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 but what does it m mean when we are attacking microbes in the grand scale at this level how does that sort of provoke the more virulent behavior . When antibiotics came out in the 1940s, it became widespread. People were like game over. Wevee done it and get even the people who discovered were like whoa, whoa these things could stop working because of evolution, because the bacteria are evolving really fast and you could end up with bacteria that are resistant and unfortunately nothing really happened. There was no resistance crusade back then and now finally they are coming to terms with more and more resistance and its a struggle because we dont have a lot of new drugs in the pipeline. So we are starting to see over the horizon the situation where you are going to have the period that arpurecode that are resisto everything weve got so if you iget infected with it and they can figure out combining the resistance genes is going to be nothing people can do for youhi and already its been estimated maybe 700,000 people around the world die of antibiotic resistant bacterial infections and that could go up unless we do something. Again, i dont mean to be a dark cloud in your day, but its like the same of smallpox we can do something abouthi this. We are smart and if we show some dedication we can solve this problem. We got rid of smallpox. We can solve problems and this is a problem that is solvable. There are clearcut things we can do if we can overcome resistance so for example, stop using antibiotics on farms. Theres a huge resistancthere io that because understand farmers like to give antibiotics to farmers give you good animals, they get bigger because of the micro biome and they get bigger, more meat, more money. You have to set that against the colossal cost of treating the illness from antibiotic resistance which is being part of these farms and we need to be more creative and one possibility is the viruses. Ed mentioned there are these viruses that affect bacteria into the rediscovered over 100 years ago and actually doctor who discovered them found them in people who were dysentery and he realized he could actually cope with the dysentery bacteria with these viruses and he said this could be a drug so actually incredibly people forget this but in the 1920s, you could apply powder with these viruses in it. It was being massproduced and it was quite popular. Antibiotics came on the scene and were moreti reliable and tractable because they were just chemicals that almost arrived with viruses and so there was a shift. And really the only place where this kind of approach continued to be used within the soviet union so in world war ii soldiers are getting wounded on the battlefront suffering from infections and being treated with therapy getting viruses and enand in some cases it i is wor. Since the fall of the soviet union, some of those people came to the United States and have been with scientists here trying to sort of bring therapy back into the American European medicine and its been very slow. You cant be 100 sure the viruses you are using are going to kill the bacteria that you want to cure. But there is some progress and some major trials going on now in terms of treating people with infections from burns and so on and the idea is that instead of just one chemical, you have a virus and you can do lots of things like engineer them so if the bacteria start to evil resistance you can do experiments and get them to devolve to do a better job or maybe you can just put an extra gene to help them break up the bacteria that forms. You can engineer the viruses. Theres Research Going on now so thifor this is the kind of creativity we need to fight this fight. It is worth noting that antibiotics have been such an incredible boon to our health. They save so many lives, but we use them badly sometimes and there are costs to that. Antibiotics resistance among infectious bacteria is one cost. The bacteria that we rely upon is another because antibiotics are unsubtle weapons. They are not precise. They destroy the bacteria that we rely upon whether it causes harm. So they do shift the micro biome. A lot of people look at whether those shifts can harm our health, how longlasting they are, they have resilience and often bounce back. But too many an to many and thet problems. Thats actually why we see this happen. They are almost always caused by antibiotics wiping out the Creative Space for this to take hold. So, people often ask me whether this claim is a bad thing. Dont think so. We shouldn should demonize the. Actually, the bacteria that we rely upon is very much the same as protecting us and scaling back on the use of antibiotics and using them judiciously so that leaves them when we need to end only when we need to come and that involves everything from the cultural shift to win there are doctors prescriptions to technological shifts, being able to guide us o play it is as early so if you have a viral illness for instance it doesnt do any good then. The micro biome i think is interestingnt applications in solving the antibiotic crisis. Antibiotics largely our microbial weapons, they are tools bacteria evolved to destroy each other in competition because after all it is their world. And we mind those weapons and we did such a good job that they picked all the low hanging fruit and stopped being able to discover the new ones very easily. But perhaps the human micro biome that live in our bodies might be a potential new source. A few months ago i wrote about a study how a new potential antibody was discovered among our nose bacteria about i think Something Like eight to 10 of people. This one that makes a chemical that seems to do verysp well against the microbe behind mr essa. So it might work and it mit not. Theres a lot of work that needs to happen before these things go to clinic. But the critical point here is that our bodies are battlegrounds. Theres a competition between microbes and some parts of the body in tha that competition mie especially fit so there are the places we constantly shove food down so we bombarded the nutrients. The numbers unless they were getting very weird no nutrients they are so they have to be very competitive and maybe those are the places they need to look for the next generation of good antibiotics indeed a nasal microbe. And i think this is the type of thing that you can get when you think of humans and other animals as the ecosystem as more than the individuals that we are and think ecologically about what part of the body has come to shed going to be the fiercest among microbes and where are we to find tomorrows drugs. Theres a part in your book where you call it a rain forest and the nose is like a desert. We have a few minutes for questions and there are two microphones set up. So i hope you will come ask some questions and when you do, just say your name first and then make it a question that we will also take comments, too, right . And basically fight it off. But that masks a lot of hard work that goes in to make sure that therd vaccines affect population so not with smallpox to involve figuring out where smallpox was in the world they go out there to collaborate withra Community Leaders to take vaccines on horseback into the remote areas to get the very last cases until you get the very last cases it is not over. That is what we are doing with polio. We should been done ten years ago but it is enduring and unstable places like pakistan and nigeria. And then you get killed by the taliban as a way of part of their political campaign. The virus doesnt care. There are builtin problems with vaccines also in the sense that a true virus is a paid in the neck because it is constantly churning evolutionary every Year Communications are arising mixing and matching doing their own biotechnology and you get a new strain every year. The scientist making the vaccines many are still using the basic technology of 19 fifties trying to grow it in the chicken eggs and that takes months so they have to guess in advance we are entering the flu season right now and the vaccines we decided on most of them we have to hope they got it right and a lot of times they dont so theres a situation what we really need ultimately to suggest beyond a vaccine that just targets what changes rapidly the target the parts that change never and that are essential to the flu virus the dream is to make the universal flu vaccine you get the booster once like other vaccines that would be great but we are not there yet. I have a question about the incorporation of microbes into the genome. A few years ago when i was in college i learned that it isnt just pieces of dna but actual cell types or cells one is the mitochondria the other were white blood cells that could be microbes at some point how might that have happened . The mitochondria is definitely right. All of our cells contain these little structures called mitochondria the shape things that provide us with energy they are essential foror life and they used to be bacteria it is domesticated bacteria working their way into the ancestral cell. That much is absolutely clear. One really interesting thing about the mitochondria there is some debate of just how important their origin was to all of us. Sometimes it is believe the origin was in fact the carrier the lineage of animals and plants and fungi all those contained mitochondria in the volvo only once and perhaps the reason for that singularity even though we turn them two differenttu structures because of the primacy of my dough condrey a that single probable event was critical to allow life to escape the confines to develop larger genomes and again we are talking events of billions of years ago but looking at the origins of mitochondria they were bacteria all of us carry a within our bodies. And the white blood cells are just ourselves. What is interesting when you look at them under a microscope is interesting how they forage around thats very reminiscent of single cell like a protozoan they roam around like grab bacteria. There are some ideas that the behavior of the white blood cells adjust using very old jeans from our ancestors and sniffing around looking for bacteria isnt much different than in the soil. I like that idea the slime mold sniffing around. Thats a great image. [laughter] i recently have a friend that join the peace corps shes not used tose the bacteria shes on seven rounds of antibiotics so what are your thoughts of the long term consequences in a short amount of time . It is a tough break the military is investing a lot in this research because of that problem like travel associated diarrhea and its is hard because if you bombard the body with heavy doses of antibiotics you do run into problems like c. Diff. Sometimes we dont have Better Options unfortunately but there are emerging signs the micro biome will have different ways the existence rather than using the brute force approach. Can you speculate on the possibility of change of mitochondria entering our bodies or pandemic to change the species or the differentiation and if thatss possible what it wille look like for integration to change us or split off. I can work with this. [laughter] so talking about a new species if you split it into so with that process a lot of it is driven and nature with those populations not to compete successfully. And where you fool around with the micro biome there are some cases where one could have dropped a new species so imagine theres a new plague people get sick and you can only have kids with other people that are sick with it now all of a sudden you are diverging now keep that going for 100,000 years you have a new species. Just wait. [laughter] and i want the credit. [laughter] i have a question regarding antibiotic use. More specifically in regards to feeding it to livestock and cattle given that is most likely necessary for production of meat that we produce that would retake a lot of research we will lose the habit of meat eating anytime soon so is there evidence showing in slaughtered meat of the for cattle, do you find those antibiotic molecules in significant amounts that can affect humans . It doesnt work like that. These animals are fed antibiotics they are healthy they have the micro biome and these antibiotics challenge every bacteria that encounters them so now they have a challenge if there is a mutation they could survive if not then they die so over time that will foster the evolution of the resistant bacteria and now we are talkingng about bacteria. You should not be eating meat from an animal gut you can have Serious Problems and we dont have that problem. The problem is they release the bacteria into the manure that gets into the water andnd the soil they trade the resistance genes with other bacteria and they just become part of the pool of resistant bacteria. And we put so many antibiotics into these animals it is a tremendous factor in the lives of antibiotic resistance. Thats how it happens and why we need to put a break on it. So you say it is 40 percen 40 percent, so do you look at because it is so prevalent the species that do not get it inwhy . And for example . Thats a really good question. I dont think we have a good answer for that yet we are still trying to understand what makes it so good at spreading from host to host and why in some and not others . It is in some worms that come from a different part of the Animal Kingdom which is also interesting to us because they kill diseases but yes theres more that we dont understand. Why is it so good from jumping from host to host . Is it just because of the population and it jumpsbo horizontally from one host to another . And these are all questions there is a big conference it happens every couple years with a great thriving area. Cow poop tom slime mold thank you for coming we are out of time. [applause] [inaudible conversations] good morning, everyone. On good morning everyone i am joann myers i would like to thank you for beginning your morning with us we are delighted to welcome cspan book tv to the reckless program discussing his book the next pandemic as a former Director Office of Public Health preparedness at cdc he has been on the frontlines to contain the worlds deadliest diseases but not the first to have done so throughout history fighting diseases waging a never ending