that our planet was not the center of the universe, rather elsewhere in the solar system. The Darwinian Revolution made us realize that rather than being at the top of a great chain of being, instead we were just one twig on a tree of life with many branches that have all had the same time to evolve. Then the revolution in dark matter made us realize that all of the galaxies and all of the stars that we see around us make up only 4% of the universe, and the other 96% is dark energy in dark matter that we do not yet understand. Now the microbial revolution is taking this to within our own bodies. So it turns out that each of us consists of about 10 trillion cells that carry our genome that we think are human, but we have on it inside us as many as 100 trillion microbial cells, tiny organisms too small to see with an echo die. And our whole human genome consists of about 20,000 genes, depending on what you count exactly. But our microbial gene catalog ranges from two to 20 million microbial genes. And so by that measure, we might think of ourselves as less than 1% human. You can think of this phylogenetic tree showing the relationships between different organisms as a kind of map of what we now know about life, where more closely related species are put more closely together on the tree. So on this map, here we are, for example, all of the diversity of our species is boiled down to just that one twig. And so you might wonder about the scale of this map. So on this scale, this is corn, so if you had corn flakes for breakfast, that's how much of the tree you were covering. And this is a mushroom, for example. So all of the plants and animals and fungi that we see around us are just this tiny twig of the tree, and all of the rest of life is microbial, including the microbes that inhabit our bodies. So in the Human Microbiome Project, which was a huge $173 million initiative funded by NIH to jumpstart research on the microbiome, together with a consortium of about 400 other researchers, we mapped the healthy human microbiome and 250 healthy volunteers looking at many sites in the body and the speed with which this escaped the pages of the scientific journals to the cover of Scientific American, and then to the cover of the Economist was really dramatic. So in these 250 healthy people, you might assume that there would not be much diversity, that they would all have basically the same microbes, but that's not at all what we found, despite the fact that they were essentially all medical students in their 20s from just two universities in the Southern United States. And what we found instead was this tremendous diversity, so each vertical line on this plot represents a different person. And if we just focus in on the gut, these different colors represent different kinds of microbes, and what we can see is that even these healthy people had completely different kinds of microbes from one another. Although what was fascinating is that what those microbes actually did in terms of the functions of the genes they encoded were very similar person to person, and you can see these profiles are much more consistent. And so what this means is that each of us have as a completely different species assemblage from the person sitting next to us, which is remarkable when you consider that our human genomes are 99.99% the same, but at least when we're healthy, the functions that our microbes perform are all very similar. So this was very surprising at first, but then we realized that this is exactly what we see when we look around us larger scales and larger ecosystems. Because for example, these two grasslands and these two rain forests look very similar to one another, but they're on different continents, and there's essentially no species shared between the two rain forests, despite their apparent visual similarity, and the same kind of thing goes on in the microbial ecosystems that it didn't have at each of us. So when we're healthy, the functions that are performed are pretty much the same. But when we're unhealthy, we're starting to discover that these microbes link to all kinds of different diseases ranging from inflammatory bowel disease to rheumatoid arthritis, and even in mouse models to things like autism and depression. And one thing we have connected the microbiome to is obesity. So for example, today, I can tell you with over 90% accuracy, whether you're lean or obese based solely on sequencing your microbial genes. Now you might say, hey, wait a minute, that doesn't have a lot of commercial potential as a test for obesity, because I can tell which of these two people is fat, knowing nothing at all about their genomes, nothing at all about their microbes. It turns out that if I try to do the same task of classifying you as lean or obese based on your human genome instead of your microbial genes, I can only do that slightly better than chance with 58% accuracy versus 90% accuracy based on your microbial genes. And then we can prove cause and effect by using mice. So we can raise mice without any microbes of their own and then transmit to them the microbes of someone who's fat versus someone who's thin. And what you see is that the amount of weight they gain depends on whose microbes they got. Additionally, we can even do this kind of thing for behavior. So for example, you can make a mouse more anxious by giving it the microbes of a more anxious mouse, or less anxious by giving it the microbes of a less anxious mouse. So this is really remarkable, both in the case of obesity, which a lot of people attribute to willpower or to our human genes, or in the case of anxiety. Because what this shows is that our microbes can affect these traits that affect how we think of who we are. And I mentioned autism earlier. Sarkis-Masminian, one of my collaborators at Caltech, has done a tremendous amount of work on a mouse model that resembles some features of autism, where essentially you give pregnant female mice a chemical that simulates a virus, and then their pups have many dysfunctional features that resemble autism. So they have cognitive deficits, they have social deficits, they have gut barrier dysfunction, and they have compulsive behavior, like they can possibly bury marbles. And part of the reason for this is that they have a dysfunctional microbial community that is different from the microbial community of a normal mouse. You can induce the same symptoms by injecting normal mice with one chemical that this altered microbial community produces. And then you can rescue them by giving them a probiotic, a kind of beneficial bacteria isolated from the human gut. So remember that this is mouse model work, and we do not yet know how it will apply to humans, but the potential for this kind of research to affect a wide range of diseases that you might not have thought will link to your gut is tremendous and present. One remarkable fact about the gut microbiome is if you think of it as being like an organ, it is the only organ that you can transplant without doing surgery. And this is Bill Sandborn, who's the chair of gastroenterology at the University of California, San Diego, where I work. And what he's using here is he's using medical grade stool to replace the microbiome of a patient who has severe clostridium difficile infection, a life-threatening kind of diarrhea that kills 14,000 people a year in the U.S. alone. And it turns out that you can cure this disease with 95% efficacy by transplanting the microbiome from someone who's healthy, whereas antibiotics only work 20 or 30% of the time. And so the question that faces us as a field at the moment is, for which other diseases linked to the microbiome can we achieve this similar success by manipulating the microbiome? So you might think that all of this talk of fecal transplant is kind of disgusting, but then that's part of the course in medicine. What could be more disgusting than literally picking a scab off the utter of a diseased cow and cutting your skin open and putting it underneath? And yet this is exactly the basis for vaccination, which has arguably saved more lives than any other medical advance. Cow's milk is a particularly good source of iodine, which is an essential micronutrient, but not if you live in the mountains. And a century ago, a very important disease of people in mountain regions was goiter, which affected your throat, and also cretinism, a profound form of mental retardation. No one knew at the time that it was due to this deficiency of iodine, the simple element. And if you look at all the compounds in cow's milk, there are hundreds of thousands of different compounds in there if you run it through a mass spectrometer. And understanding the complexity is something that we're only just beginning to do now. And yet that doesn't mean that it's not possible to eliminate diseases like goiter and iodine and cretinism, which have been done worldwide by iodizing salt, a very simple and very effective nutritional intervention. So you don't have to understand the full complexity of the disorder to be able to treat it on a whole population scale and to completely eradicate the disease. So I'm going to end with a slightly more cautionary tale, which is a story about depribulation. So do you know when the defibrillator was invented? Maybe you think it was 50 years ago or 100 years ago? It was invented in the 1700s in London, where a society was formed, the society for the revival of persons apparently drowned. And what they were doing is running around London with laden jars, a primitive form of battery, giving electric shocks to the hearts of people who had been pulled out of the water and people who had suddenly collapsed. And of course this was an enormously effective intervention, right? They had invented defibrillation and they were literally bringing people back from the dead. But what put a stop to it was publication of Frankenstein in 1818 and subsequent concern about the souls of the people who were being brought back. Would you really be human if you had been brought back from the dead by this medical technology that no one understood? And so in the case of vehicle transplantation, we have this very important task ahead of us, because right now no one really understands how it works. And yet it's something that's saving lives right now in the United States, in the UK, and an increasing number of countries where it's being practiced. And so one thing that was critical is that we'd not turn our back on this life-saving technology, the fear of contaminating microbial souls. Thank you.