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Stem Cell Universe with Stephen Hawking (2014)
I have spent my life
exploring the mysteries of the cosmos. But there's another universe that fascinates me, the one hidden inside our bodies... ...our own personal galaxies of cells. Today, we are on the brink of a new age in medicine, an age where we will be able to heal our bodies of any illness, all because of cell inside us... ...which have special powers. They are called stem cells. These microscopic miracle workers are, however, barely understood. Implanting them into our bodies could unleash biological mayhem. Are stem cells magic bullets or ticking time bombs? I haven't lived a very normal life. Since my 20s, I haven't had to deal with the distractions that come from being able-bodied. I have led a life of the mind. Stem cells may give you that same freedom... ...allowing you to pursue your wildest dreams without ever having to worry about the limitations of your body. Dr. Robert Lanza is one of the pioneers of stem cell therapies. He is already using them to help patients regenerate damaged body parts. Right now, we're in clinical trials to try to treat blindness using retinal cells that were generated from stem cells. We've also been able to create entire tubes of red blood cells that transport oxygen just like normal, transfusable blood. Robert's work developed from studying how stem cells create not just body parts, but entire bodies. They do this for all of us when we start out as nothing more than a fertilized egg floating in the womb. So, imagine I'm floating down the fallopian tube. And first, there's one of me, and then there's two of me. Then there's gonna be four of me and eight of me. And we continue on dividing. And eventually, when I get downstream, I'll be a ball of about 100 cells. These embryonic stem cells are blank cells. They have not yet become a specific type of tissue. But soon, they start transforming into specialized bone cells, muscle cells, and nerve cells. Nine months later, they form a complete person. Once we are born, however, these blank embryonic stem cells disappear. We lose the power that they alone possess to regenerate all of the tissues in our bodies. Robert is working on restoring that power. So, when you think of a regular cell, whether it's a skin cell, a heart cell, or a blood cell, it turns out that that cell carries out a very specific function. And it carries out that function for its entire life. So, the question is, what tells that cell what to do? And that's where DNA comes in. The way DNA is packed into the nucleus of each cell determines what function it's going to have. DNA's long double helix is wound around a huge number of tiny, molecular balls in a structure called chromatin. As we grow in the womb, certain proteins interact with the chromatin of a blank embryonic cell causing parts of its DNA to become unspooled. The parts that are unspooled determine the type of cell this is going to be. A heart cell will have one DNA arrangement. A skin cell, another. This process of cell specialization appeared to be irreversible... Until a breakthrough experiment in 1962. What scientists did is they actually took an adult cell in the case of a frog, an intestinal cell, and they put it into an empty egg. And what had happened is that that egg actually acted like a little time machine and brought the DNA back in time to a point where it could actually generate an entire tadpole and then, eventually, an entire frog. Biologists now believe key proteins in the egg undo all the specialized DNA arrangements in the adult cell. They return it to its original state... A blank embryonic cell awaiting instructions on what to become. So, we learned from this research that we could actually generate embryonic stem cells that would grow forever, that were essentially immortal, and that could be turned into virtually all the cell types in the body. Robert has spent the past two decades developing techniques that instruct embryonic stem cells to turn into specific tissues. I think we have the capacity to do all sorts of amazing things that science never had the ability to do before. Stem cells are likely to revolutionize medicine in the next several decades. But harvesting material from human embryos is highly controversial. Some see it as damaging one potential life to help another. There is, however, another way to harness the immense power of stem cells. Kristin Baldwin is one of a group of stem cell researchers who hopes to make harvesting eggs or embryos obsolete. All she uses is a patient's skin cell. So, the old way that we used to make personalized stem cells was to take the skin cell and take the DNA out of its nucleus, picking it up and carrying it over into an egg which doesn't have any DNA, and the egg can change the DNA and turn it into a stem cell that has your genome. But now there's a new way, and all that it takes is for us to put these four genes into the nucleus of the skin cell and then wait. And what these genes do is reorganize the DNA so that it starts to look like stem cell DNA. And once that happens, it changes the cell around and the cell starts to shrink and not look like a skin cell anymore and loses its outside. And over the course of a week, it starts to look like an embryonic stem cell. And the only difference now between this and an embryonic stem cell is that it has your DNA in it. The four genes inserted into the cell create four proteins that exist naturally in an egg. Those proteins appear to trigger skin cell DNA to arrange itself just the way it is in an embryonic stem cell. Kristin was not the first to create these cells, which scientists call induced pluripotent stem cells, or IPS cells. But Kristin was the first to explore whether these manufactured stem cells are really the same as the natural versions. So, an ideal IPS cell or embryonic stem cell should be able to make all the cell types that you want equally well and at the same time, not make unwanted cell types... In particular, cancer. But some of the cells actually fail to make cell types that you'd like and others can actually cause cancer, and this is a worry. So, what we are working on is to try to find a way to either improve the way we make the cells so that they're all the first kind, the good kind, or to find a way to test for the differences and identify the ones that will be bad. Kristin and her research team took some skin cells from a mouse and turned them into a colony of IPS cells. From them, they grew thousands of colonies of different adult tissue types. Eventually, after months of exhaustive screening, Kristin identified a colony of IPS cells that never turned cancerous and seemed to be moldable into any cell type. So, now that we've made the IPS cells, we'd like to make them into specific cell types in a dish, especially those which are useful for us in medicine. One type of cell that we can't get from people is a heart cell, so we can see if we could turn the IPS cells into heart cells in a dish. So, in fact, when we do this, we can make heart cells. So that's great. Another type of cell we'd like to make are brain cells, neurons, because we can't get those from people. And so, we ask the IPS cells, "can you make neurons in a dish?" And, in fact, they can. But Kristin wasn't content with making a few key cell types. She wanted to put her IPS cells to the ultimate test. What we wanted to do is take the IPS cells and try to make a whole organism out of those. And so, to do that, we wanted to make a mouse. What we did is we took the IPS cells and we then put them into a pregnant female, and we waited. And when the mouse had its babies, much to our surprise, we found live mice that we could later prove came only from the IPS cells. So now, this mouse is a clone of the original mouse that we took the skin cell from. And it's a way of showing that the IPS cells should be able to work as well to make all the kinds of cells that we want as the embryonic stem cells can. Kristin's work has shown that it is possible to manufacture embryonic stem cells without taking them from an embryo. But the technique is still very new and not without danger. As exciting as this technology is, we know that there is a risk. So it may not be time to put IPS cells into your own body. Rather, we are taking the human cells and testing them in a dish using as many assays as we can and ask which tests most predict the usefulness or danger of a cell. Before the stem cell revolution can begin, we need a safe and uncontroversial source of embryonic cells. One lone scientist has a radical idea about where to find them in a place nobody thought was possible... inside our fully grown bodies. 300 years ago, my predecessor Isaac Newton was inspired by an apple tree to formulate the theory of gravity. Newton is long gone, but his apple tree survives. This tree grew from the cutting of the original. Stem cells in that cutting were able to regenerate a completely new life form. They have the same power as the cells in a human embryo, a power we lose when we are born. But one researcher believes that if an ancient tree can do it, so can we. His name is Marco Seandel of New York's weill Cornell Medical Center. He's scouring the human body for a natural alternative to manmade embryonic stem cells. The ideal scenario would be is if we could take an adult cell where you really didn't have to do very much to it to get that cell to convert into a state where it resembled an embryonic stem cell. You could think of Marco like a talent scout, searching Broadway for a uniquely versatile actor. So, we could think of each of these Broadway shows as a different organ in the body. And like an organ in the body, each show has individual actors that play different roles. And those roles are incredibly specialized. So, we can't just take an actor out of one role and put him in another role or ask a female chorus leader to play king lear, for example. So it's the same in the body. We can't take blood cells and expect them to make brain cells. And we can't take muscle cells and expect them to make reproductive cells. Marco's desire to find naturally occurring, multi-talented adult stem cells has left him peering deep into the human body. Somewhere inside it, he believes, there is a type of super cell that's very similar to an embryonic stem cell. It may be that there's a small population of incredibly versatile, highly flexible cells that, under the right conditions, could make any of these cell types. Marco's hunch was to look for these super cells in the reproductive organs. It makes a lot of sense that the cells that would normally make eggs or sperm would have more plasticity than other adult cell types. But there's a big snag in Marco's plan. You can't tell which cells are special just by looking at them. Almost all cells look exactly alike. It's a little bit like being here in the heart of Broadway. Some of these actors might be right for the part and some not. And it's not so easy to figure out who's the right one. Let's see what you got. Can you break dance? Alas, poor yorick. I knew you when you were alive. Can you do a backspin? Oh. Keep your day jobs. After many months of scrutinizing plates and plates of cells, suddenly, one batch seemed to show Marco some unusual talent. And at one moment, I had that sort of Eureka moment where I came back and looked in the dish and realized that these cells, all of a sudden, were looking very different. And the way that I knew that this was really happening was because we got cells that looked like heart tissue, meaning the cells were actually contracting in the dish. And sperm cells don't do that. So we knew that these cells had gone through some sort of precursor stage, reprogrammed, and then started producing heart cells. It was like finding a truly versatile actor in a crowd of one-trick ponies. All the world is a stage, and all the men and women merely players. Love you like a bad cigar, baby. Expelliarmus! You got the part. After auditioning many thousands of candidates, Marco and his team discovered a cell that was able to play any role, a super cell much like an embryonic cell, but one that survives in our bodies into adulthood. This experience was one of those moments that you live for as a scientist because you don't really know what you're looking for in advance, and there are not too many moments in science that are that clear and that definitive. Marco's work could provide a huge boost to stem cell research. No more need to harvest cells from embryos and no more need to genetically engineer manmade versions. I would predict that things are gonna change incredibly fast. It's reasonable now to tell people, "well, even if we don't have the treatment for you right now, we may have that treatment very soon." This could be the shape of those treatments, a recycled organ stripped of its native cells, seeded with your stem cells, and brought back to life. There are trillions of cells in the human body, all of them arranged in a very particular way. It seems impossible that we could ever learn how to construct a human being, cell by cell. But stem cells already know how to do that. Now we are beginning to capture and control their creative force. It's a whole new world. When I was a little kid, there was a TV show called "The Bionic Woman." It's not mechanical, but we're almost there. Doris Taylor is building a heart from stem cells. Her process begins with a donated organ... Which she then turns into a ghostly corpse. What we're looking at here are rat hearts going through the decellularization process. And you can see here we have a heart that's still red and muscular. You can see one here that's part way through the process. And then here, you can see a heart that's lost all of its muscle. If we sliced the heart in half, the valves would be there, the blood Vessels would be there, all the rough inside lining of the heart would be there, but without cells. Doris' goal is to transform heart transplants. She wants to seed a ghost heart from a donor with a recipient's stem cells and then restore it to life. If we can use your stem cells to build you an organ, then you're not trading one disease for another like you do today. Today, you may get a heart, but you have to take anti-rejection drugs for the rest of your life. We'd love to be able to build an organ that matches you, is available for you. And that wasn't even fathomable 10 years ago, 15 years ago. But rebuilding in a dish what it takes our bodies nine months to create in the womb is an enormous challenge. To build a heart, you've got to bring together the extracellular matrix, or ghost heart, different kinds of stem cells, and a beat. So, we have this flash mob and it looked like it came out of nowhere, but as you can see, there were actually cues. The extracellular matrix Scaffold... The people in white coats... who are showing the cells where to go. The different kinds of cells... You see blue, green, orange, yellow... They're organized like they would be in the heart, and they're beating. Doris and her team have to coax stem cells to turn into all the different cell types that exist in a heart and get them to precisely where they need to go. They're distributed differently all throughout the heart. What's in the valve is different than what's in the left ventricle is different than what's in the right ventricle. The ghost heart turns out to play an unexpected and vital role in this complex cell choreography. Doris discovered its pale flesh is laced with chemical clues. Its different anatomical areas, like valves or ventricles, are tagged with different proteins. These proteins trigger the reorganization of DNA in the patient's stem cells and turn them into the right heart cell type for each area. And we can begin to put cells back in and the cells not only seem to know where to go, they seem to know how to organize. And they can start distributing in ways that say, "hey, I'm a heart muscle cell," "hey, I'm a blood Vessel cell." Then we hook up a pacemaker, and we teach them to beat together. And over time, they develop contraction like a normal heart. Now, we're not there yet, but we've made significant progress and gotten to the point that we can get to about 25% of a normal heart contraction. In just a few years, custom-made replacement body parts built from a patient's own stem cells will be a reality. But these two men want to push stem cell technology even further. If they succeed, it would be a profound achievement, one that would mean a great deal to me personally. Can stem cells cure paralysis? Our bodies rebuild themselves every day. We create millions of new skin cells. We regenerate our muscle fibers. Slowly, we are beginning to understand these natural repair mechanisms and to manipulate them. But some parts of the body don't seem to have any ability to repair. The nerves in my spine have been slowly degrading since I was in my 20s. No one has yet found a way to regenerate them. But Paul Liu and Mark Tuszynski believe stem cells will help them succeed where all others have failed. Mark, I found one. Oh, let's see. Okay. All right. Let's give it a go. Okay. Let's go. 16 years ago, I had a terrible car accident. It broke my spine, and I was desperate looking for medical research to cure the spinal cord injury. And that's how I found Dr. Mark Tuszynski. I write him a letter to request if I can work in his lab. So, we met, and I was really struck by his dignity, his intelligence, his potential. And so, Paul joined the team. Reconnecting a severed spinal cord is like rebuilding the electrical system of a wrecked car... Only a million times more complex. So, this is our cut spinal cord. And see, we have about 30 cut wires here. But in reality, the spinal cord has about a million. We have to connect each one of those from the right spot where we've done the cut to the right target a long distance away. Fixing a car's electrical harness is straightforward. Solder the cut wires back together, and the electricity will move along them again. But in a severed spinal cord, every nerve below the cut has to be regrown from scratch. In the real spinal cord, you have to do this a million times from one right one going to the other right one. But all these wires go away. You have to put in cells here that will grow new wires and link them up to the right targets. This is an enormously challenging task. Paul thought injecting stem cells into the injury site could automate this intricate rewiring process. But Mark was skeptical. And I said, "hmm, you know, Paul, "people have been working on that for 100 years and, you know, it just hasn't gone very far." And so, Paul basically went off and did some experiments and brought back some results, and they were absolutely astonishing. The cells that Paul had implanted, few survived. But the few that did sent their wires, their axons, for remarkable distances through the spinal cord. And this was, in a sense, the holy grail of spinal cord injury research to be able to grow axons for long distances. But both Mark and Paul knew that getting stem cells to change into nerve cells and then grow long axons was only half the battle. For a spinal cord especially, for severe spinal cord, it's a big lesion cavity. The key step then, at that point, was to fill the injury site... not have a few cells survive at the edges of the injury, but to fill the lesion sites so that more cells survive and can send out more axons. Paul and Mark decided to use a protein called fibrin, which forms a mesh over the injured area. They hoped it would create a foothold for the stem cells to latch on to. Then this amazing phenomenon happened. Almost all our graphed stem cells survived. I took a look into the microscope. I backed away my chair. I turned to him and I said, "congratulations. I have never seen anything like this." The injury site was full. It was glowing green with surviving cells that completely filled the injury. And yet, more astonishing, there were now tens of thousands of axons streaming out of the injury site for very long distances. And this in the most severe type of animal-model spinal cord injury. This is the proof that Paul and Mark's work is actually healing spinal cord injuries. This rat was once paralyzed in its front right leg. Now it can pick up food with it. This rat was paralyzed in one of its hind legs. Now it can walk across the obstacle course of this cage. It's not complete recovery, but that is a huge amount of recovery after an injury as severe as that. This is just the beginning. It show a potential. We still face a lot of challenges, like can this wire connect to the right target? We have good hope. Mark and Paul have shown that the biological fortress of the spine can be conquered, that stem calls can grow any tissue anywhere. But not everything that grows inside us is good. Cancer is our greatest medical foe. Some fear stem cells with cause cancer. But others believe they are our best hope to defeat it. There's nothing better in this world for me than spending a summer afternoon in an English garden. Here, nature Springs forth a myriad of growth. But not everything in a garden is a gardener's friend. We have weeds inside our bodies, too. We call them cancer. Just like any other tissue, cancer grows from stem cells. If we can learn how to destroy them, we could wipe out cancer at its root. U.C. Davis Professor Paul knoepfler is leading the attack on cancer stem cells. He sees them as the great enemy within, floating around inside us, waiting to unleash havoc. We've come to learn in the last few decades that cancers have two main types of cells. There's sort of a generic cancer cell, and then there's these stem cells within the cancer that we call the cancer stem cells. Paul thinks our current attempts to beat cancer are a bit like his daughter Melanie playing a game of Marco polo. In our analogy of the cells in the pool, we have the general cells of the tumor, the red cells. They're not very harmful. But the yellow cells, those rare ones, are the cancer stem cells. And they're the ones we really need to worry about because they can grow an entire new tumor. The yellow stem cells are responsible for all of the cancer's growth... Good job, Mel. ...just as Paul's daughter struggles to grab hold of a yellow ball because she can't see that her friends are moving them. Keep going. Get all those balls out of the pool. So, researchers have been struggling to zero in on the really dangerous cells in a tumor. Hey. All right, Melanie. Time's up. You can take your blindfold off. Look. You got all the red balls out of the pool, but we didn't tell you that your friends here had all those yellow balls, which are the cancer stem cells. And it's important to find those to help cure the cancer. Paul's search for these killer cells is not driven by scientific interest alone. He is also a cancer survivor. So, I've been studying cancer for a really long time. And then one day, I found out that I, myself, had cancer. And so, that was a very scary experience. When you are a researcher, it's kind of impersonal. You're studying cells and test tubes. And then all of a sudden when you have cancer, it's a totally different experience. Paul had surgery to remove his tumor and is in remission. But he may still have cancer stem cells in his body. One day, they could spring back into action. Surgery only gets part of the tumor in most cases. And so I have to face the fact that there could be residual cells floating around in my body, and some of those might be cancer stem cells. And those could cause the cancer to come back in a few years or in a decade. Like Melanie's friends sneaking away from her as she reaches blindly for them, cancer stem cells can slip past chemotherapy, radiation, and surgery. The cancer stem cells are more migratory that just the average cell in the cancer. And so that means that they can kind of jump ship from the tumor, float around in your bloodstream, and lodge somewhere else in your body and just kind of wait there like a sleeper cell to potentially cause a tumor later on. Paul is perfecting a way to detect these deadly cells. He has found that some of the same proteins that trigger DNA reorganization in embryonic stem cells are also active in cancer stem cells. All cells really have proteins on their surfaces that are kind of like identity codes. And what we're hoping is that cancer stem cells will express a slightly different pattern than other cells in the tumor. And so, that pattern might be like a signature for us to hone in on to identify the cancer stem cells and then essentially zap them and kill them. And what we're hoping is that will lead to fewer recurrences in patients. Killing cancer stem cells may finally bring us victory in the long war on this dreaded disease. But stem cell research could deliver an even greater prize for all of us... a genuine medical fountain of youth. I relish the rare opportunity I've been given to live the life of the mind. But I know I need my body and that it will not last forever. As we age and we make copies of cells, tiny errors creep into our genes. This process seems inevitable, but stem cell researchers disagree. One of them is Dr. Vincent Giampapa. He believes our body's own natural reserves of stem cells can stem the tide of decay. The origin of the aging process really starts in our stem cells because that is a reservoir of the regenerative power and the ability to have our body cells renewed and repaired as we age. The stem cells we have in our adult bodies are not all-powerful like embryonic stem cells. They are specialized to replenish specific tissues we need to maintain ourselves like blood, bone, skin, and muscle. As we age, however, this repair system begins to break down. What we've learned recently is there is a clock, if you will, inside the cells that actually changes or, if you will, ticks as each year goes by. And as that happens, certain genes get turned off and other genes get turned on. Our DNA is not frozen over our lifetime. Our environment and the choices we make influence and change our genetic profile. So, if we live in a healthy environment, that genetic clock is slower. If we live in an unhealthy or stressful environment, the genetic clock accelerates. We can think of the DNA inside one of our body's stem cells like a newspaper. So, this morning, I picked up this newspaper in my driveway, and I have a nice, clean newspaper. But I might drop that newspaper in the street and it might wrinkle or get dirty. As the day goes on, I might spill some coffee on this newspaper. It might even rain this afternoon. The key thing here is, I'm not gonna be able to get another copy of this newspaper. But as we age, what happens to those young cells is the letters on that DNA start to get damaged from normal aging, from the environment. And that newspaper or, if you will, that cell becomes less efficient. We really can't read the information. And that cell, then, can't make accurate copies of itself, which then rapidly accelerates the aging process. But Vincent believes this aging process can be reversed. His research team at the cell health institute claims it has already begun rolling back the cellular clock on our body's natural supply of stem cells. What we're really doing is using the proteins from younger cells from another person to reprogram older cells from a different person. What we've seen already in our early studies is that those senescent genes that produce inflammatory compounds and things that are directly related to cancer have actually been reversed. They've been turned off. So, that's been a very good sign that most likely, in the long run, this will certainly be a safe therapy in the next few years. In the future, Vincent Giampapa believes we'll all be able to protect ourselves against cell aging as long as we have the foresight to plan ahead. Well, one of the most recent approaches to controlling the cellular aging clock and the quality of those cells is to store those stem cells at a young age, say between 21 and 35. In essence, freezing an essential part of ourselves, put it in storage, if you will, in the bank, and be able to use that later on in life when, for instance, we might have a problem with our heart or our liver or our lungs. In essence, what we're looking to do is somehow we have to make copies of this newspaper or make copies of ourselves, put them in storage, and be able to go back to that storage when we need them for whatever purpose. This is not skin-deep cosmetics. It's true biological youth driven by the incredible regenerative power we all have inside us... The power of stem cells. Our whole focus is attempting to improve the quality of life we have, decreasing the illnesses we all suffer as we get older so we can enjoy the time we have with our families and friends and really be more productive as we age. Just as we looked at the sky to understand our place in the universe, stem cell scientists are looking deep inside our bodies to figure out how we can take a step forward as a species. Within the next few decades, I am sure they will have developed treatments that can extend human life by years. But also, I have to accept that my life has probably come too soon to witness the golden age of stem cells. And so, to those of you who will enter this age, I have these words of caution. When physicists cracked open the world of the atom almost a century ago, they unearthed a new frontier of knowledge, one that came with remarkable power... And grave risk. As we strive to master stem cell technology, we are gaining profound insights into the forces of nature that create... Sustain... And destroy life. A brave, new world lies ahead of us. I believe we will use this knowledge for the good of us all, and I hope you will prove me right. |
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