So let me ask for a show of hands. How many people here are over the age of 48? Well, there do seem to be a few.
Levanten as mans, por favor. Cantos dos que están aquí teñen máis de 48 anos? Ben, parece que hai uns cantos.
Well, congratulations, because if you look at this particular slide of U.S. life expectancy, you are now in excess of the average life span of somebody who was born in 1900.
Parabéns, porque se miran este gráfico da esperanza de vida nos EE.UU. verán que superan xa a esperanza de vida media de alguén que nacera en 1900.
But look what happened in the course of that century. If you follow that curve, you'll see that it starts way down there. There's that dip there for the 1918 flu. And here we are at 2010, average life expectancy of a child born today, age 79, and we are not done yet. Now, that's the good news. But there's still a lot of work to do.
Pero vexan o que pasou no correr dese século. Se seguen esta curva, verán que comeza aí abaixo. Velaquí a baixada por causa da gripe do 1918. E velaquí 2010, a esperanza de vida dun neno ou dunha nena que naza hoxe é de 79 anos, e isto aínda non rematou. Estas son as boas novas. Pero aínda queda moito por facer.
So, for instance, if you ask, how many diseases do we now know the exact molecular basis? Turns out it's about 4,000, which is pretty amazing, because most of those molecular discoveries have just happened in the last little while. It's exciting to see that in terms of what we've learned, but how many of those 4,000 diseases now have treatments available? Only about 250. So we have this huge challenge, this huge gap.
Se nos preguntamos, por exemplo, a cantas enfermidades lle coñecemos a base molecular exacta? Son sobre 4000, o cal é incrible, porque a maioría destes descubrimentos ocorreron hai pouco. É emocionante ver o que aprendemos, pero destas 4000 enfermidades, cantas teñen tratamento dispoñible? Só unhas 250. Temos este gran desafío, este gran baleiro.
You would think this wouldn't be too hard, that we would simply have the ability to take this fundamental information that we're learning about how it is that basic biology teaches us about the causes of disease and build a bridge across this yawning gap between what we've learned about basic science and its application, a bridge that would look maybe something like this, where you'd have to put together a nice shiny way to get from one side to the other.
Podería pensarse que non debería ser moi complicado se temos a capacidade de coller esa información esencial que estamos adquirindo sobre o que nos ensina a bioloxía básica arredor das causas das enfermidades e construír unha ponte sobre este enorme baleiro entre o que aprendemos de ciencia básica e a súa aplicación, unha ponte que se puidese parecer a esta, onde tes que percorrer un brillante camiño para chegar dun lado a outro.
Well, wouldn't it be nice if it was that easy? Unfortunately, it's not. In reality, trying to go from fundamental knowledge to its application is more like this. There are no shiny bridges. You sort of place your bets. Maybe you've got a swimmer and a rowboat and a sailboat and a tugboat and you set them off on their way, and the rains come and the lightning flashes, and oh my gosh, there are sharks in the water and the swimmer gets into trouble, and, uh oh, the swimmer drowned and the sailboat capsized, and that tugboat, well, it hit the rocks, and maybe if you're lucky, somebody gets across.
Non sería xenial se fose así de sinxelo? Por desgraza, non o é. Na realidade, tentar ir dende o coñecemento fundamental á súa aplicación, é máis ben así. Non hai pontes brillantes. En certa medida, fanse apostas. Pode que teñan un nadador, un bote, un veleiro e unha lancha e inician a viaxe, comeza a chover e a tronar, mi madriña! hai tiburóns na auga, o nadador comeza a ter problemas, oh, o nadador afogou, o veleiro envorcou, e a lancha bateu nas rochas, e con sorte, alguén conseguiu cruzar.
Well, what does this really look like? Well, what is it to make a therapeutic, anyway? What's a drug? A drug is made up of a small molecule of hydrogen, carbon, oxygen, nitrogen, and a few other atoms all cobbled together in a shape, and it's those shapes that determine whether, in fact, that particular drug is going to hit its target. Is it going to land where it's supposed to? So look at this picture here -- a lot of shapes dancing around for you. Now what you need to do, if you're trying to develop a new treatment for autism or Alzheimer's disease or cancer is to find the right shape in that mix that will ultimately provide benefit and will be safe. And when you look at what happens to that pipeline, you start out maybe with thousands, tens of thousands of compounds. You weed down through various steps that cause many of these to fail. Ultimately, maybe you can run a clinical trial with four or five of these, and if all goes well, 14 years after you started, you will get one approval. And it will cost you upwards of a billion dollars for that one success.
Ben, como é isto en realidade? Que é facer unha terapia, á fin e ó cabo? Que é un fármaco? Un fármaco está formado por unha pequena molécula de hidróxeno, carbono, osíxeno, nitróxeno e outros átomos todos conectados dunha certa forma, e estas formas son as que determinan que este fármaco en concreto alcance o seu albo. Estase indo cara a onde se pretende? Se miramos esta imaxe vemos unha morea de formas bailando. O que hai que facer, se se quere desenvolver un tratamento para o autismo, para o alzhéimer ou para o cancro, é atopar nesa morea a forma axeitada que nos provoque o beneficio desexado e que sexa segura. Se vemos o que acontece neste funil, comezamos con milleiros, decenas de milleiros de compostos. Descartaranse algúns con varios filtros que amosan que moitos fallan. Finalmente, pode que con catro ou cinco se realice un ensaio clínico, e se todo vai ben, 14 anos despois, consegue aprobarse un. E isto custará millóns de dólares para un único éxito.
So we have to look at this pipeline the way an engineer would, and say, "How can we do better?" And that's the main theme of what I want to say to you this morning. How can we make this go faster? How can we make it more successful?
Debemos mirar este funil como o faría un enxeñeiro, e dicir: "Como podemos mellorar"? Disto é do que vos quero falar esta mañá. Como o podemos facer máis rápido? Como podemos ter máis éxito?
Well, let me tell you about a few examples where this has actually worked. One that has just happened in the last few months is the successful approval of a drug for cystic fibrosis. But it's taken a long time to get there. Cystic fibrosis had its molecular cause discovered in 1989 by my group working with another group in Toronto, discovering what the mutation was in a particular gene on chromosome 7. That picture you see there? Here it is. That's the same kid. That's Danny Bessette, 23 years later, because this is the year, and it's also the year where Danny got married, where we have, for the first time, the approval by the FDA of a drug that precisely targets the defect in cystic fibrosis based upon all this molecular understanding. That's the good news. The bad news is, this drug doesn't actually treat all cases of cystic fibrosis, and it won't work for Danny, and we're still waiting for that next generation to help him.
Vou falarvos duns exemplos onde isto funcionou. Un aconteceu hai tan só uns meses e foi a aprobación dun fármaco para a fibrose quística. Pero levou moito tempo. A base molecular da fibrose quística descubriuna en 1989 o meu grupo en colaboración con outro de Toronto, e descubrimos que a mutación estaba nun xene no cromosoma 7. Vedes esta foto? Velaquí o está. É o mesmo neno. Danny Bessette, 23 anos despois, porque este é o ano, e tamén é o ano en que Danny casou, en que, por primeira vez, a FDA (Food and Drug Administration) aproba un fármaco que ataca con precisión o defecto da fibrose quística baseándose no coñecemento molecular. Estas son as boas novas. As malas son que o fármaco non trata todos os casos de fibrose quísitica, e non funcionará para Danny. Estamos á espera da seguinte xeración para axudalo.
But it took 23 years to get this far. That's too long. How do we go faster?
Levou 23 anos conseguir isto. É demasiado. Como imos máis rápido?
Well, one way to go faster is to take advantage of technology, and a very important technology that we depend on for all of this is the human genome, the ability to be able to look at a chromosome, to unzip it, to pull out all the DNA, and to be able to then read out the letters in that DNA code, the A's, C's, G's and T's that are our instruction book and the instruction book for all living things, and the cost of doing this, which used to be in the hundreds of millions of dollars, has in the course of the last 10 years fallen faster than Moore's Law, down to the point where it is less than 10,000 dollars today to have your genome sequenced, or mine, and we're headed for the $1,000 genome fairly soon. Well, that's exciting. How does that play out in terms of application to a disease?
Unha opción é aproveitar o avance da tecnoloxía, e unha tecnoloxía moi importante da que dependemos é o xenoma humano, a capacidade de ver un cromosoma, desenrolalo, extraer o ADN, e ser capaces de ler as letras neste código do ADN, os A, os C, os G e os T que son o libro de instrucións que nós, e todos os seres vivos, temos, e o custo de facer isto, que era de centos de millóns de dólares, diminuíu nestes últimos 10 anos máis rápido que a lei de Moore ata o punto de que hoxe custa menos de 10.000 dólares ter un xenoma secuenciado e axuña custará sobre os 1.000. Isto é emocionante. Que significa isto en termos de aplicación ás enfermidades?
I want to tell you about another disorder. This one is a disorder which is quite rare. It's called Hutchinson-Gilford progeria, and it is the most dramatic form of premature aging. Only about one in every four million kids has this disease, and in a simple way, what happens is, because of a mutation in a particular gene, a protein is made that's toxic to the cell and it causes these individuals to age at about seven times the normal rate.
Quero falarlles doutra enfermidade. Esta é unha enfermidade rara. Chámase a proxeria de Hutchinson-Gilford, e é a forma máis drástica de envellecemento prematuro. Só a ten un de cada catro millóns de nenos e dunha forma sinxela, o que acontece é que, a causa dunha mutación nun xene, créase unha proteína tóxica para a célula o que provoca que estes suxeitos envellezan sete veces máis rápido do normal.
Let me show you a video of what that does to the cell. The normal cell, if you looked at it under the microscope, would have a nucleus sitting in the middle of the cell, which is nice and round and smooth in its boundaries and it looks kind of like that. A progeria cell, on the other hand, because of this toxic protein called progerin, has these lumps and bumps in it. So what we would like to do after discovering this back in 2003 is to come up with a way to try to correct that. Well again, by knowing something about the molecular pathways, it was possible to pick one of those many, many compounds that might have been useful and try it out. In an experiment done in cell culture and shown here in a cartoon, if you take that particular compound and you add it to that cell that has progeria, and you watch to see what happened, in just 72 hours, that cell becomes, for all purposes that we can determine, almost like a normal cell.
Déixenme amosarlles un vídeo sobre o que provoca na célula. A célula normal, vista co microscopio, terá un núcleo situado no seu centro que é bonito, redondo e liso nos seus bordos e aseméllase a isto. Por outro lado, a célula da proxeria a causa da proteína, chamada proxerina, ten estes vultos e protuberancias. O que queríamos facer despois de descubrir isto, alá no 2003, era atopar unha maneira de corrixilo. De novo, coñecendo algo das vías moleculares, era posible coller un destes compostos que podían ser útiles e probalo. Nun experimento "in vitro" mostrado nesta animación, se se escolle ese composto particular e se lle engade á célula que ten proxeria, observen o que acontece, en só 72 horas, a célula transfórmase, para todos os efectos que podemos determinar, nunha célula normal.
Well that was exciting, but would it actually work in a real human being? This has led, in the space of only four years from the time the gene was discovered to the start of a clinical trial, to a test of that very compound. And the kids that you see here all volunteered to be part of this, 28 of them, and you can see as soon as the picture comes up that they are in fact a remarkable group of young people all afflicted by this disease, all looking quite similar to each other. And instead of telling you more about it, I'm going to invite one of them, Sam Berns from Boston, who's here this morning, to come up on the stage and tell us about his experience as a child affected with progeria. Sam is 15 years old. His parents, Scott Berns and Leslie Gordon, both physicians, are here with us this morning as well. Sam, please have a seat.
Funcionará nunha célula humana real? Isto levou, en tan só catro anos dende que se descubriu o xene ata que empezou o ensaio clínico, a probar ese composto. Todos os nenos que ven aquí participaron voluntariamente no proceso, 28 nenos, pódese ver, como mostra a foto, que son un grupo de xente nova afectado pola enfermidade, que se parecen bastante entre eles. Antes de falarlles máis disto, vou invitar a un deles, Sam Berns de Boston, que está aquí esta mañá, a subir ao escenario para que nos conte a súa experiencia como un neno afectado de proxeria. Sam ten 15 anos. Seus pais, Scott Berns e Leslie Gordon, médicos os dous, tamén están aquí esta mañá. Sam, senta por favor
(Applause)
(Aplausos)
So Sam, why don't you tell these folks what it's like being affected with this condition called progeria?
Sam, por que non lle dis a esta xente como é estar afectado de proxeria?
Sam Burns: Well, progeria limits me in some ways. I cannot play sports or do physical activities, but I have been able to take interest in things that progeria, luckily, does not limit. But when there is something that I really do want to do that progeria gets in the way of, like marching band or umpiring, we always find a way to do it, and that just shows that progeria isn't in control of my life.
Sam Burns: A proxeria limítame nalgúns aspectos. Non podo facer deporte ou actividades físicas, pero fun capaz de facer cousas interesantes que por sorte a proxeria non me limita. Pero cando hai algo que realmente quero facer e a proxeria se interpón no meu camiño, como tocar nunha banda, ou arbitrar, sempre atopamos a maneira de facelo,
(Applause)
e isto demostra que a proxeria non controla a miña vida.
Francis Collins: So what would you like to say to researchers here in the auditorium and others listening to this? What would you say to them both about research on progeria and maybe about other conditions as well?
(Aplausos) FC: Que lles dirías aos investigadores que están aquí e a outros que te escoiten? Qué lles dirías sobre a investigación da proxeria
SB: Well, research on progeria has come so far in less than 15 years, and that just shows the drive that researchers can have to get this far, and it really means a lot to myself and other kids with progeria, and it shows that if that drive exists, anybody can cure any disease, and hopefully progeria can be cured in the near future, and so we can eliminate those 4,000 diseases that Francis was talking about.
e tamén doutras doenzas? SB: A investigación en proxeria avanzou moito en menos de 15 anos, e isto amosa a determinación que os investigadores deben ter para avanzar tanto, o cal significa moito para min e para outros nenos con proxeria, e isto ensínanos que se esa determinación existe calquera pode curar calquera tipo de enfermidade, e espero que a proxeria poida curarse nun futuro próximo e que poidamos eliminar esas 4000 enfermidades das que Francis falaba.
FC: Excellent. So Sam took the day off from school today to be here, and he is — (Applause) -- He is, by the way, a straight-A+ student in the ninth grade in his school in Boston. Please join me in thanking and welcoming Sam. SB: Thank you very much. FC: Well done. Well done, buddy. (Applause)
FC: Xenial. Sam faltou hoxe ao instituto para estar aquí --(Aplausos)-- Aínda así, é un estudante de sobresaliente de noveno grado no seu instituto de Boston. Deámoslle as grazas a Sam. SB: Moitas grazas. FC: Ben feito, rapaz. (Aplausos)
So I just want to say a couple more things about that particular story, and then try to generalize how could we have stories of success all over the place for these diseases, as Sam says, these 4,000 that are waiting for answers. You might have noticed that the drug that is now in clinical trial for progeria is not a drug that was designed for that. It's such a rare disease, it would be hard for a company to justify spending hundreds of millions of dollars to generate a drug. This is a drug that was developed for cancer. Turned out, it didn't work very well for cancer, but it has exactly the right properties, the right shape, to work for progeria, and that's what's happened. Wouldn't it be great if we could do that more systematically? Could we, in fact, encourage all the companies that are out there that have drugs in their freezers that are known to be safe in humans but have never actually succeeded in terms of being effective for the treatments they were tried for? Now we're learning about all these new molecular pathways -- some of those could be repositioned or repurposed, or whatever word you want to use, for new applications, basically teaching old drugs new tricks. That could be a phenomenal, valuable activity. We have many discussions now between NIH and companies about doing this that are looking very promising.
Quero dicir un par de cousas máis sobre esta historia e tentar xeneralizar sobre como podemos ter historias de éxito para todas estas enfermidades, como dixo Sam, estas 4000 enfermidades que agardan respostas. Debedes saber que o fármaco que se está probando para a proxeria non é un fármaco deseñado para ela. É unha enfermidade tan rara que unha empresa tería moi difícil xustificar o gasto de centos de millóns de dólares para producir o fármaco. Este fármaco desenvolveuse para o cancro. Non funcionou moi ben contra el, pero ten as propiedades exactas, a forma precisa, para tratar a proxeria, e isto foi o que pasou. Non sería fantástico facermos isto máis sistematicamente? Poderiamos animar ás compañías que teñen fármacos nos conxeladores que sabemos que son seguros en humanos pero que nunca se demostraron efectivos nos tratamentos para os que se deseñaron? Agora estamos aprendendo sobre estas novas vías moleculares algunhas das cales poderían ser reorientadas ou reutilizadas, ou como lle queiramos chamar, para novas aplicacións, ensinándolles novos trucos a vellos fármacos. Podería ser unha actividade extraordinaria e valiosa. Temos moitos debates entre o Instituto Nacional da Saúde e empresas sobre facer isto que tan prometedor parece.
And you could expect quite a lot to come from this. There are quite a number of success stories one can point to about how this has led to major advances. The first drug for HIV/AIDS was not developed for HIV/AIDS. It was developed for cancer. It was AZT. It didn't work very well for cancer, but became the first successful antiretroviral, and you can see from the table there are others as well.
E temos bastantes esperanzas de que resulte. Hai abondas historias exitosas que podemos destacar sobre como isto comportou avances relevantes. O primeiro fármaco contra o VIH non se desenvolveu para o VIH. Foino para o cancro. Trátase do AZT. Non funcionou contra o cancro, pero foi o primeiro antirretroviral exitoso, e como se ve na táboa, hai outros tamén.
So how do we actually make that a more generalizable effort? Well, we have to come up with a partnership between academia, government, the private sector, and patient organizations to make that so. At NIH, we have started this new National Center for Advancing Translational Sciences. It just started last December, and this is one of its goals.
Como facemos este esforzo máis xeneralizable? Temos que chegar a acordos entre o mundo académico, o goberno, o sector privado, e organizacións de pacientes para facelo. No Instituto Nacional da Saúde, creamos un novo Centro Nacional de Ciencias Translacionais Avanzadas. Comezou en decembro pasado, e este é un dos seus obxectivos.
Let me tell you another thing we could do. Wouldn't it be nice to be able to a test a drug to see if it's effective and safe without having to put patients at risk, because that first time you're never quite sure? How do we know, for instance, whether drugs are safe before we give them to people? We test them on animals. And it's not all that reliable, and it's costly, and it's time-consuming. Suppose we could do this instead on human cells. You probably know, if you've been paying attention to some of the science literature that you can now take a skin cell and encourage it to become a liver cell or a heart cell or a kidney cell or a brain cell for any of us. So what if you used those cells as your test for whether a drug is going to work and whether it's going to be safe?
Déixenme dicirlles outra cousa que poderiamos facer Non sería xenial se puidésemos probar un fármaco para ver se é efectivo e seguro sen poñer en risco pacientes, porque as primeiras veces non se está seguro? Como sabemos que un fármaco é seguro antes de darllo a persoas? Probámolo en animais. E iso non é demasiado fiable, e ademais é custoso, e consome tempo. Imaxinen que podemos facelo en células humanas. Se lle prestan atención á literatura científica probablemente saberán que pode collerse unha célula da pel e estimulala para convertela en hepática ou cardíaca, ou renal ou derebral de calquera de nós. E se utilizamos estas células para probar se un fármaco vai ser efectivo e seguro?
Here you see a picture of a lung on a chip. This is something created by the Wyss Institute in Boston, and what they have done here, if we can run the little video, is to take cells from an individual, turn them into the kinds of cells that are present in the lung, and determine what would happen if you added to this various drug compounds to see if they are toxic or safe. You can see this chip even breathes. It has an air channel. It has a blood channel. And it has cells in between that allow you to see what happens when you add a compound. Are those cells happy or not? You can do this same kind of chip technology for kidneys, for hearts, for muscles, all the places where you want to see whether a drug is going to be a problem, for the liver.
Velaquí unha imaxe dun pulmón nun chip. É unha creación do Wyss Institute en Boston, e o que fixeron, se poñemos en marcha o vídeo, foi coller células dun individuo, transformalas en células que hai nos pulmóns, e ver que acontece se se engaden varios compostos para ver se son seguros ou tóxicos. Poden ver que este chip incluso respira. Ten unha canle de aire e outra de sangue. E ten células no medio que permiten ver o que acontece ao engadir un composto. Están contentas as células ou non? Pódese usar esta mesma tecnoloxía para riles, corazóns, músculos, calquera órgano onde se queira ver se o fármaco vai ser un problema, para o fígado.
And ultimately, because you can do this for the individual, we could even see this moving to the point where the ability to develop and test medicines will be you on a chip, what we're trying to say here is the individualizing of the process of developing drugs and testing their safety.
E finalmente, porque isto pode facerse para cada persoa, podemos ver que se encamiña ata o punto en que a capacidade para desenvolver e testar fármacos irá con vostedes nun chip, o que implica a individualización do proceso para desenvolver fármacos e probar a súa seguridade.
So let me sum up. We are in a remarkable moment here. For me, at NIH now for almost 20 years, there has never been a time where there was more excitement about the potential that lies in front of us. We have made all these discoveries pouring out of laboratories across the world. What do we need to capitalize on this? First of all, we need resources. This is research that's high-risk, sometimes high-cost. The payoff is enormous, both in terms of health and in terms of economic growth. We need to support that. Second, we need new kinds of partnerships between academia and government and the private sector and patient organizations, just like the one I've been describing here, in terms of the way in which we could go after repurposing new compounds. And third, and maybe most important, we need talent. We need the best and the brightest from many different disciplines to come and join this effort -- all ages, all different groups -- because this is the time, folks. This is the 21st-century biology that you've been waiting for, and we have the chance to take that and turn it into something which will, in fact, knock out disease. That's my goal. I hope that's your goal. I think it'll be the goal of the poets and the muppets and the surfers and the bankers and all the other people who join this stage and think about what we're trying to do here and why it matters. It matters for now. It matters as soon as possible. If you don't believe me, just ask Sam.
Resumindo. Estamos nun momento extraordinario. Para min, con case 20 anos no Instituto Nacional da Saúde, nunca houbo unha época de maior entusiasmo sobre o potencial do que temos diante. Fixemos todos estes descubrimentos en laboratorios espallados polo mundo. Que fai falla para sacar proveito deles? Primeiro, recursos. Esta é investigación de alto risco, e ás veces de alto custo. A recompensa é enorme, en termos de saúde e de crecemento económico. Hai que apoiala. Segundo, precisamos novos tipos de relacións entre o mundo académico, o goberno, o sector privado e as organizacións de pacientes, como xa contei aquí, sobre que camiño adoptar despois da reutilización de compostos. E terceiro, e pode que máis importante, precisamos talento. Precisamos os mellores e máis brillantes de diferentes disciplinas para vir e axudar, de calquera idade, de calquera grupo, porque este é o momento, amigos. Esta é a bioloxía do s. XXI que estabamos a agardar, e temos a oportunidade de collela e convertela en algo acabe coas enfermidades. Ese é o meu obxectivo. Agardo que tamén sexa o seu. Penso que será o obxectivo dos poetas, marionetas, surfeiros e banqueiros e de todas as persoas que se unan a esta causa e pensen no que tentamos facer e por qué é importante. É importante para agora, para o antes posible. Se non me cren, pregúntenlle a Sam.
Thank you all very much.
Moitas grazas a todos.
(Applause)
(Aplausos)