We have a global health challenge in our hands today, and that is that the way we currently discover and develop new drugs is too costly, takes far too long, and it fails more often than it succeeds. It really just isn't working, and that means that patients that badly need new therapies are not getting them, and diseases are going untreated. We seem to be spending more and more money. So for every billion dollars we spend in R&D, we're getting less drugs approved into the market. More money, less drugs. Hmm.
Danas u svojim rukama imamo globalni izazov zdravlja, a to znači da je način na koji trenutno otkrivamo i razvijamo nove lekove previše skup, traje predugo, i ne uspeva češće nego što uspe. Zaista nam ne uspeva, a to znači da pacijenti kojima je veoma potrebna nova terapija istu ne dobijaju, a bolesti se ne leče. Čini se kao da trošimo sve više para. I tako za svaku milijardu dolara potrošenih na istraživanje i razvoj sve je manje lekova koji su odobreni za tržište. Više novca, manje lekova. Hmm.
So what's going on here? Well, there's a multitude of factors at play, but I think one of the key factors is that the tools that we currently have available to test whether a drug is going to work, whether it has efficacy, or whether it's going to be safe before we get it into human clinical trials, are failing us. They're not predicting what's going to happen in humans. And we have two main tools available at our disposal. They are cells in dishes and animal testing.
Dakle, šta se dešava ovde? Pa, više faktora utiče, ali ja mislim da je jedan od ključnih taj da alati koji su trenutno raspoloživi da testiraju da li će lek imati efekta, da li je efikasan, ili da li će biti siguran pre nego što ga odnesemo na klinička ispitivanja na ljudima, nas dovode do neuspeha. Ne predviđaju šta će da se dogodi u ljudima. A imamo dva glavna alata na raspolaganju. To su ćelije u posudama i testiranje na životinjama.
Now let's talk about the first one, cells in dishes. So, cells are happily functioning in our bodies. We take them and rip them out of their native environment, throw them in one of these dishes, and expect them to work. Guess what. They don't. They don't like that environment because it's nothing like what they have in the body.
Hajde sada da pričamo o prvom, o ćelijama u posudama. Dakle, ćelije srećno funcionišu u našim telima. Mi ih uzmemo i izvučemo ih iz njihovog prirodnog okruženja, bacimo ih u jednu od ovih posuda, i očekujemo da će da rade. Pogodite šta. Ne rade. Ne sviđa im se to okruženje jer nije ni nalik onome što imaju u telu.
What about animal testing? Well, animals do and can provide extremely useful information. They teach us about what happens in the complex organism. We learn more about the biology itself. However, more often than not, animal models fail to predict what will happen in humans when they're treated with a particular drug.
Šta ćemo sa testiranjem na životinjama? Pa, životinje nam mogu obezbediti veoma korisne informacije. Uče nas šta se dešava u kompleksnom organizmu. Učimo više o samoj biologiji. Međutim, češće se dešava da životinjski modeli ne uspeju da predvide šta će se desiti u ljudima kada ih lečimo određenim lekom.
So we need better tools. We need human cells, but we need to find a way to keep them happy outside the body.
Zato nam trebaju bolji alati. Trebaju nam ljudske ćelije, ali moramo da nađemo način da ih održavamo srećnima van tela.
Our bodies are dynamic environments. We're in constant motion. Our cells experience that. They're in dynamic environments in our body. They're under constant mechanical forces. So if we want to make cells happy outside our bodies, we need to become cell architects. We need to design, build and engineer a home away from home for the cells.
Naša tela su dinamična okruženja. U stalnom smo pokretu. Naše ćelije to znaju. One su u dinamičnom okruženju u našim telima. I uvek su pod mehaničkim silama. Tako da ako želimo da učinimo ćelije srećnima, van naših tela, moramo da postanemo ćelijske arhitekte. Moramo da dizajniramo, napravimo i isplaniramo drugi dom za ćelije.
And at the Wyss Institute, we've done just that. We call it an organ-on-a-chip. And I have one right here. It's beautiful, isn't it? But it's pretty incredible. Right here in my hand is a breathing, living human lung on a chip.
Na institutu Vis upravo smo to i uradili. To zovemo organom na čipu. I ja imam jedan upravo ovde. Predivno je, zar ne? Ali i prilično neverovatno. Baš ovde u mojoj ruci je živo plućno krilo na čipu koje diše.
And it's not just beautiful. It can do a tremendous amount of things. We have living cells in that little chip, cells that are in a dynamic environment interacting with different cell types. There's been many people trying to grow cells in the lab. They've tried many different approaches. They've even tried to grow little mini-organs in the lab. We're not trying to do that here. We're simply trying to recreate in this tiny chip the smallest functional unit that represents the biochemistry, the function and the mechanical strain that the cells experience in our bodies. So how does it work? Let me show you. We use techniques from the computer chip manufacturing industry to make these structures at a scale relevant to both the cells and their environment. We have three fluidic channels. In the center, we have a porous, flexible membrane on which we can add human cells from, say, our lungs, and then underneath, they had capillary cells, the cells in our blood vessels. And we can then apply mechanical forces to the chip that stretch and contract the membrane, so the cells experience the same mechanical forces that they did when we breathe. And they experience them how they did in the body. There's air flowing through the top channel, and then we flow a liquid that contains nutrients through the blood channel. Now the chip is really beautiful, but what can we do with it? We can get incredible functionality inside these little chips. Let me show you. We could, for example, mimic infection, where we add bacterial cells into the lung. then we can add human white blood cells. White blood cells are our body's defense against bacterial invaders, and when they sense this inflammation due to infection, they will enter from the blood into the lung and engulf the bacteria. Well now you're going to see this happening live in an actual human lung on a chip. We've labeled the white blood cells so you can see them flowing through, and when they detect that infection, they begin to stick. They stick, and then they try to go into the lung side from blood channel. And you can see here, we can actually visualize a single white blood cell. It sticks, it wiggles its way through between the cell layers, through the pore, comes out on the other side of the membrane, and right there, it's going to engulf the bacteria labeled in green. In that tiny chip, you just witnessed one of the most fundamental responses our body has to an infection. It's the way we respond to -- an immune response. It's pretty exciting.
I nije samo prelepo. Može da uradi ogromnu količinu stvari. Imamo žive ćelije na tom malom čipu, ćelije koje su u dinamičkom okruženju u interakciji sa različitim tipovima ćelija. Bilo je mnogo ljudi koji su pokušali da uzgajaju ćelije u laboratorijama. Probali su sa različitim prilazima. Čak su pokušali da uzgoje mini-organe u laboratoriji. Mi ne pokušavamo to da uradimo. Samo pokušavamo da ponovo stvorimo, na ovom malenom čipu, najmanju funkcionalnu jedinicu koja predstavlja biohemiju, funkciju i mehaničko naprezanje koje ćelije iskuse u našim telima. Kako to radi? Da vam pokažem. Mi koristimo tehnike iz industrije za proizvodnju kompjuterskih čipova kako bismo napravili te strukture u veličini bitnoj i za ćelije i za okolinu. Imamo tri fluidna kanala. U sredini, imamo poroznu, fleksibilnu membranu na koju dodajemo ljudske ćelije iz, na primer, pluća, a onda ispod, imamo kapilarne ćelije, ćelije naših krvnih sudova. Onda možemo da primenimo mehaničke sile na čip koje razvlače i skupljaju membrane, tako da ćelije iskuse iste mehaničke sile, kao kada dišemo. I one ih iskuse kao da su u telu. Tu je vazduh koji ide kroz gornji kanal, zatim tečnost koja sadrži hranljive materije kroz krv. Čip je veoma lep, ali šta mi možemo da uradimo s njim? Možemo da dobijemo neverovatnu funkcionalnost unutar ovih malih čipova. Da vam pokažem. Možemo, na primer, da imitiramo infekciju, gde dodajemo bakterijske ćelije u plućno krilo. Onda možemo da dodamo ljudska bela krvna zrnca. Bela krvna zrnca su odbrana našeg tela protiv bakterijskih napada, i kada osete zapaljenje zbog infekcije, ući će iz krvi u plućno krilo i progutati bakteriju. Sada ćete da vidite kako se to događa uživo u ljudskom plućnom krilu na čipu. Obeležili smo bela krvna zrnca kako biste mogli da vidite kako plutaju, i kada primete infekciju, počinju da se lepe. Lepe se i pokušavaju da uđu u pluća iz krvi. I možete da vidite, možemo da prikažemo jedno belo krvo zrnce. Lepi se i migolji se između slojeva ćelija, kroz pore, izlazi na drugu stranu membrane, i upravo tu će progutati bakteriju koja je obeležena zelenim. U toj maloj posudi, upravo ste bili svedoci jednog od najosnovnijih odgovora našeg tela na infekciju. To je način na koji reagujemo - imuna reakcija. Veoma uzbudljivo.
Now I want to share this picture with you, not just because it's so beautiful, but because it tells us an enormous amount of information about what the cells are doing within the chips. It tells us that these cells from the small airways in our lungs, actually have these hairlike structures that you would expect to see in the lung. These structures are called cilia, and they actually move the mucus out of the lung. Yeah. Mucus. Yuck. But mucus is actually very important. Mucus traps particulates, viruses, potential allergens, and these little cilia move and clear the mucus out. When they get damaged, say, by cigarette smoke for example, they don't work properly, and they can't clear that mucus out. And that can lead to diseases such as bronchitis. Cilia and the clearance of mucus are also involved in awful diseases like cystic fibrosis. But now, with the functionality that we get in these chips, we can begin to look for potential new treatments.
Želim da podelim ovu sliku sa vama, ne samo zato što je toliko lepa već zato što nam pruža neverovatnu količinu informacija o tome šta ćelije rade u čipu. Govori nam da te ćelije iz malih prolaza u našim plućima, zapravo imaju strukturu nalik kosi koju biste očekivali da vidite u plućima. Ove strukture se zovu treplje, i one zapravo teraju sluz van pluća. Da. Sluz. Bljak. Ali sluz je veoma važna. Sluz hvata čestice, viruse, potencijalne alergene i ove sitne treplje se pomeraju i oslobađaju nas sluzi. Kada se oštete, recimo, zbog dima cigarete, na primer, one ne funkcionišu kako treba i ne mogu da nas očiste od sluzi. I to dovodi do bolesti kao što je bronhitis. Treplje i oslobađanje od sluzi su takođe uključene u odvratnim bolestima kao što je cistična fibroza. Ali sada, sa funkcionalnošću koju imamo u ovim čipovima, možemo da počnemo da tragamo za potencijalnim novim lečenjima.
We didn't stop with the lung on a chip. We have a gut on a chip. You can see one right here. And we've put intestinal human cells in a gut on a chip, and they're under constant peristaltic motion, this trickling flow through the cells, and we can mimic many of the functions that you actually would expect to see in the human intestine. Now we can begin to create models of diseases such as irritable bowel syndrome. This is a disease that affects a large number of individuals. It's really debilitating, and there aren't really many good treatments for it.
Nismo stali sa plućima na čipu. Imamo i stomak na čipu. Možete da ga vidite ovde. I stavili smo ljudske crevne ćelije u stomak na čipu, i one su pod stalnim peristaltičkim pokretima, ovaj protok nalik kapljanju kroz ćelije, i možemo da imitiramo mnoge od funckija koje biste očekivali da vidite u ljudskim crevima. Sada možemo da počnemo da pravimo modele bolesti kao što je sindrom razdražljivih creva. Ovo je bolest koja pogađa veliki broj ljudi. To je veoma iznurujuće, i ne postoji puno dobrih tretmana za to.
Now we have a whole pipeline of different organ chips that we are currently working on in our labs. Now, the true power of this technology, however, really comes from the fact that we can fluidically link them. There's fluid flowing across these cells, so we can begin to interconnect multiple different chips together to form what we call a virtual human on a chip. Now we're really getting excited. We're not going to ever recreate a whole human in these chips, but what our goal is is to be able to recreate sufficient functionality so that we can make better predictions of what's going to happen in humans. For example, now we can begin to explore what happens when we put a drug like an aerosol drug. Those of you like me who have asthma, when you take your inhaler, we can explore how that drug comes into your lungs, how it enters the body, how it might affect, say, your heart. Does it change the beating of your heart? Does it have a toxicity? Does it get cleared by the liver? Is it metabolized in the liver? Is it excreted in your kidneys? We can begin to study the dynamic response of the body to a drug.
Sada imamo čitav cevovod različitih organskih čipova na kojima trenutno radimo u našim laboratorijama. Ali, istinska moć ove tehnologije, zapravo dolazi iz činjenice da možemo da ih povežemo pomoću tečnosti. Tu je tečnost koja prolazi preko tih ćelija, tako da možemo da počnemo da povezujemo veliki broj različitih čipova zajedno da napravimo ono što zovemo virtualni čovek na čipu. Sada postajemo veoma uzbuđeni. Nikada nećemo moći da stvorimo celog čoveka na ovim čipovima, ali naš cilj je da možemo da stvorimo dovoljno funkcionalnosti da možemo da pravimo bolja predviđanja šta će da se dogodi u ljudima. Na primer, sada možemo da počnemo da istražujemo šta se desi kada stavimo lek kao što je aerosol. Oni koji, kao ja, imaju astmu, kada uzmete vašu pumpicu, možemo da istražimo kako taj lek dopire do vaših pluća, kako ulazi u telo, kako može da utiče na, recimo, vaše srce. Da li menja otkucaje srca? Da li je otrovan? Da li jetra može da ga prečisti? Ili je metabolizovan u jetri? Da li se izlučuje u bubrezima? Možemo da počnemo da gledamo dinamičan odgovor tela na lek.
This could really revolutionize and be a game changer for not only the pharmaceutical industry, but a whole host of different industries, including the cosmetics industry. We can potentially use the skin on a chip that we're currently developing in the lab to test whether the ingredients in those products that you're using are actually safe to put on your skin without the need for animal testing. We could test the safety of chemicals that we are exposed to on a daily basis in our environment, such as chemicals in regular household cleaners. We could also use the organs on chips for applications in bioterrorism or radiation exposure. We could use them to learn more about diseases such as ebola or other deadly diseases such as SARS.
Ovo bi moglo da napravi revoluciju i izmeni ne samo farmaceutsku industriju već dosta različitih industrija, uključujući i kozmetičku. Možemo da iskoristimo kožu na čipu koju trenutno razvijamo u laboratoriji da testiramo da li su sastojci u preparatima koje koristite zapravo bezbedni da ih stavljate na kožu bez potrebe testiranja na životinjama. Mogli bismo da testiramo bezbednost hemikalija kojima smo izloženi svakodnevno u našem okruženju, kao što su hemikalije u običnim sredstvima za čišćenje. Mogli bismo takođe da koristimo organe na čipovima za primenu u bioterorizmu ili izloženost radijaciji. Možemo da ih koristimo da naučimo više o bolestima kao što je ebola ili drugim smrtnim bolestima kao što je SARS.
Organs on chips could also change the way we do clinical trials in the future. Right now, the average participant in a clinical trial is that: average. Tends to be middle aged, tends to be female. You won't find many clinical trials in which children are involved, yet every day, we give children medications, and the only safety data we have on that drug is one that we obtained from adults. Children are not adults. They may not respond in the same way adults do. There are other things like genetic differences in populations that may lead to at-risk populations that are at risk of having an adverse drug reaction. Now imagine if we could take cells from all those different populations, put them on chips, and create populations on a chip. This could really change the way we do clinical trials. And this is the team and the people that are doing this. We have engineers, we have cell biologists, we have clinicians, all working together. We're really seeing something quite incredible at the Wyss Institute. It's really a convergence of disciplines, where biology is influencing the way we design, the way we engineer, the way we build. It's pretty exciting.
Organi na čipu bi mogli da promene klinička ispitivanja u budućnosti. Sada, prosečni učesnik u kliničkom ispitivanju je upravo to - prosečan. Uglavnom je sredovečan, uglavnom žena. Nećete naći mnoga klinička ispitivanja u kojima su uključena deca, a ipak, svaki dan, dajemo deci lekove, i jedini podaci koje imamo o bezbednosti tog leka, su oni koje smo dobili od odraslih. Deca nisu odrasli. Ona možda neće odreagovati isto kao odrasli. Postoje i ostale stvari, kao što su genetske razlike stanovništva koje mogu da dovedu do rizika neželjene reakcije na lek. Zamislite da možemo da uzmemo ćelije svih tih drugačijih ljudi stavimo ih na čipove, i stvorimo populaciju na čipu. Ovo bi zaista moglo da promeni način na koji vršimo klinička ispitivanja. A ovo je tim i ljudi koji rade ovo. Imamo inženjere, biologe, imamo kliničare, i svi oni rade zajedno. Vidimo nešto zaista izvanredno na institutu Vis. To je zapravo sastajanje disciplina, gde biologija utiče na način na koji dizajniramo, kreiramo i gradimo. Veoma uzbudljivo.
We're establishing important industry collaborations such as the one we have with a company that has expertise in large-scale digital manufacturing. They're going to help us make, instead of one of these, millions of these chips, so that we can get them into the hands of as many researchers as possible. And this is key to the potential of that technology.
Uspostavljamo važne industrijske saradnje kao što je ova koju imamo sa kompanijom koja je ekspert u digitalnoj proizvodnji u velikom broju. Oni će nam pomoći da napravimo, umesto samo jednog od ovih, milione čipova, da bismo mogli da ih stavimo u ruke što je više moguće istraživača. I ovo je ključ potencijala te tehnologije.
Now let me show you our instrument. This is an instrument that our engineers are actually prototyping right now in the lab, and this instrument is going to give us the engineering controls that we're going to require in order to link 10 or more organ chips together. It does something else that's very important. It creates an easy user interface. So a cell biologist like me can come in, take a chip, put it in a cartridge like the prototype you see there, put the cartridge into the machine just like you would a C.D., and away you go. Plug and play. Easy.
Dopustite da vam pokažem naš instrument. Ovo je instrument od kojeg naši inženjeri prave prototipe upravo sada u laboratoriji, i taj instrument će nam pružiti inženjersku kontrolu koja će nam biti potrebna da povežemo 10 ili više organa zajedno. Radi još nešto što je veoma bitno. Stvara lak korisnički interfejs. Biolog kao što sam ja može da uđe, uzme čip, stavi ga u kertridž kao prototip koji vidite ovde stavi kertridž u mašinu kao što biste vi stavili CD i krećemo. Stavi i pusti. Lako.
Now, let's imagine a little bit what the future might look like if I could take your stem cells and put them on a chip, or your stem cells and put them on a chip. It would be a personalized chip just for you.
Hajde sada da zamislimo kako budućnost može da izgleda ako bih ja uzela vaše matične ćelije stavila ih na čip, ili vaše matične ćelije i stavila ih na čip. To bi bio personalizovani čip samo za vas.
Now all of us in here are individuals, and those individual differences mean that we could react very differently and sometimes in unpredictable ways to drugs. I myself, a couple of years back, had a really bad headache, just couldn't shake it, thought, "Well, I'll try something different." I took some Advil. Fifteen minutes later, I was on my way to the emergency room with a full-blown asthma attack. Now, obviously it wasn't fatal, but unfortunately, some of these adverse drug reactions can be fatal.
Svi mi ovde smo pojedinci i te individualne razlike znače da bismo mogli da reagujemo veoma različito i nekad i veoma nepredvidivo na lek. Pre nekoliko godina, i ja sam imala jaku glavobolju koja nije prestajala i htela sam da probam nešto drugačije. Uzela sam Advil. Petnaest minuta kasnije, bila sam na putu u hitnu sa teškim napadom astme. Očigledno je da nije bio smrtan, ali, na žalost, neke od ovih neželjenih reakcija bi mogle biti smrtne.
So how do we prevent them? Well, we could imagine one day having Geraldine on a chip, having Danielle on a chip, having you on a chip.
Kako da ih sprečimo? Mogli bismo da zamislimo da jednog dana, imamo Džeraldin na čipu, i Danijela na čipu, vas na čipu.
Personalized medicine. Thank you.
Personalizovana medicina. Hvala.
(Applause)
(Aplauz)