Danas imamo jedan globalni zdravstveni izazov na nasim ledima, a to je da je nacin na koji trenutno otkrivamo i razvijamo nove lijekove preskup, traje predugo, i mnogo cesce nas razocara nego sto obraduje. Jednostavno ne funkcionise, a to znaci da pacijenti ne dobivaju terapiju koja im je prijeko potrebna a bolesti se ne liječe. Cini mi se da se trosi sve vise i vise novaca. Tako da za svaku milijardu dolara koju potrosimo za istrazivanje i razvoj manje lijekova dobije dozvolu za koristenje. Vise novaca, manje lijekova. Hmm.
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.
Pa sta se to desava? Pa, u igri su mnostvo faktora, ali mislim da je kljucni faktor taj da su alati koji su nam danas dostupni za utvrdivanje da li je lijek djelotvoran, da li je uspjesan, i da li ce biti siguran za upotrebu prije nego ga pocnemo testirati na ljudima, nedovoljni. Ne mogu predvidjeti sta ce se desiti u ljuskom organizmu. Ono sto imamo dostupno za upotrebu su dva alata. Celije u posudicama i testiranje na zivotinjama.
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.
Porazgovarajmo o prvom, celije u posudicama. Pa, celije sasvim uredno funkcionisu u nasim tijelima. Mi ih izvadimo, otrgnemo iz njihovog prirodnog okruzenja, ubacimo u jednu od ovih posudica, i ocekujemo da i dalje funkcionisu. Ali pogadate: to ne funkcionise. Celije ne vole tu sredinu koja ne lici na sredinu u ljudskom organizmu.
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.
A testiranje na zivotinjama? Zivotinje mogu i pruzaju nam izuzetno korisne informacije. Na njima ucimo sta se desava u kompleksnim organizmima. Ucimo vise o samoj biologiji. Medutim, cesto se desi da ovo testiranje ne moze predvidjeti sta ce se desiti u ljudskom organizmu kada budu podvrgnuti terapiji sa odredenim lijekom.
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.
Zato nam trebaju bolji alati. Potrebne su nam ljudske celije, ali moramo naci nacin da ih drzimo u prirodnoj sredini van nasih tijela.
So we need better tools. We need human cells, but we need to find a way to keep them happy outside the body.
Nasa tijela su dinamicka okruzenja. Konstantno se krecemo. Nase celije to osjete. U nasim tijelima, one su u dinamickom okruzenju. Pod stalnim su mehanickim uticajima. Ukoliko zelimo da kreiramo jedno takvo okruzenje, moramo da postanemo arhitekti celija. Treba da dizajniramo, izgradimo i planiramo dom van doma za celije.
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.
Mi, na ViS institutu, smo ucinili upravo to, i nazvali smo ga organ-na-cipu. I upravo imam jedan ovdje. Prelijep je, zar ne? Ali je i prilicno nevjerovatan. Ovdje, u mojoj ruci, se nalaze ziva, ljudska pluca na cipu koja disu.
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.
I nisu samo lijepa na izgled. Sa njima se moze uciniti mnogo toga. U ovom malom cipu imamo zive celije, celije koje se nalaze u dinamicnom okruzenju koje medusobno djeluju sa drugim tipovima celija. Mnogi ljudi su pokusali da uzgajaju celije u laboratoriju. Probali su razne pristupe. Cak su pokusali da uzgoje male mini organe u laboratoriju. To nije ono sto mi ovdje pokusavamo. Jednostavno pokusavamo da rekonstruisemo u ovom malom cipu najmanju funkcionalnu jedinicu koja simulira biohemiju, funkciju i mehanicka opterecenja kojima su podvrgnute celije u nasim tijelima. Kako to radimo? Pokazat cu vam. Koristimo tehniku industrije za proizvodnju racunarskih cipova da bi izgradili ove strukture na razini relevantnoj i celijama i njihovom okruzenju. Tu se nalaze tri kanala za tecnosti. U centru se nalazi porozna, fleksibilna membrana na koju mozemo postaviti ljudske celije recimo iz nasih pluca, a ispod njih se nalaze kapilarne celije, celije u nasim krvnim zilama. Zatim mozemo na cip aplicirati mehanicke sile koje rastezu i skupljaju membranu, tako da celije osjecaju iste mehanicke sile kako i kad disemo. Dozivljavaju ih na isti nacin kao i u tijelu. Kroz gornji kanal prolazi vazduh, a kroz krvne kanale ulijevamo tecnost koja sadrzi hranjive sastojke. Da cip je zaista divan, ali sta mozemo sa njim postici? Mozemo postici izuzetnu funkcionalnost unutar ovog malog cipa. Pokazat cu vam. Na primjer, mogli bismo simulirati infekciju, tako sto dodamo celije bakterija u pluca. A zatim dodamo ljudska bijela krvna zrnca. Bijela krvna zrnca su nacin na koji se nasa tijela brane od invazivnih bakterija, i kada osjete upalu izazvanu infekcijom, iz krvi ce da udu u pluca i okruziti bakteriju. Sada cemo to vidjeti uzivo na ljudskim plucima na cipu. oznacili smo bijela krvna zrnca kako biste ih lakse uocili dok prolaze, a kada uoce infekciju, pocnu prijanjati. Prijanjaju, a onda pokusavaju da produ iz krvne zile na stranu gdje su pluca. A kao sto mozete vidjeti ovdje, mozemo si vizualizovati i samo jedno bijelo krvno zrnce. Prijanjaju, probija svoj put kroz slojeve celija, kroz pore, izlazi na drugu stranu membrane, i upravo sada ce da okruzi bakteriju koja je markirana zelenom bojom. Taj mali cip vam je omogucio da budete svjedoci jednom od najosnovnijih reakcija koje nase tijelo ima na infekciju. Tako nase tijelo reaguje--imuna reakcija. Poprilicno uzbudljivo.
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.
Zelim vam sada pokazati ovu sliku, ne zato sto je divna, vec zato sto nam pruza ogromnu kolicinu informacija o tome sta celije rade unutar cipa. Vidimo da celije iz malih disnih puteva u plucima, ustvari imaju ove male dlakice koje biste ocekivali da vidite u plucima. Te strukture se zovu cilija, i one pomazu u izbacivanju sluzi iz pluca. Da, Sluz. Bljak. Ali sluz je ustvari veoma vazna. Sluz hvata cestice, viruse, potencijalne alergene, a cilije kretanjem izbacuju sluz vani. Ako se ostete, recimo dimom iz cigarete na primjer, ne rade kako trebaju, i nisu ustanju izbaciti sluz. A to vodi do bolesti poput bronhitisa. Cilije i izbacivanje sluzi su takoder kljucni kod groznih bolesti poput cisticne fibroze. Ali sada, zahvaljujuci funkcionalnosti u ovim cipovima, mozemo poceti da trazimo potencijalne nove tretmane.
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.
Nismo se zaustavili samo na plucima na cipu. Imamo crijevo na cipu. Evo jednoga. Postavili smo ljudske crijevne celije u ovo crijevo na cipu, i one su pod stalnim peristaltickim kretanjem, ovaj protok kroz celije, i mozemo imitirati mnoge funkcije koje bi inace ocekivali da vidite u ljudskom crijevu. Tako da sada mozemo poceti da kreiramo modele bolesti poput bolesti upaljenog crijeva. Ovo je bolest koja muci veliki broj ljudi. Oslabljuje organizam, a ne postoji bas mnogo dobrih tretmana.
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.
Imamo cijeli niz razlicitih organa na cipu na kojima trenutno radimo u nasim laboratorijama. Ali prava snaga ove tehnologije ustvari dolazi iz cinjenice da ih sve mozemo fluidno povezati. Posto kroz ove celije tece tecnost, mozemo poceti da povezijemo razlicite cipove kako bismo formirali ono sto mi zovemo virtualni covjek na cipu. Sada ste stvarno uzbudeni. Nikada necemo kreirati citavo ljudsko bice na ovim cipovima, ali nas gol je da budemo ustanju kreirati dovoljnu funkcionalnost kako bismo bolje mogli predvidjeti sta ce se desiti u ljudskom organizmu. Na primjer, mozemo poceti istrazivati sta ce se desiti kada ubacimo neki inhalatorni lijek. Oni od vas koji imaju astmu poput mene, kada uzmete inhaler, mozemo istraziti kako lijek ulazi u pluca, kako ulazi u tijelo, i kako moze uticati, recimo, na srce. Da li mijenja otkucaje srca? Da li je toksican? Da li ga jetra ocisti iz organizma? Da li metabolira u jetri? Da li se izlucuje u vase bubrege? Mozemo poceti da izucava dinamican odgovor tijela na lijek.
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.
Ovo bi mogla biti revolucija i promjena nacina dosadasnjeg rada ne samo za farmaceutsku industriju, vec za citav niz raznih industrija, ukljucujuci i kozmeticku industriju. Mogli bismo koristiti kozu na cipu kojutrenutno razvijamo u laboratoriji kako bismo testirali da li su sastojci u ovim preparatima koje koristite stvarno sigurni za nanosenje na kozu i to bez potrebe za testiranjem na zivotinjama. Mogli bismo testirati sigurnost hemikalija kojima smo izloceni svaki dan u nasoj okolini, poput hemikalija koje se nalaze u obicnim sredstvima za ciscenje. Takoder bismo mogli koristiti organe na cipu za testiranje izlocenosto biohemikalijama ili radijaciji. Mogli bismo ih koristiti da nesto vise naucimo o bolestima poput ebole ili drugim smrtonosnim bolestima poput SARS-a.
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.
Organi na cipu bi takoder mogli promijeniti nacin na koji cemo u buducnosti raditi klinicka ispitivanja. Trenutno, prosjecan ucesnik u klinickom istrazivanju je upravo to: prosjecan. Obicno je srednjih godina, cesto zena. Necete naci puno klinickih ispitivanja u koja su ukljucena djeca, iako djeci svakodnevno dajemo lijekove, a jedine sigurnosne cinjenice koje imamo o tom lijeku potjece od ipitivanja na odraslima. Djeca nisu odrasli. Mozda nece reagovati na isti nacin kao i odrasli. Zatim druge razlike u populaciji, poput genetskih koje mogu dovesti do rizika od nezeljene reakcije na lijek. Zamislite kada bismo mogli sakupiti celije svih ovih razlicitih populacija, staviti ih u cipove, i stvoriti populacije na cipovima. To bi stvarno moglo promijeniti nacin na koji vrsimo klinicka istrazivanja. Ovo je tim ljudi koji to rade. Imamo inzinjere, histologe, klinicare, i svi rade zajedno. Sudjelujemo u necemu zaista izvanrednom na ViS institutu. To je takvo uskladivanje disciplina, gdje bilogija utice na nacin na koji dizajniramo, na nacin na koji stvaramo. Uzbudljivo je.
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.
Uspostavljamo veoma vaznu industrijsku saradnju poput ove koju imamo sa kompanijom koja ima iskustvo u proizvodnji digitalne opreme na veliko. Pomocice nam da napravimo samo jedan ovaj, milione ovakvih cipova kako bismo ih napravili dostupnim sto vecem broju istrazivaca. A to je kljucni potencijal ove tehnologije.
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.
A sada cu vam pokazati nas instrument. Ovo je instrument za kojeg nasi inzinjeri upravo sada izraduju prototip u laboratoriju, a on ce nam omoguciti strucne kontrole koje su nam potrebne kako bismo povezalo 10 ili vise organ cipova zajedno. Radi jos nesto veoma vazno. Posjeduje jednostavan interfejs za korisnike. Histolog poput mene moze doci, staviti cip u kasetu poput prototipa kojeg ovdje vidite staviti kasetu u masinu kao sto biste vi stavili CD, i to je to. Ukljuci i pokreni. Jednostavno.
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.
A sada razmislimo malo kakva bi nam mogla biti buducnost kada bih mogla uzeti vase maticne celije i staviti ih na cip, ili vase maticne celije i staviti ih na cip. To bi bio presonalizovan cip samo za vas.
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.
Svi smo mi ovdje individue, a te individualne razlike znace da bi mogli veoma razlicito reagovati a ponekade. i na ne predvidljiv nacin na lijekove. Licno sma, prije nekoliko godina, imala veoma jake glavobolje, kojih se nisam mogla rijesiti, pa sam odlucila iprobati nesto drugo. Uzela sam ibuprofen. Petnaest minuta kasnije, bila sam na putu za hitno pomoc sa napadom astme u punom zamahu. Ocigledno je da nije bila smrtonosna, ali nazalost, neke od ovih nezeljenih reakcija na lijekove moze biti fatalna.
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.
Kako to mozemo sprijeciti? Mozemo zamisliti da cemo jednog dana imati Geraldine na cipu, imati Danijelu na cipu, imati tebe na cipu.
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.
Personalizovana medicina. Hvala vam.
Personalized medicine. Thank you.
(Aplauz)
(Applause)