 So it's time to start I guess Thank you for coming all. This is my updated Abstract mainly in this now has reached every corner of China and The continents although I haven't come across anything specifically indicating that South America Has had cases, but it's If not, then it's just a short matter of time I'm sure because they're involved in international travel as much as any other Region of the globe But at this point we have 9700 pieces and 213 deaths that was as of about 15 hours ago WHO declared this a an International health emergency, which I think is appropriate. Yeah, North North America is certainly involved This is a slide I made just for fun. I used the image of a MERS virus, but in the collective consciousness, it's The idea of viruses is pretty scary. It even ends up in lyrics of music The reason this virus that came out of Wuhan, China is called 2019 in covee is because it was 2019 really probably the index case or first case occurred in late November and It was December before they realized they had something going on and so as 2019 was the year it started Yes, I am going to talk about that in a bit date and In stands for new or novel that's it's not unique the usage of the modifier in Is not unique to this particular virus. It's used with other coronaviruses as well. And of course cov refers to coronavirus So that's the that's the basis of the name the name's pretty simple and Want to find information about it? You could always write Wuhan coronavirus, but if you do a search for 2019 and covee Then you will get a lot of stuff. I Like this slide and I have used it in the past Because it goes over the traditional phylogeny, but a Point I want to make is They Have traditionally applied this genus species family order and so forth As well as they can to viruses. I don't think viruses are alive, but Genus and species give a familiar handle almost humanized The virus if you can put a name on something you can get your head around it or get a sense that you have Handle well they reproduce by taking over the machinery of other living things They're not stand alone and I Think of viruses I made this analogy earlier as Sometime in the future will have a lot of autonomous vehicles Imagine if some of them get hacked or subverted or someone inserts Messes with the code someone wants to hop up their autonomous vehicle and so it Makes mistakes Because it's not doing what it was intended to do and people start getting hit on the street by Autonomously driven trucks and things That's sort of like catching a virus These things are little machines. They're biological machines. I don't think of them as alive, but at any rate in 1993 I really liked virology and I I wanted to pursue it and I would have loved to Inverted myself into a professional virologist that didn't have the Resources and choice to just go off and do something I wanted to do So I just remained a faculty member in a medical school But I wrote a book chapter in 1993 and respiratory viruses and there's an easier to read Bit here I use this slide back when I talked about Type 1 double-stranded DNA viruses like human papillomavirus or HPV This is the David Baltimore classification of viruses. It goes back to 1971. That's when he's really distinguished brilliant guy But it only makes sense to classify these things based on their genetic machinery and That's what determines how they behave and the genetic machinery is really pretty distinct and Amazing amazingly intricate even for these little Little strands There are five cold viruses common cold viruses, and that's one of the things I covered in my book chapter back when The most common is probably the rhino virus and they were like 17. I don't know Now those are type 4 viruses with Single strand RNA virus type 4. There's one type of virus for every day of the week and so You can think of the cold viruses Or some are spread over these Two of them are in type 4. I put the four snowflakes and yellow there To emphasize I want you to grab on to type 4 and think of positive single strand RNA meaning that The RNA in this virus acts just like messenger RNA um We're starting to get in what is life kind of discussion here. I guess but One could debate all that but I better stay focused for the moment Um the Adenovirus can cause colds. It's a double-stranded DNA virus. It tends to be a nastier kind of cold and There's in young adults often military Training camps will have an outbreak of those and that kind of thing. That's where it comes up And and has been studied Also influenza and para influenza or type 5 viruses Antisense negative strand RNA single strand RNA 4 and 5 are both single strand Of course plus 5 is an odd number think of that as negative maybe And so These cold viruses don't have to have any They like I say they're in all these different groups better spare it I have a hantavirus there, which is a type 5 virus. That's a zoonosis and zoonotic Organism if you want to call it or an infectious agent And I mentioned that later in the talk But the coronavirus is the one I want to focus on today and particularly Say what we might be able to know about this Likely epidemic we're dealing with so if you can remember david baltimore And seven types of viruses and this corona virus is a type 4 And these RNA viruses generally they operate in the cytoplasm and so they're Kind of in the underground economy They're not dependent on this M phase with mitosis and What the nucleus is doing for their? Business and so that's reason why I put this slide in I'm going to stop and just talk with this slide present. This is a MERS virus I'm going Introduce these things and talk in more detail Over time but This One thing about this virus is you can see why it's called a corona virus. It's an electron micrograph It's about 125 Nanometers in in size a diameter and there are spikes that stick off of it. These are enveloped viruses And these spikes they're they're four structural proteins to this. It's uh, and I Suggested for previous group. Um, if you want to know about this Um, use this acronym men's With a small e because the e envelope Protein is of less abundance the M is the membrane protein and the n is the nuclear Nuclear capsid protein and the s is the spike protein We are all going to die at some point, but Not today. I hope um At any rate The s spikes are um Really quite interesting and they uh define the affinity for the host cell in the SARS virus and I don't know about the MERS if this is true for that I don't know exactly what the receptor is but in the SARS virus, which is the one that uh, started in uh, jordan and was in saudi arabia um around 2012 um, I'm sorry 2002 Missing and messing this up the SARS virus was from china in 2002. Um And what I want to say is that the SARS i'm talking extemporaneously here and just from my slide It It's uh receptor is the angiotensin type 2 receptor now That is a um part of a system that the body uses to make the blood pressure go up In fact, there's there uh anti-hypertensives that are angiotensin inhibitors But this uh, the knock on the door For the is through this s protein spike that you see sticking out of the corona of this corona virus And it uh goes to wherever there are east type 2 or Geotensin 2 receptors in terms of the SARS at least um Again, I'm not sure what the receptors are for MERS. Uncertainly don't Are new one. Um I want to point out that up to 2002 corona viruses for humans were considered pretty benign They were just thought of as cold viruses that caused mild respiratory infections Now they were a problem for livestock and pets and wild animals. They could kill them um, they could cause encephalitis and pigs and uh Flu like symptoms and camels and all kinds of things but uh, generally, uh They were species specific um Trouble is that these viruses reproduce at such a rate and they can undergo a little mutation here and there and uh find a Receptive host um, that's uh trans species um, so this This virus uh has One One long strand of RNA one single Strand of RNA It's not a double strand and it's got about 30,000 bases 30,000 nucleotides on it and of uh rival Uh nucleic acid DNA has deoxyribonucleic acid uh So uh It's that codes for about 16 non structural Genes and or non structural proteins and four structural proteins and a lot of the non structural proteins have multifunction it's really a Fascinating mechanism how it takes over. I'd like him to think to a thug that comes to your door and um weasels their way in and This comes to the door and knocks on it at the um Let's say that in this case of MERS of the SARS anyway the ace inhibitor the ace receptor ace type 2 a receptor And it merges with the uh, so membrane it's got an envelope and There's debate about it, but in that process it, uh, releases or, um Injects its uh Uh single strand um positive sense RNA Uh genome into the cytoplasm And so like a thug that you happened to mistakenly or using bad judgment let into the Into the um Uh No RNA can be double stranded um Anyway, uh, you happen to let this thug into the into your house Get in the locked door where the You know the screening takes place and then they take off their their capsule or their jacket and you see what a thug They look around and say I think I I think I like it here and um, they have uh Immediate access They they tend to associate with the uh endoplasmic reticulum. They have immediate, uh interaction with, um Your own ribosomes And because it's a positive sense RNA it'll produce um A protein products It produces a number of protein products that are Generally referred to as non-structural proteins that will symbol in a complex as multifunction Uh, one of the functions is to replicate the Uh original RNA and to make a negative strand and um Then uh, so it does that um And there is some and evidence it tends to block your own, um messenger RNA transcription Or translation So it has an it's it makes a Some negative strands and then it does two things it will do readings of um parts of that And create positive strand, uh RNA Uh pieces that are sub genomic meaning less not the whole 30,000 Pair base Polymer but pieces of it that uh Go on to be read by the ribosomal machinery and produce proteins structural proteins and others Uh for the cell to have and uh It will also act as replicates to in reverse to re reproduce the whole genome so It's it gets involved through the endoplasmic reticulum to the Golgi process and uh these um the M protein or membrane protein Tends to be the dominant or most important the e protein or envelope protein is of less abundance But uh m protein by itself will not let it if you create those and put them together You won't get self assembly to make viral like particles or v lps Which is how you can make vaccines That's how the hpv vaccine was made for different Types of hpv In this case you would have to have at least the m and the e protein and the nuclear capsid protein Is even even better, but that's what is um intimately around the genome apparently And uh it gets packaged there in the Golgi process and the spike gets added Excuse me if There are extra s spikes. Well, it gets then released And can spread to other cells Now if there are extra s spikes The s spike can get in your own cells membrane and attract it to other um susceptible cells that Often are already infected and they fuse and you can end up with multi nucleot nucleated cells That have virus swarming through both. So they increase their um their space Uh, they increase their neighborhood without getting exposure to the immune system This thing is really a thug This is a street smart uh Under the economy thug that uh takes over and uh Does what it wants and it uses you And it looks at the nucleus there. It doesn't need it and it regards it like deep state Once it gets in there and it's taken over It's like you can't impeach it because your immune system can't get to it So, you know, it's it's a situation you got It's almost like biological politics So anyway I'm just making metaphors um, I wanted to give some Uh definitions Before I leave that whole idea. I just wanted to say you could make a career Studying and research in coronaviruses if you're interested in your right place in your life and that would work It is absolutely fascinating. It's going to be important um And it'll have its uh surges like now uh over time but uh It's it's a Kind of marvelous little machine Uh in terms of its intricacy now a cute um Respiratory distress syndrome, uh That's a serious situation and that's a common outcome of a lot of things sepsis chest trauma I I had mentioned earlier uh Blood transfusion reactions are so unusual people often don't think of them when they see them um, I've seen a few over my career They weren't horrible or severe, but they were they happened, um But blood bank and blood typing and that sort of thing is so carefully done and It's pretty well understood these days um Aspiration uh acid from the stomach is very noxious to the pulmonary epithelium down in the air sacs and anything that causes inflammation term pneumonitis Anything that causes inflammation can make the little walls of the alveoli uh Get inflamed infiltrated with uh inflammatory cells and stiffen So it's they lose their elasticity and um also have inflammatory effects in the smaller airways and um um They fill with fluid And when they fill with fluid that's the hallmark of um of um Acute respiratory distress syndrome. I'll show you some x-rays after a bit, but I will it's an important Uh situation. I wanted you to know about it. Its symptoms would be Difficult rapid breathing dyspnea and uh hypoxia levels of oxygen in the blood Because your ability to exchange gases Get rid of carbon dioxide and absorb oxygen Uh is impaired if you don't have the surface area Have fluid filled spaces there. You're not going to get oxygen exchange um Or gas exchange There's a lot of information on this slide and again, I put I just I know I get People saying these slides are too busy But I figure when people if they are interested enough go back and look at the pdf There'll be more for them to think about um, but ARDS is by no means uh rare uh I dealt with it. I did general surgery Uh, it was a significant part of my training. Um, and I dealt with trauma and um And well As a surgeon type person, uh, that was the most common etiology I dealt with infections you would have uh medical people, uh I won't use the uh Slang term fleas Except to mention it exists Uh, but they deal with those sorts of things, but at any rate, uh It's pretty horrible and you see young people die from it Um, most of the cases when they come in they're moderate to severe That's because as soon as this starts happening start to give us kind of a process of inflammation and uh A status that will uh lead to fluid Um Filling in the air spaces in the lung Uh, which again is the Hallmark Uh, it goes quickly and it goes downhill So most of the people that come in with mild you don't send them home and uh, you know just say take a steroid or something you have to watch them because uh They have a really good chance of going very quickly to moderate severe and um I also mentioned this morning if uh like young people somebody 22 who has a flu a bad cough and Feels terrible tries to drive home Uh A few hours drive or something they get home. They're worn out go to bed and they die from ARDS um The overall pooled mortality is 43% You can the mortalities for mild moderate and severe disease are down at the bottom And uh, you notice 45 for severe disease. So, um The fact that the pooled overall mortality is 43 tells you how How often uh People just stay at mild or even moderate levels. This thing tends to worsen And you basically have to correct whatever's causing it if you can And um give supportive care, which means intubation and ventilator and every To Oxygenation Okay Here's the viruses that we're going to talk about The SARS came first then MERS and then uh in 2012 and then we've got this 2019 and CoV Um, they're all very similar. I think uh in terms of what they do once they get in the door Uh, they do what thugs do They take you apart And One of the main things that happened is ARDS Uh, that's one of the main causes of death from these kinds of viruses and these In contrast to the traditional coronaviruses have increased specificity for respiratory Now the um angiotensin Two receptors they're located in kidneys got Lungs brain. I mean they're all over the place. So, um I reason why the lung gets wiped out and makes such a big impact is because it's a Uh High priority vital organ and uh, that's where the virus gets inhaled and that's what it has primary access to um So it's spread by contact people coughing uh spreading uh aerosol Of respiratory droplets that tend to dry the same sort of thing happens with tuberculosis uh, the droplets will um quickly decrease in diameter and um They stay in the air for a while now if you're in a place with ultraviolet light like for To say and I don't know if this is absolutely true But uh used to say eight seconds of um ultraviolet light from sunlight Open sunlight will kill tuberculosis Um, generally anything with dna doesn't do well in uh light but uh, so open air fresh air and uh Such is probably a good idea if you want to stay healthy um What occurs to me and I don't have any proof. I I noticed one time Uh, right at uh as a light changed uh from uh was a red light and I was in the car behind This guy and he rose down his window and he had a cigar because I could tell um Do a big puff of uh cigar smoke out I had my windows shut and he drove off and I drove and After just a matter of a few seconds. I was smelling cigar smoke like it had been blown in my face and What occurred to me is if somebody's Coughing out or there's an aerosol or of any sort of chemicals or infectious agents Even out on the road. I know you can end up breathing it. Um And um, you can have that exposure to it pretty quickly. So, um, uh, just a Statement about how hard it is to You know, you got to breathe Of contact is easier to avoid. Don't shake hands Uh bump elbows or just you know, say, uh Hi there Uh Hi there. I'm a gringo or something whatever you want to do. Um Mers, uh, by the way is uh in camels and uh Um the SARS came from the civet cats uh a Mast palm civets, uh in southeast asia They look like this And I don't think I'd try to pet it. I think you'd lose a finger or two. Um, but they're omnivores and uh I expect they ate Uh bats when they can get them For this current virus, um the corona the um 2019 ncov corona virus It's been sequenced. It was sequenced in china pretty quickly And uh, then there's a lot of analysis that can be done and there are some, um Areas in the sequence where Uh, it looked like it might have relatedness to snake coronaviruses and that's possible because um The um, uh, this new virus is it's it's it's from bats All these uh, really highly dangerous, uh, coronaviruses these beta coronaviruses are Originally from bats. It's a zoonotic infection But um, it may have passed through snakes because uh snakes will eat bats I would root for the bat like bats um So Okay, there's a point here that uh Humans may have acquired the SARS first from butchering food preparation when blood and organs um But it it's clear uh very quickly clear that these become a person to person transmission as a motive uh of um Spread uh and uh Again for respiratory secretions, but uh people cough and shake hands and uh, you put your hands on your face I mentioned this morning if you rub your eyes with your fingers unwashed um, you're maybe inoculating yourself because your tears Um, which are being secreted by basal secretors and your lacrimal gland and sweep across the cornea to keep it from drying And then they go in the medial aspect. There's two to punk tie and openings and they drain this little canaliculi to a nasal lacrimal duct to the nasal cavity down the throat and uh I've noticed when someone's about to cry and right before they do they might go And they kind of snore it because they're getting an overflow of Fluid coming through the nasal lacrimal ducts and then all of a sudden they get epipheresis or Overflow of their tears at any rate the eyes are a good way to get um affected So touching your face Your hands unwashed Is not a good idea actually All right this is the origin originally of The beta coronavirus that led to SARS um This little guy is he's just a bad is found out through throughout southeast Asia and Even up and uh along the border with india to in places and um the map of distribution looked like it had uh Wasn't continuous but at any rate It's a chinese horseshoe bat They can take a lot of specimens and uh Map them and organize them by similarity. It's called molecular phylogenics. I talked about coral wars uh from University of Illinois in uh urbana um who uh uh used that kind of technique to analyze uh um bacterial ribosomal RNA and uh found uh that uh There really are three domains of life There are prokaryotes like bacteria and eukaryotic cells that have nuclei and then there's a or primitive perhaps uh type of uh organism Which is a different domain uh archaea um organisms um and um Uh at any rate that he was sort of a godfather of this uh technique and others helped develop at david baltimore others molecular phylogenics and you can use it to define uh um The genealogy of an infection See its family tree and you see sars there. Uh, it's right there with a bat Um types of viruses, um, it's nested so Okay, so what does sars do uh, I'm gonna talk about this because I think it's this is a model for What you're gonna see with the corona virus out of wuhan Um, it can cause liver damage. That's usually not too severe Um, and but it does seem that there may be a direct viral impact on Damage to the liver from the virus rather than it just being a secondary effect from multiple organ failure Um, cardiovascular complications are Seemed to meet mostly secondary secondary to physiologic collapse um shock uh hypoxia stress and Uh someone that's at all vulnerable Someone older has a previous heart disease A bigger one. No is, um Um, uh kidney failure. Um, it's not uh It's not uh real common, but it's uh, they say it's uncommon I don't know if I would say 6.7 percent is uncommon. It's close But uh, it's that's pretty significant to my thinking Uh, especially in a fact that uh Um, acute renal failures associated with a higher mortality. Um, in fact This was something something you would um uh This I'll I'll address that question in a second, but uh, if you ever are In an intensive care unit setting managing patients Um, if a patient's slipping away, uh, it's you can look for a multiple system failure Of course, you usually can recognize that in real time because you monitor them so closely You know if the liver's failing or if kidneys are failing along with the heart or lungs or They have a Melting away. It's a domino effect. You start to get multiple system failure. Your prognosis gets worse and worse Uh question was how do bats transmit these diseases? It's contact. They're droppings They shed the virus if somebody eats them um if And then somebody eats that animal like the civet cat, uh, Probably ate bats When they could find them they you know, probably just scavenging around and like I said they were omnivores They'll eat fruit as well, but uh Um, so, uh the um Important point here is if you get renal failure in this it's worse. Uh, it's a worse prognostic indicator Um acute tubular necrosis is The thing I want you to remember remember acute respiratory distress syndrome because the uh respiratory Damage you get from these corona viruses is is basically in that model It's not it's not greatly different. It has the same physiologic effects or pathological effects and if you get damaged the kidneys It usually is acute tubular necrosis not involving the glomeruli the glomerular uh structures are out in the uh Cortex i'm going to show you a picture of the kidney in a bit I've been having a cortex and a medulla Sir like a mantle and core and the crust Crust is like the can the capsule I suppose The outer layers have these glomerular filtration units that where the blood Will force fluid through a little membrane and down into these collection tubules and it percolates down into the medulla and back up and descending or efferent and afferent um Tubules and then convul and there's convoluted parts of them and uh those are uh ducks of henley called and then they eventually drain into the ureter um to the bladder and that's um Have filtration and then have absorption secretion and excretion um And it's all a lot of that's um Filtration is not so much energy dependent. Um, except that You're forcing blood you're working to get your blood flow there Uh to the kidney, but the rest of it's all energy dependent down in medulla of the kidney It's high metabolic activity going on because you're having a lot of vital work done to remove toxins um from the bloodstream and excrete them or to retrieve um amino acids or uh glucose or uh salt or Uh water gets dragged along with these when you have active Resorption of salt for instance in the kidney so that you don't end up hypotensive um Makes it so you don't have to live in the ocean uh And, uh Even if you do you probably need some way of Cleaning uh if you're a mammal cleaning your uh bloodstream, uh, but the uh Hypoxic effects And probably hypotension can play in this results in lower perfusion of the kidneys Lower blood flow and if that's severe and lasts for at least 30 minutes, uh, your kidneys may shut down You put in a catheter and you'll get what's called bladder sweat It you won't have urine output. That's a pretty serious thing these days. Uh, you in an intensive care unit setting you can uh Go to various forms of dialysis on an emergency basis um But um if You have a kidney failure By the way, if you got previously existing liver disease or uh diabetic Nephropathy meaning that your kidneys have been damaged by Long-term diabetes usually it's long term um So the kidneys aren't so healthy to begin with you have a little more chance of developing a tubular necrosis in these uh infections and um the mortality of acute tubular necrosis Is like varies from 50 to 70 percent depending on the Study you look at but it's up to if you got the acute respiratory distress syndrome on top of that then About 80 of those people just die no matter what you do um And they can be of any age I've seen too many young people Had situations so These are pretty serious disease if it gets out of hand And one last thing atn in general it's a it's a it's a kind of a common thing um That can happen as a result of a type of insult Uh can be ischemic or toxic insult Like nephrotoxic drugs like gentamicin can uh Enoclicosides like gentamicin can cause uh Uh tubular necrosis uh type effects And this is just for the next slide. I like this word clade rhymes with blade It's um I don't know if you recall uh if you've heard my talk on um human papillomavirus and I was talking about the archaea bacteria um that uh carl warce Defined as a third domain of living organisms, but um They have people who are looking for luca l u c a the last common Last universal common ancestor So, um That's looking for the ultimate clade Kind of the trunk of life This is a clade is generally like a single branch of life Okay You know you can apply that technique of um Molecular phylogenic study uh to uh mer's and uh you'll get this Sort of a pattern where you can define it I'm going to use the term loosely genealogy or um an origin of the human infection from that type viruses and That is the best uh smoking gun evidence uh that you can have of uh just about of Of its source now in terms of camels there, I mean there was one case in uh um, I think Saudi Arabia where a man uh Got mer's from his cat. He was like putting the sab on the nostrils of the uh camel had a cold And uh, it was mer's and he got mer's and they did it was a tentacle virus So he got it directly from messing with the camel and having contact with the secretions of the camel You know camels tend to spit on you anyway Uh They have no respect Uh So let's see I'll keep going here I guess I got time I I I wanted to share I I saw this picture and this uh this reminded me of something Uh, you can have camel flu these these animals Uh, these are dromedary camels at that camel up in there, right? It reminds me of this story. Um There was this uh, this camel looks like he's saying I I don't know and I don't give a damn You know this is kind of a defiant careless look about him This kid was just trouble in school and um, so the principal calls in the father and uh He says, you know your son, he just he's just disruptive and he won't do anything We asked and he's you know, it was a lot of problem and he says like what do you mean? He says well everything he says he he answers uh Uh in an insulting way and he says For instance, he turns to the boy and he says johnny Who signed the declaration of independence? And johnny looks at him with that same camel look there I don't know and I don't give a damn And his father turns to him He says well if you sign the damn thing son just say so So that's my joke That's the one joke I'll tell for this whole thing. Anyway camel urine. Yeah, there are people in uh, um The Middle East who um Use camel urine for medicinal purposes apparently um, so the who actually World health organization actually recommended avoid drinking camel urine Because they can shed viruses Through that There are lots of dietary practices around the world which are not wise a friend of mine shared a um sort of disgusting video of An asian man who was identified as chinese I had no way of really ascertaining origin Or location or anything of this video, but he was living he was eating live It looked like baby rats With chopsticks and showing them they were wiggling and stuff and he put them in his mouth and chew them up And he opened his mouth and showed that he was chewing them up Like it was something to be proud of Um, that's a bad idea Uh, I was telling people earlier and I'll say to you all don't eat bush meat don't eat roadkill And in fact with roadkill You know they're talking about camel urine and you know I can imagine americans laughing at that and making derisive comments, but in tennessee which is a A very red state pretty red next state actually know tennessee really well, uh, and um In 1999, uh, they passed a law that people could collect and um Eat roadkill And and I figured that was um uh Just to show how redneck they were and that trying to be like david crocket and Bragging their buck knife was longer than anybody else's buck knife and that kind of stupid stuff It's all a bad idea And I saw eating squirrel brains. It just seems uh, another horrible idea that's um, eating neurological Tissue is a great way to get a prion disease like uh, spongiform encephalopathy or yacob cratesfeld disease So Okay, continuing on a boy an equation. It's actually not a difficult equation Uh This is an important number. It's called r naught r naught. It refers to um Basically how infective something is uh, how many people are going to end up infected by a um Um An infectious agent the trouble is it averages things and it looks at a population and you can have whatever I I couldn't think of the title of it. Uh, and I remember it now. Um, Maybe you know my second cup of coffee helped um super spreaders You can have um nine people who don't Spread it to a disease to anyone else even though they have it and one person that spreads it to 20 people And so then you could think that the um um Trans transmissibility would um be Uh involve one person For every one person you'd have two people getting infected um, and it would be um Uh skewed So sometimes these numbers come out and as you get bigger populations or uh, it uh, something it doesn't reflect a um An extreme like from calculus of variations Uh, something more averaged out A better sample maybe is a way to say it. Uh, you get better numbers, but You look at this uh infection per contact. That's the transmissibility the likelihood that A contact will result in infection And then you have to look at how long the time is of contact and on average and uh How long the person's infected how long they're and generally for these it's 14 days About 170 people were just brought back back from wuhan by the to the united states by the united states government I guess and they are in quarantine for One of the measures being taken to try to control this To a pandemic um, if you do um, uh Dimensional analysis of this equation it helps simplify it for you You look at the numerators and denominators cancel each other out and our knot is a dimensionless um Um value It's a scalar with um all the the various units all become one when multiplied together um the um Contact time That's a rate and time of infection um, that's an inverse rate, but uh something per unit time is a rate So sometimes people say basic reproduction rate and that's the wrong term or not is a is a is a scalar that Uh has that factored in Anyway, that's an important concept So it's a number of secondary cases one infection would have on average Uh create and it's and it assumes kind of free mingling in a group Yeah, our knot of two Uh would suggest uh like one person's going to infect two people Now let's look at measles How bad is measles? Are not 12 to 18 so Just a little side Take home point One child with measles on average will affect will infect 12 to 18 other children and Thinking about the fact that one in 20 with measles end up with pneumonia Which is the number one cause of death In measles when it goes bad Three in a thousand and can end up with respiratory or neurological complications one in a thousand Get encephalitis and measles infecting their brain That can result in um Both delays developmental delays or um Mental handicap um intellectual handicap for the rest of their life Um, and I I've seen patients who had uh permanent Sensory neural hearing loss in both years from having had measles I've seen a lot of patients over the years. Uh got less uh with um Uh use a mumps vaccine, but um mumps Was long considered the number one cause of unilateral sensory neural hearing loss Um that doesn't come back. That's hearing that's it's gone Curred to me a distemper Is that Measles like that uh virus and dogs people any decent pet owner would get a canine distemper shot Um to help us therefore a dog not to get sick with you know distemper um So I think that would make sense You know, how would it not make sense to have your children immunized um I just Hope people will think that through Okay This is my favorite uh slide. I think it's my most important slide in the whole talk I'm approaching the end It's the are not values and um case for fatality ratios are often discussed cfr. I just listed as deaths here Uh over 8,000 cases of SARS from beginning to end. SARS is not in existence now It's cleared last known case was 18th of 8 2004 um It began the 16th first index case was traced back to november of 2002 8,000 cases 8,000 plus occurred each person that got it had Between Estimates two to five Other people would get infected So if the are not is greater than one that means that if you have an infection You can go out and you can spread it and you're going to more than replace yourself as part of the infected population So it will increase the number of infections So if it's if it's one or less then it's generally not sufficient to cause panic Pandemic does that make sense? It's almost like a zero birth rate Everybody has one kid That'd be That'd be about the same thing. Okay. MERS Had a higher death rate. So for a smaller number of cases. So That was in a way more virulent. Um and uh um On the other hand the are not is pretty low. It's less than one So which is kind of a surprise. So it's not as infectious and a lot of the people that got it tended to be in the hospital um, so Well, that's a good point. It's sort of like, yeah, it's like Is it going to be exponential growth or any if it's an exponential growth and it's uh The exponent is one or less. It's going to be It's going to involute or control itself. It's going to remain The same um or lessen finally, uh estimates now the we've got um number of cases almost uh Premably have well over 20 000 cases. We just don't know it yet But confirmed cases means that they've swabbed the nasopharynx or they've lavaged the airways and they've uh, to get a sample lavaging the airway with bronchoscopy Is the best way to get sample and uh, then they do um PCR test reverse transcriptase and the pcr and look for fragments of the uh Virus and identify it um Normal flu it would depend on the flu. Um uh generally Most of the time normal flu wouldn't have this high a death rate. It could be pretty contagious Influenza is pretty contagious If you look at the spanish flu as a contrast to these uh, the r naught of spanish flu of 1918 which can be estimated pretty well at this point because we have A lot of information about it was 2.5 or less. I don't know something in that interval there 1.4 to 2.8 Uh, but one in three Uh people on the planet roughly got this uh infection And um, uh 50 million people died This is worldwide in spanish flu if that's what you're referring to So How to deal with it? There's a cdc or center for disease control in Atlanta recommends if healthcare workers use washing hands mask gloves Uh, I would recommend goggles and dealing with viruses too. I I was lucky. I've been uh Exposed to tuberculosis Or most people I know Uh, I never converted. I never got it. Uh, I got histoplasmosis from growing up on a farm Which is a fungal infection in the lung Uh, but it's pretty, um Limited, uh, it doesn't cause the damage tuberculosis does it's not contagious. Uh, but I I had patients who coughed in my face when I was trying to examine their throat and stuff like they ended up having tuberculosis Uh, so I was sort of lucky Uh, but these masks uh they are In 95 masks meaning they're carefully they they'll filter out 95 percent of the particles Down to 0.3 microns, but again, uh, that's 300 nanometers and the Uh, corona virus is about 125 nanometers. Uh, the idea is that the uh Um Corona virus is not a Byron particle on average, but would still be in a glob of Material that's just kind of suspended in the air so wearing a high filtration mask like that is Generally thought to be effective and uh, it's pretty uh reassuring if you've ever worn one, they're very uncomfortable hard to breathe through feel like uh Feel like somebody's put their hand over your mouth and nose and um Maybe pushing a pillow down on it or something I didn't I didn't like having them on but um, I didn't like the alternatives either. So I I I cooperated certainly um Washing hands washing hands washing hands uh suds sudsy water Disrupts these viruses and these corona viruses particularly are in uh, they have an envelope which is a high lipid content and soap emulsifies lipids So it disrupts the envelope. It also would disrupt the spike protein that Uh is the key to getting in host cells so um Wash your hands This is uh, I just thought this was cool and you can look at it if you want to look at the pdr this was uh reminded me of old models of the tracheal bronchial tree Which were made with woods metal. This is a Tactic alloy meaning its melting point was decreased eutectic alloys. They have a lowered And uh, it used all these elements combined um I'm sort of surprised gallium wasn't used because that's got a low melting point um In alloy um, but at any rate um That kind of model resulted in a faulty uh um No, or the the the interpretation of this of this kind of a model and resulted in a faulty uh Concept for the alveolar Spaces, um, so you have two lungs three lobes on the right two on the left and You have your trachea carina at the bottom of that and Then kind of diverting off of blightly Is the left main stem bronchus and then the right main stem bronchus. Those are the primary bronchi uh foreign bodies and aspirates like uh chemicals or uh Acid from the stomach if you happen to aspirate GI contents Like happened to Jimi Hendrix uh The before they took him to guys hospital. He had aspirated his vomit It will burn the lungs. It'll cause us the wipe out humanitis, but these um, I don't know if you trace it out here on the on what's Left to you is right for the patient. This trachea is turned with the front part toward you and the larynx is at the top there like a like a um 1700s or 18th century hat um, but you look on the left um patients left Um, you'll see two main branches and uh on the right. You'll see three those lead to Bronchopulmonary segments I used to do bronchoscopy for cancer Uh, and if we found something we needed to be able to describe exactly which bronchopulmonary segment That's pretty tricky when you get down in there and you're Just seeing the tube Uh, I really keep oriented This way I just threw in for again for the pdr. I I I mentioned this morning. I came old school with um embryology followed by uh, Atomy in my basic science training and it made anatomy so much easier As you could see how things had formed and the names and uh If you want to really understand the uh structure of the endodermal derivatives, uh Uh, the lining along the endodermal and mesodermal, uh, then you might want to look at this, uh Slide in the pdf, uh, and it has three links here for really nice short Explanations, I wish that I'd had access to stuff like that when I was studying embryology just Read books Until Got it And that kind of technical reading mean, uh Reading it repeatedly and thinking and reading it again going back and rechecking and such anyway It's incredible how information is so much easier now Accessibilities Bronchopulmonary segments are the functional elements of the law They lead to, uh specific, uh regions of Alveolar spaces I threw this in because it's a nice little glossary surfactant. It's important surfactant is Uh, something that in small quantities will if you have these alveolar spaces and the airways they're lined by water Uh, then when you expand them, it's it's like Uh, the water tension surface tension of the water is, uh The model's been you're you're dealing with a bubble of water um surfactants, uh um tend to disrupt of the, uh High surface tension and makes it almost effortless to expand the lungs the lungs Naturally tend to be Unexpanded they have a certain residual volume, but they have elastic recoil If you get stabbed or shot, uh, your lung will tend to collapse and the space will go up with air and then blood um Newborn if they're still born you take the lung and you put it in water if it sinks they never got a breath Uh, so it's uh, if it floats they they got a breath in um at any rate, um You expand the lung by the diaphragm Which is at the base. It's a dome and you have muscles in a kind of circumference way It pulls it down expands the lungs especially at the base And so the models that were used to Figure out lung physiology. We're not really accurate. This is a kind of a traditional Model, but it it shows these alveolar sacs and blood supply and such but They are not grapes and they're not like bubbles They're more like this Where there are little pores between alveolar spaces and it's like a network of little septated, um Spaces that you wander almost From any one place to a lot of places nearby So it doesn't tend to collapse readily. It also has a Ash or a network of uh effective tissue that holds it open I thought I wanted to add this As soon as 2002 I was thinking it was 2003 uh, Henry Prange at Indiana University published this about arguing that the surfactant and Laplace's law applied to lungs Uh, was overblown and not really accurate and I had to agree. I I thought it always bothered me in medical school um I didn't have time to go Work it out because um, it's like drinking from a fire hydrant and uh You're not supposed to spill any So there's no time to really go into things in the depth you'd like at times, but I found it Satisfying to discover somebody had really dug into that and we find uh concepts of physiology on Fung Here's ARDS where you start to get thickening of the septae Remember the other one looks this very defined and wide open spaces And this not so much. This has always fluid material in the spaces and Um including blood cells so there may be some bleeding into some of those spaces That might be artifact. It's hard to know but uh, that doesn't look so good Okay, this is more from frange. I'll let you look at that if you want to Uh in the pdf This is a normal chest x-ray notice the diaphragm is at the bottom. There's a stomach bubble on the left on this Look at the left side of this And the heart shadow in the center that tends to the right and Just one of the reasons the lung on the left has two lobes It I said tends to the right tends to the left Um And the left lung has two lobes the right lung has three lobes and it has more space Uh Look down at the angles and you look at the bones and you can see the trachea if you look at the top You can see a tracheal shadow Can you follow it down and uh down? at the about a finger breadth below Where you have that oxbow of the clavicles you can see it bifurcate And so that's a normal lung This one not so much This is an example of the changes start to see with acute respiratory distress syndrome where Uh, they're hard to ventilate and their lungs are tending to be collapsed and they'd require positive End expiratory pressure or peep In fact, normally people have about five centimeters of peep Um, because the upper airways will tend to collapse some Give uh some resistance to air egressing Here's um respiratory distress syndrome in an infant and um This one like the one before Uh, if you look you'll see all kinds of attachments. Uh, you can see an endotracheal tube up the top in the trachea And you can see a little tube that goes down into the stomach That's a sick person in uh intensive care and uh Say it was similar for this one year one day old Sorry One dimension hantavirus is kind of interesting and I don't want to get off on it, but uh And it occurs in andes and it like rodent droppings rodent excrement uh antivirus, um can Uh cause ARDS like a lot of insults In fact, uh, this is what you see with this is here's a young healthy uh physically fit Navajo gentlemen was uh developed rapidly increasing shortness of breath and disney on died From respiratory failure all because of exposure to this hantavirus that he probably contracted from nature so I think vaping vaping has a lot of risks So i'm not going to dwell on this because it's not the main topic, but you can look at it in the pdf But it uh, I thought it's kind of related to the ARDS part I've talked a little bit about you can look here on the uh to the right and you see the kidney as a capsule, um a cortex and these pyramidal medulla that drain into Scalics and down the ureter Which is the white thing This uh these loops of these tubules That get acute tubular necrosis are in those pyramids um glomerular apparatus bowman's capsule and the regular tufts They're in that cortex Some are longer and some are shorter, but there's a Bowman's capsule and uh glomerular tough blood vessel tufts On the left and there's the tubular Dual apart on the right in this one just to show you what it looks like and atm You get loss of definition and the tubules have loss of their epithelial cells and they can slough and form cast and the drainage becomes muddy And so that's basically it the uh We're gonna have to see where this uh new virus goes and uh The best weapon you have against it is fresh air and soap and water I don't think you need to use bleach or uh disinfectants with uh antibacterial agents Which can be pretty weird and you can absorb through your skin possibly and uh A lot of them have alcohol alcohol is not really a very good Thing for sterilizing things. It's a It's dissolved stuff Now one other point I made this morning. Uh, there's two points. I want to make it real quick. One is that uh viruses on a porous surface tend to die more readily and it's thought because of the Porous Nature of the surface it's on it will draw away moisture which disrupts the virus Uh a virus on formica or a doorknob of smooth metal or plastic toy may be Able to survive much longer and there are people that do studies that find viruses That here in vivo In vitro rather Viable even five up to five days out Now it's questionable to my thinking if they Would be still infectious for uh in in the real world but it uh I thought that was rather interesting one other point I made I think is really really a big one And I say this because there's crazy craziness anymore The world needs uh Stable good governments so that people can prosper and progress and uh live in safety and uh You have people talking about no money except for defense things like that or Do you know that uh a bad pandemic can do more harm to a country than a war It can take out um the uh uh A core of people of all ages right out of the center of a society and uh in an untimely fashion and Uh, it can disrupt the economy and it could lead to a ruling uh and public health and Things like what I like to say are three of the greatest achievements of the United States government Which are the creation of the national institutes of health in the center for disease control um and the world health organization and europe has its uh comparable organization now and china has one that uh that uh Has done a pretty remarkable job in being prompt And and even building hospitals new hospitals in two weeks Was their existing facilities were overwhelmed Um centralized authoritarian governments can do that But there was some written about um how We'll we'll hung Food market was cleared out and disinfected uh so quickly that specimens were not Not collected as well as they could have been and evidence was lost to trace What had happened there? It's sort of like handling uh The murder weapon, you know with uh before you get the fingerprints but um As I said this morning, I don't want to criticize the chinese government I think that they've got a lot on their platter dealing with this and them well and uh really the whole world has to work together on this And we require intelligent cooperation and respect To be able to deal with this sort of thing It's gonna has the potential for causing a lot of misery So Any questions? Thank you mike. Thank you shantel Thanks sir. I don't know about rates for um emergence of Viruses these are sort of random um Rare events. I think uh But Even though they are there are so many um viral virons produced in any one infection and um The mutation rate is low, you know in these 16 non structural proteins In coronavirus coronavirus has a fairly stable genome and it has uh non structural protein 14 actually has exon or x ribonuclease Uh function whereby It has a couple of functions it can do biochemically, but it actually um Is a de facto proof reader of the genome being transcribed so there's Careful regulation in the makeup of the coronavirus that it gets it's of its RNA virus um genome directly Which is really amazing that that this is uh The coronavirus is really an intricate and fascinating uh array of uh Of strategies um It's pretty efficient because a lot of these uh molecules combine in different ways and do different jobs But the same molecules they don't have to have lots of separate genes um So it's like 16 Unstructural proteins and four structural proteins sometimes five structural proteins Uh and 30 it's a it's a large RNA genome, uh 30,000 um Units of nucleotides um And it's a single strand Uh Well I fear there's uh Going can we develop such viruses? You mean there's a weapon or is uh, I'm not sure what tool it would be uh being able to um Develop delivery systems for uh Um DNA or chemotherapeutic agents or something like that to uh attack specific cells would be cool uh but um I think that um nature Is uh running its own experiment and we're um We're um either rating it or we are the subjects of its uh experiments um more than um humans developing viruses We can modify viruses but uh So far like I don't think the CIA started AIDS and that sort of thing It's There's potential for lots of uh conspiracy theories there any other questions Thank you Shantan I appreciate everyone's interest and uh attendance um It's an honor to speak to you. Thank you Thank you. Thank you It's hard for me to believe that um Governments are not storing viral material. For instance, uh smallpox is still stored in atlanta georgia and in russia um Two sites in the world Well southeast asia is um uh It has um Rich biological diversity and uh forests and uh wildlife and uh Sort of like the amazon has been a rich reservoir and the jungles of uh central africa uh incredible uh uh Reservoir of biological uh Mashups Well, even even if there's hygiene in the markets if you have an infected animal um That uh is being marketed uh That's still a danger to the public And that's why I say public health is is uh as important as uh military defense May be more so because in a they In the Forest countries that uh they can arm themselves and go shoot at people easy uh compared to uh the cost and uh Attention required to develop a health care delivery system that can hit off a pandemic It seems to me most anyone can pick up a gun and shoot it. That doesn't take much cleverness Thank you for coming xergy So any other comments or questions? Thank you everyone. I'm going to turn off my microphone now