[0:02][Music] as a boy I never had the doubt as to who
[0:11]I wanted to be well look at this I wanted to be an astronomer of course I wanted to study Stars and the space in between them except it was not going to
[0:22]be my destiny because you see I happen to have been born in Russia and I happened to have been born Jewish and that at the time was not a good
[0:32]combination in the infinite wisdom the Soviets established strict quarters on everything a Jewish in just about every field and my relatives and my friends
[0:44]whose opinion I highly respected they kept telling me that I shouldn't even think about going to a physics department of Moscow State University
[0:54]for a very simple reason I would never make it my brain was telling me they were right but the teenager inside me was fighting that so it was a dilemma
[1:05]and I said to myself God give me the serenity to be wise and God granted me
[1:17]wisdom and I switched the fields to biology where the quarters was much the course was much more relaxed in due time
[1:26]my young family my wife and my kids toddlers really at the time admit raynella's we left Russia for good we
[1:36]went to the US and settled down in Boston for good and for the following several decades I was studying this and
[1:45]these are not enlarged images of stars as you can see them through a telescope instead these are enlarged images of bacteria as you can see them through a
[1:56]microscope so I switched from the largest to the smallest and two things happened first I never regretted the switch and second I never forgot my
[2:07]dreams in the realization came that it really doesn't matter what you study what matters is to have a big challenge in front of you an intellectual one to
[2:18]resolve and enough passion to do so in your lifetime there are many challenges
[2:28]in physics and astronomy there are many challenges in biology and microbiology but there is one at least one the curiously enough has a very same name
[2:36]and the name is dark matter that young boy from 1960s went from stars to
[2:44]microbes but in hope that one day maybe it just may be that one day he will be back so now let me switch switch gears
[2:56]and go to microbiology here is a petri dish with a mutant medium and we put microbes from soul on it and some were
[3:06]happy what you see is small disks these are colonists those heavy cells forms what you do not see is that there are many many many many cells that for some
[3:16]reason never grew there so what is the number what is a difference between the number of organisms that form colonies and the number of organisms that do not
[3:25]the difference is very large indeed here is a box if the blue box is the number
[3:34]of microbial species on the planet then a red speck in the middle this one is the number of species microbial others have been able to isolate and study and
[3:45]utilize over the past hundred hundred fifty years so how much have we learned from that Transpac well they actually learned a great deal so all the original
[3:56]ideas of how microorganisms are related to each other into ourselves it came from that small dot here our books on microbiology it's a general microbiology Medical Microbiology
[4:07]microbial ecology you name it and most of this knowledge came from the red speck more importantly the drugs or more specifically antibiotics overwhelming
[4:18]majority of them came from that red speck so what is it that the rest of microbial world contain how we can access it how we can grow it
[4:28]and how we can utilize that that is the question so let me go back to the pizza
[4:36]dish the basic idea in microbiology 400 years was that we can guess what
[4:47]microorganisms need we can figure it out what an unknown species needs and provided with in the form of right temperature right nutrients in petri
[4:57]dish and the idea works up to a point and that point it was red red red dot so guesswork brings incremental success
[5:08]but only in in small steps is it possible to eliminate guesswork from the work of microbiologist is it possible to cultivate microorganisms by
[5:20]design well let's go to nature how do we grow plants why well we grow them in soil why because soil of course contains
[5:31]everything that the plants need but doesn't the same logic applies to microbes isn't it doesn't soil here it's
[5:40]filled with microorganisms there all the nutrients they need all the growth factors pheromones
[5:48]whatever they need is there that mix may be very complex how can we guess its composition why do we have to guess because because we already know where
[5:59]that makes exist that's in the natural environment of the microorganisms we we're going to grow so thinking this way
[6:09]we create the device it's very simple really and I will take you over the diagram in steps this works is very
[6:17]simple take sample of soul and take cells out of it and then we suspend them
[6:24]in a beaker then we put them say plastic plate with small holes into that cell suspension and of course each hole will
[6:35]capture a small volume of that you will always the lose at suspense and such that each hole will capture on average one self-assemble contain two
[6:46]others will contain nothing but most will contain one the next step now the the plate which we loaded with cells in
[6:55]is in the middle the next step is to put membranes next to them to the plate that membrane will help holes they're small enough to contain bacteria inside they
[7:07]cannot cross it but they are large enough to allow chemical diffusion to occur in the future then we press that device tightly
[7:16]together and we put it back into the soil as expectation is that now chemical diffusion will bring from soil everything my crops need all the
[7:27]nutrients growth factors pheromones and hormones the cells inside will never know when manipulated them they will be easily able to grow in nature they should be able to grow inside that
[7:38]device and if they grow they will form a colony so that in due time will remove remove the device disassemble it and here it is with those colonies of
[7:49]unknown microorganisms we grow we grew not knowing why but we drew them we call that device and isolation chip or ID chip for short and here it is a simple
[8:00]piece of plastic it's a very low deck as someone said a tall dreamer I think it's not just low-tech it's a drastic way
[8:08]low-tech but that was in serious that was just an idea but in theory as we all know there is no difference between
[8:19]practice and theory but in practice there is so we of course needed to conduct some experiments and actually show that we can grow microorganisms on
[8:30]a device and they're different from but we you can cultivate in the lab so here we're putting that a chip into soil to incubate and see what we can grow in it
[8:41]and what we discovered was that the device was teeming with life when please microbe is recovering the number of cells that for ponies not by 5% relative to
[8:53]conventional technologies not by 5% not by 10 not by a hundred percent by thirty thousand percent we knew we were getting
[9:03]access to the micro bill dark matter and we use that technology and its modifications suggest about everywhere from standard soils to Arctic Lakes to
[9:14]human bullying and that was very interesting by the way that a number of interesting bugs but a realization came that the device may have a very
[9:23]interesting practical application and then the colleague of mine Jim Lewis also from Northeastern University like myself we formed the company a startup
[9:34]that had a mission to utilize those technologies to grow novel microorganisms in the search for novel antibiotics I'm switching gears again
[9:44]I'm going to tell you something interesting I think so this is a timeline of the discovery of antibiotics
[9:53]over the years you probably see the spike 1940s 1950s 1960s we discovered most of the known classes of antibiotics
[10:04]the discoveries were coming every day and then stopped and lately it stopped completely for the past 30 years we have not discovered a single normal class of
[10:15]antibiotics but microbes don't know this they still really still develop resistances so the resistances are on the rise and the pipeline of new
[10:25]antibiotics is dry that's a problem and the problem is today in North America over 20,000 people die every year from
[10:35]infectious diseases that cannot be treated with any antibiotic alone and the number is about the same in European Union and the global estimate is 700,000
[10:45]people per year and if the situation does not change than the estimate is that by 2050 we will have 10 million people dying every year because of lack
[10:56]of antibiotics so why we are not discovering inch bags why would the was it so easy in 40s and 50s and so difficult to impossible today
[11:07]that's what it's actually really simple you remember that red dot that is what was in these available today to discover a novel antibiotics and we probably just discover it everything that red ball
[11:19]contains that's it but there is another 99% one 99.9% that's the microbial matter careful look there well when you
[11:29]do cultivate them but now we know how so the company I mentioned was working with these technologies trying to discover
[11:40]novel antibiotics and indeed 30 new ones in short 10-12 years the rate of discovery of novel chemical compounds whose essential microbial properties
[11:50]while utilizing the technology I was talking about is hundreds to thousands them higher than the industry standard
[11:59]now among these antibiotics there is one that is particularly interesting that we named takes a button we reported the
[12:10]molecule in the paper we published a couple of years ago and here's the you know structural formula of this compound and the photos a microorganism from that dark matter
[12:20]that produces it it's a very interesting molecule not because it kills pathogens though it does it's interesting in how
[12:30]does so he antibiotics I kill typically by targeting a target in the cell the cell can respond the result can mutate
[12:41]the central cell can change the target and then 90 but it no longer works it happens with low nonzero but low probability that's not how takes a button works fix
[12:53]the button works in several ways in two ways so it kills the cell using two targets independently so if the cell changes changes one target it's not going to help the cell it's still being
[13:05]called been killed in the second way right likewise changing the second target is not going to to help because the first target Hugh
[13:14]makes the cell phone durable so what that's cells ooh well it still has to mutate but now you have to multiply one low probability by not a low probability
[13:25]and you get infinitely small probability of the cell being able to develop resistance so if I take the button ever becomes a drug the resistance to it will
[13:35]not come indicates gene has room to breathe to develop whether means to combat infectious diseases takes a
[13:45]botanist a monkey on preclinical development it's who can fail any day in phase 1 and phase 2 it doesn't really
[13:55]matter too much because we did not discover takes a baktun by chance we discovered it by design as the National
[14:05]Geographic put it takes a bottom is not the best part of its own story that owner falls on a chip the tool used to discover it they said that takes a
[14:16]baktun is a fish the eye chip is the rod and having the rod guarantees that we will get more fish and buy desperately need more so that is the source of
[14:26]optimism so today is good the work is good the future let me talk about the
[14:34]future a little bit for the future it's that's precisely where we're going to spend the rest of our lives we made all kinds of devices we adapted them to
[14:45]different environments fine-tuned them and they work well however all of them share one at least one aspect and this aspect is actually a liability
[14:55]same as all the conventional cultivation technologies as well and that is all of them require microbiologist so there's got to be a microbiologist who takes a
[15:06]sample extract cells loads them into a chip or Budiman petri dish microbiologist is inseparable for the method microbiologist is using they
[15:15]have to be together therefore we cannot do microbiology on mars because there is no microbiologist there
[15:25]and there is not going to be to be one anytime soon so for several years have been thinking how to separate microbiologist from the to microbiologist using so we can use it
[15:36]to anywhere and when I say anywhere I mean anywhere let me introduce Gulliver the new device that does not exist is just a concept but it will in a few
[15:47]short years it will be device that will be able autonomously sample the environment sample single cells allow them to grow inside it will have
[15:58]non-essential built into it that will measure aspects of growth of this microorganism how this parts how it releases co2 all kinds of physiology can
[16:08]be measured and remotely transmitted to your iPhone so where is a microbiologist well microbiology sees with an iPhone and that can be anywhere and Gulliver
[16:19]and we wherever you want therefore it can do a Mars or it can be on Europa or on the best thing that they took Harbor
[16:29]microbial life today and sawdust and if we do that and I strongly believe we can build a logger and send it there then
[16:38]perhaps one day that way from the
[16:42]sixties will go back to stars thank you [Music]