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TEDxBuenosAires - José Cibelli - 04/08/10

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Good afternoon A few weeks ago Two saturdays ago I was looking for a place somewhere to write this talk for TED I got in my car and I drove two towns beyond the town where I work, which is a very small town And I walked into very classy a restaurant, a McDonalds, and I sat down to see if i could - - Actually first i checked to see if they had wifi. This is a town of about 1000 inhabitants Where I was looking for a spot to write The McDonalds is located between what would be the library and the town hall. So all the big stores where located there, none of which I knew So I was in the queue, waiting to get my coffee I had my backpack on me, and I noticed a man staring at me And one can always tell when someone is staring at you cause they want to start a conversation Of course, I wanted to be alone, but this man kept on staring, until he came up to me and said: "I used to have a backpack just like that, many years ago" Naturally, he then followed to tell me his life's story, his name was Jimmy And I tried to get away from him, crawling into my booth, but he would follow me He was a very short man, with very thick glasses He had a beard, which was very bad shaven, one could tell that his hand was too shaky to shave properly So I find my seat, and he passes before me and grabs a seat at a booth next to mine, where an old lady was sitting She had white hair, was about his age and she had her walking frame beside her And I couldn't concentrate, I could hear them talking And he would tell her "Yes, you see, my grand daughter just had her hair cut, and it looks very good!" And the lady answered "Oh, so you have visited her lately" -"Actually, no , I haven't, cause I lost my license, and I can't drive to her house no more" And that's what I call, the little cumulative injustices of old age They actually are irreversible, I mean, there is no way that he is going to get his license back And this got me thinking about the experiments we did when we first started working with cloning The truth is, that if I did the math, with my 46 years of age, I was closer to them than to the little kids running around And while I worked a lot of years on raising a family, and doing all the things a that a person my age does The years have been really harsh on me I challenge you, to take a picture of yourselves two years ago, and to compare it to one of today Or even if you are braver, take one of five years ago, and compare it to the taken today You might want to have a drink before you do so. Well, aging is something, that we have to acknowledge face to face,unless we remove every mirror in our homes It is something that we will have to face, that we are facing And if one, -Its like Woody Allen once said: "I hold nothing against death, but I don't want to be there when she starts looking for me" But, well, the truth is, that if one looks at what science has to offer whereas to the process of aging, there is very little We know what is happening, we know why it is happening But science has no answers as where how to stop it, or even less about how to turn back the clock The problem is that if you ask yourself "how is it that in this world, where science has made incredible advances on subjects as Cancer, nanotechnology, stem cells, how is it possible that there are no advances on the subject of aging? Aging is a very common thing, something that happens to all of us And if we are lucky enough to escape death from a cronical disease, or a fatal accident, old age will eventually kill us all But even so, what science knows on this subject is very little. The definition of aging is that the human body, as time passes, it defends itself from agressions Whether it is from cosmic rays, toxins, low quality food, bad TV, whatever it is The body tries to defend itself, and it reaches a point where these these agressions, they mount up to the point where we lose the battle The problem is, that to science what we absolutely must have before starting any experiment is to have a very clear idea of what we want to measure For instance, if we where to study cancer, we would need to know very accurately when the experiment stops and when do we measure the tumors that is what in the subject of science we call "in-point" the point where one stops, and measures It can be cancer, not be cancer, how much blood leaves the heart in order to measure heart failure, etc. In the process of aging there is only one in-point that is the age at the time of death And so, if any of you is going to take up a scientific career and study the subject of old age it is very difficult that you will experiment on humans For no one will be willing to lend you money to perform an experiment which could last for 70, 80, or 90 years That is why today, old age is experimented on worms, fruit fly, or yeast Therefore only on organisms of a very short life cycle and whose lives can be very easily recorded, and therefore any change in the experiment one can then verify very quickly. In 1961, Leonard Hayflick, professor of UCSF, back then he worked at Wistar Institute, Philadelphia He was an assistant professor, he had bearly started his career part of his job then was to produce fibroblasts, which are primary cells This is the only type of cells that I will mention on this talk, so relax, no problem. Fibroblasts are cells that one can find for instance below the skin And they are primary cells, and by that I mean that these cells they divide up for some time, these are very different from tumor cells which divide up permanently Back then Hayflick would create fibroblasts for people in other labs, where vaccines were created for humans Back then, it was believed that if any cell were removed from an organism and placed into a farming enviroment, with the ideal conditions, then those cells would multiply themselves indefinitedly. What happened to Hayflick was that he removed fibroblasts, he put them to grow, and no matter what he did or how he fed the fibroblasts, after six months the cells would stop diving themselves. He was very frightened by that discovery because it contradicted the dogma He was a new professor, he wanted to keep being hired, and so he was afraid to publish it He didnt know how to break the dogma The dogma had been previously been established by a doctor in New York, Alexis Carrel Who had won the nobel prize for other reasons, so it was very diffucult for him to change the dogma So what he did then was, he gave the cells to the labs, and he told them: "Do me a favor, use the cells for your vaccines, but meanwhile, keep a sample on the side, until those cells stop" "But don't worry about it, you won't have to grow them for a year, because in six months these cells will stop dividing up" And obviously, after six months he started getting telephone calls asking "how was this possible?" "that the cells have stopped dividing themselves!" "How did you know that this would happen?" "Well, I knew, because the theory that I'm working on is that cells have a biological clock, and that at one point they will stop dividing themselves. "Don't ask me how this works, but I call it the third face, or the limit" He called it "third face" or "limit" because we start off with a cell like this one Which multiplies itself in a constant matter, logarithmically. And what he did next was to measure it, by putting up a graph On which he demonstrated the quantity of cells on one side, and the time on the other And so he discovered what is called the "Hayflick Limit" And people didn't just adopt this thought and said "ok, cells get to the third face and stop", people said cells get to the Hayflick Limit So right now, the dogma is that any type of primary tissue, as long as it is not a tumor, will get to a point where it will stop And at the time, he proposed it as a way to study the aging process on a grow plate And so he thought that from there on, other ways of studing old age would come up Sadly, until this very day, there is no other way of studying old age , unless one waits for the person to pass away. Back in the year 1996, I was doing my doctorate on the University of Massachusetts in Amherst I was working on genetically modifying animals My project was to take cells, induce a gene which was not from that specie, on my particular case it was a simply a marker gene And then from that try to produce a cloned cow We already knew by that time, year 1996, we could produce bovine fetuses But the cells wouldn't divide! Is like saying I had ran into my doctorate's limit Hayflick celebrated when he discovered his limit, and I was cursing Hayflick for having a limit and the cells wouldn't divide. This was why I went up to my doctorate boss And asked him "what would happen if we took these cells that don't want to divide up" And we merge it with an ovine ovule, we transfer it into a cow. And see if we can really produce a fetus or not. Of course, he first said that it wouldn't work, secondly that it was a very expensive experiment And that we didn't have the time. Until we started to produce embryos, he got ecxited and said that we should transfer it to the cows We transfered it into the cows, we get a call from the VET and he says that the cows are preagnant. That's where my boss started to smile. And not only were they pregnant, but they had fetal heartbeat. And that's when we asked for the fetuses, and right away we asked ourselves "What happens then if we grow the fibroblasts that we removed from the fetus?" We started off from a cell that wouldn't divide, what happens when we remove it from a fetus? This is the cell's morphology, on the left you have the cells before they were placed on a fetus And on the right you have the fibroblasts we got after cloning. The ones on the left are very old cells for those of you who know a little bit about cell growing, and the ones on the right are very young This is the only graph that I will show you. Each line is a fetal line The first column indicates how many times the fetal line could divide before producing the fetus, And the one on the right shows how many times they divided up until they found the Hayflick Limit Then we asked the question: "Can we make complete cloned animals with these cells that wouldn't divide up?" And the answer is Yes, it can be very easily achieved And so for the first time, we were able to prove that the ovule has the capacity of reversing the Hayflick Limit After us, many other labs repeated the procedure, and discovered that Not only has the ovule the capacity to reverse the Hayflick Limit but also to rejuvenate that DNA, In many other aspects, not only in the capacity to divide itself in a constant matter But I'm not going to propose that we should make a human cloning factory, only to live forever The idea is to be able to understand what is there in the human ovule, what are the proteins in the human ovule That can have an effect to "jumpstart" the cells that we have that are getting old In order to tip the scales a bit to the side of youth, rather than to old age's side This is a picture of a humar ovule, just to tell you that we still don't know what's inside of it He have recently published all the genes that weight in the human ovule, but we still the interaction between genes Is still a subject on which we have to keep on investigating This is just to ilustrate, this is the world of the ideas. And what is written below the drawing is "You should be a little more specific on this step" And the step on which the teacher wants to know about the pupil has written "then a miracle happens" Meaning that we don't really have an answer for what happens We used to be in the dark, well we pretty much still are in the dark, but But in the year 2008, and published in the year 2009 One of the best pupils, with whom I had the honor of working with, on my lab is Nok Nok is a veterinarian from Thailand, who is getting her PHD next week She was capable of showing, in a very simple formula, if anyone is interested, The Zebra Fish The Zebra Fish, is a fish that for those of you who dont know, is a perfect model for the study of human diseases Weather it is on the development of Cancer, Alzheimer, Huntington's, it's just extraordinary as an animal model. And of course, it has the advantage of not living over four years Those who get past the fourth year is because it is an exceptional case The experiment we are proposing is the following, Well, this is so that you can see what a regular zebra fish looks like And the experiment we are proposing is the following: We start off with an old animal's cell And that you are seeing would be the ovule of a zebra fish And what we do, is we remove a specific factor which we chose based on the proteins we found on human ovules Because we have a candidate list of genes that have an imact on aging So we add this factor and we ask ourselves, how long can this fish live after he is cloned Well the first thing we need is a donor, and here you can see Tha, tha means good in Thai Tha is a the age limit, he was close to dying, and as you can see, he is very similar to a human old age model He's spine is crooked, like a very aged person, he doesn't want to swim anymore He had to be mouth fed, and was also very grumpy, just like any old person And those are the cells which we are working with, so this an idea. And it's an idea that can succed either in our labs or in that of our competition But we wouldn't be doing this if we didn't have the hope of achieving it The idea is to be able to have a molecule in the future Capable of reactivating our body cells which always lose the battle Maybe in the future we will be able to say that Jimmy can drive to see his granddaughter And when you see a picture taken 5 years ago, maybe you can say that you look better today Thank you

Video Details

Duration: 16 minutes and 33 seconds
Year: 2010
Country: Argentina
Language: Spanish (Spain)
Genre: None
Producer: TEDxBuenosAires
Director: TEDxBuenosAires
Views: 146
Posted by: ivanautin on May 28, 2010

José Cibelli talks on TEDxBuenosAires 04/08/10

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