Demystifying Medicine 2017: Global Warming

There are enough new faces that i have to explain the logo and those of you who have heard this many, many times just relax because the best is yet to come. So do you know what this is? What is it? Come on, diane. The brooklyn bridge. Now, it’s the most famous bridge in the world. It’s the first suspension bridge. And it’s the logo for this because it illustrates what the purpose of this course is, which sort of bridges advances in basic biological and engineering sciences with huge problems in human health. That is new york on the other side. You’re over here in brooklyn, and we are the people standing on the catwalk. And we’re going to be treated to an extraordinary experience this afternoon in discussing several major, major issues which we don’t discuss every day or with great frequency even here in the united states.

The other important thing in the logo is that life is never the same on either side of a bridge once it’s built. The farmers in brooklyn thought they were going to cause deterioration of the neighborhood, and those in new york thought the same. Instead we have two vibrant incredible cities filled with all sorts of stuff. I won’t belabor the point. Now, bruce ames, who was a friend and a leading micro biologist, i think had a talk given here at the nih quite a few years ago, he made this comment, that the battle on the surface of a cabbage is more violent than a war between men. Of course what he was talking about are all the things that live on the surface of the cabbage and how the cabbage survives in the face of lord knows how many different kinds of bacteria, fungi, you name it.

So the cabbage has defense mechanisms against it. This was in an era when the discovery of drug-resistant transporters, proteins, mechanisms, was really in its earliest. So in thinking about today’s topic, a couple of thoughts came to my mind which i’ll just throw up here and maybe for those who don’t think about this particular topic very much have your own ideas. At any rate, today we’re going to have a discussion of wildlife diseases, natural products and global warming. So .1, all living things have evolved and sustained chemical mechanisms to protect against predators and sometimes those things are what are necessary for their own survival. Biology is filled with this. Even most recently, i read that a scientist at mit had discovered that the round worm actually se secretes a bioacid, which is what protects it against predators.

Who would have ever dreamed that? At any rate, it goes on in many different species. The other important generalization is that many, and i’m not qualified to say most, but i suspect so, but many effective clinical drugs in cancer, infectious disease, think antibiotic, and others, are derived from natural products. Many different sources. These sources can be plant, they can be microbial, et cetera. Then a big question came to my mind, and maybe we’ll have some consideration of this, in the genomic silicone imaging era, where drugs and structures are put together with the aid of a computer, have we reached the end of the line when it comes to natural product searching in the natural environment. And we’re going to hear from an expert about this. Now intraspecies disease, including us, are transmitted by viruses, bacteria, fungi, and they can involve insects and other vectors, all of whom have their complicated lifestyle and requirements, environment and so forth, so a huge question is, how is the changing world, global temperature, oxygen deprivation, pollution of different kinds, and this applies below the water as well as on the surface, how has this changed these paradigms above, and where do we stand regarding this? So this seems like a very excite exciting arena to discuss, and we’re very fortunate to have two individuals who have a great deal of knowledge and experience regarding this.

So i’ll introduce both of them. Our first speaker is going to be jonathan sleeman. Jonathan graduated from the university of cambridge in zoology and veterinary medicine. He eventually came to the united states, i believe in around 2005, where he was a wildlife veterinarian here next door in virginia in the department of game and inland fisheries. Somewhere along the line, he did studies involving the guerillas igorillasin africa and their environmental problems. Maybe we’ll hear something about that. And in 2009, john went to the united states geological survey. He’s the director of the national wildlife health center there, part of the department of the interior. Now i always thought that geological survey were the people who just made maps.

When i first met jonathan in caskazakhstan of all places, there’s a lot more to it and we’re going to hear a major part of what’s more to it, because as you’ll see, that branch, of which he is the director, plays a major role in wildlife health and in mapping diseasings, diseases, et cetera, et cetera, in wildlife throughout the country and in conjunction with others around the world. Our second speaker is david newman, known to many of you. David also comes from the other side, if i can find my notes here. So david has a broad training, he has an advanced degree in organic chemistry from the university of liverpool, a ph.D. Degree in microbial chemistry from the university of sussex, and then later on, acquired a master of science degree at drexel university, when he got in to information science, which is where some of his work is now. Dr. Newman is well-known here at nih because he was the scientist and chief of the natural products branch of the nci at frederick since 1991, until the time of his, i guess, semi-retirement or whatever you call it, is that correct? And he’s interested in natural products as a source of pharmacologically active peerl, both marine, microbial, natural product toxins, which can be developed for therapeutic range, metals, and a whole range of interactions at different levels of biology.

So we’re going to look forward to both of their presentations, and jonathan, if you would, please, begin. >> thank you, win. Thank you very much for that kind invitation. It’s a pleasure to be here with you this afternoon. It’s kind of interesting, when i first met win and others, it was as he mentioned a workshop on kakazakhstan on climate change and biodiversity. Of course they came from the perspective of looking at natural products for drug discovery. Our interest was more in terms of climate change and drivers of emerging disease and impacts on wildlife and conservation, but it was clear that we had a lot more in common than differences in terms of interest in biodiversity. I hope to illustrate some of these things in my presentation today, which is really a focus on the importance of biodiversity to human health. When we first met also in kazakhstan, it turns out we’re both from the same hometown? We went to the same primary school.

What’s of most interest is we went at the same time. This is an exercise in aging. [laughter] so what i’ve got for you this afternoon is i’m going to give you a little overview of the drivers of emerging disease, different environmental factors causing these diseases to emerge. I’m going to talk about some of the examples of emerging diseases. I picked three. One is purely wildlife disease, very good illustration of some of the impacts of environmental disease. Hemorrhagic disease, bluetong viruses, avian influenza, the bats and disease, and then to end, i’m going to talk about the one health approach and perhaps some of the things we can do to help manage and prevent these things from occurring in the first place. It’s kind of interesting, you look back in the literature in the 1950s, the 1960s, there were very few publications on diseases of wildlife origin. It was very much a neglected endeavor scientifically, they weren’t really considered important in terms of impacts on wildlife populations.

There weren’t that many examples of zoonotic diseases, maybe rabies and others. Around the same time, it’s inlikely that he said this quote, dr. William stewart, the surgeon general back in the 60s, but i think it reflects the sentiment of the time with the advent of antibiotics and vaccines that we very much had won the war against infectious diseases and we should shift our focus to more chronic diseases like cancer, heart disease and so forth. I live in madison, wisconsin so i’d be remiss not to mention al dough leopold, founder really the modern wildlife man amongment here in north america, the almanac, seminal publication on wildlife conservation. He was prescient in his understanding of the role of disease in wildlife populations, as well as the importance of the environment being a major factor in causing disease emergence in the first place.

So fast forward several decades and i think we can agree that the book on infectious diseases had been largely dusted off. We’re living in a global environmental situation very much favoring emergence of new and novel diseases, mostly infectious diseases. And what’s of particular interest to us is the fact that many of the diseases that are emerging have a wildlife origin or a wildlife connection. I think 60% of emerging diseases are of animal origin, of which 70% of those are of a wildlife connection. Again, i think there’s general consensus that these drivers of diseases are largely a result of human activity, probably the biggest category, and we’ll talk about this in the examples, is laplandscape change, changing farming systems, bringing mild life, domestic animals to humans, encroachment of humans on wildlife habitat, exposure of species they hadn’t been previously exposed to. As for climate change, i put it in this category, again, we’ll talk about some of the changes of severity and distribution of diseases as a consequence of climate change, and a picture of the polar bear up here in climate change.

Do you know why? So it’s the first species to be listed as endangered as a consequence of climate change. The satisfy pack ice uthey’re no longer hu nting on the — they moved inland and they’re scavaging, hunting on birds and other species, and we’re seeing some health effects as a consequence of this. As well as they’re getting into more conflict with people, living on this land, so it kind of interesting that the ripple effect. Human demographic and behavior changes. 2007 when we — mostly rural communities to most people living in an urban environment. Increasing urbanization having an impact. Also the issue and constant concern about deliberate release of agents as bioterrorism, weapons. Most also have some wildlife connection, plague, actua tularemia and botulism. I think for me the biggest category is global travel and trade, the movement of people, the movement of products has broken down those geographic barriers used from diseases to jump from one continent to another, we’ll see some examples of that. These microbes of biological organism, they undergo evolution as a consequence of selective pressure, so we’re seeing changes to genetic structure and behavior, probably the biggest example is multidrug resistant bacteria.

Again, there’s some predictions with some of the common antibiotics will no longer be useful in the next 20 years. But some of these organisms undergo evolution of change, influenzas, drifts in the genetic structure — shifts of — where they form different subtypes. This may seem like an odd category, but lack of infrastructure, if you don’t have the surveillance systems, we don’t have the mechanisms to respond, the research, these teases, outbreak, consequences tend to be more severe. We see that when we get in wars and famines where there’s breakdown in public health infrastructure, but also we really lack the same type of infrastructure that we have for public health and domestic animal health for wildlife health. We don’t have that sort of network of laboratories across the nation, we don’t really have that capacity to respond quickly to disease outbreaks and i think as a consequence, we all tend to be behind the game and kind of play catchup when we see these disease issues. I probably don’t need to explain to you the impacts of these diseases.

Several examples, want today go beyond the public health impacts but one of the best examples unfortunately is hiv, which is now known to be a mutated form of the simeon — probably spilled over from hunting, butchering of primates in africa, and there are now estimated to be 35 million people liveing with hiv infection globally. Also had an impact on food security. 400 million poultry culled since 2003, 2005, in efforts to control outbreaks of highly pathogenic influenza in some southeast asian countries. Recognized as the — the biological and ecological consequences of these diseases. They’re now causing some premarked declines in populations, some of these have very important ecological roles. Probably the best example is colony collapse disorder of bees, major pollinators in some areas of the world where plants have to be — crops have to be hand-pollinated.

Here in north america, how many of you are familiar with white-nose bat syndrome. A plug for us, so we still don’t really understand what colony collapse disorder is caused by, it may be multi-fak to recall, usda is very much trying to research that. Usgs, we figured out the syndrome within six months and we’re much better than usda in these types of investigations. Kind of an interesting graphic, kind of shows the types of diseases that we’ve investigated since our foundation in the 1970s. You look at the top line, diseases like avian cholera, avian botulism, they can cause a fairly large die-off but they’re not a human disease, not an agricultural disease, doesn’t really have economic impact. Remain confined to a specific geographic location and don’t really threaten the persistence of wildlife population. Where if you look at the diseases since the 1990s, especially the number of new diseases popping up, seems every two or three years, we’ve got some new novel disease to address, amphibian diseases in the 1 1990s, west nile virus, monkeypox, 2003, chronic wasting disease in 2002, and the avian influenza outbreaks.

Actually now dealing with three different fungal infections. United states has the highest biodiversity species richness of salamanders in the entire world. I think the consequence of these diseases are far more severe, they spread very rapidly across large geographic areas. Defex in new york in 1999 to the west coast in 2003, within four years. Causing large scale population decline. Amphibian diseases, can also cause distinctions. White nose syndrome, some species are predict today go locally extinct in the next tweb years. There are also increasingly public health and agriculture actual disease. Avian influenza, i think being the classic example. So i think increasingly we’re having to work across these sectors to address these issues of mutual concern. I’m going to give you a few example of these diseases of wildlife origin. For example, i have to illustrate some of these drivers. I’m going to talk a little about the dichotomy of wildlife in that they’re obviously the origin of source of these diseases but they’re also impacted by these diseases and how can we kind of balance those two different almost competing interests finally talk about the one health solutions we look to implement.

So climate change. So the intergovernmental panel on climate change published a report in 2007, predicted unprecedented rises in global temperatures, rises in sea level, and changes in precipitation pattern, not just global warming but entire change to the climatic system. Will have significant impacts on animal and human diseases, and we are starting to see and have seen for a number of years these particular impacts. They’re having some profound impacts on the geographic distribution of diseases, the incidence of disease and some of the severity of some of these diseases. So we’re witnessing changes in geographic change, higher latitudes and altitudes that previously didn’t exist. We’re seeing changes in plant and animal phenology. This is having consequences not just for wildlife conservation but also in disease transmission, tick borne diseases. We’re seeing some direct effects of these climate change, heat stress in moose in minnesota, where they’ve evolved to survive in a much colder climate and cannot cope with the increased winter and summer temperatures. We’re seeing changes in the virulence and genetic diversity of these organisms, particularly for example like west nile virus, we’ve seen evolution of new strains of west nile virus that are far more severe, far more pathogenic.

And we’re seeing some changes in patterns in these diseases and we’re going to talk about some of the impacts of climate change on coral reef and declines of reef ecosystems. So i mentioned the disease i sort of want to use to illustrate the impacts of climate change is so-called bluetong and hemorrhagic disease. This is mainly a disease of agricultural production and also a disease of wildlife. It’s caused by — viruses and transmitted by culicoides midges. Mostly a disease of late summer, early fall. High outbreak, causings o causes of very acute disease, domestic and wild reuruminants, marked edema, causes a cyanosis, t ab mall can’t breathe. Animal can’t breathe, edema within the eyelid. They can die within 24 hours of the development of clinical signs, it’s a rapid disease. The classic presentation is they get a very high fever, they often congregate in water sources so you get these sick, dead deer and kind of conjugation in ponds. You may hear about it every few years, they get some fairly major outbreaks.

Actually quite common here in virginia, c.D. Area. It’s also a disease of sheep and goats and cattle. We’re starting to see dramatic extension of the virus in europe. It used to be confined to the mediterranean region. Several years ago, in 2005 in particular, they started getting outbreaks of bluetongue here in central and europe and into england, great britain, scandinavia. Around the same time, we’re starting to see changes in distribution of hemorrhagic disease here in the united states. So it was confined actually right here the sort of m.D. State line, it really wasn’t seen much further north than this line but now we’re starting to see outbreaks up here in wisconsin, up here in new york for the first time in 2007.

Starting to spread further west. Serotype 6 was found in the u.S. A few years ago. Now we look at the map here, this is showing that the change in average surface temperatures of europe, what you can see is actually northern europe northern central europe, has increased to the warmer pace than the rest of europe. While it’s correlative, we believe that this warmer climate is allowing these vectors, allowing them to transmit the disease, — the viral load in these — also higher higher population levels of these vectors because of life cycle of these vectors. Strong evidence of climate change and geographic distribution. What we believe is novel stereotypes — travel and trade in emerging diseases — try to get more data, we did a study where we looked at hemorrhagic disease here in the united states to see if there was any correlation between incidence of the disease and different cla matic factors.

In addition to causing acute disease, it can also cause a chronic infection, and one of the primary signs — i don’t know how many people hunt deer in this room. If you hunt deer, you — this interruption in the growth of the hoof, so when they get the viremia and when they get the fever, it causes lesions in the coronary band of the hoof and cause as split. Sometimes the hoof can actually split off. So this, and the growth rate of the hoof, if it had hemorrhagic disease one year, by the time you see it next year, it would have grown out. So it actually turns out to be a very good measure of incidence, where we can measure the number of new cases that happen each year. And so we collected data at game check stations, where hunters bring in their game to have them checked, we were able to measure the percentage of deer that have these hoof lesions, and we did some analyses to look at the incidence of hemorrhagic disease, summer temperature, precipitation patterns and so forth.

What we found, and this is just a graph showing the incidence or the percentage of deer that have this cracked hoof leagues, and what we found is the years that we find this higher incidence, higher winter and summer temperatures, as well as the years that have lower rainfall. What we believe is these high summer/winter temperatures increases vector — allowing them to transmit the virus at a much higher rate and viral load as well as increasing the abundance of survival and — frequency. What’s interesting is summer rain fall, what it probably is doing is improving increasing the bleeding site of these mid midges. When you get — condition, you get the receding of the water line. This exposes the — that’s the prime breeding grounds, muddy flats. So what we think is happening is it’s improving habitat for these animals, for these mijs to breed breed. Hot, dry summers, they may be stressed and more susceptible. So i think it’s a great illustration from the complexities and some of the consequences of climate change on disease incidence and distribution.

The next example i want to touch upon is avian influenzas, probably more familiar to this group but as you probably know, wild birds are the natural — the oral type a influenza viruses. They’ve been isolated from over 100 different species of wild birds, but mostly water fowl, ducks, geese, as well as the shorebirds. You probably know the classified classified — they’re also classified into low pathogenic forms and high pathogenic forms based on their ability to cause disease in poultry, and that does not relate to their ability to cause illness in people or in wildlife. The public health significance, the progenitors of all the pandemic human viruses that have the been identified so far. These are schematics of the different genetic structure of the flu. They all have an avian origin, but it turns out the 1918 spanish flu was a pure avian influenza virus.

Both have large economic costs. As i mentioned earlier about the effort to control h5n1 in asia cost up to $12 billion. To those economies. Last year there was a large outbreak of — influenza here in the united states that resulted in about $4 billion in economic losses, both from trade restrictions on poultry products as well as efforts to control the disease. Southeast asia — h5n1, h7n9, kind of interesting, low pathogenic — poultry, but causes human disease, which is a very unusual property. H10n8, h5n8 and so forth. Highly likely as i mention, it’s a farming and market system particularly in china that are driving the emergence of all these new strains of avian influenza. This is a map showing distribution of water fowl populations in china. As you can see, they overlap quite nicely. A lot of open farming systems in china where they raise these poultry, the rice patties w they where they can commingle with wild birds, they transport these chickens to the markets live, slaughter them on the spot, again increasing human exposure. So there’s very much this kind of farming and market system that’s driving is semi tem.

The system. The challenges, these viruses have not just spilled over from water fowl to poultry, they’ve spilled back into wildlife populations. And there were over time these birds have evolved to where they can carry these viruses over large distances. One of the main projects my center has been involved with is the surveillance for avian influenzad and wild birds. We’ve been doing this since 2005. And then actually in 2014, we detected a high pathogen h5n8 in north america in wild birds for the first time. Timing in disease dee coincides very much with migration pattern, and we were able to demonstrate these water fowl could be asymptomatic carriers of these viruses. If you look at this map, you can see the specific — overlaps east asian flyway, likely these birds pick up the viruses during winter, in southeast asia, then they comingle with north american species for breeding, then migrate back south and cause these outbreaks. About the same time that we were having an outbreak, south korea and japan also suffered some outbreaks, in wild birds and in poultry in their countries.

Sure november when we did phylogenic analysis, it was found that all 8rna segments were greater than 99%% similar to the group a 2014 south korean h5n8 strains. It was the first time a pure you’re asian strain had been found. As i mentioned t went on to spread very raptly across the country, causing some pretty large poultry outbreaks. You can see here this virus crossed centimeter the eur — asian strains — you can see here all the north korean samples. We do a lot of wildlife outbreak investigations, in 2013 there was a large die off of harbor seals up in new england. Turns out they died from the h3n8 influenza virus. Infection — again, when we did characterization of this virus, it turns out to be very similar to a virus — north american water fowl, but have mutations indicating its adaptation to ma mammalian hosts. As you know — hypothesis, you get ai avian viruses and human viruses intermixing in a host like pigs and that’s how these viruses recombine into these pandemic bonds. Actually i wonder, this case illustrates the sort of role of the call it direct pipeline of viruses, where this is perhaps more frequent and more common than we thought previously or historically.

Again it illustrates the dichotomy of wildlife. A lot of people regard them as villains, the sources of these disease outbreaks, the source of human pandemics. They’re also equally impacted on human virus. Turns out that raptors are highly susceptible. Also raises concern again in my wildlife background, you know, about safety of consuming of water fowl from hunting activities, raises questions about public perception of water fowl, participation in recreational activities related to water fowl. It became quite a controversial issue, blaming the wildlife for these outbreaks. I’m getting to sort of the conclusion of my presentation but i found this nice little quote from this publication looking at biodiversity of influenza, emphasis is — rather than pointing fingers about who’s to blame is, let’s focus on intervention roles where we can sort of allow wildlife, humans and domestic animals to coexist. For aif van influenza, improving biosecurity at poultry farms and markets, they’re always going to be carriers, but finding those routes of transmission and focusing their efforts on that, i think is going to be the most cost-effective control method finally bats, fascinating creatures as far as i’m concerned, with you fascinating from a public health perspective in that they seem to be the source of some of these major emerging viral infections.

Corona viruses, sars, mers, nipah viruses, hendra viruses, ebola virus. Raises a question about what’s unique about bats? Is it simply their biodiversity? They’re the second most biodiverse group of mammals behind rodents in about 1300 species of bats out of about 20,000 species of mammals. Or is it something unique about our immune system that allows us to coexist with these viruses? So a lot of questions being raised about the role of that. Doing research on thee diseases to see if we can develop a vaccine to vaccinate upstream. Rather than coming to prevent the spillover of these viruses,; hopefully we’ll be able to extend it to some of these other diseases. Also trajly tragically again bats are victims to these diseases, what makes them unique also makes them prone or susceptible to some of these disease threats. I think all of you have heard of bat white nose syndrome.

We discovered it in 2006, 2007. It’s characterized by large scale die-offs, you can see the bat carcasses littered op the cavtered on thecave floor, as well as the growth of this white fuzzy material, hence the name white nose syndrome, but you can also see it on the unfurred, non-furred parts of the body. Turns out this is a fungus, newly described fungus that’s never been described previously. It’it’s also the first time a fungus in this genus has been recorded as a pathogen of a vertebra. So it’s a completely new group of pathogens. Like many times with something novel like this, it took a while for the scientific to accept this was the actual etiology of the syndrome. Primarily pathogens, athlete’s foot, it’s irritating but it doesn’t kill you. There are also some other examples. It turns out these fungi are not just remaining on the superficial layers on the skip. Skin. This is a cross-section of a wing of a bat. You can see how the fungal — invading deeply into these tissues. It’s a very invasive fungus.

Here’s the bonus points. Whrwhat else do you notice about this? Are there any pathologists in the room? If you get this, you’re a genius. So there’s no inflammation. Normally when you get an invasive — you’ll see inflammatory cells, so either this fungus releases immunosuppressive factors or these bats, because they’re hibernating, their immune system is naturally downregulated or suppressed. So this fungus attacks in a very vulnerable part of our life cycle. We’ve proven this is the actual primary cause. We’ve done experiments to demonstrate how it actually kills the bats. What happens when you get these severe infections — you get a lot of water evaporation, as well as salt imbalances, very high hyper kalemia, which can cause physiological disturbances, also causes them to — body fat, they go foraging for insects in the middle of winter, when there are no insects around, that’s why we see these large scale die-offs. What was kind of interesting, we started publishing our findings, we got contacted by colleagues in europe saying hey, we’ve seen the same thing in europe but we haven’t seen the mortality impact.

So they sent us some samples and we sequenced them and they were the exact same fungus as what we found in north america. Except what we had in north america was a single species, a lot more die strers nit europe diversity, so what we believe is this is a european fungus that somehow has been brought over into north america. That could be why bats in europe don’t suffer the disease and we still don’t really know. There’s a couple hypotheses. One is bats behave — the larger body species in europe, they also congregate in small ur groups so we think they may be more resistant to the fungus, they may have evolved with this organism. Several thousand years ago, there was a layer with a large number of backbones. They somehow underwent a mortality event a long time ago and these are the remnant population. But it’s certainly true population density in europe is a lot lower than it is in north america. So that’s a couple of theories, but this ability of these pathogens to jump continents, hitchhike or piggy back on people and equipment, products and so forth.

It’s had some pretty major consequences. This is also a great illustration of some of the economic illustrations of biodiversity. Bats are primarily predators of insects, they provide very important ecological services. They’re said to be able to consume their body weight in insects every evening, so tons and tons of insects are removed from the environment every night when they emerge from their roosting areas. And they’re probably going to have — lots of bats are going to have ecological repercussions that we probably cannot predict. There may be some human health effects, increased abundance of vectors of disease as a consequence. We do know there’s going to be agricultural and economic impacts. They pervade a lot of — destruction of crops and forest products, and we did a study to show that bats contribute up to $50 billion to the u.

S. Agricultural economy to the insect control services alone. Now we’re going to see increased use of pesticides as an environmental consequence as a result, so coming back to the main theme t illustrates the biodiversity, human health and well-being. So how can we coexist with bats? The villians, the source of emerging diseases and also the victims. I just want to walk you through this nice little study and this story. I think it points to some of the things we did k can do in the future. As i mentioned, fruit bats are thought to be the major reservoir. The cdc went in and did the study where they seasonally sampled these bats to look at the shedding of ebola — from these bats and they found that shedding occurs at two major times of the year, during breeding season, where the juveniles emerge, and that’s very consistent with what we know about most emerging diseases, the juvenile bats are very susceptible.

The virus in larger amounts. What was interesting is, 85% of the human cases occurred during the time of the year we saw major peaks of shedding. The cdc informed the local population of these results. Do you know what they did? They wept in an went in and killed all the bats. They decided they couldn’t coexist. They used the caves for mining activities and obviously for tourism. As an interesting sequelae, since then the cave has been repopulated by other bats, they’ve gone back in and repeated a similar study, and actually they have bats that have returned have a higher prevalence of ebola or marburg virus than what they did previously. So not only have you not solved the problem, you’ve made the problem worse. All the interventions we can do for humans and bats to coexist. Could we allow — close off the pace during the high risk times of year? What are we mining for, alternative ways to get those products that don’t need to access the caves for their lively hoods. Perhaps a little outside the box thinking, it’s something we do to help some of these challenges challenges. So just to conclude, i’d like to pull this together a little bit and go over the one health concept, how it’s interconnected within the context of ecosystem health, environmental health, and the fact that all these drivers that are driving wildlife are also driving human diseases.

Also when we get changes in environmental health or ecosystem health, particularly loss of biodiversity, you start to jeopardize these ecosystems on which all life depends. So the idea or the definition of one health at least most commonly accepted definition is collaborative effort of multiple disciplines working locally, nationally and globally to attain optimal health for people, animals and the environment. The emphasis is on optimal. I think to me these key on utilization of a one health approach. Can we take a systems approach to developing these interventions to which you balance the needs of humans and wildlife. We’ll show you a few illustrations of that. Some of this, we’ve talked about. Rather than blaming wildlife and culling wildlife, focus on increased biosecurity, prevents these viruses getting into poultry but also prevents viruses getting into wildlife. I mentioned about spatial and temporal separation of humans and bats to prevent marburg spillover, but other examples where we can implement that type of intervention.

I think that a lot can be done in risk communication approach approaches, changing attitudes. Many of these diseases have some sort of human behavioral component to it. I really like this advertisement, sort of campaigning against the legal wildlife trade but the message is that not just this is endangering their lives, it’s endangering your life as a movement of these pathogens. In zoo into tick disease. Improve public health and food security. So i was reading on the usa ids website, they got this big emerging pandemic threat program, and one of the campaigns is to prevent the spillover of viruses in bushmeat into people. Their intervention is to provide education and training to hunters on personal protection and hygiene.

That may prevent your viruses spilling over but there’s nothing to stoff th stop the bushmeat trade, so maybe this should be viewed as a food security issue and other alternative sources of protein for these communities that could be generated that decreases the demand for bushmeat, prevents these zoonotic diseases and spilling over but also allows a healthy ecosystem to coexist. I think ultimately, this may seem an obvious message, but focusing actions on what is the ultimate driving for for these things, i think it’s going to be most cost-effective point of control and alleviating poverty so less depletion of resources, less environmental degradation ga, less exposure to diseases, to me the common point of interest that we all have in managing these disease issues. Finally partnerships, we need to develop partnerships and government structures to address these concerns and build up our capacity.

This is a plug for my field because we got public health, domestic — the wildlife leg is missing and we very much lack that infrastructure and capacity to address these wildlife diseases, and i think that’s a major gap in a holistic approach to management of these disease issues. That’s all i have. Questions now or later? >> well, we’re running just a little bit — maybe we have time for a couple of questions. Are there any? Jonathan, did i understand that you can identify the mutation in influenza virus in birds just beginning their migratory cycle? I don’t know how long it takes for them to fly, but what impact does that have on vaccinating development which are specific for the mutations for influenza? >> so i think — these viruses can remain unchanged, so you can see this sudden introduction of a novel strain, so i think that does have some implications in the vaccine strain. Some of the viruses we’ve isolated — part of a suite of viruses they use when they develop vaccines.

I think it also — why we need to be constantly vigilant, these viruses constantly — other strains and develop new properties, we’ve got it in wild birds, that’s a game changer, a whole ee coke system, these viruses have got to play with that they’d not have before, so we start to sew more and more of these strange viruses emerge. So wildlife agricultural interest is also a potential public health issue. >> i have a quick question with the recent emergence of zika virus, is there rea confirmed that the human is the only species affected by zika? Is there anything in the animal world that looks like zika virus in the microcephaly syndrome? >> that’s a great example now, what we believe thus far is early primates and/or humans, there’s no evidence thus far that there’s a wildlife connection, but interestingly enough, we’re starting to do some experimental work to see if the birds are the species — like anything, when these viruses come to new ecological niches, they often change behavior and they may find a species that they didn’t have previously before that could be a very competent reservoir, so again, i think we need to be very vinl lent abou vigilant about these issues.

So right now the answer is no but we’re looking quite closely to see. Thank you. Appreciate it. >> thank you very much. [applause] >> now for a slightly different perspective, i should add that i joined the natural products pran cbranch in 1981, my chief, when he retired, i became chief, which is 2004. 2005. But i’ve been involved in natural products predominantly microbes for a significant number of years, let’s put it that way. Now, the question, why natural products. Both win and john referred a little bit to this. This is as of 2014, end of it, and the green of not this you go low looking yellow, as it turns out, the green others materials are natural products. These are all drugs. The total number of small molecule drugs was 1211. That’s approved worldwide, all diseases. And they counted one time. So if europe defines a drug and improves it, then a year later, the united states approves the same drug, it’s only counted one time.

If you look at what pharma says of the number of drugs in clinical trials, they’re using what one might say their statistics, because they count, and i’ve gone through their website many times, you have one drug and five cancers, that’s five drugs that are being checked. So d divide by 200 or something like that to get some accurate figure. But the essential point here is that everything — those are either natural products or are chemical kissing cousins of the natural products. You look at cancer, this now goes from 1940s, actually 1935 was probably the first year, this is the proportion of none natural product. These are actually natural product-like synthetic molecules. Atp mimics in a lot of cases, or they fit into an atp cleft. So you can see the vast majority are, in fact, natural products.

Now, if you look, and i’ve done this in 1981, if you look, just taking natural products now plus the yellow, what are the yellow? The yellow are what — why we decided to use the — but in practice, those of modified nucleosides, modified adrenaline, pushback from some of my chemical colleagues of calling them natural product arrived in practice they are. You may know, those of you who are physicians may well know of molecules such as — which is also used as one of the antiviral agents. But it turns out that this particular — these two molecules down here are the ones that revolutionized antiviral, and for that matter, a fair amount of the — cancer work, because these came from a sponge, in the 1950s. Now, prior to the discovery of these two natural products, it was axiomatic that you could play games around the base of the five knew clee types or nucleosides, but you have no biological activity unless — if you look at this and you remember your chemistry — merely an — it turns out there’s more — around than ribose, but until these compounds were found, they did not have any agents that were bubiologically active — the moment that these two were found, and i might add they were isolated from sponges, they’ve now been reisolated from a microbe, from the original spopg.

Though i might add, 60 years later. And its microbial origin — so that’s why we call them — they really should be natural product derived, and this gives you some idea of what the molecules are that descended or ascended from those starting from –, where you now have arra a. Arra c is synthesize bid a group that knew of the — discovery, and arra c is now being found from the microbe as well. As — is extremely well-known. Well, if you can play games with the sugar, what happens if you’ve got the sugar? These are — you put a — group on the sugar and you end up with something that’s quite well-known. Then this one is the one that is your $80,000 drug treatment for hcv. In six weeks of treatment, you cure hcv. It actually is a mass nucleoside nucleoside. In fact, those are very recent court case where merck had now just received a significant sum of money from gilead because it turns out that some of this was from merck patent of which people did not know. However, let’s look and see what happens when you play games with climate change. And you get carbon dioxide. High volumes of carbon dioxide.

As you know, plants basically use carbon dioxide and water to further synthesize. I might add, so do algae. Anything that has a color fill group in it or something akin to color fill uses carbon dioxide. If you start playing a games with the amount of carbon die ox tied that comedioxide that comes in, now w hen you increase or decrease the ratio of nitrogen to carbon dioxide, wherever you are, you start getting strange things occurring with plants. This is not hypothetical, this has already occurred. So you can get decomposition of what you don’t want, you get — composition, which you may not want. Either of these can be dangerous, some of these can be useful. When you start getting into above groundwork, you start getting some crazy things going on. Bear in mind that as john mentioned, most of these are a repository or a depository for microbes. From single celled organisms, plants do not exist in the absence of a single cell organism.

If you look at a plant, you’ve got single celled organisms — bacteria, in the risosphere, which is this area down the roots, you’ve got them in, on and swimming in close formation on the leaves as well. So you have to think of a plant as an ecosystem. I might add you might get some strange effects from some other ecosystems because mephane is one of the rather nasty gases that is naturally produce that actually does act like carbon dioxide. But what are the sources of it? When you look at it, anthropogenic sources and other remnants, you get a fair amount generally — from the organism, the wetlands themselves also produce it. Now this is predominantly bacterial or fungal. You can see in some of these where they have come from. So what you end up with is a problem. Normal living produces an agent that you really don’t like or you don’t realize it. If you look at — you’ve also god — angot — people do not rize this, but if you go to — off the coast of north america, actually they’re off every coast, because of the physics of methane, when you have pressure, you can actually crystallize methane as a hydrate, so you get a methane sink which are off the coast of the states of the major countries where you’ve actually got what looks to be crystal in methane, which is methane coming from the normal microbial rug, if you will, in the sea bed.

But it stays there as a crystal. The microbes that live on these are actually extremely useful in producing c1 compounds and all people have to think of, anybody wearing nylon, it’s due to a nice happy little microbe doing some work originally. From methane. There was a very large amount of work done by a british company that did this. On the phantogens and how to produce raw material — so methane is something that’s not thought about but it’s a problem. Now, let’s move a little to what can we hope never does but what can happen. This is a moon’s eye view of antarctica. Why do i say the antiar ti ka? It’s the sixth continent. The arctic is merely a sheet of ice. There is no such thing as the north pole. Within that ice, you have the world’s largest supply of freshwater. And in fact, if this area of the antiarctic ever melted, l.A. Will now be a rather damp place, it will be about 6 feet under water, i live in philadelphia and i’m 180 feet up, let’s put it this way, i would have an oceanfront property if that melts. This is one of the things that can happen.

So this is an absolutely worst-case scenario. You can see the various and sundry options and things that occur. You’ve got ip vai siev got invasive specie s, and now what happens when you get a certification? Sea birds, classified organisms go down, fish die, predators can go up and down depending upon whom they are. So all of this is a problem. If you look at the current antiaantiarctic, you can see if you do get some version of melting, you’ve got all sorts of nasty things occurring that will affect everywhere. However, let’s look at the more slightly different perspective. This shows you the freshwater which i’ve talked about. I might add, there are freshwater lakes a mile deep under the ice in antarctica, and they are being investigated tbr a micro biological perspective because they’ve been sealed systems. So it will be extremely interesting to find out what is there.

Let’s move now so something that john alluded to. The coral reefs and one that everybody thinks about is the great barrier reef. Last week i was actually on the great barrier reef. I was in brin bane at th brisbane, 4,000-kilometers in length. I’ve been there many times. Uncle sam paid for a fair number of them in my day, and i’ve been there other times as well. But water has begun to rise in temperature. Up to over 2 1/2 degrees in centigrade. Now this is from noaaa. This just gives you an idea of what happens with coral bleaching. Corals live effectively by photosynthesis, although you may not realize it. Within the coral, there are gipg el celsinksingle cell to multicell organisms, they actually produce the energy within a coral bed. This gives you some idea of the danger that’s going on. This is at the moment, this is not hypothetical. This is actual. This is just what can happen if you start doing — placing probabilities and look for the — stress in the next three months.

So as you can see, it’s already started. This is just an idea of evolution under ideal condition. However, if you increase the temperature or decrease the temperature, your ideal conditions are no longer there. So this is what it was. What it’s going to be is a good question. However, this is what happens. This, the el nino, which has been around for 2 1/2 years in the pacific has caused the rise in sea temperature of approximately 2 degrees centigrade. This is what it should look like. This is what it does look like currently. Two example, one in american samur where you can now see the coral reef is predominantly white. This is a stag head coral. That can take centuries to grow to that level. It’s now white. Do they recover? Sometimes. Do i believe they will recover? Maybe 25% of the time.

This just gives you an idea of world temperatures around the world. This is where jonathan and i and win and luber were last here, this is kazakhstan. The normal temperatures here are plus 35 in the summer, minus 35 in the winter. I theng you ca think you can probably add 5 degrees on both sides of that. That is a desert. So this gives you just some idea. This gives you a scale. Why is there a problem with coral reefs and drugs and sources of interesting molecules molecules? One reason is this. This particular sponge, it looks red, it’s actually called a yellow morph. Molecules from this spong have been looked at for many years. There was always a debate, what produces the molecules? Bear in mind, nci funded most of this work, and gordon and i spent a lot of our professional lives working with these things. Getting agents from marine invertebrates and others.

And it turned out you started looking and realized that it’s quite possible they’re produced by microbes in and around the sponge. Carol is across the road in building 4. This was — she was the one who was working on the — back in her graduate school days, approximately 20, 25 years ago. It was thought to be is this possible. Some absolutely beautiful work, almost kno nobel-level work, they acisolated every cell — don’t ask me how many millions in cells — 1536s, they actually did. But the publication list on this has almost more authors than the article. But they found that this particular compound, they found genes corresponding to the biosynthesis of this, and i might add that this part of the molecule, i have another set of slides that i gave in brazil a few years ago, wearing a scuba set, because this part of the mol couple is peterin, a toxin which we know is produced by — this comes from the shallow water sponge of okinawa.

So having found that, they then proceeded to find a absolutely unknown microbe that has not been fermented yet but has had its complete genomic sequence obtained starting with one cell. Pcr does work, ladies and gentlemen, but it takes a few years and a lot of graduate students. However, when they did this, they actually found that from that particular sponge, there were 32 at this time, this was 2014, there were 32 known agents that kill cancer cells. I’ll call them that. Cytotoxic agents. Entirely different structures. 31 of them had their genomes or their genetic machinery in that particular microbe. What is even more fascinating is at the start of every one of those molecules was ribosomal peptides. The best way i can describe it is how it works. For those of you with an agricultural background including — excluding john, a disk harrow, which is the device to turn over the soil and you have a series of disks.

Think of an empsyc an enzyme or enzymes that are a series of disks. For this particular compound, disk 1, 5 and 7 operate, that’s enzymes 1, 5 and 7. This one, enzymes 2, 4, 5 and 6, it’s the same ribosomal peptide. And this is a beautiful piece of work, and now it’s being shown to be very, very common, so when you were taught a lot of these were not ribosomol peptides, they actually are. Now, here’s the point. Not all compounds are produced in microbe invertebrate interactions but i will go out on a limb and say probably 80% of them are. What happens if you now go the other way and you now go from a very wet environment to a very dry environment. The desert in south america is rather warm, just leave it at that. And it has a chalk-like consistency. One of the chaps i know well actually started looking at the microbes that coexist on that. Effectively these are dried out microbes. They started finding some very interesting molecules when they did the spectra, they actually found algae, but — they call them algae, but they’re actually cyanophytes. Now you start looking at the particular genome of those molecules that produce and they start producing some very, very interesting and very strange peptidic-like molecules.

This is a chemist that did this work, journal are organic chemistry. And it’s actually from a greum agroupfrom university of aberdeen. The reason why this exowpped is a rather interesting one is this is what is known as a lasso peptide. It’s a peptide that has a ring, but it then has a tail that loops back through the ring so you can think of it as a knot. And these are very, very common as toxins. Plants — is it a plant a good question, produce a lot of these as insecticides. This is what they started working on and discovered they could fish the genes out. Again, you don’t have to ferment the microbe. You end up with a gene. Now, this is basically a simple way of looking at it. It doesn’t look simple but it actually is.

You’ve got an endophyte is an organism within the host plant, an epiphyte is something on the host. When you start looking at these, this is now an idealized schematic of what you have between a plant cell here and a fungus here which, as john showed in the bat example, the fungal — i call them epithelia, go inside of the plant from the outside, the bacterial cell is outside the plant, but kem chemistry and talks to the plant by chemistry. I might add that is very common in us as well. There’s a comment i often use, the question is how human are you? The answer depending upon how you wish to ke define it is somewhere between 10 and 15%. You count the number of single cells in the body versus the number of mammalian cells that compose the body. And the answer is, less than 20%. So that’s the microbiome. This is the equivalent in a plant.

You have chemistry talking between the microbes, here you’ve got chemistry going back and forth between the plant, the fungus and bacteria. If you start interfering with this, you then have a very unhappy plant. If that plant happens to be a foodstuff, then you fall into exactly the situation jonathan was talking about with food security. And you don’t know what’s going to happen. But what is even more intriguing is that these interactions produce compounds that have been known compounds of abuse and compounds of use. That’s lsd. These are very well-known products that the ergo of rye, which is an epiphytic — of the rye plant and is an argument that the witches of salem were due to the hallucinogenic effects of these particular molecules on rye that have become infected with ergot and there’s also another one, it’s also a version of this is used to induce — to reduce prolatin secretion in both men and women.

To bring down the levels of prolactin, therefore women that can’t conceive can, because of the presence of very low levels — came from this molecule, came from this particular fungus. You lose that fungus, you lose your hallucinogenic effect, also lose rather than interesting effects. When you start looking at this, i always joke that this is the sort of work that tells you that lysenco may have been correct. If you remember your genetics, mendelian genetics is one, but — claim that you can have induced traits that will transfer vertically. It so happens that these are transferred vertically by the plant. These microbes are actually part of the seed. And what you end up with, there is a microbe part of the seed itself that carries upwards as you get a new generation. The same thing happens, i might add, with another very well-known compound in our field which is — you have two types, those that contain an endophytic bacterium and the ones that don’t.

The ones that don’t, you simply have — so there is a possibility that some may have been correct, we know it now. Of course if i say that in a school audience, i get howled off the stage or dragged off and tarred and feathered. Here, i can say it. Now, you just get some other examples. The odor from plantsz or flowers flants or flowers that you like are also due to these molecules known at terpenes, usually produced by microbial components of the flower. So one might say the flower looks nice but it’s lost its smell or it’s odor, one of the reasons being a loss of bacteria bacteria. I keep saying th we’re losing microbes, how do you find them? Classic method is fermentation. I spent something like 25 years of my professional life trying to do this. Sometimes succeeding, sometimes not. Today you hire your local gene jockey and also someone who knows their way around the computer. Because effectively what you do is you get the jea gene clusters so you don’t have to ferment them anymore, just have the microbe, and then you can idealize it.

You can use various and sundry techniques only known to those — use an lcd screen and come up with ways of playing games, and you end up with molecules or the genes that allow you to find molecules you didn’t even know existed. Here’s a simple one. So what you can do is you now have — and this, by the way, i took this from the slide and realized that they had made an error. This should be bgc. Biogenetic gene clusters. Everywhere else, they talk about bisynthetic gene clusters but they obviously — i know fish back quite well, i’m going to have a kidding the next time — he needs to have his graduate student do better proofreading. However, this is what you can do. You can now group these using computerized techniques and you now can come up with, okay, this is actually a molecule that producproduces erythromycin. One of the first drugs ever used against tb and it still is used. So you can find these without even fermenting. Now let’s ask a different question.

You’re finding these today. If you get a rise in temperature and it’s coming from a marine based microbe and it’s part of a coral reef, it’s no longer there. So we don’t even know, a, what’s there, or b, what you’re missing. This is where the computer jocks go crazy. They take the complete biogenetic sequences and proceed to cluster them, and in fact, i’ve seen this done and i didn’t believe it. I do now. You can actually do this with a consortium of my groabs, and this is actually how a lot of the microbiome is being done. And you put them into clusters depending upon what genes you have there. Then when you find another gene or gene cluster, you can say, oh, it corresponds to this one. And this one, i know, contains genes that produce a, b, c and d. Therefore, i’ve got something that is related to a, b, c and d. So this is what’s being done now, rather than the way i spent my life trying to ferment the little buggers and failing miserably or only getting one compound, and bear in mind that about anywhere from five to 15% is the highest i’ve seen of the genes in microbes actually have the capability of producing molecules.

The problem is what you get them on. Again, we don’t know — this is an example of where you got into interplay now between a termite, fungi, and bacteria. And what you found from this, this is just a termite now, you can see the little critters here, what you find is that you get some very, very interesting molecules, some of them i spent an awful lot of time, money, that uncle sam — we grew over 3-kilograms of this particular molecule. Because that was the precursor for 17aag, which we took food to — to face the clinical trials, and variations of it. But it’s produced by the same microbe that produces this. We had no idea of this. Nor this one. And a couple of these. We’d seen others. But we didn’t know. So now what happens is that by looking at the interplay between microbes, insects, and others, you start seeing molecules that you didn’t even know existed.

In fact, this goes back to a point jonathan made about sim biosis and the interplay between molecules. One of the things that i did before i retired a few years before i retired, we started doing some playing up at frederick where we took fungi and bacteria that had never seen each other, and proceeded to grow them together. We start getting molecules switched on that we didn’t even know ec existed. We didn’t find the genes, we looked for the molecules. So there’s an enormous amount, there’s an enormous number of potential molecules out there, and this is one of win’s comments about ensilica, my answer is you’re not going to find a damn thing in silica that you don’t already know about. Whereas if you look at them use using modern genomic techniques and ways of playing using in silico — you now realize that there’s an enormous number of molecules out there. In one fungus, there are over 75 different clusters identified, and that does not include terpene — which have at least another 20. So you’re looking around a hundred different genomic clusters that had the potential for molecules we’ve never seen before.

Or in some cases, as in this case, they produce molecules we haven’t seen, molecules we already know about. And that’s basically our take-home message, which is because we don’t know what’s there to begin with, we don’t know what we’re losing, but we know that we are losing. This was the slide that we put together many years ago, this shows some of the materials we played with at the natural products branch. The background here is in fact fact — this no one in the audience ever wants to meet face to face. But this is the — that produces it. — i have a lovely story about this one. I was giving a talk at coldspring harbor many years ago, and i was asked what does nci collect? So i said, well, if it’s brightly colored, slow moving, has no obvious means of defense, and i added, is — over 40, thank imod sh god she didn’t put the “over 40” in the article because what i’m describing is this little creature. Now these raping i range in size from about my fingernail to about 35 centimeters and weigh up to a kilogram. They are shellless mollusks, so think of them as a snail without the shell.

But nothing touches them and that’s breakfast for anything up the food chain. The reason being that they nibble, eat, ingest, whichever you wish, molecules, usually cyanophides and all other bacteria, and the toxins are then put on to their backs so that anything comes along and goes jump, die, a predator is four — its fins are up and it’s floating to the surface. Those are organisms we like to look at. We now know, some of you may remember when — statins were put into clinical trials at nci and other places, they came from an organism like this. We now know that they actually produce — they’re actually produce bid a blue green a algae, from the toxins, there are about 25 of them, are in the fat layer of the organism. So we don’t even know what’s there, but if this little organism gets either too cold or too hot, they’re not going to be able to find them.

Flowcial that’s basically the story. So anybody wants to throw rotten tomatoes, particularly when i tell him a plant is nothing more than a host. He’s a botanist. So many thanks indeed. >> thank you, john. I hope we have some questions or or — >> what is the main — in methane, is the main reason it’s such a bad gas the heat capacity or other — >> it’s basically the heat capacity and the fact it’s highly volatile. So it will sit in the tropo troposphere and it’s actually much worse than co2. >> one other question. In your — examples, is there any change in the distribution with the climate? >> that could well be, becauser becausergot is a fungus that is a spore former, so depending upon winds and what i didn’t put on any of those was the increase in wind velocity in certain areas, you’re going to get spreading, so one doesn’t know. >> but there’s no change in ergotism? >> i haven’t looked.

There could be an awful lot of this. But people don’t look for this. I look as a chemist trying to find ergot, trying to find the molecules back in my youth, but how they came about is only learned later. >> i will ask you in all honesty, are there any groups of compounds yet that you — that are still produced to our knowledge only by plants? >> by plants? Yes, there are. And off the top of my head, i cannot — not all are alkaloids, no. Some of them are alkaloidal. Some of them are produced by fungi. I know i wrote this in one of my more recent articles, but i’m blanking on which it is, when they ro removed the bacterium from the plant, the other molecules are still produced by the plant. So yes, there are molecules that are plant. There are other molecules that may well be pr produced by interplay between the plants, plant and the agents.

But there are molecules such as matancin, which originally was considered to be a — published this in a chapter with flass, where it was thought that a precursor to matancin was known to be produced by — in the risosphere, in the roots. And that the plant then did a — to produce matancin. A year and a half ago, a group discovered that, no, it was actually bacterium in addition to the — producer that did that. And it does not occur in the plant at all . The plant absorbs it and uses it as a protective agent. So as we learn more, the paradigm shift. >> one quick follow-up. Where are we now with taxol? >> there’s a very, very interesting story on that. There’s a paper that just came out, i write a fun article for me every quarter, and i just use this as an example, what happens in the u tree, when it buds or basically you get a twig or branch coming off, the bark cracks. A couple people in canada, the beautiful piece of work, where they looked at the fungi, really the microbiome, that area, and discovered that within taxis, there was a fungus that was an endophyte of taxis, when they looked hard, they discovered that taxol — in the lipid layer, so you can think about it being little lipid droplets, and when there was a crack, you’ve got a fungus getting in that was a lignen hydrolyzing fungus, that taxol, they laid down basically a death wire, cross this and you’re dead, because taxol was originally and still is a very good antifungal agent, so what happened was it killed it.

So they fished out that bacterium — i’m sorry — that fungus, and discovered that when they fermented it outside, if they put — chloride, a breakdown — in there, the level of taxol production went like that. Now, is taxol a plant product? A fungal product? Or are the two — rather two roots the taxol? That’s a question that is not yet definitively answered. Maybe say a word about it, we keep hearing on the radio that there’s an epidemic of lyme disease permeating around in the central atlantic coast. We all have deer wandering around, we don’t know whether they’re the culprits or what can be done, and then there’s this whole business of great concern about chronic taxol — chronic lyme disease, many articles, people should be treated for two years with antibiotics and what not. Looking upon this from the perspective of animal, wild animal, how would you fit an approach to the one habitat, just to put it locally or — it’s more than local but — of the lyme disease and — >> >> i didn’t touch upon in any of my presentation but basically one of the — we believe we’re seeing a high incidence of lyme disease is the way that we live in these types of suburban environments.

You have homes close to these forested areas and it’s caused fragmentation of these forests so we have a lot of edge on these forests, and the research has shown that you get a higher abundance of the main re reservoir for — the wet footed mouse in these — these pristine forests have a higher biodiversity of rodents, whereas these fragmented forests have a single — mostly a single species white footed mouse. So one of the theory is what we’re seeing is that the lots of the dilution of — tick seeking a host, it’s going to find that host and get infected. If that tick is in a forest with other species that aren’t competent reservoirs, then the probability of becoming an infected tick decreases or declines. So i think one factor is the way that we live in our suburban environments. The other factor is these suburban environments are a perfect habitat for deer.

You probably all know this, impossible to grow a garden in this part of the world without deer eating it, so you’ve got a very high — very high-density of deer, higher densities of ticks so that’s probably another factor, but i think the main factor is the loss of the dilution effect from biodiversity. — would have been a good example to use. It’s also actually being impact bid climate change. Lyme disease is creeping further north, migratory birds taking the ticks and dropping them, again they’re able to survive at these higher latitudes. What to do about it is a big question that’s being discussed right now, there’s a number of techniques being used. Virginia, public game, one of the things they’re starting to use with these stalls the deer would come in and get treated with pesticides, treatment for ticks.

Obviously culling deer, keeping populations down is important. That’s not easy in these suburban environments — people don’t usually mix very well. There’s a lot of discussion about modifying habitats to try and prevent ticks from coming in to people’s yards. I think again we get some creative solutions to these problems, one of the research — areas of research — developing a vac neen upstream, can we develop a vaccine where we can put in these forest areas so we can vaccinate the mice to prevent transmission. So i think right now you’re stuck with deet and checking yourself for ticks ach you come in froafter youcome in from the yard but i think there may be some creative solutions in the future. >> now that was — the dilution effect was actually mentioned a couple of years ago, a meeting i was at in d.C., where it was actually — it wasn’t there, this was epa amazingly, we’re talking about the fra fragmentation and the lack of dilution. Similar thing has happened also, happened with cholera in the four corners area with — virus where you got changes there and you had much more in the way of mice coming in to feed on grains that happen to be in the houses.

So you had — these were areas where young students would live, hence you have this apparent infection of youngsters, not guys my age, because i wasn’t going to live in the outback. They would. John and i were 30 years apart in the primary school, i should add. Although i understand my face was on the wall, we don’t know this guy. >> i want to thank you both for a very, very informative, very interesting talk. >> thank you..