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 anti microbial discovery center at northeastern university dr louis is an internationally recognized expert in microbial drug resistance and lately he's been in the news a great deal because slabs breakthrough just development of an antibiotic that seems to overcome drug resistant bacteria this is a very significant thing because as you know antibiotic resistance has led to a public health crisis dr lewis is a permanent member of the end i drug discovery and drug resistant study section he's also a fellow of the american society of microbiology and he's received numerous awards and patents for his work in addition he's the founder of two biotech companies novo by addict pharmaceuticals an area it has corp today dr lewis will discuss his latest and possibly greatest innovation and apparently fail proof and a biotic called take so that has caused a great deal of excitement in both the scientific world and in the media it is a great honor to welcome dr kim as our conversation of holes all tell you more about ok that's just fine but it can i start though with just getting some background i think people are aware that we have a crisis with  you know the anti arctics today can you give us a little background about how antibiotics were discovered and what happened yes of course so the first highly successful and  and he was focusing on the you know my seats that turned out to be the most prolific producers of antibiotics that he would take one colony of acting the my seed at the time apply it to a petri dish overlaid with when they did all these great and wonderful things that looked like the cure for everything what happened that people maybe didn't expect initially the that made that led to the antibiotic them as they were being discovered and entry and introduced but that did not seem at the time at the time meaning the forty's in the fifty's and sixty's like a big problem because there was plenty antibiotics plenty of classes of antibiotics are being discovered and the discovery far outpaced resistance acquisition and and spread by the pathogens so resistance seemed more like a nuisance rather than  in our meat it's in everybody is taking them all the time was that the difficulty or would it have been inevitable just because of the mutation rate yeah there were there were two different factors overuse of antibiotics using antibiotics when people really have viral infections for example that has been pretty standard or very rare or why do use of antibiotics as over the counter medications in a lot of third world countries where you do not need a prescription yeah so so that's has been of course a major component and then of course also the use of antibiotics  you know for growth promotion of farai but apart from that if we would have continued the discovery at the pace of the forty's and fifty's we'd probably  probably be ok today in spite of the misuse of antibiotics but that was not the case the rapid discovery in introduction of new classes abruptly seized in the early sixty's like somebody turned off the discovery process and why so that we can fairly confidently trace the over mining of the main source of antibiotics that someone waxman was working ninety nine percent of species for a variety of reasons do not want to grow on our petri dishes and so if you have a limited resource of something that of course that's going to be over mind right and so  after the sixty's people realize that they are spending their time rediscovering penicillin stripped of mice and i see instead of discovering new classes of antibiotics so let me get this straight part of this was the problem of the cultur ing in the petri dish what could be cultured in the petri dish this is where you come in i think that you turn back to where ninety nine percent of the bacteria were and you came up with a very different method so  that this is a fascinating basic science problem we were motivated just by the process because of that live a say of course we realized the probably useful if we learned how to grow them but our primary motivation of the time was to solve the problem right what is the yes the problem was that is the problem why do bacteria not grow in our petri dishes when we seemingly had wonderful nutrients yeah oldest problem solve problem microbiology with problem by the way with penicillin two they couldn't make enough of it did that have anything to i didn't that's a different product so they of course they could grow the fungus but in the beginning the fungus did not want d you know there's a vast negative experience of trying to come up with a wonderful media that's to grow everything we realize that that's not going to work that's not what we want to do we're also realize that uncultured bacteria do grow when they're not true environment yeah so that's where we are going to grow them then the question was coming up with a gadget to do that and the gadget we came up with is so i'm tempted to ask that too why didn't somebody get it sounds like ok you know tankard so i wanted to try to find out how long that took but you know the the everybody knew about the benefits with another thing of course microbiologists of sort about this problem and there there was there was you know a list of reasons why possible reasons why they don't grow in the lab and what was really a killer one of the reasons  potential reason yeah so one of the explanation was that these are simply the vast majority of bacteria and environment are simply extremely slow growing so maybe they divide once a problem and secondly it will have no practical significance or stand yeah and that was another barrier that i think prevented right a lot of people from from going there right so were you in a distinct minority then start up by a tech company in cambridge not far from here and the initial diffusion chamber is still working ok it's still working but since then we came up with a number of modification was focusing on the chemo my seeds and showed that they're the most prolific producers of antibiotics and we thought that it may be useful in a perfect world i to have a diffusion chamber that only grows a after a while they crawl in the form colonies of though you have a trap that only grows a few of mice so so that was one thing that was developed in my lab and then moved to another by attic and then slobber in his lab developed what you probably heard more of the same but in a small gadget but more importantly to samal tenuous lee isolate and culture yeah an organism that is cheve in the eye chip course a big problem is how to move them into the lab tempt them into the lab so what we discovered together with slava is that once a cell forms a colony  works given a bacteria that is the target that it's going to have to attack how it works there are different ways in which these selected microbes attack a five new compounds of which are the latest and perhaps the most exciting has been take some back then and that's what they buy a lab at our collaborators have been focusing right what's so great about takes a back to seeing as you've got an array here of possibilities what and how does that work right so one thing that we've been looking for is of course a ntibiotic to which there will be low probability of resistance to the yes right and so you know we have a very simple test to do that if you're isolated then you  about the cell wall it's made of are two major polymer right and there is another very important twist to the story which is relevant to resistance so becky we have a number of resistance mechanisms some of them are highly sophisticated like there's a whole by chemical pathway that modifies the target right but usually these highly sophisticated mechanisms come from an organism that produces the antibiotic that kind of makes sense if you by out of course you need to protect yourself right and the simplest way is to protect your target to modify it and so so we were wondering what's what's going on with the producer any sporting the scientist that they were by had a pick that absolute so she discovered this bacteria and felt that it's interesting enough to follow the follow through so gram negative bacteria have s that's why that's so resistant so so so what this is so now this bacterium that's making takes a back to it protects itself from just tells us that that is obviously not the only compound like that out there right we only scratched the surface literally of the plot so you  think it's not necessarily so rare as it would look like at the moment that you discovered it there may be others that have evolved this kind of mechanism absolutely i'd be astonished if we were with a fairly modest effort bacteria will always develop resist yeah and so then you have really one option and your one option is to discover compounds faster right than resistance going to develop right people have been  advocating also another if not approachable very useful thing that's judicious use of antibiotics good stewardship that's of course absolutely necessary but in reality we can introduce such things in europe in america but it is considerably harder especially in short term to introduce such things in third world countries where actually barracks are going to be sold over the counter or the foreseeable future and so really then our only very limited propensity resistance to build it's really quite amazing and that this is if effective as far as you know against you mentioned tuberculosis which has been a disaster because it's s a number of these things where you used to be able to take care of infections and diseases that were bacteria suddenly they lose as really ominous but this it looks like because it's a different avenue it looks like it's highly effective yet well it is effective is effective in mice cures mice of a number of difficult to treat infections but of course it's not taking on the medicinal chemistry approach to get down the logs of takes a back to improve side ability so these are sort of two parallel paths i'm not clear on that is that in order to determine what dosage can deliver that larger right so we need to be prepared for that eventuality right i see this looks very exciting there is this it had to be a big thrill for you and your lab and your colleagues yes i think it's amazing just because it's a great leap forward so to speak it seems like a great leap forward what do you predict for the future of part from developing this which seems to be you know a given but the other is it sounds as though there's a whole new track for microbiology now that people will be doing things in a different way of what is the future yeah here and that's what hopefully we'll be able to do to enlarge that effort ultimately of course we people will have to learn how to synthesize terrific we're just not there yet but you do anticipate that they will synthesize this that they well of course there's there's no reason we shouldn't be able to save of the state of the art in chemistry and rational drug design is not quite there yet but i think we'll get there it's a really thrilling a moment i think it must be tremendously gratifying at just this moment when people were throwing up their hands about bacteria about these bacterial infections that you've come up with a fabulous discovery so i think it must be very exciting on your end for well to be feared that everybody was throwing off there has i mean there's a number quite a number of labs and groups and companies that are working successfully on the problem i think what we've contributed rather uniquely  to the problem is to show that there is a method not just a single compound but there is a method that can be exploited this discovery platform yeah that will allow us to discover additional companies i c does this in tale also we training people who are going into microbiology looking into this sort of thing does this is just so i don't think you know it's fairly simple is  k beginning of of this conversation the question was you know it's so simple why didn't people think of it so i don't think this requires a lot of all right so so it will it will it will be a different avenue in any case i would like to point out before we close here that you've done some really exciting work on lyme disease and a number of other things that i hope to pursue and the other point  that your lab is really something that i hope because of the recent published city will become much better known to the general public now but i thank you very much for joining