welcome to the science for the public lecture series science for the public is an organization committed to bringing science information and issues to the general public visit our website for our program connor is an associate professor of microbiology at the university boston university school of medicine his lab is well known for innovations in virus research and also in new technologies for a virus identification you can visit the page for the event on our website to get articles and other information about his work he's been in the news quite a bit dr conner received his ph d from duke university and joined the faculty of boston university in two thousand and seven his background represents an important trend in science today and certainly in virus for search the convergence field and his case expertise  pharmacology genetics molecular biology and engineering quite a lot major area of dr conner's research focus is on the mechanisms by which viruses take over the cells machinery replicate themselves and understanding of this process is essential to the development of an occupation against infection another area of dr conner's research involves the development of point of care virus identification tests he'll explain the challenges of this process will also explain the great difficulties of containing viral infections in today's global community where travel and urbanization facilitate the spread of viruses tonight will leave here with a healthy respect for viruses and a great appreciation for the work of scientists like dr connor who are contributing so much to public understanding of viruses on the one hand and to the medical advancements that will prevent in sections on the other we're very honored to welcome dr john connor i think i'm talking in a way that folks can hear me is that if i begin to trail off somebody please just let me know we we've seen what i'm guessing will be my first slide i thought i would start just by introducing who i am and the things that motivate me i'm a microbiologist which means i study small things all day this is me studying for my first exam more i'm most relevant to this talk most of what i do is study viruses and how they function in terms of where i do that work i do that work here this is the national emerging infectious disease laboratories it is just adjacent to boston medical center part of boston university school of medicine this beautiful blue sky picture i don't know how long it took them to find this day but it wasn't this day that they took that picture i thought i'd start out by really  defining the bacteria and viruses the differences between them and focus then in on my particular interest which is viruses the stem field of microbiology studies fungi and bacteria and viruses always a really interesting but one person can't look at all of them and my focus on viruses has been driven in part by the the differences between bacteria in the interests that i find in understanding how viruses function so from my perspective the way i look at bacteria is that they are able to replicate and divide on their own they can live in a bunch of different environments and they of genes they're genetically fairly complex and this is of stark contrast to viruses which are obligate parasites they can make copies of themselves without any help and that means they have to find a host and they essentially have to figure out how to take advantage of that host and how in fact to steal a lot of things from the host in terms of comparing them to a virus to bacteria viruses  genetically very simple they can have anywhere from one to most three hundred genes the overwhelming majority of viruses you'll find they have a about a dozen maybe two dozen proteins again they're all good parasites and they're incredibly small and just to give you an idea of how small they are my laboratory can use a regular microscope to look at them however we still think they're very captivating this is what i'm putting up here is just a general size diagram ranging from below and then a meter to about a millimeter and what you can see is that in at the low end of this scale you can see atoms at the upper end of the scale is a frog so at no point are we talking large things but when you ask where viruses land within this they're right in this range which is they viruses range in size somewhere around one hundred nanometers in terms of being able to look at them light microscopy will allow you to see bacteria allow you to see mitochondria as well as cells of all different types it fails to allow you to see flu viruses or any virus of that type you have to use much larger much more expensive microscopes such as electron microscope however doing this allows you to see a hundred pretty neat things and this is just one of those things so what i'm showing you here is an electron micrograph a cell that was infected with a virus and then a little bit after infection people looked at what was happening right at the edge of the cell so what you can see here this dark mass is essentially a lot of cellular protein there's a cell membrane right here and these things right here popping off are viruses that are budding from the cells so they the viruses use the cell to its own advantage there's a lot of viral proteins of viral nucleic acid polarized right here and you can essentially see the process of new viruses being bought it off and then floating away and you can begin to see in this floating away from the cell it looks like these these but it variants actually have a significant amount of structure to them and when you take viruses after they've gone through this bonding process and look at them and in the electron my caress you see exactly that and so this is just a collection of viruses that have been purified you can see there are all the same shape there all the same size and you can within that image begin to see a glimmer of additional structure that must be present based on the repeating patterns you see in and light and shadow there and if you pile lot of these electron micrographs up you can begin to get a very good idea of what viruses look like you can identify their three dimensional shape even though we have a hard time doing it by conventional microscope the electron microscopy really allows you to see what's going on and this is just an example of one virus this happens to be dengue which is the causative agent of dengue fever it is a virus that uses proteins to make up its outer shell you can see them in various different colors here you can see how they that's stuck inside can eventually come out and you can see the other colors representing different proteins with different types of symmetry this is a two fold symmetry here you have three fold symmetry and all these fit together very nicely to make an elegant casing for the viruses genetic material which is going to carry from one place to the next and this type of shape is very common in viruses however if i can go the right direction it's not the only shape so this is another image i'm showing you here add in a virus you can see it has that same central almost bucky ball like shape however this virus manages to put spikes on the end that help it attach to the cells that they want to enter and get in this this shape is not only interesting from my point of view as a scientist you also find people that are captivated for other reasons i grabbed this image from an artist who's decided that looking at electron micrographs and cartoons wasn't nearly the right way to look at viruses he actually blows glass and this is  coronavirus that he put together out of a number of different glass components you can see the outside of the virus and the nice part about the glass images you can see straight through into the genetic material and i just put these together because i think they're really pretty this is just another way of lighting that same type of structure so viruses are really small they have a very nice very tight architecture  they're fun to stare at they're fun to do art with but on the other hand viruses are incredibly dangerous viruses are one of the greatest threats to human health that have been seen throughout  human history smallpox is estimated to have killed at least three hundred million people this is the twentieth century estimate alone there are probably many more before that influenza you i have no doubt have gotten lots of talks about how you should get your flu shot and you should but it is a disease that continues to afflict humanity the  flu resulted in at least one hundred million deaths hiv is another example of a virus that can take hold of the human population going from a non existent virus to  very well established virus now that has a very large impact on human health these are what i would consider known threats and but what i also want to point out is they're not the only ones i just sat down and a few minutes came up with a large additional set of viruses that are emerging where people understand that these viruses exist they've caused human disease in some cases there is severe human disease but in most cases  not really become what would be considered an epidemic which is a large number of cases what they are very good at is causing a lot of fear here what you can see is the response to the sars outbreak in two thousand  three this is just a group of people who are trying to prevent transmission by wearing ear loop masks this is an example of an ebola response you can see it's a little more severe than what's going on here the individuals are going out into a resource poor area fully clothed in order to try to keep any skin to skin contact any contact with infected fluid from occurring in situations where they feel that it might be  present one of the things i want to emphasize by both of the things i've told you is that i think viruses are a paradox they're both very simple and they're dangerous and complex at the same time the fact that they're small and genetically simple  makes me think of them as a toy book they however have quite an ability to cause harm to humans which are much more genetically complex and we've got about twenty five thousand different protein so in this analogy we appear to be the nimitz class aircraft carrier and the virus is the toy boat however in terms of who ends up winning an encounter often it's the virus often it's the toy boat that seems to do a much better job of causing harm and it does so through a fairly set pattern vire all all the viruses that i've mentioned essentially do the same basic thing from  thirty thousand foot feed right of virus will come in attached to a cell it will then insert its genetic material into the cell along with some support machinery and use that cell that infects in order to make copies of itself once it's made a lot of copies of his genetic material and then packages that genetic material to make new variants usually hundreds or thousands from an individual cell and goes and starts that cycle again if you think about that in terms of a multicellular event so these are a bunch of different cells they're not all as though i recognize the similarity if n n one virus comes in and infects one of these cells makes copies of itself then spreads it to neighboring cells and this happens over and over and over and this is what takes virus infection and changes it to virus consequence and there are many consequences from sneezing to rashes to downright cute feeling badness and in some cases very severe disease that can lead to hospitalization and as straight on the earlier slide viruses really can be associated with a variety of events either sniffles and feeling cruddy that's usually rhinoviruses several different i know viruses but they can also be associated with high fatality and one of the things that has been a very serious question is how do you know what virus is going to do what in terms of causing significant illness so because there are so many things that are unknown i have things to do during the day and on the weekends and a lot of the things are trying to answer the questions that are up here right trying to get past the fact that right now we don't know as much about viruses we want to and i think that puts us at a disadvantage in what is an ongoing competition and the things we are really sort of unclear on is how is it the mechanistically that they make us sick what is it that makes us get either just a week old or a very strong life threatening disease and also equally importantly how do we detect viruses quickly in all cases where you get a virus if you need to be treated the faster you can identify that infection the more likely you are to have a happy prognosis if you're caught early and one of the other things that my labs spend some time on is understanding how you can limit disease how do you develop new treatments and vaccines and the idea behind this is that my lab other labs are working to make certain that we're prepared against both existing and emerging viruses and as i put up earlier there's lots of examples of this including sars the recently identified middle eastern respiratory virus chicken good which is steadily hopping its way across the globe to be closer to being an demick in the united states and there are also other viruses that i would say drive this home directly and currently the object lesson in why we need to know more is the goal of virus so this is an electron micrograph showing ebola it's not a round virus which is what i showed you earlier it is what's called a feel a virus you can see it's nice extended sort of rope like shape and you may have noticed a bull has been in the news a little bit recently what i think about when i think of the virus are the points here and that is that all of viruses unknown since the one nine hundred seventy six to be a very severe virus it causes what's called hemorrhagic fever and it's essentially the paradigm pathogen of this type of disease the infection with the virus leads to a very severe  infection that is associated at end stages with uncontrolled bleeding which is how you get the the moniker of being a hemorrhagic fever in terms of what type of virus it is it's called a feel a virus because it has that filament that you saw in the previous slide it in terms of the details at the non segmented negative strand r n a virus i would love to talk about that for the rest of the time but i'll save you guys the pain of it one of the real important aspects  right now there's no specific treatment or vaccine for ebola this was brought to the fore it is the known previously that this was going to be an issue there have been at least twenty outbreaks of ebola and also marburg which is a cousin virus of people in africa over the last number of years and every time these outbreaks happen the comment was made you know there really is no treatment we really need a treatment and every time the outbreaks were fairly small right now they are going outbreak has completely changed that calculus this is just an image here of all the different outbreaks that are known to have occurred you can see most of them cluster in the central africa right here up until this spring it was thought that there was no ebola virus in western africa however as we know  now that's not true in terms of how evil of virus jumps into the human population as i said it's been responsible for sporadic outbreaks and people been trying to understand how that is because if it was something like smallpox which is only transmitted by humans you wouldn't get sporadic outbreaks you would get a constant set of infections what's believed to happen now is that the virus exists in a reservoir meaning some other animal in which it's able to replicate happily and not cause severe disease the most popular hypothesis is that this reservoir  and that these bats through still an unknown mechanism transmitted to humans it's not very easy because it doesn't happen very frequently these outbreaks but it's known that there are some antelope and also that non human primates can support this virus that can replicate the virus and it's known in the places where outbreaks occur people end up eating all three of these things and so it's likely that part of the ju is made when humans come into very close contact with an infected animal maybe an animal that was especially easy to catch because it was sick it's not really known but it's it's is direct contact and requires direct contact for transmission so they have sort of bled into talking about this virus because there's an outbreak in western africa now and the the way that this outbreak came about i think is a perfect example just generally of how virus infection can bloom and how it can go from being something that very few people think about to being something that is a very serious concern to the world at the current outbreak and what has happened it was recognized that there was an outbreak in march and the number of cases i'm showing you here this is the number of new cases tracked over time you can split up by country where guinea is in blue liberia is in green sierra leone is this spring color nigeria for those of you who who have really sharp eyes is stuck right in here in gray so what you can see is this outbreak happened as one would expect a classic outbreak to happen there were a few initial cases those initial brought it to others you can see that in guinea there was an that what happened is that the outbreak sparked you got an increase in cases then looked like it was resolving until there was some sort of additional transmission event that transmission event spilled from guinea into liberia and into thier leone and at that point the outbreak has cascaded and increased weekly recently there's been suggestion that it has not been expanding but that's the first indication over the last two weeks that it was not continually expanding this is data that only goes up to september i thought i would also put in the graph here which i think is  fairly informative as well i took this from the economist which has been doing a very good job of trying to visualize what's going on so this is showing western africa where the major outbreak is happening this is showing the number of infections in the large circle the number of death in the dark circle that's slightly smaller what you can see is the infections that are here in guinea sierra leone and liberia you can also  see right over here these cases in the congo it turns out that there was a separate outbreak of ebola that also happened it began in this this summer and was successfully contained and closed down the country was officially declared  free a month ago but this just illustrates that these types of outbreaks are happening and they're happening not regularly but with increasing frequency if you look over the last twenty years this outbreak has led to spillover not only to senegal and mali which are right next door but also to nigeria through plane travel when you look at the severe it in this outbreak what you can see is this is when they first discovered ebola there were a couple hundred cases in this outbreak you can see a huge space where there was no more introduction and then as we get into the ninety's and early two thousand and so you can see that there begin to be more and more regular outbreaks this single outbreak here has been catastrophic when you compare it to these other outbreaks in terms of the number of people infected and again that's a light bar and the number of people that have succumb to disease which is in the dark bar so this is really changed how people understand the threat that the bullet faces but this is something that has been seen before in terms of what do viruses dramatic graph but still this is very telling in terms of what can happen to an infectious disease when you have an outbreak scenario and of course one of the things that hat is more and more recognizable is when something happens anywhere in the world right now it is not necessarily that far from anybody's door what i've put up here is just a map of air travel this is in the green traces are individual flights leaving from one country and going to another and what you can see here is that pretty much all of the the continents are well connected in some way or another you can go from africa to europe to anywhere you can go from south america to either europe or the united states and then anywhere and what this means is that when there is an infection people can get on a plane and people can move quickly we've seen that that happened and it happened because when you start looking in detail at that air flight map what you can see is from western africa the regular flights of people going to the u s going to europe going to asia even going to other parts of africa so this type of travel means any type of infection event that happens or really anywhere can start moving you can imagine the same thing being looked at in a reverse line where people can say hey those things that happened over in north america might be moved to us and in fact might have been moved to us and so now we're in a situation where as one might predict air travel has moved the virus it travels move the virus from western africa to the united states it's moved it to spain where there have been either unintentional infectious events or transmission events when people that were known to have the disease were brought back to the home country i'm hopeful that this number of countries don't get any larger but i also think that it is a serious thing to consider one of the things that happens when these outbreaks happen is that you have a second dependent outbreak and that is an outbreak of concern and fear and hyperbole and here i just went and pull up a couple of points here you can see that the major news outlets are really trying to understand what to do here and  trying to compare it to other current events or trying to understand whether the country should take severe measures in order to deal with the fear that's associated with an outbreak of a virus in this case it's a bolo but it could be any virus and one of the things that's especially apparent is when these outbreaks happen all  sudden people want answers to very specific questions and they're here the questions are you know where the treatment and where the vaccines and where the diagnostics and why are they not on the shelf because now we need them and the underlying question is why isn't anybody even thinking about this that we got hit with it and one of the reasons i'm here is to say actually people have been thinking about this before this particular outbreak  dozens of scientists that had already been concerned about this and working on it and significant progress has been made and that is in large part thanks to the american taxpayer so you guys should be proud of that one of the things i wanted to put up is a comparison of the sars outbreak and the able outbreak the current ebola outbreak when sars was first discovered and people started asking these general questions one of the first things they wanted to know is is there a diagnostic test for the virus and at the beginning the answer was no they wanted to know is there any treatment and the answer was no much less one that was f d a approved and the second i guess the fourth thing they wanted to know was how is it transmitted and it's beginning it was really an open question it really was not known there were a lot of unknowns and a lot of things that people had to find out fairly quickly in terms of this outbreak a lot of these questions can be answered in the affirmative when ebola was diagnosed in western africa the first tests the dye first diagnostic tests got there within a week they have been improved since then but in terms of response time it was incredibly fast there are several treatments that are already in advanced testing for this virus so when people say where is the vaccine the answer actually is there are three good candidates and all of them are now in phase one making certain that they're safe before they get rolled out and a great deal actually is known about how this virus is transmitted and how this virus gets moved from one person to another which is another potential advantage in terms of being able to address the outbreak and being able to address what's going on so i say that to say that in these situations there is a great deal that needs to be known but also that through a lot of investment it is possible to have most of that ready to use now i also want to say there's a lot more that still needs to be accomplished and one of the things that i'll highlight is it would be very nice to have an f d a approved ebola that was a statement that a lot of people made in two thousand and eleven and it didn't happen because of a lack of financial push but i think it will happen now it would also be really nice to have drugs that can alleviate suffering from the disease again there are a lot of people that are working on that there are some advanced stage compounds that could be very effective and one of the things that i think is really still the on the solved problem that is plaguing the current outbreak is the ability to do easy diagnosis something that is easy to say but it is hard to do these are resource limiting environments where it's very hard to get power much less a good diagnostic test to where you want to go so having said all that is an introduction i'm of course going to talk about some of the work that my lab does that directly tries to address this and i'm fortunate to work with a lot of people who have the same goal which is we would like to try and provide solutions to the existing challenges for infectious disease and we have a number of different things that we look at one of the things that we're interested in is trying to find small molecules that will derail a virus replication we've been interested in a bowler for a long time and so we've been looking at that and generally what the question is can we find a small molecule something that is not necessarily a drug but that is a probe lead that can identify what kind of drug you want to make that will stop the virus from making copies of itself and essentially how we do this is we've worked in the lab to set up a bunch of tests that can follow virus replication and we have wonderful collaborators at the in the chemistry department in boston university who have a separate question which is how can we make the neatest and most complicated molecules that have a drug like properties and we work together and essentially what we do is my interest is in running these compounds through these tests to try to find ones that keep viruses from working those throw a whole bunch of viruses of compounds in to these tests and what we want to know is what comes out when we run the tests well we'll find something a molecule that looks like this for instance and it allows us to then test it and say ok this worked in our specific test in the lab can we also show that this works not only in  my lab but in other people's labs and against these high consequence pathogen and we've with the luck of finding molecules like this we have found such molecules so we do have small molecules that block cyrus replication one of them was featured in one of the top one hundred discoveries of twenty thirteen because we found a small molecule that blocks not only a bullet but other viruses suggesting that we can have one drug that could actually act against multiple different viruses which would be lovely i don't want to labor that i want to talk about another thing that the lab has been trying to do which is to try to make better diagnostics and the reason for doing that is i think apparent in the current outbreak where there are delays of up to four or five days for patients to be determined either ebola positive or negative at that time when they're waiting for their response there in a large group of people that are suspected as you can imagine there are some people that are going to be positive and some people are going negative in those populations but they're all sit in the same if you can't get diagnosis done some of the people that probably were not infected at the beginning of that test cycle will be infected by the time they get to the end and so one of the and that's one of the things that we would like to try to block and keep from happening and we're trying to do that by developing the century lighter and cheaper and less energy requiring machines and less energy requiring tests it all goes to the central clinical problem which is when people have a viral disease often they show up looking generally sick they'll show up with general symptoms like look i feel i have the flu and that could mean you could have any number of infections so how do you limit that means you have to do a molecular test to actually find the virus and say which one it is and you can't just rely on somebody's symptoms but those are often very complicated and the current tests use and zines and enzymes are great if you live in the west and you have a constant supply of power you have fed ex deliver it to deliver enzymes on dry ice where you can use them they're much more difficult to use in africa where you have none of them one of the other issues is a lot of tests will look for one virus you guys may have gotten a rapid flu test or rapid breast tauruses actual virus test that checks for one thing when you have nonspecific symptoms you'd like to have a test that looks for about seven different things in order to identify what you actually have and so both of these are our real difficulties for current virus detection schemes which center based on a pull him or a chain reaction assaye and also you can do direct culture to watch the virus grow out in a lab and in terms of time doing culture is really not very satisfactory it's going to take days to figure out what you have that's not a good sign but p c r analyze it can be very good they can work in a few hours a problem is they require a great deal of sample preparation in order to use them and they're anchored to a clinical lab this is an example of that so this is a friend of mine this is her in in liberia she is running some of the bola diagnostic tests you can see the machine there you can see and another technician back here doing the same thing this is great work it's really important work however one of the things that is limiting how fast they can do the tests is this right here that's a power plug with this totally filled up in order to run all these machines they needed a dramatic amount of power this is generator based this is not something in order to put up this diagnostic facility they needed a tremendous amount of infrastructure it's very hard to push out of a large city and at the side of need which may be rural and so this is one of the things that my lab has been trying to fix to try to make a machine that really does not need a tremendous amount of power when the inspiration from this for this comes of course from late night t in my case this is the university alumnus modeling what i hope to have is a virus detector which is a tricorder and what i learned from watching star trek is that this thing can do virus diagnostic in about thirty seconds this is great i want this also you can see is tremendously portable so of course that's in the future my question is how do we get to the future the first answer is you just wait a while and then it's here but that doesn't work too well in the laboratory and so one of the things that we've been focusing on is starting with a diagnostic approach that we know works and making it faster making it easier and making it more sensitive so we started with an assay that's called a platform that's called and the way that works is you take your sample that you think has a virus and in this case the virus is green and you put on a plastic plate an antibody that will capture that virus and when you incubate these guys together this an body will capture that virus then you need to figure out that that's happened and in order to do that you need to add a second antibody that has a label on it that will shy in and say all right i'm here this is a great asset these these are used clinically all the time but they take a while one of the things that we were concerned about was maybe we could short cut this maybe you could we can make a faster essay by getting rid of this label step and then just go here and look for the answer and so how do you do that the idea that we've been following is usually in the analyze acid the thing that you stick the end of body to is in earth what would happen if we made it so that it was active on its own so that if there was no virus present you wouldn't see any signal from it but if there was a virus present what the antibody was bound to would tell you that something was there and that's a great idea there's a lot of very expensive ways to make that happen but we of course were looking for something that you could take to the point of care which means it probably can't be expensive and so we asked if we could use something really simple like like lights really easy to get it's really easy to get in all countries and so what we've been studying is something called interferometric reflect what that is is really similar to what happens when you see rain a rainbow in a soap bubble so what is happening when you see that rainbow is white light is coming in to that so bubble some of it's bouncing off the top some of it's bouncing off the bottom and the wavelength of light that you see represents the distance between this outer film and the inner field what that means in terms of measurement is you are able to see three or four nanometers of difference in the thickness of that soap bubble so your eyes are becoming phenomenally sensitive to very very small change and that's really cool it's fun to watch so bubbles it's fun to watch in water but it's also something that if you are an engineer you can reduce to a simple instrument you can reduce to a silicon and glass interface that will do essentially the same thing that if you have small changes at the surface of that that glass that's on the top of this little wafer here you can measure that you can see very very small changes and this was something that was being developed by a colleague of mine saleman lu this is saline here working the machine this is me looking like a doofus watching him use the machine and what i'm doing here is saying can we use this to detect viruses and the idea that we followed was this we were going to put in a body on this active surface and we were going to look at it it's going to give us some signal that comes out and the idea was is if a virus got bound right at that surface that when we bounce light off it now that signal would be slightly different that there'd be a difference that we can actually quantify the nice aspect of this is this is really cheap silicon is really easy putting a glass surface on it is even easier the super the semiconductor industry has been helping the telecommunications industry helping the computer industry make these types of chips for decades we can call up california and say we would like fourteen thousand chips believe and that costs us three weeks of time and a thousand bucks which is less than a dollar per chip which is great that you want an asset a cost in the end so and general the idea here is that one of the other advantages is in allies or you end up using a single antibody to get a single answer if we use this chip we can a re a number of different antibodies down on the surface and so you can imagine we can look for multiple different things at the same time i think is the gives rise to the idea of this multiplex concept where we've got a hold bunch of strips of antibodies here and you can imagine them binding various different infectious a and reporting that out when they're present this is something that saleman i've been working on for the last several years and the nice part is that we know it works now so we can detect virus binding  very easily and very sensitively which is important for these asses and we can look for several viruses at once and one of the additional things is the simplicity of the essay is really i think a strength of how we would like it to work this is already published and it's got lots of scientific mumbo jumbo in this article so i won't belabor the point when i do want to say is what we're at now so the current essay looks like this you can take a sample which is either blood or serum it doesn't matter you get it with a little centimeter sized chip for about thirty minutes maybe forty five even wash it and you can read it it's a very simple straightforward  assay if we were going to do an ally's a you would start with the same sample but you would only have a single thing that you could look at rather than three which is what we've got up here you'd have to do that same incubation step wash label weight in our washington and then read so essentially what we've done is cut the time of the essay down while keeping the sensitivity well keeping all of the other aspects that are good about analyzing this of course has gotten lots of people excited we've got people calling from computer world which never talks to me asking how we were going to use nanotech to solve the world's problems and what the reason i didn't put the article in here is what i told them is we're not going to solve the world's problems but we might help diagnose the disease earlier and of course this leads to people doing additional questions of how do you address this problem and how do we address this lack of a mobile tast right now the diagnostic that we've developed has been picked up by two separate high containment labs that are testing it we just sent our initial chips to sierra leone a couple weeks ago to see how they work and we're optimistic that we can push this paradigm so that you can get very simple testing that you can get effective testing using this technique and that said i don't want to leave you with the impression that we are all the way to where we want to go the things that we still have to do is we need to shrink our detector into a portable system we like this size and we'd like to get to this size we also would really like to get to the point where the the diagnostic interface that we use is incredibly simple where you you're either unhappy with your diagnosis or you're happy your diagnosis and we still need to work that part out so that i've talked for plenty long now i think i'll stop at this point the thing i wanted to do before i do that is to say i've stood up here and talk to you about all the fun things the lad does and these days i don't do any of them  that's done by the people that you see here and it's a large group of people as i mentioned a lot of the virus detector work we've done with my colleagues selene moon had a tremendous group of graduate students and post docs i fortunate to have wonderful people working for me the anti viral compound that i mentioned briefly we developed with john snyder boston university and we're also very lucky to have good collaborators outside of the boston area  people at the university of texas medical branch which is in galveston we've gotten lots of readings from people who've been very nice when i've called them up and asked for them they've given us and bodies and we asked this includes all of these people here who've given us tremendous support out of the work that i talked to you about today we managed to kick one postdoc out of the lab the successful part of that was that he went and started his own company called next generation and they've picked up on the technology that's been developed and and have now commercialized it you can see this is the detector that i showed you in cartoon this is david this is his colleague george w both of been instrumental in sort of pushing this technology to where it is today and making what is now a clinical laboratory type instrument and moving towards a portable instrument in the future so i think i will stop there you right so so how do you ever win correct and so the the simple answer is that there are two things the first is that they're what are called innate defenses that your cells have so there they deploy several danger sensors both on the outside of their cells and inside that look for patterns associated with virus infection and when those happen that starts transcription a program that produces a large number of anti viral proteins that not only try to attack the viruses in the cell but also send signals to neighboring cells saying prepare yourself there is a virus in the neighborhood and that can be somewhat effective there is another thing however and that is your adaptive immune system so those your t cells and your b cells the ability to make antibodies and that are specifically directed against whatever pathogen is in your body at that moment and also to develop t cells that also recognize cells that are infected engulf them and get rid of them so the two separate ways that the body i'm sorry i've just explained two separate lives there are probably one that i haven't been really well defined right now but the i think the second part of your question is why do you just get sick with someone why do you get really sick with others that's why i think there's a big gap and knowledge right now or when you look at viruses it's not that easy to say just from looking at their genetic material oh yes this is going to be a bad one no this one won't it's something that has to be done in experimental and unfortunately that experimental is  s right so so you can probably guess in that they don't work effectively and one of the things that viruses are known to do is to deploy essentially deploy their bear with me viruses are no dummies if they have evolved to become successful they have figured out ways to untag and ais a lot of these signals right so that many viruses bring in molecules that they don't need in order to just complete their replication cycle you can get rid of them and put them on cells in a tissue culture dish and they are just fine but then you try and put them in an animal and they no longer cause disease and when you look at what happened what that protein does normally you find that that protein goes in turns off part of the immune response sometimes is that innate response sometimes it's the adaptive response but a lot of the viruses that are associated with very severe pathogenesis make these innate response or adaptive response interfering proteins and that's certainly part of it but while i say that there's also a lot of viruses that don't cause severe disease in us that produce similar proteins so it's not i don't know that it's really well understood exactly what that switch is i would that's what i'm going to say while i still at the same time i cringe at that at the fact that that describes a brain to something that has twelve proteins so i'll take the second question first and the answer is yes so they're there are so sorry so the second question was if you have had ebola and now you  are now you have recovered are you cured are you free are you completely free of the virus and so the answer that that we know is yes the so the the entire process of the disease is when you are initially infected the virus for lack of a better analogy starts out winning right so it gets into your cells it begins to replicate it will move to various different organs and continue to do that and make more and more and more of a self the entire time what your body is trying to do is to dial in the right response to dial in the correct antibodies that are going to recognize that virus keep it from entering additional that solution right so if they're doing a rubik's cube they don't solve it before the virus replicates too much those that do make a very strong antibody response that recognizes the virus and parts of the virus and what that does is it completely clears the virus from the person's system but also will protect them in the future if they see that again so  if if they have survived they are essentially vaccinated it's not a vaccination process that any of us would want to go through but it is it is one that that confers protection so th e second question which you asked first is you under the impression that viruses have a hard time jumping and the answer unfortunately answer there is very specific to an individual virus so the classic example of something that has a hard time jumping from species to species was small pox right so smallpox had one organism that it could infect and it was us and for many centuries it did a great job of doing that when a vaccine was developed and and disseminated in the proper fashion and this was in the sixty's and seventy's that it was really pushed very hard once you got to the point where you vaccinated in the areas where smallpox was present it died out it's now in no longer in circulation there's nowhere where it's hiding except for certain freezers at the c d c but it's safe there the so that's an example where the virus did not have another reservoir to sit in however things like flu are the opposite of that so you'll remember the two thousand and nine flu pandemic that virus was a virus that likely circulated in pigs and also there is genetic evidence that it circulated in birds  and it was part of those jumps that allowed it to come back into humans so different viruses have different abilities to do that so i guess another good example is hiv which is  restricted to us it does not cause disease even in very genetically closely related non human primates so there are a lot of vagaries in my answer which i'm i'm sorry about viruses don't conform to a specific paradigm but some are very easily transmitted among species some not at all right so so the question is has the bowl of virus mutated since one thousand nine hundred six absolutely it has every time there has been an outbreak the sequence has been different than the previous outbreak there has not yet been a situation where the exact same genetic the virus with the exact same genetic sequence has shown up that said a lot of the outbreaks the viruses are very very similar so the current ongoing outbreak is more than ninety seven percent identical to what was seen in the congo in one thousand nine hundred seventy six so the the answer is there are there are certainly mutations and even now as this virus is passed from person to person in western africa there will be additional mutations whether that makes it easier for the virus to transmit and makes it more pathogenic or makes it less pathogenic i think i don't know the answer there are two opposing possibilities one is that as it passes as it  essentially goes through life cycles in different humans it may become easier to transmit and therefore more pathogenic right that's the scary one the less scary one is as it goes through multiple cycles it may become less pathogenic and therefore easier for the virus to transmit so this would be an analogy to  epstein barr virus most of us have seen bar most of us have not noticed that we have the virus so the virus is incredibly successful at being carried around by all of us have being transmitted to multiple generations of people is not at all pathogenic sorry i missed it it's not tremendously pathogenic it can lead to some bath agenesis but most people really won't notice it at all and so there are those two potentials in every virus i would say that the potential to remain highly pathogenic and the potential to become less pathogenic i would say from what i have seen so far this the very significant pathogenesis associated with this outbreak i don't believe it is due to the virus itself i believe it's due to the situation in the countries where the outbreak is so rampant that that is what's allowing it to be transmitted for so long and the reason i say that is that in senegal and in nigeria where they had transplanted cases they were able to contain it very readily and if there were a change in the transmission pattern i wouldn't expect that