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. Im gonna
pick on the people in theback so 1,2,3,4 youre 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 youre good
sports and didnt come beat me up. You can try.

Today. Thanks for coming. This is a two hour lecture, well take a break. I have a short quiz
for you that you will absolutely enjoy and I guarantee everyone whos here will get an A+.
Yea. If you listen carefully to what I say today you dont 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 dont know where youll 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. Lets give it a try.

The topic today underpins everything there is to do with the human condition with
infectious diseases, and Im gonna talk about infectious diseases, and Im gonna tell you
why its important. And I could ask you know why you think infectious disease is
important. Hey Im a dentist. What do I need to know about infectious diseases? Well I
suggest to you that the two major diseases, and Ill 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, theyre gonna ask you why you consider this is an infectious
diseases and what aspects. And theyll 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
thats another story for another time. But it caught everybody by surprise because we
didnt know much about HIV. And that study was done by the CDC and its a beautiful study
but we dont 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 Relationship
So 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. Its an old term but its convenient to use and its 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 its an old term and its gonna
be convenient for us to use. So think, Ill define the host and Ill 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.
Itll help you navigate. At the second part of the lecture well talk about the indigenous
biota, used to be called the indigenous, the other genome, the other part of the human body
Transcribed by David Landsman 8/1/14
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 were going to bring dental caries into the argument because its 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 its gone. No, its not. You dont have time for
the walking dead! Of course not, I dont 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 dentists
Why 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 dont understand, its rising, its falling in some populations. We dont 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 well go through that
gyration as well because it is of great national and international concern. So we dont know
what is causing an increase in caries. I do, I will tell you that at some point. But its 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 didnt 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 dont really address the cause. Ya, we need better approaches to caries
management. We dont want to put ourselves out of business right? Not until we pay off the
student loan, right? Ok. So. Thought Id make that point. And youll be surprised that your
patients are better informed today and theyll read articles from the obstetrician that say
dont, if your babys pacifier falls on the ground, mothers sometimes pick them up and put
them in their mouth to clean them. I wouldnt 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, its like a folk myth that has gone on and now the transfer of these bacteria
and how theyre done and its totally untrue. And yet it gains more and more prominence.
So youll see this all the time. And the patients will ask you. And other advice people say is
dont share your utensils with your children. Generally we dont, I dont, but I dont know. If
you got some mashed potatoes, got some grits, youre gonna take a spoon and put it on the
kids plate but youre not gonna lick it, well you might, but thats some more advice given
by the dental association is dont share utensils. Duh! So, and thats not how its transferred
anyway. Thats 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.

Transcribed by David Landsman 8/1/14
Slide 5
Dental 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 6
So heres 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 its due to
crowding and other things, but its 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 heres 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 dont know how to do that, some of you would be susceptible if it was
influenza. Some of you would get it, youd wake up in the morning and youd be missing a
bunch of teeth. Im exaggerating. But if its 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. Its 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 its not transferred
horizontally like influenza and others. Ill develop a theme. So its called non-communicable
which its a chronic disease, and its listed with heart disease, diabetes and asthma. Its
probably appropriate.

Slide 7
All 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 Im gonna
define the host parasite relationship, big picture, applies to all infectious diseases and then
well go and move back into caries, back into infectious disease, back into caries.

Slide 8
Definition. 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 thats, 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. Arent we? We think we are. So anything
less than human has got to be a parasite, right? So thats how that came about. It doesnt
really Ill show you an example, and itll be part of the quiz- of where that is probably not
true. Parasites live at the expense of the host. And theres 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 doesnt 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 were infected, everyone here is infected with
bacteria does not mean, or viruses, doesnt mean you have disease. In fact, most infections
Transcribed by David Landsman 8/1/14
dont lead to disease. And well develop that theme. So most infections, we use the word
infections, just simply means cohabitation. And its mostly harmless. And it is symbiotic.
But well do the exceptions ok.

Slide 9 Rule #1
Now 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 were here is because of mutations, mistakes, DNA didnt replicate properly. Youre
ancestor, there was a couple mistakes in there and thats why youre such, you know, smart
guys, sitting in the front row. Because of those mistakes weve mutated and where we are,
going to lectures and going to dental school and looking at our google mail. So nothings
100%, theres an exception to everything, so no matter how clever you think we are at
evading infectious disease or defeating it theres always a way around it. So nothing that I
say is 100%, theyre general rules and theres exceptions to everything. We just found a
couple today that were exceptions. We didnt 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 its still not final
but anthrax probably came from a mammal that is now extinct and just couldnt find the
right host. Ill tell you more about that a little bit later.



Slide 10 Venn Diagram infectious Dx
This 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 whats called
a carrier state, this is traditional, so Strep pyogenes which causes strep throat, George
Washington died of Ludwigs angina. Strep pyogenes, 20% of you in this room are carrying
Strep pyogenes as a carrier, youre not really sick. How many people just feel really tired, a
little malaise, yea every day right? No. Youll feel different today. 20% are carrying Strep
pyogenes, youre asymptomatic carrier. So theres carrier states, its important that people.
More people carry pneumococcus. Some people carry influenza, so theres 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
Transcribed by David Landsman 8/1/14
So heres the Venn diagram for caries, same Venn diagram same. But we put in bacteria
because we know its 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 theres other factors that influence
dental caries than just bacteria. Now this is a microbiology class so Im 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 dont 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, its got caffeine and just tons of sugar. You
almost have to weigh the sugar in there to get mountain dew to go into solution, its so
much. Best thing for dentistry in the world, Ill tell ya, mountain dew. No its not because
you cant fill those teeth, you cant restore them, not this lecture another one Ill show you
some restorations we did in Tennessee on a kid doing the dew.

Slide 12 Infectious diseases of humans
Ok so, infectious disease, just read through this its 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 its 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, theres a lot of them and more
coming. Because theres so much information now with the molecular aspect of infectious
disease, we went back and tried to apply whats called Kochs postulates, Ill talk about that
later, youve heard of Kochs postulates to dental caries. And since the 1960s it seemed that
that was the way to go. Its totally wrong but we didnt 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 epidemics
Now when you think of the great epidemics and theres 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
didnt. The flu, Italian, influenza. Under the influence, Im feeling a little sick today. Im not
going to dental school micro class today because I got a little flu-like, Im flu-ish. Influenza
killed more humans than any infectious disease in the history of mankind. 1919, 1918
killed 50 million people and thats only what they could get on the census, its probably
more than that. So this influenza, not necessarily whats going around you get those little
Transcribed by David Landsman 8/1/14
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 dont wanna get measles, dont
want it. So make sure you got your vaccinations. You have to have them for dental school
right, for measles. Dont they check that? You dont want it guys, men you dont want it.
Women dont want it either but men particularly dont 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. Wasnt 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 couldnt swim in Lake
Erie, well it turns out you dont 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 its not a good place to swim. Our mother didnt care she would take us up and
say go swim in lake Erie, because youre a pain in the ass, and actually dont come back. No
she didnt really say that. But polio was a big deal. If you got paralytic polio you spent the
rest of your life in whats called the iron lung, where youre 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 didnt
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,
well talk about a little bit later.

Slide 14 is caries like this?
So when we think about infectious disease now, and Im a cariologist so Im talking to my
physician friends in infectious disease next door and they want to know, well, were dealing
with bubonic plague, are you trying to tell me that dental caries is an infectious disease?
Youve 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 its a horrible way to
die. Dental caries, most prevalent infectious disease of modern humans, is it gonna turn
into the plague? Its 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. Youve 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? Wheres our model? Heres a woodcarving from Daniel Defoe.
Anyone tell me what Daniel Defoes famous book was? Gets extra points with me, dont tell
me now. Daniel Defoe wrote this book called the journal of the plague years. Its amazing.
Its absolutely amazing reading. This is the wood cutting, this is the guy who walked around
Transcribed by David Landsman 8/1/14
the village and he had the stick he had the hat, this is the first OSHA, you know how youre
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 couldnt 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 dont
know, it is a kind of hipster look. But I couldnt get the nose, and Im giving this talk in the
biggest dental school in the world, by the way, in Mexico City. I dont know if you know
which one that is but its 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 Im 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 its 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 its 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 didnt get the plague. Now it wasnt because of the nutmeg, maybe,
maybe not, it was because you were rich. But still, they correlate, doesnt mean causation.
Ill move on a bit quicker. The biggest death of humans was 1918 called the Spanish
influenza, right? Spanish influenza, 50 million people, shouldve 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 thats actually where it came from, the big pig
farms -- so we didnt want that so we called it Spanish influenza, a PR masterpiece.

Slide 15
Well this is in the New York Times, I wont go into the word quarantine. You know, hold
somebody quarantine them for 40 days. Its in Italian, I just kinda trying to learn some
Italian.

Slide 16 infectious diseases controller of human populations
So 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. Youre 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
Transcribed by David Landsman 8/1/14
infectious disease because Im gonna teach you, youre 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 history
So all the history is underpinned, again I told you Mexico, theres 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 Im hearing? Can you cough again, I can recognize what I told you
not to sit in the front! Youre gonna get picked on, my favorite people no doubt. American
civil war, far more people died of infectious disease than gunshot wound. Im gonna tell you
a tiny bit about the Napoleonic wars, some people in years past dont want to hear about
Napoleon, they cant figure out what Napoleon had to do with dental caries or cutting a
class II prep. I dont 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 wouldve 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 theyd march them through the streets of Rome. Well these
captives also had infectious diseases that didnt make them sick because they grew up with
them. So if somebody came back with a malarial infested area theyd bring that back to
Rome, theyll bring back yellow fever and other infectious diseases. So people in Rome
became very susceptible, theyd 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 its what I call un-natural selection because well make the Darwinian case in a
minute.

Slide 18
But Ill show you the book Ive been looking for the book I got this from for a long time.
Anybody read French? Parlez vous Franais? Ah! Can you read this? Well you dont have to
read it for the class. Basically so you know Im not lying thats all. Ok. What I tell you is the
truth, its 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 Ill 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 havent experienced what a real, culminating chronic tooth ache is like its 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
Transcribed by David Landsman 8/1/14
see your first patient with a chronic cellulitis tooth and you touch it youll know what Im
talking about. So this was a big problem with the French army and they ate a lot of
carbohydrates so the food wasnt that great, but theyre eating a lot of carbohydrates, of
course theyre 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 youd twist like this and pull out the tooth, no anesthesia,
called the French key. I should, Ill 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 dont have tooth decay.
So they did and they mapped it. So this is a map done by Napoleon Bonapartes 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 theres a term used in todays military called 4F. Any of the
guys done military service? You dont 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 dont know. If you got a 4F you were exempt. Well 4F is
used in todays 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? Hes 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 someones ear off if you run out of ammunition.
Youre 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 didnt have four teeth
and people were charging, and youre there nibbling at the thing, youre not gonna be very
good on Napoleons front line. So if you were missing four teeth, so in the Vietnam war,
theres 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 didnt
want to bring you into the army because they had to fix it before they sent you so theres
people who actually had teeth extracted to avoid the draft. Thats pretty drastic. I went to
dental school so I was fine.

Slide 19 The rules
Ok, I shouldnt talk spend so much time. So heres the rules. And theres 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, theres a
Darwinian selection on the host but also on the parasite, theres 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 theres another aspect to this at the molecular genetic
level called the selfish gene. But lets just think about bacteria, for example, and humans.
Theres 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-
Transcribed by David Landsman 8/1/14
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, Im not exactly sure if this is still true, as the host
becomes more complex, this is thinking about humans, the parasites become more
complicated. Im not sure thats true. Im not sure thats true. What its 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 (contd)
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 Ill 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, youve been reading about Ebola, Ebola wipes out
entire villages its probably been doing that forever. But when people in villages can travel,
and one of the physicians whose been treating it whos 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 its Darwinian all the way. Its important that the host, its
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 thats 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 thats only found in humans, you could make the judgment
that its fairly well evolved. If you find a bacteria that just infects pigs, cows, camels,
everything else, it maybe not be that well evolved. So its all in the process of evolution, Ill
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 dont colonize the tongue, the throat. Strep pyogenes colonizes
epithelial cells of the throat but they dont colonize the teeth so theres a specificity that
develops. Specialized niches. This is evolution. As you evolve you become more specialized.
As you go to dental school, youre not a specialist, you become a DDS, as you specialize,
evolution or something. I dont know. Thats probably not the best, I could do better than
that but let me warm up.

Infection is the rule. Ive 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 whats wrong with it you can work on fixing it. Parasites almost always
outnumber the host. Of course, sorry the exception to that. And then theres a really great
concept I would love to give 30 minutes to an hour on parasitic degeneration, guess what, I
dont have time. But this is a common theme thats very important. Parasites, look if I could
Transcribed by David Landsman 8/1/14
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 its more efficient to better parasites if they
degenerate. Sounds like a contradiction doesnt it? Youre degenerating but youre getting
better. Right? Ill give you an example in a minute.

Slide 21 Co-evolution
So again, co-evolution, co-evolution, co-evolution. Nothing happens by itself. So you think
youre getting smarter while youre studying at night. Dont study this lecture because
youll 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? Its totally bad
metaphor but theyre not just sitting there they are co-evolving too so if youre evolving
getting smarter, learning about infectious disease, theyre reading up on it too. I dont know
what kind of books they have but theyre reading the DNA. One base at a time.

Slide 22
[Skipped]

Slide 23 Co-evolution
So heres co evolution, your ancestors the hominid, we call em. And exogenous bacteria
lets say Strep pyogenes, a 100 million years ago, no they wouldnt be your ancestors.
250,000 to a million years ago, depends if you want to go to homo erectus or further, lets
say 2 million years ago, when Strep pyogenes first came in contact with your ancestors the
relationship was very very antagonistic. Lets say Strep pneumonniae, lets not use
pyogenes, Strep pneumonniae, and one would kill the other. They both couldnt 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, doesnt 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 wont hurt you, you wont
hurt me. You benefit me, Ill benefit you. And what we are, the human body, is mostly
bacterial cells, Ill show you that, but we have co-evolved. We have co-evolved and theyre
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 24
So 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. Its 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 theyre
Transcribed by David Landsman 8/1/14
looking behind them, theres something else coming. Look at where theyre looking. When
you go to the museum try and find out what theyre looking at. Its far scarier than the fat
and the taste of the meat. Give you something to look forward to.

Slide 25 Spectrum of host-parasite relationships
So 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 its very unstable. I dont
like you, you dont like me. Im gonna kill you, youre gonna kill me. Thats the way the
relationship is. Its like when you meet a stranger, first time you meet him, like you guys in
the front, were kind of wary of each other. But as you get to know each other, we become
more friendly. Its possible I dont 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
everyones happy. HIV will evolve at some point to become like in chimpanzees,
indigenous. It doesnt kill chimpanzees. Theyve learned how to co-evolve and its 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, theyve co-evolved, they are part of our body. And Ill make that case why
theyre important.

Slide 26 Parasitic degeneration as a result of co-evolution
So let me try and go a little Im not gonna do parasitic degeneration. You got the concept.
So heres 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 dont
want to lose too much but if you have a host thats making it and taking care of you, you
dont 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 youd say well
bacteria is smarter than a virus, because the virus is just a little tiny thing, well actually the
virus is smarter, its more evolved. Who would guess? 5.6 kb of coding, what a stupid
organism, it cant even live by itself. No, its evolved. Highly evolved because its got the
host doing everything for it. Does the replication, does everything. So highly evolved
parasite is a virus. Well we now know theres 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 rules
So when you have disease, disease is the exception to those rules, so when you have disease
theyre accidents. They violate the rules. Disease is not supposed to happen, its unstable.
Bad for the host, bad for the parasite. Most infections are what we call subclinical, you dont
Transcribed by David Landsman 8/1/14
see them. Theyre just subclinical. Thats the clinical name. Infection, the rule. Disease the
exception. Infection, the rule. Disease if you have disease theres something wrong with
the host parasite relationship.

Slide 29
[skipped]

Slide 30 Species jumping
Well its because of this phenomenon. Ill just cut through it. How can disease be the
exception, why is it so exceptional. All forms of disease, major diseases I listed and Ill 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 doesnt have
that co-evolutionary experience. And so when influenza comes from ducks and from pigs
into humans and theres a mutation that occurs its extremely lethal. The pigs fine. Ducks
ok. Co-evolution with them. But when it mutates from that host its 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. colis not
lethal weve 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 humans
So 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, dont belong in humans. They belong in another host system, that has co-evolved.
And theyre happy in those hosts. When they jump species, maybe because its a very cold
winter in England and all the rats move into the house, it has happened, its called the
bubonic plague, and the fleas have nowhere to go and everyones crowded and the
sanitations 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
didnt 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, youve been to central park, and so they would get the virus and the children would
develop immunity. Well when the horses disappeared the children werent getting that
dose, its 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 didnt 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. Theres a lot of subspecies of chimpanzees, and they found
Transcribed by David Landsman 8/1/14
the chimpanzee that was the carrier of the original HIV. Its 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, youve heard of SARS. Bats. MERS, the new one. Middle east. About 90% of
Saudi Arabians, middle east, respiratory syndrome. Its a virus, a coronavirus. Its host,
where did it come from? Looks like it came from camels. Maybe not camels, maybe bats
because its related to SARS. Bats bit the camels. This is complicated stuff. Whos 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, its an infectious disease. You cant! It
doesnt, its not because the natural reservoir of dental caries is us. Humans. Theres no
species jumping. Theres 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.
Wasnt pretty. OK, I wont tell you the second reason. I wont go.