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.
Temos un reto global para a saúde nas nosas mans, e trátase de que o xeito no que descubrimos e desenvolvemos novos fármacos é demasiado caro, leva moito tempo, e falla a miúdo. Simplemente non funciona, o que significa que os doentes que precisan novas terapias de forma urxente non as están a recibir e as enfermidades non se están tratando. Estamos a gastar cada vez máis e máis diñeiro. Así, por cada mil millóns de dólares que gastamos en I+D hai menos fármacos aprobados no mercado. Máis diñeiro, menos fármacos. Hum.
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.
Así que, que está pasando aquí? Ben, hai múltiples factores en xogo pero penso que un dos factores clave é que as ferramentas que temos para ensaiar se un fármaco vai funcionar, se é efectivo, ou se vai ser seguro antes de facer ensaios clínicos en persoas, estannos a fallar. Non están a prever o que vai acontecer en humanos. E temos dúas ferramentas principais á nosa disposición. Células en placas de cultivo e ensaios con animais.
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.
Falemos da primeira ferramenta, os cultivos celulares. As células funcionan felices dentro do noso corpo E nós collémolas e sacámolas do seu ambiente natural, poñémolas nunha desas placas, e esperamos que funcionen. Adiviñade que. Non o fan. Non lles gusta ese ambiente porque non ten nada que ver co que teñen no corpo.
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.
Que pasa cos ensaios en animais? Ben, os animais poden proporcionar información moi útil. Móstrannos o que acontece nun organismo complexo. Aprendemos máis sobre a bioloxía. Con todo, na maioría dos casos, os modelos animais non permiten prever o que pasará en persoas cando se lles subministre un fármaco concreto.
So we need better tools. We need human cells, but we need to find a way to keep them happy outside the body.
Así que precisamos mellores instrumentos. Precisamos células humanas, pero temos que descubrir como mantelas felices fóra do corpo.
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.
Os nosos corpos son ambientes dinámicos. Estamos en movemento constante. As nosas células experiméntano. Atópanse en ambientes dinámicos no corpo. Están baixo forzas mecánicas constantes. Así que se queremos facer felices as células fóra do noso corpo necesitamos transformarnos en arquitectos. Temos que deseñar e construír un novo fogar para as células.
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.
E no Wyss Institute é o que acabamos de facer. Chamámoslle órgano nun chip. E teño un aquí mesmo. É fermoso, verdade? Pero é realmente incríbel. Aquí na miña man teño un pulmón humano nun chip que respira, vivo.
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.
E non é soamente fermoso Pode facer moitas cousas. Temos células vivas neste pequeno chip, células que se atopan nun ambiente dinámico interactuando con outras células diferentes. Moita xente intentou cultivar células no laboratorio. Probaron moitas estratexias diferentes. Incluso intentaron cultivar pequenos miniórganos. Nós non intentamos facer iso. Simplemente estamos a tentar recrear neste pequeno chip a unidade funcional máis pequena que representa a bioquímica, a función e a tensión mecánica que as células experimentan nos nosos corpos. E como funciona? Deixádeme amosarvos. Empregamos técnicas dos fabricantes de chips informáticos para facer estas estruturas a unha escala relevante tanto para as células como para o seu ambiente. Temos tres canais fluídicos. No medio temos unha membrana porosa, flexible, onde podemos incorporar as células humanas de, por exemplo, pulmóns, e, por debaixo, están as células capilares, as células dos vasos sanguíneos. Podemos agora aplicarlle ao chip forzas mecánicas que estenden e contraen a membrana de forma que as células sofren as mesmas forzas mecánicas que cando respiramos. E experiméntanas igual ca no corpo. Hai aire que flúe polo canal superior e entón circulamos un líquido que contén nutrientes a través do canal sanguíneo. O chip é moi fermoso, pero que podemos facer con el? Podemos obter un incrible nivel de funcionalidade dentro destes pequenos chips. Deixádeme amosarvos. Poderiamos, por exemplo, imitar unha infección, engadíndolle células bacterianas ao pulmón. e a continuación podemos agregar glóbulos brancos humanos. Os glóbulos brancos son a defensa do noso corpo contra bacterias invasoras, e cando notan esta inflamación por mor da infección, entrarán dende o sangue ao pulmón e fagocitarán a bacteria. Agora imos ver como acontece isto nun pulmón humano nun chip. Marcamos os glóbulos brancos para poder velos fluír, e cando detectan a infección, comezan a adherirse. Adhírense e entón intentan penetrar no lado do pulmón dende o vaso sanguíneo. Como podedes ver aquí, podemos visualizar un único glóbulo branco. Adhírese, móvese entre as capas celulares, a través do poro, sae no outro lado da membrana e aí vai fagocitar a bacteria marcada en verde. Acabas de presenciar nese chip diminuto unha das respostas máis fundamentais do noso corpo fronte a unha infección. Así respondemos a... unha resposta inmunitaria. É moi emocionante.
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.
Agora quero compartir esta imaxe con vós non só porque é moi fermosa, senón tamén porque nos dá unha gran cantidade de información sobre o que fan as células dentro dos chips. Dinos que estas células das pequenas vías aéreas nos nosos pulmóns teñen estruturas parecidas a cabelos que esperariades ver no pulmón. Son estruturas chamadas cilios, e moven a mucosidade fóra do pulmón Si. Mucosidade. Que noxo! Mais realmente a mucosidade é moi importante. A mucosidade atrapa partículas, virus, alérxenos potenciais, e estes pequenos cilios moven e expulsan a mucosidade. Cando son danados, por exemplo polo fume do tabaco, non funcionan correctamente e non poder botar o moco. Isto pode derivar en enfermidades coma a bronquite. Os cilios e a limpeza da mucosidade tamén están relacionados con enfermidades tan terribles coma a fibrose quística. Mais coa funcionalidade que conseguimos nestes chips podemos comezar a buscar novos posibles tratamentos.
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.
Non paramos co pulmón nun chip. Temos un intestino nun chip. Aquí podedes ver un. Puxemos células intestinais humanas nun intestino nun chip, baixo un movemento peristáltico continuo con este fluxo goteando a través das células podemos imitar moitas das funcións que un esperaría ver no intestino humano. Agora podemos comezar a crear modelos de enfermidades coma a síndrome de colon irritable. Esta enfermidade afecta a moitas persoas. É moi debilitante e con poucos tratamentos efectivos.
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.
Agora temos toda unha gama de órganos en chips diferentes nos que estamos a traballar nos nosos laboratorios. Non obstante, o potencial real desta tecnoloxía atópase no feito de que podemos conectalos a través de fluídos. Hai fluídos circulando sobre as células, de xeito que podemos comezar a conectar diferentes chips xuntos para formar o que denominamos un humano virtual nun chip. Isto é realmente emocionante. Nunca imos recrear un humano completo nestes chips, pero o noso obxectivo é poder recrear a suficiente funcionalidade e poder facer mellores predicións do que acontece nos humanos. Por exemplo, podemos comezar a explorar o que acontece cando temos un fármaco en aerosol. Os que coma min padecedes asma, cando usades o voso inhalador podemos explorar como o fármaco chega aos vosos pulmóns, como entra no corpo, como pode afectar o voso corazón Cambia o latexo do voso corazón? É tóxico? É eliminado polo fígado? Metabolízase no fígado? Excrétase nos vosos riles? Podemos comezar a estudar a resposta dinámica do corpo a un fármaco.
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.
Isto podería revolucionar e ser un punto de inflexión non só para a industria farmacéutica, senón tamén para moitas outras, incluíndo a industria cosmética. Poderiamos empregar a pel nun chip que estamos a desenvolver no laboratorio para ensaiar se os compoñentes deses produtos que estades a usar son seguros para aplicar na pel sen ter que facer ensaios en animais. Poderiamos ensaiar a seguridade dos produtos químicos aos que estamos expostos cada día no noso contorno, coma os dos produtos comúns de limpeza. Poderiamos tamén empregar os órganos en chips para aplicacións en bioterrorismo ou exposición á radiación. Poderiamos usalos para aprender máis sobre enfermidades coma o ébola ou outras enfermidades mortais coma o 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.
Os órganos en chips poderían cambiar como facemos os ensaios clínicos no futuro. Agora mesmo, o participante medio nun ensaio clínico é iso mesmo: medio. Tende a ser de media idade, tende a ser muller. Non atoparedes moitos ensaios clínicos nos que participen nenos, e aínda así, medicamos aos nenos a diario e a única información que temos sobre a seguridade dese fármaco é a que obtivemos con adultos. Os nenos non son adultos. Pode que non respondan do mesmo xeito. Hai outros factores coma as diferenzas xenéticas entre poboacións que poden levar a poboacións de risco ao perigo de sufriren unha reacción adversa ao fármaco. Agora imaxinade que puideramos coller células de todas estas poboacións, poñelas en chips e crear poboacións nun chip. Isto podería cambiar a forma na que facemos ensaios clínicos. E este é o equipo e a xente que o está facendo. Temos enxeñeiros, biólogos celulares, temos médicos clínicos, todos traballando xuntos. Estamos a ver algo realmente incrible no IWyss Institute. É realmente unha converxencia de disciplinas onde a bioloxía está a influenciar o xeito no que deseñamos, o modo no que proxectamos, a forma na que construímos É moi emocionante.
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.
Estamos establecendo importantes colaboracións con industrias coma as que temos cunha empresa con experiencia en fabricación dixital a grande escala. Eles vannos axudar a facer, non un, millóns destes chips, para poñelos nas mans do maior número de investigadores posible. Isto é chave para o potencial desta tecnoloxía.
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.
Deixádeme ensinarvos o noso instrumento. Este é un aparello que os nosos enxeñeiros están a desenvolver como prototipo no laboratorio, e este instrumento vainos dar os controis técnicos que imos precisar para unir 10 ou máis órganos en chips. Fai algo máis que é moi importante: crea unha interface de usuario simple. Así, un biólogo coma min pode chegar, coller un chip, poñelo nun cartucho coma no prototipo que vedes aí, colocar o cartucho na máquina igual que farías cun CD e listo. Conectar e xogar. Doado.
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.
Agora, imaxinemos un pouco como podería ser o futuro se puidese coller as túas células nai e poñelas nun chip, ou as túas, e poñelas nun chip. Sería un chip personalizado unicamente para ti.
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.
Todos os que estamos aquí somos individuos e esas diferenzas individuais significan que podemos reaccionar de xeito moi diferente e ás veces dunha maneira imprevisible aos fármacos. Eu mesma, un par de anos atrás, tiven unha xaqueca realmente forte, que non pasaba e pensei: "Probarei algo diferente" Tomei Advil e 15 minutos despois estaba de camiño a urxencias cun grande ataque de asma. É obvio que non foi fatal, pero, desafortunadamente, algunhas destas reaccións aos fármacos poden ser mortais.
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.
Como os podemos previr entón? Ben, poderiamos imaxinar que un día teremos a Geraldine nun chip, teremos a Danielle nun chip, terémosvos a vós nun chip.
Personalized medicine. Thank you.
Medicina personalizada. Grazas.
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