 With that, science is awesome, the microbiome is awesome and here's Jessica Richmond. Wow, with an introduction like that, that's pretty amazing. None of the things I'm going to show you are going to glow. So I apologize for that. Yeah, I know. Most of the things that are in your poop do not glow. So I have a few questions for you. I'm so curious, who has heard of the microbiome before this? Just wanted to get an idea. There are evidently some contributors to your biome in the audience. Want to see who all those people are? Wow, that's awesome. So I'm going to take you on a journey through a few different things and then tell you a little bit about our project for those who are not familiar with it. So first we're going to talk about what the microbiome is and why that completely changes the way that we think about ourselves and microbiology and what it means to be human in a lot of ways. And then I'm going to tell you a little bit about citizen science, which is a new way of looking at science that I feel like all of us nerds can very much appreciate. And then a little bit about the project that we did that kind of unifies these things. So first thing is what is the microbiome? So most of the cells in our body are not human cells. 90% of the cells in our body are bacterial cells. So they live on and they live in us and they contribute, for example, 30% of the small molecules in our blood are not made by human cells, they're made by bacterial cells. So you can kind of get an idea of how much of an influence on us these bacterial symbionts that evolved with us really have. So the question is if this is so much a part of our bodies, our metabolism, so much involved in our biologies I'll talk about later, why didn't we know about this earlier? So basically before the germ theory of disease came about when the microscope was invented because people could actually see that there were these small organisms that lived on us and that was a huge advance, enabled understanding hygiene, having antibiotics, all these things. But the next, and then people used, were able to culture those organisms and base the research on what organisms could be cultured. The problem is that only 5% of the organisms that live in our bodies can be cultured and those are not necessarily the important ones to us. Those are the ones that can grow in a culture medium in the lab. So you can see how all of our research is biased for things that are easy to grow and not things that actually make a difference to us. But then DNA sequencing technology got really inexpensive and that's what enables us to see this huge diversity of organisms that live on and within our bodies. We can now see in the same way that microscope enables us to see their organisms at all and stop thinking about the demon theory of disease. Now we can sort of start a new way of looking at our organisms. So basically, we are a habitat for other creatures to live in. You think about yourself as a human being, you think we know who we are, but we're actually just an ecosystem on which other things live. So if you think about it, it's a little bit different to be an organism that lives on your nostril than to be an organism who lives up your nose. It's one of them's a little warmer than the other, there's a constant flow of moisture. It's a very different place to live. Same thing if you think about your digestive tract, your genitals, your armpits, it's kind of gross if you think about it, but it's also kind of interesting because we're just a place where these other organisms live and when we think about the microbiome and what it can tell us, it isn't magic, it's just what things live in those places and then by looking at them and how they interact with us, it can be a proxy for understanding ourselves. So how have people stayed this before? So there was the Human Genome Project, I'm sure everyone here knows what that was, and then there was the Human Microbiome Project from 2007 to 2012, just finished up at the end of 2012, and the Human Microbiome Project, and then there was a European version called MetaHit, which was sort of similar except in Europe, that spent $173 million of the National Institutes of Health's money to investigate the microbiomes on healthy individuals, and they only looked at 250 individuals actually, 240 individuals. So, but it established a baseline for future projects that are trying to compare the microbiome to a set of controls. So, in addition to that study of healthy people, in which they found that we're all covered in bacteria where they're healthy or sick, there have been thousands of studies about the microbiome and basically everything, the microbiome in obesity, the microbiome in diet, alcohol, caffeine, coffee, there's actually some studies where they looked at how much coffee you drink, and then they took some of the active ingredients in coffee and studied how that affected your microbiome. The things that you might expect, bowel disorders of various kinds, antibiotics, and then some things you might not think about, like anxiety and depression. There's clearly they take, these stages are designed in such a way that you have the, you have 100 depressed people and 100 non-depressed people, and then you look at their microbiomes and they're different. They're not designed to help you figure out causally what's actually going on. It's just, wow, there's a difference between these two things. So, and in the case of antibiotics, that's actually a really, really interesting one where they would take a sample of the gut beforehand, then you would take antibiotics, and then they would check a month out, six months out, two years out, and the gut microbiome had never grown back to where it was from before taking antibiotics, which gives you some idea of how powerful the effects of antibiotics are. Basically what we've done when we take antibiotics is we're just clear cutting the rainforest. We're just killing all the organisms that are there, and sometimes that's good because you might die from the organism that's there, but you're also killing all these other things that we don't even fully understand the effects of what that means. So it's not just your gut. Of course, these bacteria live all over you in every part, inside of you, and every part on you. So chronic sinusitis is basically can be understood either in the old paradigm as there's a pathogenic bacteria that's bad, and if you kill it, then that's good and you're fine. Or it can be understood in the new paradigm, which is that there's a dominant species that grows to take over the ecosystem inside your sinuses. And if you can disrupt that dominant species, then yay, you've changed the ecology inside your sinuses. And the same thing is true with the penis microbiome and bacterial vaginosis, for example, which is really interesting. So there's an interaction between microbiomes between people when you do things like kiss each other, have sex, move in with each other. So did I miss one? No. Okay, so let's talk about the future of the microbiome. So there have been some really interesting studies. So there have been some really interesting studies in mice where they take a mouse that is sterile, has no bacteria in it, and they give it a human, obese microbiome. They give it basically shoot poop up inside of it from an obese person. Yes, it's very gross. And then they find that mice, given that same diet, when they have the human obese microbiome or not, have the obese microbiome get fatter. So basically the microbiome is more efficient in the obese person. It's causing you to get more energy out of the same food. So it's not just you are what you eat. The author of the study said in kind of a cute way. It's not just you are what you eat. It's you are what you eat as mediated by the microorganisms in your distal gut, which is not as catchy, but you know. So where does all this go? So there's sort of the idea of targeted probiotics. Right now you can eat yogurt, but you're just taking a bunch of bacteria. There's some kind of helpful. No one really knows what the actual effect of that is. But sort of another frontier of personalized medicine is that you can take the probiotics that are exactly the organisms that you need. No one can do this yet, but you can see it's very close to being done. And there's a really cool thing about called Repupulate, which was done about a month ago, where they basically took... So somewhere between poop and a probiotic, there's like a continuum between those two things. One kind of leads into the other. And as you refine poop, you get closer and closer to a probiotic. So what Repupulate did was they were trying to cure an infection called C. diff, which can be cured with fecal transplants where you take the poop from one person and put it into another person. So they refined this a little bit more and created something called Repupulate, which can also cure that infection. So there's a lot of very grossed out looking people in the audience right now. But this is the future of probiotics, folks. So I want to switch gears entirely and talk a little bit about citizen science because what we're doing with you, Biome, is citizen science. We're sort of using the microbiome as a first platform for citizen science. So a lot of people have heard about the microbiome, but I don't know how many people have heard about citizen science. Is this a phrase? It's a really nerdy audience, so I'm sure you guys have heard of this. Yes, yeah, citizen science. I think this is great. It's basically citizen science, although I don't think this is the best name imaginable, but citizen science is the idea that you and me and everyone else who's not credentialed by the system to be a scientist and permitted to study and think about things can be involved in scientific efforts. So the question is, could someday a citizen scientist win a Nobel Prize? Right now, citizen science is generally limited to things like there's the SETI project where you can process data about extraterrestrial life and your computer in the background. The Audubon Society will let you take pictures of birds and send it to them. But what if you could integrate much more deeply into science? And the average person's thinking, hypothesis-generating, data analysis, just you as a thinking person can have an impact on science. I think this is really important, because right now all of us that are not professional scientists don't have a way to direct research, don't have a way to do analysis of data, don't have any way to get involved in this. And science is, well, I mean, we're all nerds here, right? Science is what pushes our understanding of the world and even our control of the world further. So where could this go? I mean, could this be integrated into grants? Could this change the way that professional science is done? So this is an organization, you can look this up, sciencesand.org, that we find to help scientists structure projects to bring people into them. And UBIOM is sort of a first example of that, because what UBIOM has done with the microbiome is to bring your ideas and your tests about citizen science into studying the microbiome. So what we're going to do with our project, which I'll talk a little bit about in a minute, is we're going to allow you to sort of analyze the data of our full dataset of human microbiomes and bring in your questions, like how does my diet affect the microbiome? How does a specific health issue affect the microbiome? And bring your thoughts and your hypotheses into science. So this is sort of the boundaries of citizen science now that people can do this, but I hope those boundaries will go way further and the average person will be able to involve themselves in science in a totally new way. So what was UBIOM? UBIOM is a crowdfunding project. We raised $351,000, which is totally unexpected to us and really awesome and everyone here contributed. Thank you very much for doing that. It was the largest successful citizen science project in history. We've involved over 2,500 people, which is 10 times the human microbiome project to give you an idea of the power of citizen science. And we finished crowdfunding, so I'm not here asking you for money, but if you want to sign up for a mailing list or if you want to write to me at nerdnight at ubiome.com, that would be great. So, questions. So the question is, what happens when you drink alcohol because alcohol kills bacteria? So there are some effects of alcohol on the gut microbiome, but this is way downstream. So one really interesting metaphor they use for the gut microbiome is that the tube that goes from your mouth to your butt is like the Amazon River. And the end of the mouth of the Amazon River is your feces, right? So, you know, it's alcohol when you drink it and it has some effect, I would imagine, on your oral microbiome, although I don't know a study about that. But by the time it gets all the way down, it's been changed into a lot of different things. So we're sampling sort of the end of that river. And of course, a really interesting question is not all the way up that river because things change as they go down the river. And that's harder to test, but that's definitely something that people will be looking at going forward. Over there. That's such a good question. So the question is, most citizen science projects use the public as mechanical turks just as sort of non-thinking lever pushers to analyze data or to play a game that folds proteins. And the question is how do, I guess the question is, what are the incentives to scientists to involve the public in citizen science? And I think it's just an unleashing of human ingenuity and human intention. I mean, I think right now, the way the system is structured, it's mediated by these large institutions that require credentialing and require all these sorts of things to have people be involved. And to scientists, yeah, first, of course, at first it's free labor, but why not have it also be just, there's a lot of information out in the public. There's a lot of creative thinking out in the public that can make science much better. And ours was the largest project, but there are a lot of other projects that were really amazing that are starting to get funded. And I think that most, I was saying, I haven't started the numbers exactly, but I think that most of these citizen science projects are done by graduate students. And there's small amounts that supplement a PhD stipend. So as those graduate students move further through the system, they'll involve the public more, at least, I hope so. Yes. This is a really good question. So we've just finished crowdfunding. Oh, sorry. I should restate the question. The question is, what was the diversity of the human microbiome project versus our sample, which is a lot greater? We've just done crowdfunding. We haven't sent out any of our kits. We're sending them out in May. So once we do that, we'll have, you know, people will use them and then send them back to us. And probably by late summer, we'll have some data and everyone can take a look at it. We'll make sure to send something to nerd night so they can send things around or you can just get on our mailing list and we'll send things out. Yes. So our sample with Ubiom is international, was open to anyone who could sign up on Indiegogo, which is people in 196 countries. So we have over 40 countries, I think, represented. So it's mostly American, but there's also Canada, the UK, Chile, Uruguay, Estonia, all sorts of places. Right there. So the question is, how can we do such a large sample size for so much less money? Well, I think part of it is that we're standing on the shoulders of giants. A lot of the techniques were refined by the Human Microbiome Project. A lot of the sequencing costs have decreased rapidly even in just those five years since the Human Microbiome Project. I think also, we don't have university overhead. We're going to be in the lab unscrewing caps on tubes and sticking Q-tips into solutions and we're really going to be doing this ourselves. And I think that's another advantage it says in Science Can Have is that we don't have the university overhead and we don't have the structure. We just need to actually deliver on what we promised. So way, way, way in the back. Oh, so the question is, what are the implications of the microbiome for developing young babies? This is really interesting. So a baby gets its microbiome from its mother and this is a really interesting thing. So the vagina of a pregnant woman right before she gives birth will change to have more microbes that are milk digesting, which is just kind of nuts, right? I mean, it's not really interesting. And so, and then there has been a difference in babies who are born vaginally who acquire those microbes and babies that were born by cesarean who didn't. And how long that distance persists and what exactly that means is not known yet. But there's definitely, there's definitely a lot of implications for how the microbiome develops in a baby. My co-founder Will, who is unfortunately not here tonight, had a baby in December when we were in the middle of this project and he has sampled every single poop of that baby. So he has a freezer full of baby poop, which I think is really awesome. So this is probably going to be the most sequenced baby in the history of the world because I don't know if anyone else does this to their children, but it's great. So it should be really interesting to see how, I mean that's not a study, obviously it's one baby, but it will be really interesting to see how this develops. Right here. So the question is what happens if you have Giardia or an amoeba that moves into your gut and what does that do? I haven't looked at that specifically, so I'm not sure to stay specifically on that, but one thing I should say about Ubiom is that we're sequencing the bacterial microbiome. This is not deep sequencing. So deep sequencing would cost thousands of dollars and that would sequence everything. If you have worms, the lettuce that you ate last night, human cells, everything. What we're just sequencing are bacterial cells. So as DNA sequencing costs go down, we'll be sequencing all those other things too. So we'll sequence, you know, protists and worms and everything. And that gives a much more complete picture, but that's not at a level that can be used. And frankly, there are thousands of studies that are just using bacterial DNA and there are a lot of correlations there, but as time goes on, more people will study that too. So, right in the back. Oh, so that's a good question. So the question is how do you know that a piece of bacteria, that DNA is from a bacterial cell as opposed to another cell? So there's a region of bacterial DNA that we amplify that can be used as a signal that that's a bacterial cell and then we sequence the rest of it. So we're basically identifying bacterial cells by that signature. It's the 16S region for all the biologists in the room who are cooler than the chemists, by the way. Sorry. Okay, out there. So the question is, what kind of access to the raw data are we planning to provide? So this is going to be an opt-in process. We're not just going to make everyone's data public. We're trying to balance concerns of privacy and concerns of open access. And there's sort of great arguments on both sides. From the privacy perspective, people don't want their data out there. Who knows what this will mean five years from now if that's out in the world? How identifiable that will be, what that will mean. On the other hand, open access means more people can look at the data and it's more valuable to the world. So what we're going to have is an opt-in consent. And if you'd like to be involved in the dataset, then you can be. And if you don't want to be, then you don't have to be. And that will sort of balance those two things. Microbial, by the way, microbiome data is not uniquely identifiable in the way that the human genome is. There will be many, many duplicates, especially at the level of analysis that we're at. But it is conceivable that if you combine it with, you know, your gender and where you live and all these other things, it could be uniquely identifying what your microbiome is. Because you may be the only person with those other characteristics who also has this microbiome. Yes, there. So the question is about IRB processes. So IRB is, for those who don't know, probably most of you do. But an IRB is an institutional review board and it makes sure that you're conducting research in an ethical manner and that you're making people aware of the risks and the benefits of what you're doing. So we did something a little bit unusual. Because we're a company and we're not an academic research project, we're not required technically to have an IRB because basically we're giving you, you give us money and we give you your microbiome and that's it. If we want to publish in academic journals, you have to have an IRB. So what we did was we've done the crowdfunding first and then we're going to get the IRB. There's some controversy about this because most projects that are funded by institutions require you to have an IRB first. But we were just, we were citizen scientists, like we don't have thousands of dollars to pay for an external IRB or the university affiliation. So this is a really good question as far as citizen science goes and how to ensure the future of citizen science is conducted in an ethical manner, is conducted in a, you know, meets all the standards that academic science does, but can still involve the public in a way that's really powerful. So we're in discussions with UCSF about this. I have a call at the NIH in a couple of days because this is, all the stakeholders involved in this are really excited about the possibilities of citizen science and involving the public but also want to make sure that it's done ethically and we don't have, you know, people hacking up their neighbors in the garage saying, oh, it was science, you know. So it's very, that's a very good question and that's something that we want to, we want to help other projects be able to conduct their research in an ethical way too. Okay, one more question. Well, maybe no more questions, I don't know. Okay, yes, over there. So the question is, how much do we have enough of a sample in other countries to make meaningful comparisons to the U.S. dataset? And the answer is in some cases, yes and in some cases, no. We definitely have enough in the U.K., we have enough in Australia, we have enough in Canada and some of these things are not, you know, national boundaries are not what's important. You know, if you live two miles across the border that may or may not have any impact on your microbiome. But what we want to do with this project and sort of as we go forward is to be able to sequence parts of the world that just have not been researched in this way. In the U.S. there's a lot of research money that goes toward this, in Europe there's less but there's still some. But in other parts of the world, particularly in the developing world, no one to sequence it. I mean, there's no national institution that has the money to do these sorts of things. We're very happy to have some developing world countries in our sample and to be able to involve the developing world in this kind of research. But we don't in all countries have a statistically significant sample which is unfortunate, but we're hoping we get more so that we will. So thank you everyone.