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 imamo globalni zdravstveni problem u našim rukama, a to je da je način na koji trenutno otkrivamo i razvijamo nove lijekove preskup, predugo traje, i češće ne uspije no što uspije. Jednostavno ne radi, a to znači da pacijenti koji ozbiljno trebaju nove tretmane njih ne dobivaju, i bolesti ostaju neliječene. Čini se da trošimo sve više i više novca. Svakom milijardom dolara koje potrošimo u istraživanje i razvoj, imamo manje i manje lijekova odobrenih za tržište. Više novca, manje lijekova. 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.
Što se ovdje događa? U igri je više faktora, no mislim da je jedan od ključnih taj da nas alati koje trenutno imamo na raspolaganju za provjeravanje hoće li lijek raditi, biti učinkovit, ili pak biti siguran za uporabu prije nego što počnemo s kliničkim testiranjima na ljudima, oni nas izdaju. Ne predviđaju što će se dogoditi u ljudima. I imamo dva glavna alata na raspolaganju. To su stanice u zdjelicama i testovi 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.
Idemo popričati o prvom, stanicama u zdjelicama. Dakle, stanice sretno obavljaju svoje zadatke u našim tijelima. Uzmemo ih, iščupamo iz njihovog prirodnog okruženja, bacimo u jednu od ovih zdjelica, i očekujemo da nastave raditi. Pogodite što. Ne rade. Ne sviđa im se ta okolina jer nimalo ne sliči onoj koju imaju u tijelu.
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.
Što s testiranjima na životinjama? Pa, životinje mogu dati i daju nam izuzetno korisne informacije. Poučavaju nas tomu što se događa u kompleksnom organizmu. Naučimo više o samoj biologiji. No, životinjski modeli češće ne mogu dobro predvidjeti što će se dogoditi u ljudima kada im damo neki lijek nego što mogu.
So we need better tools. We need human cells, but we need to find a way to keep them happy outside the body.
Stoga trebamo bolje alate. Trebamo humane stanice, no trebamo naći načina da ih održimo sretnima van tijela.
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 tijela su dinamična okruženja. Stalno smo u pokretu. Naše stanice to osjete. One su u našim tijelima u dinamičnom okruženju. Pod stalnim mehaničkim silama. Stoga ako ih želimo održati sretnima van naših tijela, trebamo postati arhitekti stanica. Trebamo dizajnirati, izgraditi i osmisliti dom izvan doma za stanice.
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.
A na Institutu Wyss, smo učinili baš to. Zovemo ga organ-na-čipu. I imam jedan upravo ovdje. Predivno je, zar ne? Ali je vrlo nevjerojatno. Upravo ovdje na mojoj ruci je dišuće, živo plućno krilo na čipu.
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 predivno. Može raditi golemu količinu stvari. Imamo živuće stanice u tom malom čipu, stanice koje su u dinamičnom okolišu i imaju interakcije s drugim tipovima stanica. Puno je ljudi pokušalo uzgojiti stanice u labosu. Isprobali su različite pristupe. Čak su probali i uzgojiti mini-organe u laboratoriju. Ovdje to ne pokušavamo. Samo pokušavamo rekreirati u ovom malom čipu najmanju funkcionalnu jedinicu koja predstavlja biokemiju, funkciju i mehanički napor koji stanice doživljavaju u našim tijelima. Pa kako to radi? Pokazat ću vam. Koristimo tehnike iz industrije računalnih čipova da stvorimo ove strukture na razini stanica i njihovog okoliša. Imamo tri kanala za fluide. U sredini imamo poroznu, savitljivu membranu na koju postavimo humane stanice iz recimo, naših pluća, pa potom ispod imaju kapilarne stanice, stanice naših krvnih žila. I možemo potom primijeniti mehaničke sile na čip što rasteže i kontrahira membranu, pa stanice doživljavaju iste mehaničke sile kao kada dišemo. I to na isti način na koji su ih iskusile u tijelu. Zrak prolazi kroz gornji kanal, pa potom uspostavimo protok hranjive tekućine kroz krvnu mrežu. Sad, čip je stvarno prekrasan, no što zapravo možemo s njim? Možemo dobiti izuzetnu funkcionalnost u ovim malim čipovima. Pokazat ću vam. Možemo, na primjer, oponašati infekciju tako što dodamo bakterijske stanice u plućno krilo. Potom možemo dodati humane bijele krvne stanice. Bijele krvne stanice su obrambeni mehanizam našeg tijela protiv uljeza, i kad osjete ovu upalu zbog infekcije ući će u plućno krilo iz krvi i opkoliti bakterije. Sada ćete vidjeti kako se to odvija uživo na pravom ljudskom plućnom krilu na čipu. Označili smo bijele krvne stanice tako da ih vidite kako prolaze, i kada detektiraju infekciju, počnu se priljubljivati. Priljube se i pokušavaju ući u plućno krilo iz krvne žile. Kako vidite, možemo zapravo prikazati pojedinu bijelu krvnu stanicu. Priljubi se, promigolji se do međuslojeva stanica, kroz pore, dođe na drugu stranu membrane, i upravo ovdje, pokušava opkoliti bakteriju koja je zeleno obojana. U ovom minijaturnom čipu upravo ste svjedočili jednom od osnovnih odgovora našeg tijela na infekciju. To je način na koji odgovaramo – imunosni odgovor. Vrlo je 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.
Sad, želim podijeliti ovu sliku s vama ne zato što je tako lijepa već zato što nam daje golemu količinu informacija o tome što stanice rade unutar čipova. Pokazuje nam da ove stanice iz malih hodnika u naši plućima zapravo imaju ovakve četkaste strukture koje biste i očekivali u plućima. Ove stanice se zovu cilije, i one zapravo miču mukozni sekret van pluća. Da. Šlajm. Fuj. Ali mukozni sekret je vrlo važan. Mukoza zarobljava čestice, viruse, potencijalne alergene, i ove cilije pomiču i izbacuju mukozni sekret van. Kada se oštete, recimo, zbog dima cigarete, ne rade kako trebaju, i ne mogu izbaciti mukozni sekret. To može dovesti do bolesti poput bronhitisa. Cilije i čišćenje mukoze su također uključeni u teže bolesti poput cistične fibroze. Ali sad, s funkcionalnošću dobivenom ovim čipovima možemo početi tražiti potencijalne nove tretmane
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 se zaustavili na plućima na čipu. Imamo i crijeva na čipu. Možete vidjeti jedan čip ovdje. I postavili smo humane crijevne stanice u crijeva na čipu i rade pod konstantnim peristaltičkim kretnjama, što provodi kroz stanice, i možemo oponašati mnoge funkcije koje biste očekivali u ljudskim crijevima. Sad možemo stvoriti model bolesti poput sindroma iritabilnog crijeva. Ovo je bolest koja zahvaća velik broj osoba. Vrlo je otežavajuća, i ne postoji puno dobrih načina tretiranja za nju.
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.
Sad imamo cijelo postrojenje različitih čipova s organima na kojima radimo u našim labosima. No prava moć ove tehnologije, pak, zapravo dolazi iz činjenice da ih možemo povezati fluidima. Preko i kroz ove stanice prolazi fluid, tako da možemo povezati različite čipove u seriju i sastaviti ono što zovemo virtualnim čovjekom na čipu. Sad smo stvarno uzbuđeni. Nećemo nikad sastaviti cijelog čovjeka na ovim čipovima, ali naš cilj je da budemo u mogućnosti osposobiti dovoljnu funkcionalnost koja će nam omogućiti bolja predviđanja onoga što će se dogoditi u ljudima. Na primjer, sad možemo početi istraživati što se događa kad stavimo lijek, recimo aerosolni lijek. Vi koji imate astmu kada uzmete vaš inhalator, mi možemo istražiti kako taj lijek dolazi u vaša pluća, kako ulazi u tijelo, kako može, recimo, utjecati na vaše srce. Mijenja li vam puls? Ima li otrovna svojstva? Uklanja li ga jetra? Metabolizira li ga? Izlučuju li ga vaši bubrezi? Možemo početi proučavati dinamiku odgovora tijela na lijek.
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 stvarno revolucionizirati i promijeniti pravila igre ne samo farmaceutskoj industriji, već i jako puno drugih industrija uključujući kozmetičku industriju. Možemo potencijalno koristiti kožu na čipu, što upravo razvijamo u labosu, da testiramo jesu li sastojci proizvoda koje koristite uistinu sigurni za staviti na vašu kožu, i to bez potrebe za testovima na životinjama. Možemo testirati sigurnost kemikalija kojima smo izloženi svakodnevno iz naše okoline, poput kemikalija u preparatima za čišćenje kuće. Možemo isto tako koristiti organe na čipovima za primjene u bioterorizmu ili istraživanju radijacije- Možemo ih iskoristiti da naučimo više o bolestima poput ebole ili drugim smrtonosnim bolestima poput SARS-a.
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 čipovima bi mogli promijeniti i način na koji ćemo raditi klinička testiranja. U ovom trenutku prosječni član test grupe u kliničkom testiranju je upravo to; prosječan. Najčešće srednje dobi, najčešće žena. Nećete naći puno kliničkih testova u koje su uključena djeca, no ipak svaki dan dajemo djeci lijekove, i jedini podaci o sigurnosti tog lijeka su oni dobiveni od odraslih. Djeca nisu odrasli. Ne moraju odgovoriti na isti način kao mi. Postoje i druge stvari, poput genetske razlike u populaciji što može dovesti do rizičnih populacija koje su rizične po tome što mogu dobiti negativnu reakciju zbog lijeka. Sad zamislite kad bismo mogli uzeti stanice od svih tih različitih populacija, staviti na čipove, i stvoriti populacije na čipu. Ovo zbilja može promijeniti način na koji radimo klinička istraživanja. A ovo je tim ljudi koji radi na ovome. Imamo inžinjere, stanične biologe, imamo kliničare, svi rade zajedno. Zbilja vidimo nešto jako nevjerojatno na Institutu Wyss. To je zapravo spajanje disciplina, gdje biologija utječe na način na koji dizajniramo, oblikujemo i izgrađujemo. Vrlo je 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 važnu kolaboraciju industrija poput one koju smo osnovali s tvrtkom koja ima iskustva u digitalnoj proizvodnji širokih razmjera. Pomoći će nam napraviti, umjesto samo jednog, milijune ovakvih čipova, da ih možemo predati u ruke što većem broju istraživača. A ovo je ključ potencijala ove 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.
Da vam pokažem naš instrument. Ovo je instrument čiji prototip naši inženjeri upravo izgrađuju u labosu, i ovaj instrument će nam dati inženjerske kontrole potrebne da povežemo deset ili više organskih čipova. Također radi nešto drugo, vrlo bitno. Stvara lako sučelje za korisnika. Tako da stanični biolog poput mene može doći, uzeti čip, staviti ga u postolje poput prototipa koji vidite ovdje, staviti postolje u stroj na isti način na koji biste stavili CD, i to je to. Uključi i igraj. Vrlo 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.
Idemo sad zamisliti malo kako bi mogla izgledati budućnost kad bih mogla uzeti vaše matične stanice i staviti na čip, ili vaše stanice i staviti na čip. To bi bio vaš personalizirani čip.
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.
Sad, svi ovdje smo individue, i sve naše individualne razlike znače da možemo reagirati na lijekove vrlo različito i na ponekad nepredvidljive načine. I sama sam, prije nekoliko godina, imala tešku glavobolju, nisam ju mogla otresti i pomislila sam, "Pa, idemo probati nešto drugačije." Uzela sam jedan Advil. Petnaest minuta kasnije bila sam na putu za hitan prijem u bolnicu sa izraženim napadajem astme. Naime, očito je da nije bio smrtonosan. No nažalost, neke od ovakvih negativnih reakcija na lijekove mogu biti fatalne.
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.
Pa kako da ih spriječimo? Mogli bismo zamisliti da jednog dana imamo Geraldine na čipu, imamo Danielle na čipu, imamo vas na čipu.
Personalized medicine. Thank you.
Personalizirana medicina. Hvala vam.
(Applause)
(Pljesak)