19: Host Parasite I

Transcribed by David Landsman 8/1/14

Microbiology – Lecture 19 - The Host-parasite Relationship, Part I and II by Dr. Caufield

Slide 1 – The host-parasite relationship[Dr. Caufield] - Check, check. Check. Can you hear in the back? Thank you. Good. I’m gonna pick on the people in theback so 1,2,3,4 you’re gonna be my favorite and let the front row relax a little bit, except for you because I picked on you before. And him too. So you’re good sports and didn’t come beat me up. You can try.

Today. Thanks for coming. This is a two hour lecture, we’ll take a break. I have a short quiz for you that you will absolutely enjoy and I guarantee everyone who’s here will get an A+. Yea. If you listen carefully to what I say today you don’t have to go study this material. You study it as I talk. I will give two or three examples of every point I am making and for you to go home and listen to this video again, I don’t know where you’ll find the time. You can study as the lecture goes, ask questions, and I will lay this out very carefully. You will know everything I want you to know by the end of this lecture by simply paying attention. That saves you hours, right? Yea ok. Let’s give it a try.

The topic today underpins everything there is to do with the human condition with infectious diseases, and I’m gonna talk about infectious diseases, and I’m gonna tell you why it’s important. And I could ask you know why you think infectious disease is important. Hey I’m a dentist. What do I need to know about infectious diseases? Well I suggest to you that the two major diseases, and I’ll tell you this, that we treat are infectious diseases. So when you have conversations with others like physicians, nurses and others as we expand into healthcare, they’re gonna ask you why you consider this is an infectious diseases and what aspects. And they’ll talk to you about other infectious diseases. There was a time when HIV was transmitted by a dentist in Florida in the ‘80s and it caused such a huge ripple in the entire medical surgical world and it was a single dentist and anyway that’s another story for another time. But it caught everybody by surprise because we didn’t know much about HIV. And that study was done by the CDC and it’s a beautiful study but we don’t have time to do that today. So infectious diseases impacts everything that we do. Let me see if I can make that case.

Slide 2 – The Host Parasite RelationshipSo the old terms that are used in the classic literature is called the host-parasite relationship. Classic literature, host-parasite, think of me as the host and bacteria that live or infect me are parasites. It’s an old term but it’s convenient to use and it’s what is still used. The definition of a host and a parasite has shifted somewhat as we understand more things about DNA and prions and other infectious agents but it’s an old term and its gonna be convenient for us to use. So think, I’ll define the host and I’ll define the parasite. So this has to do with all infectious diseases and particularly to do with humans because we like to talk about things that affect humans. There is a set of rules for infectious diseases, I will teach you the rules and then you can apply them. Any infectious disease that comes on board, you can go back to your rules and say is it this type of infectious disease or another. It’ll help you navigate. At the second part of the lecture we’ll talk about the indigenous biota, used to be called the indigenous, the other genome, the other part of the human body


and then I will weave into every aspect of this dental caries. So that it relates to you. So my appointment in the school of medicine is in infectious disease, so everything I tell you has some ground in what I would tell physicians and what we would do with other infectious diseases we’re going to bring dental caries into the argument because it’s very important you understand it. Now 60-70% of all dentistry addresses dental caries and infectious disease. So the #1 disease we treat.Slide 3 – Center for disease control and prevention (CDC)So the center for disease control, you know where that is, in Atlanta. Watch the Walking Dead? So you know where the CDC blew up, so it’s gone. No, it’s not. You don’t have time for the walking dead! Of course not, I don’t either, I just happen to live in that area for 25 years, so hey. Center for disease says dental caries, your disease your income your livelihood is perhaps the most prevalent infectious disease of human beings. How about that! Is that true? Wow. The CDC said it, it must be true.

Slide 4 – Why this is important to dentistsWhy is this important to you as dentists? We treat two diseases: periodontal diseases and caries, I use the plurals. They are both infectious diseases. We have a problem with caries we don’t understand, it’s rising, it’s falling in some populations. We don’t know exactly why. And so when you bring in an infectious disease team to look at caries in the Navaho or the Lakota Indian reservations, south Dakota, Lakota in south Dakota, you have to ask the question is this an infectious disease that has gone epidemic. And so we’ll go through that gyration as well because it is of great national and international concern. So we don’t know what is causing an increase in caries. I do, I will tell you that at some point. But it’s what we all say. So we are really good, all of you, your hand skills are probably 50 times better than mine were at this point of your career. We didn’t actually work on typodonts until third year, so, but we did do the little waxing, wax on wax off stuff upstairs, but not here. Somewhere else, it was fun. My favorite part. So we are very good at restorations of the disease but we don’t really address the cause. Ya, we need better approaches to caries management. We don’t want to put ourselves out of business right? Not until we pay off the student loan, right? Ok. So. Thought I’d make that point. And you’ll be surprised that your patients are better informed today and they’ll read articles from the obstetrician that say don’t, if your baby’s pacifier falls on the ground, mothers sometimes pick them up and put them in their mouth to clean them. I wouldn’t do that, I was brought up German, we throw it away. But in that NY obstetrician article they say that the mothers should not clean it in her mouth because she could transfer the bacteria that causes caries. And this is common knowledge now, it’s like a folk myth that has gone on and now the transfer of these bacteria and how they’re done and it’s totally untrue. And yet it gains more and more prominence. So you’ll see this all the time. And the patients will ask you. And other advice people say is don’t share your utensils with your children. Generally we don’t, I don’t, but I don’t know. If you got some mashed potatoes, got some grits, you’re gonna take a spoon and put it on the kid’s plate but you’re not gonna lick it, well you might, but that’s some more advice given by the dental association is don’t share utensils. Duh! So, and that’s not how it’s transferred anyway. That’s how other infectious diseases but not caries. So these things come up all the time and you as dentists need to be the people who know the answer. You will know the answer today.


Slide 5Dental caries is an infectious disease but we have to define what that means. We have to define what that means, and if you can understand that…

Slide 6So here’s the situation, you can see all the time, we go to places, our research on dental caries, early childhood caries on young children, this is what we see. 50% of the Lakota American Indians have this disease. And so when you take a group of physicians and other infectious disease people look in and say this is a virulent, virulent infectious disease that has swept through the community like [unknown word] virus, for example, and it’s due to crowding and other things, but it’s an infectious disease. And they come to me and they say well is it an infectious disease I say yes it is an infectious disease but here’s the questions. Is it an infectious disease? Yes. Is it contagious? No. Is it epidemic? How do you define epidemic? Epidemic means transferring across a group of susceptible people. So if I were this child and I had this disease and I was up here spreading the bacteria that from my mouth for example, I don’t know how to do that, some of you would be susceptible if it was influenza. Some of you would get it, you’d wake up in the morning and you’d be missing a bunch of teeth. I’m exaggerating. But if it’s an infectious disease like that, maybe mother has it, she transfers it to the baby, baby gets it. Baby in the community, children share popsicles or candy or what have you, so all these imaginations have come up, none of which are true for how this infectious disease manifests. It’s now called, the CDC now lists this correctly as a non-communicable disease. Communicable is an old terminology like host parasite, so probably needs to be revised. What they mean by non-communicable is it’s not transferred horizontally like influenza and others. I’ll develop a theme. So it’s called non-communicable which it’s a chronic disease, and it’s listed with heart disease, diabetes and asthma. It’s probably appropriate.

Slide 7All these interactions to do with microbes. All infectious disease they either conform or violate what we call the rules or the tenants of the host parasite relationship. So I’m gonna define the host parasite relationship, big picture, applies to all infectious diseases and then we’ll go and move back into caries, back into infectious disease, back into caries.

Slide 8Definition. Parasite is an organism smaller and less highly differentiated than its host. This is a classic definition of a parasite. Smaller and less differentiated. Now that’s, again, thinking about the human, at the time some of these ideas were conceived, humans were the most sophisticated forms of life on the planet. Aren’t we? We think we are. So anything less than human has got to be a parasite, right? So that’s how that came about. It doesn’t really – I’ll show you an example, and it’ll be part of the quiz- of where that is probably not true. Parasites live at the expense of the host. And there’s all kinds of ways of deriving expense. Infection, infection, let me make sure you get this definition. Infection is habitation of the host by a parasite. So infection doesn’t mean you have disease. And in the common lexicon, people say ah I got an infection. I went out with this –no, I went to a conference and I got infected by a cold virus. Yes you did, but we’re infected, everyone here is infected with bacteria does not mean, or viruses, doesn’t mean you have disease. In fact, most infections


don’t lead to disease. And we’ll develop that theme. So most infections, we use the word infections, just simply means cohabitation. And it’s mostly harmless. And it is symbiotic. But we’ll do the exceptions ok.

Slide 9 – Rule #1Now I talk about my rules and these are my rules, that have been vetted with my colleagues, but none the less remember that nothing in biology is 100%. Because the only reasons we’re here is because of mutations, mistakes, DNA didn’t replicate properly. You’re ancestor, there was a couple mistakes in there and that’s why you’re such, you know, smart guys, sitting in the front row. Because of those mistakes we’ve mutated and where we are, going to lectures and going to dental school and looking at our google mail. So nothing’s 100%, there’s an exception to everything, so no matter how clever you think we are at evading infectious disease or defeating it there’s always a way around it. So nothing that I say is 100%, they’re general rules and there’s exceptions to everything. We just found a couple today that were exceptions. We didn’t know where anthrax came from. Have you heard about the CDC containment leak with anthrax and the BSL 3 lab? So I was in the BSL 3, I used to live in Birmingham Alabama and CDC was our closest partner. We had worked with anthrax. And so that leak –and this concern with anthrax, we never knew about anthrax was where it came from. The spores and what were their host and it’s still not final but anthrax probably came from a mammal that is now extinct and just couldn’t find the right host. I’ll tell you more about that a little bit later.

Slide 10 – Venn Diagram – infectious DxThis is a general relationship with all infectious diseases, all host parasite relationships, you need three parts: you need a host, you need a parasite -- parasite could be a bacteria, could be a virus, could be a transposon, could be a prion -- and you need environment. If you have a host and parasite together but not the right environment you have what’s called a carrier state, this is traditional, so Strep pyogenes which causes strep throat, George Washington died of Ludwig’s angina. Strep pyogenes, 20% of you in this room are carrying Strep pyogenes as a carrier, you’re not really sick. How many people just feel really tired, a little malaise, yea every day right? No. You’ll feel different today. 20% are carrying Strep pyogenes, you’re asymptomatic carrier. So there’s carrier states, it’s important that people. More people carry pneumococcus. Some people carry influenza, so there’s these conditions where you have a carrier state. When you have the environment and you have a parasite together you have what is called a natural reservoir, so these are definitions. A natural reservoir for infectious diseases can reside often in water, food, etc. those are situations where you have a natural reservoir that holds the vector or the infectious agent. In using the Venn diagram and its proportions, disease only occurs when you have the right conditions of environment parasite and host. And notice how small that area is. So disease is the exception to the rule. Host parasite relationships, disease is not supposed to happen, and it does happen in the right situation. Dental caries was never meant to happen.

Slide 11 – Venn diagram – Caries


So here’s the Venn diagram for caries, same Venn diagram same. But we put in bacteria because we know it’s a bacterial disease. We put in the diet because carbohydrates are the major pusher as we talked about in biochemistry last year. And the host. And the host is both the teeth but also saliva and other parts that the host contributes. The size of the fissure, some of you have anatomy on your fissures that are really wide and some have really tight fissures. We have different types in incisors and etc. So anatomy does play. Some people have crowding, most Europeans have crowded dentition and when the baby, when the child becomes 2, 3 years of age you see this crowding develop. They lose all their primate space and so they can develop proximal caries. And this has to do with environment in terms of the host characteristics. So there’s other factors that influence dental caries than just bacteria. Now this is a microbiology class so I’m gonna tell you about the microbiology. And we can talk about all three of these components and every one of them is essential and I would suggest to you that in the case of dental caries diet may be the single, if I had to say the most important and I hate to do that, diet would be the most important the most difficult to control. I don’t see any sugar beverages today, coca cola, mountain dew is big in the south. Anyone from Tennessee? Do the dew? Hey, doing the dew. 20oz bottle of doing the dew. Teeth end up looking like meth mouths. But you are doing the dew, doing your thing. Love that stuff, it’s got caffeine and just tons of sugar. You almost have to weigh the sugar in there to get mountain dew to go into solution, it’s so much. Best thing for dentistry in the world, I’ll tell ya, mountain dew. No it’s not because you can’t fill those teeth, you can’t restore them, not this lecture another one I’ll show you some restorations we did in Tennessee on a kid doing the dew.

Slide 12 – Infectious diseases of humansOk so, infectious disease, just read through this it’s on your notes. Infectious disease in humans I would suggest to you is the major influencer of human history. Every bit of human history that you could possible dig up has got an infectious disease behind it. And this is what we teach in medical school, a dental school. Infectious disease it’s all centered around these infectious diseases principally of humans. So when I was a student you had to memorize and learn each of the different infectious diseases, there’s a lot of them and more coming. Because there’s so much information now with the molecular aspect of infectious disease, we went back and tried to apply what’s called Koch’s postulates, I’ll talk about that later, you’ve heard of Koch’s postulates to dental caries. And since the 1960s it seemed that that was the way to go. It’s totally wrong but we didn’t know that back then. So infectious diseases should have a bearing on what we do in the clinic and our risk assessments for example.

Slide 13 – The great epidemicsNow when you think of the great epidemics and there’s lots of them but you read, you hear through your lifetime. Influenza. Does influenza scare anyone in this room? Hey I got the flu! Does the flu bother you? Do you get hot sweats at night thinking of getting the flu? I didn’t. The flu, Italian, influenza. Under the influence, I’m feeling a little sick today. I’m not going to dental school micro class today because I got a little flu-like, I’m flu-ish. Influenza killed more humans than any infectious disease in the history of mankind. 1919, 1918 killed 50 million people and that’s only what they could get on the census, it’s probably more than that. So this influenza, not necessarily what’s going around you get those little


vaccines for influenza, but the real thing, was extremely fatal. And so influenza we understand a lot more about influenza. How about measles? Is anyone concerned about measles? You all got vaccinated. Most of the time men, you don’t wanna get measles, don’t want it. So make sure you got your vaccinations. You have to have them for dental school right, for measles. Don’t they check that? You don’t want it guys, men you don’t want it. Women don’t want it either but men particularly don’t want it. Smallpox, scare you? Whipped out most of the new world, whipped out the Aztecs, the Incas, the great civilizations of the new world, whipped out. Smallpox and measles. One-two shot. 2/3 of the population died. Wasn’t the Spanish conquistadors, they were just a bunch of guys dressed up in tin cans with swords. There was like 50 or 60 of them, Cortez, maybe 600 of them. And there was 10,000 Aztecs. Smallpox, measles, swept through and killed them. Plague, cholera, polio. When I was a child living in Cleveland, I grew up in Cleveland Ohio, thank you. We just got Lebron James so I want to respect…

[Student] – Boooooo!

[Dr. Caufield] – Oh wait a minute! This is all being filmed on camera so that boo over there… you might as well check out today. Polio when we were kids, you couldn’t swim in Lake Erie, well it turns out you don’t want to swim in lake Erie anyway at the time, it was so polluted from the Detroit river, remember our river caught on fire Cuyahoga river caught on fire, so it’s not a good place to swim. Our mother didn’t care she would take us up and say go swim in lake Erie, because you’re a pain in the ass, and actually don’t come back. No she didn’t really say that. But polio was a big deal. If you got paralytic polio you spent the rest of your life in what’s called the iron lung, where you’re laying like this in a big vacuum chamber and you were able to breath by billows coming in and out. Franklin Delano Roosevelt had polio, it was scary. It was frightening. It affected people that you didn’t expect to be affected. And it all had to do with henry ford and the automobile and horses, another story. And then we all know a lot about HIV and you get a lot of lectures on AIDS, we’ll talk about a little bit later.

Slide 14 – is caries like this?So when we think about infectious disease now, and I’m a cariologist so I’m talking to my physician friends in infectious disease next door and they want to know, well, we’re dealing with bubonic plague, are you trying to tell me that dental caries is an infectious disease? You’ve probably seen some of this in the Dutch museum, this is the plague years. And people just died all around the world, there were four different periods. The plague, bubonic plague. And so this picture called the triumph of death, but it’s a horrible way to die. Dental caries, most prevalent infectious disease of modern humans, is it gonna turn into the plague? It’s an infectious disease. Is it like this? Where John Snow in England curved the cholera epidemic by removing the pump handle from the central water. And I saw Fred walking out. You’ve probably heard this story of john snow, first epidemiologist in tracking. So is dental caries like that? Should we take the water handles, cut off the water, is it water born? Where’s our model? Here’s a woodcarving from Daniel Defoe. Anyone tell me what Daniel Defoe’s famous book was? Gets extra points with me, don’t tell me now. Daniel Defoe wrote this book called the journal of the plague years. It’s amazing. It’s absolutely amazing reading. This is the wood cutting, this is the guy who walked around


the village and he had the stick he had the hat, this is the first OSHA, you know how you’re required to wear the little mask and stuff in the clinic and you dress up with the gloves. No open toed shoes, it all came from this. This is how I feel when I go up to treat children and I look like something from outer space. But I couldn’t figure out what the nose was about, the big long pointed nose, I got the gloves I got the sticks because it was actually caused by fleas on rats. I got the stick part, I got the gloves, I got the gown. I kinda got the hat, I don’t know, it is a kind of hipster look. But I couldn’t get the nose, and I’m giving this talk in the biggest dental school in the world, by the way, in Mexico City. I don’t know if you know which one that is but it’s the biggest dental school probably in the world. They have a part time student class, so you come to dental school and then you go back to your family business, make some more money for a year then you come back to dental school. They have a lot of students in this rotating program. So I’m giving the talk and the dean there comes to me and he had done some infectious disease, he actually found the source, the reason they had the nose is they packed it full of spices. And back in the time of the plague, if you had something like nutmeg, you put it in your pumpkin pie, not too much – if you put too much in it’s too much. Nutmeg was so valuable that the Dutch traded to the English the island of Manhattan for the island of Run where they grew nutmeg. Why? Because nutmeg was thought to be protective against bubonic plague. And for the Dutch that was more important than Manhattan. So this stage and this very dental school is because of nutmeg that was put in that mask to ward off not only the bad smell, but it’s antibacterial, and nutmeg actually is. So if you were rich enough to afford nutmeg you were probably rich enough not to have rats running around your house as well, but if you were rich enough to have --you probably didn’t get the plague. Now it wasn’t because of the nutmeg, maybe, maybe not, it was because you were rich. But still, they correlate, doesn’t mean causation. I’ll move on a bit quicker. The biggest death of humans was 1918 called the Spanish influenza, right? Spanish influenza, 50 million people, should’ve been called the American influenza because it started in America but that was bad for the World War I propaganda and the press so you were not allowed to talk about this epidemic in the American press. The Spanish were free press at the time they were not affiliated, they were neutral, and so they reported this massive epidemic of influenza happening among American troops, and subsequently European troops, 50 million people died, the Americans called it the Spanish influenza because the Spanish reported it. That is PR, that is Madison avenue, that was clever. Because who wants the greatest killer of human beings on the planet called – how about calling it the Iowa or Idaho, because that’s actually where it came from, the big pig farms -- so we didn’t want that so we called it Spanish influenza, a PR masterpiece.

Slide 15Well this is in the New York Times, I won’t go into the word quarantine. You know, hold somebody quarantine them for 40 days. It’s in Italian, I just kinda trying to learn some Italian.

Slide 16 – infectious diseases – controller of human populationsSo the major cause of death at the turn of the century, 1900, was infectious disease. The average life span at the turn of the century, 1900, was 45 years of age. You’re not even gonna get your student loan paid off by 45 years of age. If this were still 1900, you know, your practice is just getting started and you die. Bummer! 1900. But since you know about


infectious disease because I’m gonna teach you, you’re not gonna die. But imagine in 1900, and this was, my father was born it was after 1900 but image his generation and his grandparents, 45 was the average lifespan. Now a lot of that was due to infant mortality. It was the discovery of Louis Pasteur, in Paris France, who changed all of this, not by himself but because of the germ theory. So hygiene, sanitation where the greatest institutions for cutting down on infectious diseases so that we now live a lot longer and you get lectures from people like me.

Slide 17 – Examples of the influence of infectious diseases on historySo all the history is underpinned, again I told you Mexico, there’s a book called the taming of the wild west and they talk about these gunslingers. No, the wild west was tamed by infectious disease because it killed off all the natives. You guys have a little influenza down there, huh. Is that what I’m hearing? Can you cough again, I can recognize what… I told you not to sit in the front! You’re gonna get picked on, my favorite people no doubt. American civil war, far more people died of infectious disease than gunshot wound. I’m gonna tell you a tiny bit about the Napoleonic wars, some people in years past don’t want to hear about Napoleon, they can’t figure out what Napoleon had to do with dental caries or cutting a class II prep. I don’t know if I can tell you how to cut a better prep from Napoleon but I will tell you that Napoleon was very much concerned and one of the first epidemiologists involved with dental caries. So this is a great Napoleon Bonaparte, and his primary concern – and I will show you in a minute – was dental caries. Who would’ve all thought? Well, the fall and decline of the Roman empire, I know you all had to read that somewhere, it is like that thick. Boring! Has nothing to do with the conquest of by Caesar, Augustus or any of the other legion generals. It had to do with the fact that when the Romans went to Egypt or the rest of the world, they went to all different parts of the rest of the world, they would bring captives back to Rome. And they’d march them through the streets of Rome. Well these captives also had infectious diseases that didn’t make them sick because they grew up with them. So if somebody came back with a malarial infested area they’d bring that back to Rome, they’ll bring back yellow fever and other infectious diseases. So people in Rome became very susceptible, they’d never seen these infectious diseases before, became very susceptible. Some would say the fall of the Roman empire was due to infectious disease. And then it’s what I call un-natural selection because we’ll make the Darwinian case in a minute.

Slide 18But I’ll show you the book I’ve been looking for the book I got this from for a long time. Anybody read French? Parlez vous Français? Ah! Can you read this? Well you don’t have to read it for the class. Basically so you know I’m not lying that’s all. Ok. What I tell you is the truth, it’s all there. Napoleon was very concerned about recruiting people for his army. Many millions of men fought in Napoleons army, and so what he realized early on was that men, sorry women I’ll get to you later, men who fought in his army who had bad teeth were bad soldiers. So imagine 200,000 men parked out, camped out you know around the campfire with their rifles and stuff and somebody had a tooth ache. Well for those of you who haven’t experienced what a real, culminating chronic tooth ache is like it’s awful. And in his army, soldiers would rather. First of all they kept everyone up at night and number two, soldiers would rather die than suffer that pain. The pain is just unspeakable. When you


see your first patient with a chronic cellulitis tooth and you touch it you’ll know what I’m talking about. So this was a big problem with the French army and they ate a lot of carbohydrates so the food wasn’t that great, but they’re eating a lot of carbohydrates, of course they’re oral hygiene stuff which had nothing to do with it but was really bad. The dentist at the time was the French key, which was a little extraction device that you put on the tooth that had a T shape and you’d twist like this and pull out the tooth, no anesthesia, called the French key. I should, I’ll find a picture for you. Well half the time it broke off the buccal plate, so it ended up fracturing the mandible or the maxilla. Terrible, terrible remedy. Anyway so Napoleon says go, and he had savants and these savants were from Alexandria, Egypt, they should go to the country and survey the men in different parts of France. And tell me where the best place is to recruit soldiers who don’t have tooth decay. So they did and they mapped it. So this is a map done by Napoleon Bonaparte’s savants, 1800 or so, of the caries rate in France. Amazing. So he would only recruit from those parts that had low caries rate. Now there’s a term used in today’s military called 4F. Any of the guys done military service? You don’t have to raise your hand. If you got a 4F that means you were exempt, you had flat feet, you were mentally incompetent, all kinds of reasons, you smoked too much marijuana I don’t know. If you got a 4F you were exempt. Well 4F is used in today’s military and it comes from Napoleon. And what 4F means is four front teeth. 1, 2, 3, 4. Why would a solider need four front teeth? He’s not going to be meeting too many girls in camp. Why would a soldier need four front teeth? Well how would you know this answer? Because I told you before, did I? No, you never heard it before? Ok tell me why.

[Student] – Biting?

[Dr. Caufield] – Biting? Good. So you bite someone’s ear off if you run out of ammunition. You’re partly right. The muskets’ that you loaded you had to bite the gun powder off with your teeth. You put the musket ball and then you rammed it in. If you didn’t have four teeth and people were charging, and you’re there nibbling at the thing, you’re not gonna be very good on Napoleon’s front line. So if you were missing four teeth, so in the Vietnam war, there’s many people including myself who were conscientious, objectors , whatever, but one of the exemptions was missing front teeth. If you had too many restorations they didn’t want to bring you into the army because they had to fix it before they sent you so there’s people who actually had teeth extracted to avoid the draft. That’s pretty drastic. I went to dental school so I was fine.

Slide 19 – The “rules”Ok, I shouldn’t talk… spend so much time. So here’s the rules. And there’s only a couple of them for all infectious diseases. And you can apply these. So any time someone gives you a lecture on infectious disease of any kind try to think of these rules. Number one, there’s a Darwinian selection on the host but also on the parasite, there’s selective pressure for both of them to survive and perpetuate the species. This is old, old stuff. But it happens to both the host and the parasite. Ok? So there’s another aspect to this at the molecular genetic level called the selfish gene. But let’s just think about bacteria, for example, and humans. There’s Darwinian pressure for both of them to survive. And if they live together in the same compartments, for example the same space, the same ecosystem, they need to co-


evolve together. So co-evolution means that if I evolve, my parasites evolve. Every host that has parasites, and they all have parasites, they have to go through co-evolution, both evolve. So as this is an old statement, I’m not exactly sure if this is still true, as the host becomes more complex, this is thinking about humans, the parasites become more complicated. I’m not sure that’s true. I’m not sure that’s true. What it’s trying to say is that as the host develops more and better immune systems, better ways of evading parasites, the parasites figure out ways to cope.

Slide 20 – The “rules” (cont’d)Now evolution favors stability. So we live in environments full of quote parasites, they outnumber us and so we need to make friends with our parasites and we need to co-evolve so that neither one hurts the other too much. And I’ll make this point, HIV is a very good example. Early on introduced in the humans from the chimpanzees. Very lethal, very unstable, not good for either one. Ebola, you’ve been reading about Ebola, Ebola wipes out entire villages it’s probably been doing that forever. But when people in villages can travel, and one of the physicians whose been treating it who’s able to travel can bring the disease elsewhere. But in the old days, if there was a virulent infection it would wipe out the entire population that were susceptible, there were maybe a few survivors who would then go on to the next generation. Those survivors would then have children that were also resistant and it would go that way. So it’s Darwinian all the way. It’s important that the host, it’s important that the parasite not kill off all the host. If you do that you lose self interest, you lose your free ride, so a parasite that’s too lethal is not a good parasite.

As parasites and host evolve, and this is particularly true with a bacteria involved with dental caries, the parasite becomes more species specific. So we have an E. coli in our GI tract and cows and pigs have another E. coli, one of which is 0157, and both E. coli, same species but they habitate different hosts. So when 0157 gets in the human it causes lethal disease, but it really evolved and belongs in the cow. So species specificity, so if you find a bacteria associate with humans that’s only found in humans, you could make the judgment that it’s fairly well evolved. If you find a bacteria that just infects pigs, cows, camels, everything else, it maybe not be that well evolved. So it’s all in the process of evolution, I’ll show you in a second. As parasites become more evolved with their host they become specific to tissue and sites. So bacteria that may cause dental caries affect the teeth, they colonize only the teeth, they don’t colonize the tongue, the throat. Strep pyogenes colonizes epithelial cells of the throat but they don’t colonize the teeth so there’s a specificity that develops. Specialized niches. This is evolution. As you evolve you become more specialized. As you go to dental school, you’re not a specialist, you become a DDS, as you specialize, evolution or something. I don’t know. That’s probably not the best, I could do better than that but let me warm up.

Infection is the rule. I’ve gotta say this a million times. Infection just means co-habitation. Disease. If you have disease, something is wrong with this host parasite relationship. Once you understand what’s wrong with it you can work on fixing it. Parasites almost always outnumber the host. Of course, sorry the exception to that. And then there’s a really great concept I would love to give 30 minutes to an hour on parasitic degeneration, guess what, I don’t have time. But this is a common theme that’s very important. Parasites, look if I could


get someone else to do my work for me, why should I expend an ATP for every base pair of replication if I could get someone else to do it. Why should I make an amino acid arginine if my host can do it. Free lunch. So, the less of that that I have to do, the less work I have to do, the more I can get rid of DNA. And boy that would be great, to get rid of that DNA, because it costs a lot of ATP to make that DNA. Lots of ATP. So parasites degenerate, they lose more and more of their DNA, or RNA, why? Because it’s more efficient to better parasites if they degenerate. Sounds like a contradiction doesn’t it? You’re degenerating but you’re getting better. Right? I’ll give you an example in a minute.

Slide 21 – Co-evolutionSo again, co-evolution, co-evolution, co-evolution. Nothing happens by itself. So you think you’re getting smarter while you’re studying at night. Don’t study this lecture because you’ll know everything. Your bacteria on your body are probably also reading little books too, they are co-evolving, they are keeping up with you. Does that help? It’s totally bad metaphor but they’re not just sitting there they are co-evolving too so if you’re evolving getting smarter, learning about infectious disease, they’re reading up on it too. I don’t know what kind of books they have but they’re reading the DNA. One base at a time.

Slide 22[Skipped]

Slide 23 – Co-evolutionSo here’s co evolution, your ancestors the hominid, we call ‘em. And exogenous bacteria let’s say Strep pyogenes, a 100 million years ago, no they wouldn’t be your ancestors. 250,000 to a million years ago, depends if you want to go to homo erectus or further, let’s say 2 million years ago, when Strep pyogenes first came in contact with your ancestors the relationship was very very antagonistic. Let’s say Strep pneumonniae, let’s not use pyogenes, Strep pneumonniae, and one would kill the other. They both couldn’t co-exist. With time, eons and eons of time, we are talking millions of years so hundreds of thousands of years, these bacteria with their host became evolved to co-evolve to the point of symbiosis. Now they never quite got to symbiosis necessarily because that means everyone lives in a happy state, doesn’t happen, but the bacteria we called indigenous bacteria are the result of co-evolution that has occurred with our ancestors originally started very unstable, very antagonistic and co-evolved into a more friendly I won’t hurt you, you won’t hurt me. You benefit me, I’ll benefit you. And what we are, the human body, is mostly bacterial cells, I’ll show you that, but we have co-evolved. We have co-evolved and they’re happy. I talked to them this morning, I said how you guys doing? Got a little sun and took two weeks vacation, got a little sun. Are you happy? And they told me they were happy. They like their grits and their ribs, that was the best part.

Slide 24So your ancestors, not mine, but yours. On the Serengeti. If you ever get a chance to go to the American museum of natural history this is one of the dioramas. It’s in the origins of humans, on the first floor, and that was done by a colleague who works with us on our grant in dental caries, Rob Dasalle [?], he was the curator of that exhibit, and you look at this but you know what they were gonna take some meat but look at both of them they’re


looking behind them, there’s something else coming. Look at where they’re looking. When you go to the museum try and find out what they’re looking at. It’s far scarier than the fat and the taste of the meat. Give you something to look forward to.

Slide 25 – Spectrum of host-parasite relationshipsSo think of all infectious diseases as some form of co-evolution. And so in the very beginning of the relationship between the host and the parasite it’s very unstable. I don’t like you, you don’t like me. I’m gonna kill you, you’re gonna kill me. That’s the way the relationship is. It’s like when you meet a stranger, first time you meet him, like you guys in the front, we’re kind of wary of each other. But as you get to know each other, we become more friendly. It’s possible I don’t know. HIV is a good example, recently introduced into humans, unstable antibiosis, as this evolves we have indigenous bacteria. Now pathogens, all pathogens, pyogenes, pneumonniae, anyone you can name, any virus, influenza, falls somewhere on this spectrum. And by knowing where it is on this spectrum you can probably calculate how many hundreds of thousands of years it would take to evolve until everyone’s happy. HIV will evolve at some point to become like in chimpanzees, indigenous. It doesn’t kill chimpanzees. They’ve learned how to co-evolve and it’s probably taken a very long time. Is that clear? So every infectious disease can be put somewhere on this. So bacteria that cause dental caries is on this end of the spectrum. They are over indigenous, they’ve co-evolved, they are part of our body. And I’ll make that case why they’re important.

Slide 26 – Parasitic degeneration as a result of co-evolutionSo let me try and go a little… I’m not gonna do parasitic degeneration. You got the concept. So here’s the question, what infectious agent represents the ultimate example of parasitic degeneration. I told you losing DNA or RNA is in your best evolutionary favor, you don’t want to lose too much but if you have a host that’s making it and taking care of you, you don’t need to code for arginine and every other pathway, get it from your host. This is what the indigenous biota and many pathogens do. They evolve or they lose the ability to live free. So they become dependent. Dependent is a one way street, you can only go to more dependent. So what infectious –so when we think of… In the early days you’d say well bacteria is smarter than a virus, because the virus is just a little tiny thing, well actually the virus is smarter, it’s more evolved. Who would guess? 5.6 kb of coding, what a stupid organism, it can’t even live by itself. No, it’s evolved. Highly evolved because it’s got the host doing everything for it. Does the replication, does everything. So highly evolved parasite is a virus. Well we now know there’s more…

Slide 27 – Parasitic degeneration…other forms that are just segments of DNA. That infect the host and completely change its metabolism. Prions, who would have ever thought? Ok so we are not gonna be talking about those.

Slide 28 – Disease violates the host-parasite rulesSo when you have disease, disease is the exception to those rules, so when you have disease they’re accidents. They violate the rules. Disease is not supposed to happen, it’s unstable. Bad for the host, bad for the parasite. Most infections are what we call subclinical, you don’t


see them. They’re just subclinical. That’s the clinical name. Infection, the rule. Disease the exception. Infection, the rule. Disease… if you have disease there’s something wrong with the host parasite relationship.

Slide 29[skipped]

Slide 30 – Species jumpingWell it’s because of this phenomenon. I’ll just cut through it. How can disease be the exception, why is it so exceptional. All forms of disease, major diseases I listed and I’ll go through them in just a second, have to do with species jumping. What does that mean? That means that the species that has co-evolved with a pig jumps into humans, it doesn’t have that co-evolutionary experience. And so when influenza comes from ducks and from pigs into humans and there’s a mutation that occurs it’s extremely lethal. The pig’s fine. Duck’s ok. Co-evolution with them. But when it mutates from that host it’s called zoonosis. Let me show you the term. Zoonosis. So when E. coli 0157 comes from cattle in the feed lots due to antibiotics and all the bad things that happen and they get into humans, extremely lethal. Would you call E. coli lethal to humans? No, not my E. coli. My E. coli, your E. coli’s not lethal we’ve co-evolved. But it the E. coli comes from another animal, species jumping into humans, then we have major problem. Got the idea? Zoonosis. Species jumping. All disease is in effect, in effect is from species jumping. Now think about caries, just think about it.

Slide 31 – High morbidity diseases have natural hosts other than humansSo all these infectious diseases that we studied, I spent a lot of time in dental school, post doc and even undergrad studying infectious diseases. These are the classics: influenza, the plague, polio, tetanus, you can read them, smallpox, malaria, HIV. All of these are not human, don’t belong in humans. They belong in another host system, that has co-evolved. And they’re happy in those hosts. When they jump species, maybe because it’s a very cold winter in England and all the rats move into the house, it has happened, it’s called the bubonic plague, and the fleas have nowhere to go and everyone’s crowded and the sanitation’s terrible you get the bubonic plague. So influenza, ducks, pigs. Fleas, black rats. Polio was found in horses so Henry Ford when he invented the model T automobile to replace horses in America and other countries if you had horses, who rode horses right? I didn’t but my father did. And so when the automobile came into all the horses started disappearing, well children who were getting polio virus from the horses. Subclinically as young kids because there were horses everywhere, so horses would drop their stuff, you know, you’ve been to central park, and so they would get the virus and the children would develop immunity. Well when the horses disappeared the children weren’t getting that dose, it’s called the hygiene theory, and so what happened was that polio took off, became epidemic because children were no longer experiencing polio as young kids. They got it later as teenagers, it was devastating. OK so that was the Henry Ford story. Tetanus, measles, smallpox, cows, Europeans had measles and smallpox but they had cows. The people who lived in the Americas didn’t have cows, animal husbandry, so Europeans came in with measles, smallpox, subclinical carriers and gave it to the American Indians, etc. HIV, chimpanzees, this is recent. Beatrice Hahn and Paul Sharp went through Africa to come ten years sampling chimpanzees. There’s a lot of subspecies of chimpanzees, and they found


the chimpanzee that was the carrier of the original HIV. It’s probably been there for a long time but when you can move people out of the Congo and other parts to other countries it happens. SARS, you’ve heard of SARS. Bats. MERS, the new one. Middle east. About 90% of Saudi Arabians, middle east, respiratory syndrome. It’s a virus, a coronavirus. It’s host, where did it come from? Looks like it came from camels. Maybe not camels, maybe bats because it’s related to SARS. Bats bit the camels. This is complicated stuff. Who’s the original host. Lots of bats flying around with SARS and MERS and they inadvertently bite a camel, the camel gets infected and infects humans. Species jumping. K? Dental caries fits into here anywhere? Where can I fit dental caries, it’s an infectious disease. You can’t! It doesn’t, it’s not because the natural reservoir of dental caries is us. Humans. There’s no species jumping. There’s two reasons for you to have a girlfriend or boyfriend with bad teeth, the most important is you need them for the boards. My ex-wife will attest to that. Wasn’t pretty. OK, I won’t tell you the second reason. I won’t go.

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19: Host Parasite I