Thank you for coming this is a Panel Discussion in which we will reveal our microbes are our puppet masters i should first start off by pointing out that viruses our microbes as wellir but we have ed yong a writer for the atlantic author of a new book teethree about micro biomes, i contain multitudesel and we have Science Writer from the New York Times and author of many books including up one a planet of viruses iam sophia shah author of pandemic and all of these books will be for sale by barnes noble and we will be signing them after that signing table letter h. So you can join us there. Is anyone here actually a microbiologist . So now we cant make anything up. [laughter] so it is an interesting time to talk about microbiology because it has been a paradigm shift in recentus years. Think back to the late 19th century we thought abouten microbes as the malevolent intruders to target with precision one surgical precision i call that microbial zeno phobia. And it makes sense back then for what we could detect those that we can grow in a dish in a lab for like tuberculosis but what we now know through genetic sequencing is that microbes are everywhere, they are all aroundd us it is their planet. They were here before we got here so all of our interactions have evolved in the context of a microbial world. So now we know everything our moods to dietary preferences are linked between the actions between microbes we need a new way to think about the microbial world that is the work that carl and ed do is so important to get us to understand the science and what it means for us. So there is a real urgency to that question because we can all agree that microbial zeno phobia as a paradigm has basically failed with increasing emergence of highly resistant bacterial pathogens with every single class ofsi antibiotics that chemical onslaught is creating the problem in many ways and then we had over 300 new pathogens out of nowhere like the ebola virus and zika. Is actually benign in its environment but then killed 11000 people in west africa. So we will have a conversation with you every time we have a new microbe i feel the responses range from the powerlessness from panic and hysteria to denial and dismissal so where do we fall on that continuum . Zika virus is an emerging disease that has gone from being completely unknown to something that we talk about at the water cooler within a matter of months. s and unfortunately this is not a new thing. It is a familiar routine were going through like mers in the middle east of the nobody even knew aboutbo before. So it is interesting when you are working on a book about viruses, the First Edition of my book came out in 2011 you try to update as much as you can to withstand the test of time and then my editor said you barely say anything about ebola people want to know about ebola. So i have the opportunity to write about ebola. And update the book in general. And there i made sure there will be a bola because of medical outbreak like we have never seen before. But those relatively small outbreaks affecting just a few hundred people in various parts of central africa. And then it looks like in december 2013 the first person to get stuck with a new outbrea outbreak. It is something people were aware of through spring 2014 and the by october it hit its peak. And actually not until june 2016 that the last case was recorded so we had just a few months without one recorded it has been years of the outbreak. There were over 28000 cases with a 40 percent mortality rate. Terrifying. Ty i dont know your thoughts but this was an opportunityy to see how Public Health is something we have been anticipating for a while. Monitoring was terrible. The vaccine was ridiculously slow. And has been in the works for many years but nobody wanted to pay to do more research on it. Because who gets sick with ebola . So actually for those that put the experiments into humans to get them ready they actually started to do testing on it in spring 2016. Way after the peak of the epidemic. A lot of people died many deaths couldve been avoided. So now the last few flareups where you vaccinate people in the area, thats great why didnt we have that for years . Ago . So i tried to get as much of that as i could in the second edition but i could do a third edition right now because now with the zika virus it is familiar to ebola because back in the forties to identify and a monkey it uganda and then people had antibodies to zika virus which suggested they were exposed to it. That people did not Pay Attention to it it was many obscure viruses. So they gradually emerged it is transmitted by mosquitoes and then in 2007 where we really registered in outbreak and it was not uganda it was tunisia. So now i made its way around the world there were a couple more outbreaks relatively small and then last year it showed up in brazil and then things just exploded. So as of now the 2015 outbreak there are 55 countries now that have zika virus that did not have a before puerto rico, miam rico, miami, throughout the new world except canada and chile and uruguay probably they dont have good weather to carry that. I think people are aware how bad things are with us outbreak puerto rico it is especially bad. We are not sure how many of these cases have been caused. Probably in the hundreds and then it causes baby to develop very small brains. The latest count there were 43 local cases and that just happened recently. They try to stop the miami but this thing is on the move. So how have we done with zika virus . Not terribly well. Its here in the United States with Animal Research on vaccine but we will probably just Start Testing vaccines in january. And here in the United States we are not putting out the money to control this. Congresses stuck. Bear in mind to care for these kids is 10 million for a lifetime. To be penny wise and pound foolish we are not even being penny wise. So that is what we are looking atki again. And the other parallel that is striking is it shows yet again how remarkable viruses are. So if you are happy about the microbial world, yes. The zebra virus has ten genes ebola has seven. We have the immune system going over billions of years they find a way around it. And what is happening is there are all these viruses in the Animal Kingdom and they are spilling out going further into the ecosystems going out into monkeys and other wildlife finding a nice new abundant host. So just a couple weeks ago a great man died who led the eradication of smallpox. Which is way worse than ebola or zika virus and we wipe that out from the planet. We just cannot ignore them pretending they will take care of themselves. If you want to talk Good Cop Bad Cop he is the bad cop but these come into the human populations and it isou really horrible totally susceptible with no immunity so what happens over time . We get use to certain viruses and they become part of the ecology. That is the microbe i own research that you are covering. I am definitely the good cop in this scenario. With any of those concerns and the more beneficial side i talk about how microbes have been with us for the longest time. And to t this date all of us depend on microbes for our development every human body can tell on contains tens of trillions of bacteria. And to calibrate the immune system. And even helps to shape the behavior. We have many orders of magnitude more viruses and bacterial cells in our body. It is part of the teaming ecosystem. Included witr own dna to kill and defuse the immune system of the capitalist targets and in this case a vir virus. An one thing i want to talk about now is the case where humans have actually engineered a relationship between an animal and a microbe to help to improve our health. This story begins in 1924 when a couple of microbiologists describe a new type of bacterium that lives ined the cells of the mosquito they collected. Knowing what this was they didnt know whether it was common and it took 12 years and one of them named it after o his friend and it took many decades to work out what he did that inn the 60s, 70s it is like insects and other arthropods given day are already the most diverse on the planet. They cloned themselves so they dont need t is for males at al. They can sit with him and continue to be even as the world guys around them. Of training to introduce the bacterium into a species of insect that it doesnt normally in fact and it spreads yellow fever and the reason is twofold. One, when it contains more, for some reason it becomes really bad at spreading the virus is behind these diseases. So it is effectively zikaproof. Because it is good at manipulating its hostss as they talked about, it is good at spreading through a wild populations of the idea is if you release a small number of these into the wild when there is a few generations of their kind which in a few months in our time, the entire local population should carry a microbe and bust be unable to transmit these important human diseases. This has been tested in the laboratory and a simulated in mathematical models and was posted in 2011 for the first time in a couple of australian suburbs where the mosquitoes were released into the wild and very quickly in the span of months you saw the prevalence went from zero to 100 in the mosquitoes in the areas about tharea is aboutthe organizationd this approach has been testing iin Different Countries around thee world they are scaling up and going global. They are testing the approach in brazil,zi colombia, indonesia ad vietnam gearing up to release the mosquitoes over cities with millions of people to see if the same approach canit indeed workt the larger scale and whether theyt will spread or dominate as much as they expected to and exd crucially whether that can then drive down the harm. I think that it has a lot of advantages. Its gotot the backing of the world health organization. Its interesting because it is cheap and probably quite safe unlike insect decides that are toxic and need to continuously be re sprayed. It should theoretically be good to go once you release them and you only need to release them once. There is no gender modification involved here. It seems that stops the spread through many different groups, competing and stimulating the immune system in many ways and that is reassuring because they have a habit of running rings around us and no biologist would back the approach. The bacteria allows them in many different ways as many different types of resistance they would theoretically need which would beul hard. So, here we have a really interesting approach to the point i want to make us all of f this started with basic curiosity about the microbial world. Back in 192 1924 the people that discovered it couldnt possibly have predicted that this is where the science was going to gobe. In fact one of them died in the 50s before anyone realized how common it was. He could not have foreseen where this would lead to now and in many ways but as th is the studf the animal micro by biome and thinking of them to be irrelevant to us and then we went to a period of fearing them and now we are in an area of exploration again and appreciation of realizing the crucial role they play in our lives and theur entire Animal Kingdom and we are starting to manipulate those partnerships for our own interest and our attempts at doing so is tremendous potential and i think that is where it will lead us in the future and fight its area that excites me so much and i felt compelled to write a book about it to instill. We want to think of them as really good or really bad. We have this dichotomy and what you are talking about is a different context. The returns we need to destroy but also the idea we are just another habitat to them theyve been another world and we are just another drop of sweet water. It comes in many strains and some are beneficial to their hosts and some are harmful, some are both at the same time. I talked about the wasps. The relationships are very contextual t and dynamic. They can change on tha on that e need ways of containing and keeping those relationships nappy. The question is when theres a conflict of interest between those we are encountering wake smallpox and ebola and what they want to do with what w that buto do and you could define that as disease. For any parasite, for anything living inside of something else, if its activities to g kill off its hoo soon, thats bad news. Its going to become extinct because its basicall basicallyt down its own house. But if you can raise a family and to say its tim say its tie house, go find another one and then burn it down, thats okay. So they evolve to Different Levels of deadliness and sometimes you can actually is a them the wild. For example some fool decided it would be a good idea to introduce rabbits to australia and was a horrible deadly virus that killed in europe and they said we will bring it to australia, problem solved. It started killing them like crazy and then it started to become less deadly. Its still not a good idea. It actually sort of evolved and essentially adjusted its deadliness to be able to get the host announced efficient way. We think about things as being good and bad in a very egocentric way. These things are evolving not just over the course of a few years. They are devolving over millions of years in our language. So, viruses can be good for us. In fact none of us would have been born without the virus is because millions of years in the past, our ancestors got infected with viruses and they actually basically harnessed some of those genes and used them to make proteins. These are crucial. For example mice have a similar version ofsi this. They cant have kids it just doesnt work. Just recentlyy discovered they were also harnessed from muscle so basically there are proteins that appear to be generated from a virus. Thats good. But in order to get back, ouren ancestors probably went through some horrific epidemic that nearly wiped out the speciest ad then finally we achieve immunity over them and went on from there so the whole language of good and bad doesnt really capture. There were some that played a role in our immune system. I talked about the bacteria like lunar landers and its the idea we have loads of them in our bodies and there are millions or trillions of these stock waiting to infect bacteria that passes by and they hope to keep the population that live with us under check and they hope to select for the species of microbes that live within us. Its a nice idea but i think it also highlights another aspect that we need to keep these populations in line into the balance matters of who was there and who isnt. Many are the work of one microbes the one disease but you can also get an illness when communities shift from healthy states intall thestates into an. When no particular member is responsible for the disease if its just the entire community has gone out of whack. Maybe you have new species that are notbe there anymore or lost some critical defensive ones that we see this all over the place. It might apply the human body, too. Many have been linked to changes in the microbiota for there it is diabetes or allergies or asthma, obesity, heart disease. Its still clear in many of the cases whether it is changes leading to disease or whether there are consequences. But, the principal that its not going infectious organism that a shift in the community is what is important, and we will learn more about that in the decades. That is interesting because in effect wit affects we still w because probiotics have become such a Huge Industry already so this whole idea that if you take the good bacteria and line your god with all that but somehow thats going to, you know, improve your health. But we still dont know if they are associated with certain kind of micro biome changes to that cause it or did that happen afterwards and so what are the limits of how much we can really manipulate our micro biome through these new type of you probiotics for example flex its very hard. They hav have leasehold claims attached to them, but they dont live up to a lot of them, so they seem to be good for some cases of infectious diarrhea, but by and large, when you think about all the other conditions that have been linked to the microbiota, evidence can help its quite inconsistent and i think thats because these are very difficult problems. We talked about trying to engineer as complicated as closebrace. That is a tough thing to do. And we are trying to solve the problem by getting products that contain a small quantities of bacteria, so hundreds of thousands of times lower than already exist. Strains that are actually not in the gut that were chosen often for historical reasons. Its almost like releasing a small number of captive animals into the jungle and hoping that they thrive. And in many cases, they dont. So there is another approach you could try, try getting people large communities that are wellsuited and that is the logic behind a very unorthodox treatment called a fecal transplant which is what it sounds like. You take stool from a healthy donor and put it into a sick recipient often than involving a blender and some tubing and they get better. [laughter] i should have brought props. [laughter] this is proven t has proven to y effective at treating a condition, and infectious bacterium that causes severe hard to treat cases of diarrhea and while antibiotics can cure a quarter of the cases of this infection in global trials, these transplants have had 90 success rate. Theyve been very effective at even v these treatments you are taking a Massive Community of microbes and putting them in a person was theoretically a diseased community. Even that doesnt work consistently fo for a lot of the other conditions ive told you about that have been linked to the micro biome like irritable bowel syndrome. Many trials of the fecal transplant and the results are less consistent because even here it is hard to reset. We are still in the early stages of understanding how they work like what determines who and why my micro biome is different than yours o or your us and ourn we can manipulate them. So how do we get them to establish themselves . Do we need to feed them to give an advantage, and how well they stand up against the immune system. There is still so much fine tuning we have to do despite the early successes in the field. At the same time, you are talking about these very subtle shifts and its a fragile kind of balance in the ecosystem with microbes and get what we do we think about using this antibiotic 80 we use are for farm animals, so that is just out in the environment over the place and then we have a lo hadf medically unnecessary use off antibiotics so we are manipulating the context at the same time. And i wonder you mentioned we could do more with vaccinations for sure