Pathogensof avian coming out of the middle east and the whole range of airborne pathogens, dengue, of mosquito borne pathogens, dengue, chikungunya, and zika of course. So the question i wanted to ask is how do Microbes Turn into pandemiccausing pathogens. You think of an microbe is a little thing with no locomotion, but it can cause these huge amounts of death and destruction. I wanted to look at that was a twopronged approach. First i looked at the history of one of our most successful pandemiccausing pathogens. That is cholera. It has caused seven global pandemics since it first emerged. The latest one is still going on off the coast of florida and haiti. With reporting from places where new pathogens were coming up. Went to places like new china and south china and new delhi to try to see how cholera could shed light on where these new pathogens might be going. Choleraearned is that emerged in many ways in the same way a lot of the new pathogens are coming out today. It came out of the natural environment. Cholera is a bacteria that normally lives in marine habitats. It lives in conjunction with days will clinton with a zoo plankton. Of cholera are full bacteria. Salty. Alf fresh, half this is where the major rivers are draining into the bay of bengal. For the longest time, people did not live in areas like this. They are covered in men growth swamps, tidily flooded twice per day, there are cyclones and tigers. People did not really live in cholerarich environments which all changed in the 19th century. The british decided to turn these into rice fields. Of 19 centuries, 90 of the aurea of the area is settled. And our bodies, it does not perform very you ecological function but it can kill people within a matter of hours. 50 of people infected will die if not treated promptly. It certainly into russia and of into the industrializing cities of europe. This is the same thing that is happening today. Of our new pathogens are coming out of the bodies of animals. It come in it happens when humans invade wildlife habitat, forcing wild animals to come in to our territories. From bats we have ebola, from monkeys, hiv, malaria, and most likely zika as well. Birds, we have the west nile virus, and others. Provide these new pathogens great opportunities to amplify which allows them to better adapt to prying upon human populations. We first started doing this the. 9th century people were abandoning farms and coming into the new cities for factory jobs. In places like new york and london there was not suburban transit to take people outside of the city to sprawl. In places like manhattan, there were 77,000 people crowded into every square kilometer. 1 12 of the city was covered with cesspools and outhouses. People were ingesting but two teaspoons of fecal matter every day which provided a great opportunity for the cholera bacteria to explode. Of urban expansion that started in the 19th century is really reaching its peak now. 2030, the majority of the populations will live in cities. I like stockholm or washington, d. C. Not like stockholm or washington, d. C. They will be cities like monrovia. About 2 billion people are expected to live in slums by 2030. New pathogens have already decided to take advantage of this process of urbanization. Consider ebola. We have had Ebola Outbreak since the 1970s, but it had never affected a place with more than a few hundred thousand inhabitants until 2013. Within a few weeks of emerging reacheda, ebola had three Capital Cities with a combined population of nearly 3 million. Why the major reason outbreak was such a huge concentration. You can also argue that sica is capitalizing that zika is capitalizing on urban expansion. Rarely infected people because it was carried by a forest mosquito that mostly bites humans and doesnt bite people very much. What we see now in the americas is being carried by a different kind of mosquito. This is a mosquito that has dramatically expanded its range with human, urban expansion. People andving near will breed drop of water. All of our plastic garbage provides perfect breeding sites. Unlike forest mosquitoes, egypt only bites humans. We are not only crowding people together, we are crowding animals together. We have more animals under domestication right now than in the last 10,000 years of domestication until 1960 combined. Huge numbers of livestock we are keeping right now and many live in these factory farms. They are basically the annual equivalent of urban slums. This similarly allows pathogens to amplify and change in ways that can make them more relate. Virulent intothe virus is dropped these factory farms where these captive animals are crowded together they start to change. They replicate and mutate. They become more virulent. We have had an increasing problem with these more. Went forms of influenza virulent forms of influenza. We have started carrying path annuitants pathogens around anymore efficient way. Steam travel. We started skimming across the atlantic and with clipper ships. Steaming around the rivers and waterways. We used steam engines to build canals and it connected all of our waterways together. We had this Nice International network which is perfect for cholera to take advantage of, which it did, again and again. The erieanal canal in particular. We do it even better today. Weh our Flight Network, dont have just a couple airports and capital but hundreds of airports with tens of thousands of connections between them. Spreadvery rapidly across the rest of the planet. So Flight Network is influential in shaping the epidemic, that you can calculate where and when an epidemic will strike next just by measuring the number of direct flights between infected and uninfected cities. A map that plus that same food pandemic i just showed you but this is a map of cities connected by direct flights. You can see that the flu pandemic resolves into these perfect series of waves. These are just some of the ways in which the way that we live allows microbes to turn into pandemic causing pathogens. We dont just take these things lying down. We put up political defenses and medicadefenses. It is only when political defenses fail that pandemics occur. In 1830 two, doctors in new york state collected this data that we know. It shows a pretty clear picture to us today. Cholera is coming down the hudson river and heading straight for new york city. Response would have been to consider a quarantine. Closed on the traffic on those waterways and protect the city. Nobody wanted to do that. Quarantine was considered too disruptive to trade. Said, it might look like its coming down the river, but actually its being carried by this was based on that0yearold theory diseases like cholera were spread to the smelly heirs that rose up just smelly airs that rose up these smelly airs that rose up from decomposing things. Violentlye were scapegoated during cholera epidemics epidemics. There were countries making money selling cholera contaminated water to 19th century new yorkers. The epicenter of the epidemic of cholera in new york was a slum called five points, pictured here. It is actually the subject of the movie the gangs of new york, if anyone has seen that. That slum was built on what was once a pond. It was filled up with garbage in the slum have been built on top of that. The ground underneath was very lowlying and unstable. The groundwater was easily contaminated by all of the leaky privies and outhouses on top of it. The company that the state of new york chartered to deliver Drinking Water to the people of new york, instead of tapping clean them a upstream sources of water, which the new would taste better and be cleaner, they sank their well in the middle of that slum. That water to one third of the people of new york. The reason that they did that is the same reason that people in flint michigan flint, michigan decided to change their water intake. They wanted to save money. They wanted to save money because they wanted to build a bank. Does anyone know the name of the bank of the Manhattan Company today . J. P. Morgan chase. The biggest bank in the country. Eventually, new york did move there well from the slum of five points up to westchester county. Cholera ended for good then. What is interesting is why they did it. They did not do it to protect the Public Health or because they throughout their theory of the air and decided that cholera was in contaminated water. The did it because the city brewers demanded better tasting water for their beer. Tasting water put them at a disadvantage. I think its better today, but we can do a lot better. The question is, will we find the political will . That is something i hope we can talk a lot more about. Thank you for listening. We have a great panel of speakers today. Our first speaker will be dr. Lipkin. For thee Director Center of infection and immunity at columbia university. If anyone has seen the film contagion, i will add that the scientist in that film is modeled on him. Dr. Lipkin i am also the john snow professor which is particularly apt given that so much of this concerns cholera. I was told about this meeting and i generally accept these invitations. I was told that i could just skim the book and i began with that intent, but i read it cover to cover. I thought it was a beautiful book. For those of you who have not looked at it yet, you saw a bit of an example. Au have burr versus hamilton, whole description of the London Underground and slumming. It is an elegant book. What ive decided to do today is something a little different, though i hope during the q a we can talk about some of the interesting aspects of the west nile virus, and mers, and sars, and talk about things that may be of interest to you and talk about sonias next book. That is the future of infectious diseases. The emphasis in this particular book is on the q diseases. The ones are associated with severe illness. Pneumonia, hemorrhagic fevers, things that kill us. Then we have these other disorders which are typically thought of as noncommunicable. There is a part in the book where you talk a little bit about this. The ways in which microbes have modeled us through evolution. The have contributed to our ability to become mammals by having an impact on whether or not another a mother will reject the fetus. What is a fetus but a tumor growing inside of us . There are retroviral elements that prevent rejection of the fetus. If you look at the genomes, they are riddled with retroviral sequences, and others as well. These have important impacts. When you basic sense, look at microbes and sells, what you are really doing is examining the ability of the body to recognize something as self or not self. We are always dealing with an onslaught of things that may represent nutrients or microbes. And developrow, this relationship we have had with microbes. There is a wide variety of these noncommunicable diseases which i will show you shortly, have an infectious trigger. They range from coronary disease, stroke, diabetes, psychiatric disorders like autism, autoimmune disorders like Rheumatoid Arthritis and many forms of cancer. Treated to cancers infectious agents may not be fully appreciated by many of you. Particularly, when you look at Subsaharan Africa and represents one third of these cancers. Most people who have cancer are under 50 years of age. Hepatitis b and c have human papilloma viruses. Here is an example of hepatitis b which causes a carcinoma. An infectious lymphoma also found in africa and human papilloma virus described as recently as yesterday as being largely eradicated as a result of vaccines. Hiv, cap are ceasing, lymphoma hiv, as you begin to look at these other infectious causes of cancer, as a think more broadly, it may be possible as we begin to think more bradley, and maybe more broadly, it may be possible to eliminate them. Preventableccine illnesses. We can literally eradicate human papilloma viruses through vaccination programs which means that we can probably eradicate cervical carcinoma, and many other forms of carcinomas as well. Most of the diseases that sonia be alluded to can probably prevented by using a variety of vaccines. These are diseases which are fairly straightforward to approach. Infection is likely to be implemented in a wide range of diseases of the cardiovascular system, including stroke and artery disease. Inflammation is the leading attribute. We now know that something as simple as bad periodontal disease can result in an increased risk of stroke. Ce times,y in the scien some of you may have read this article that appeared. To Donald Mcneil several months ago, when we started talking about autism. Then we started talking about microcephaly couple weeks ago i said, this is probably just the tip of the iceberg. Discuss, i to presented him some of the data that i will show you now. Disorder that we tried to model in mice. This was a disorder that has been associated with streptococcus and dramatic heart by ase first described british internist. What we found is, that there were a group of children who were thought to have schizophrenia, but did not have it. They had an obsessivecompulsive disorder which we associate with the sorts of repetitive behaviors such as you see here. Were treatedildren with a plasma to remove intravenousor an treatment, we were unable to remove the disorders. We could not identify the trigger. We replicated it by injecting streptococci and then went back and found these children were affected. This was worked on by our group in new york, and by paul patterson, who died a couple years ago who was at caltech, to look at historical associations between influenza viruses and other pandemics and stressful environments, and later occurrences of schizophrenia, autism, and other neurodevelopmental disorders. What we found is, if you look at the association of these disorders, it made sense. You would see, outbreaks or what looks like outbreaks of schizophrenia following outbreaks of influenza and other viruses. If you look some four to seven years out with autism, you would find examples there, too. We were able to model this with mice. That if you could examine mice that were halfway through the animals would be withdrawn in the cage, as opposed to the adderalls that has as opposed to the animals that had some sort of a normal just two thirds of the way through gestation, these animals become hyperactive, running all over the cage. Indicating that, what was important is not so much the infectious agents per se, but the host response to infection. The other thing that we have begun to learn a great deal more about is the micro biome. There is an excellent exhibit literally across the park at the museum of natural history. Here, we try to cover through the course of this, to understand something through that micro biome, the implications of disease. We have begun to understand now that the micro biome is important in tuning the immune system, is probably important in thinking about algae. It has a role in colon cancer, obesity, and cardiovascular disease. The flipside of the contagion hypothesis, sonia was talking , as a reciprocal relationship, we see that as we know longer have those risks, we see an increased risk of asthma and a wide range of other disorders. It is becoming clear that we cannot only think about pathogens. Have to think about balance between microbes and humans. Biomelook at the micro over the course of a lifespan, you can look at individual types of bacteria. The normal progression which we see here has become subverted by this modern life, where we formula feed babies, treat ourselves with antibiotics, we have obesity, and a wide variety of intervention, which has led to all sorts of outcomes which have a tremendous impact right andon the way that we live, the types of diseases that we begin to see. If you look at the composition the gut microbe biome microbiome, it is still very different from the fiberrich diet that you see in africa. There are consequences of this. We have begun to see the appearance of diseases associated with some of these bacteria which are killing people. We have been unable to eradicate these now with modern antibiotics. Fecal beginning to use microbiota transplants as a way to address these problems. Because there has been so much success of treatment with using these microbiome transplants, people are beginning to use them for a wide variety of other applications as well. I am not advocating this, but that thereting out are theories they can reverse autoimmune disorders, irritable bowel syndrome. Their efforts to use it to treat multiple sclerosis, autoimmune diseases, as well as some form of colon cancer. , as youorward, sonia begin to think of what your next book. Not to say that we have resolved all of these issues with respect isacute infectious diseases, important to think about ways in which we can bring microbes back into balance, when we can begin to understand the role of microbes and our responses to of a widehe genesis range of disorders ranging from autism to cancer. [applause] ms. Shah thank you for that, after lipton dr. Lipkin. For my next book, he has already done an outline. Doctor whost is a was one of the great sources for my book pandemic. If you pick it up you will see there are a bunch of pages about him and his fabulous work which he will share with us. Thank you. About this book that other authors have not touched on is the repeated cycles throughout history we have gone through with pandemics that we are still in. We aree the point today, still doing the things that led to cholera around the world. We think about these issues of these badd lives, and conditions as being over there. But we are connected to everywhere on the planet by less than a days flight away. That is what microbes do. The exploit new niches that we put up, adapt, and infect us. We created this perfect system. I would like to hope we are at the end of it. I would like to propose in a more positive and optimistic way, that in 50100 lets think about the ways we can Work Together to get rid of the pandemic trap. Then we can deal it other issues we are discovering. All, i am in an organization, a nonprofit in new york. We work on emerging diseases to try to understand what drives them and what are the underlying causes of pandemics. What is the Science Behind it . Can we prove something is attached to the driver of a pandemic that leads to the spread, and then can we do something about the driver . First of all, we need to know if they really are a big issue. The book lays it out clearly. What is the science, the real evidence that emerging diseases are on the rise . A few years ago, probably about a decade, a group of us sat around and studied this. I had just finished working at cdc. I was working on wildlife diseases, including a global the emerging disease of frogs that spread globally that wiped out species. Even more significant in the 19