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				Born Again Nerves Scientists train newborn nerve cells to repair spinal cord injuries.
		Select text to jump ahead in the clip: at a challenge that just a few years ago most scientists would have said is simply beyond our reach. The challenge is to repair broken or damaged nerves particularly in people who have suffered a disabling accident which has left them paralyzed. There's now real progress being made in stimulating nerves to repair themselves although it's still at the lab level and a long way from being applied to people. Then we're going to look at a different kind of approach to the same problem. This is a true marriage of biology and technology in which actual hardware is being implanted in the body to restore functions that no longer work. MAN: Go ahead and stand up. ALDA: Nerves are being replaced with computers and wires. So there's some terrific science going on in these areas but we're not going to lose sight of the fact that this is all for one thing: to help the people who need it. Later on in the program I'm going to be talking with Christopher Reeve who, since his accident, has become an important advocate on behalf of disabled patients. But first we're putting on our white coats and heading into the laboratory. And in the laboratory we find laboratory rats. But what a rat! This one had a crippling spinal cord injury and it's literally back on its feet. This story is about how that was done. I'm with John McDonald, a neurology professor at Washington University in St. Louis. What we're going to look at is an actual transplantation procedure where we're going to take the embryonic stem cells that have been instructed to become nervous tissue, and we're going to put those into the middle of the damaged spinal cord of a rat. ALDA: Repairing damaged nerves is one of the possibilities opened up by an exciting new area of research using embryonic stem cells. ALDA: You have stem cells in here? Yes. Let me show you how we grow the stem cells. What we're looking at here if you look closely... ALDA: Oh, yeah. You can see small clusters of hundreds of cells. In fact, each one of those very closely resembles the early embryo after fertilization. ALDA: The cells have not yet started to differentiate into everything that goes to make, in this case, a mouse like bones, muscles or nerves. ALDA: What kind of stuff tells them to become nervous tissue and how does it work? I don't get... that's an amazing idea. What kind of stuff is it? It's very interesting. In the early embryo, the switches-- the major switches-- are very simple things. And the expression of a chemical called retinoic acid is all that it takes to tell these cells to become nervous tissue. And you synthesize that? You can make retinoic acid, as much as you want? Exactly. And you just squirt it around on that stuff and they start to turn into nervous tissue? Yes. ALDA: The embryos are treated with retinoic acid for four days. Then an inhibiting chemical is used to stop them from developing further while they multiply. McDONALD: If we begin the week with one of these flasks, we end the week with 256. So it's really an unlimited supply. The cells divide almost every 14 hours. So let's take a look at these. ALDA: At this stage, they're called neural precursor cells. They're ready to make any of the three kinds of nerve cells but while the inhibiting chemical is present they just multiply as precursors. What we're seeing here are one individual cell that's now just finishing division. The two dark areas are the DNA. And the cell will cleave across here. ALDA: A single transplant needs a couple of million cells so there's a continuous precursor cell production line running in the lab. Then when the inhibiting chemical is removed the nerve cells themselves grow. These are neurons, with their connecting axons. McDONALD: What we're looking at here is a culture dish filled with cells that have now become neurons. You can see the little round circle is a neuron, a cell body. Uh-huh. And that coming out of it-- is that an axon? This is the axon. There are millions and millions of the axons and connections-- those same ones that need to be repaired. ALDA: Here's another kind of nerve cell, called an oligodendrocyte. Its job is to wrap the axons with insulation. McDONALD: What's showing here in green is a single oligodendrocyte in the culture. And these are all the branches. And you can see that this oligodendrocyte reaches out and wraps only one part of that axon and then it continues, unwrapped. Here's another connection that's wrapped multiple times in multiple segments. So this one oligodendrocyte is wrapping many different axons or connections. That's right. Typically in the spinal cord, an oligodendrocyte will wrap up to 15 different axons, or connections between cells. ALDA: Here's an axon wrapped with its new layers of insulation like a plastic cover on a copper wire. Damaging the insulation is an important type of spinal cord injury in people as with this injured cord of a lab animal. The cord is not severed but there's a serious loss of function mainly because existing axons have lost their insulation. By transplanting about two million nerve precursor cells into the injury an astonishing recovery of function has been achieved. The researchers think the animals' bodies signal the transplanted cells to make oligodendrocytes, which rewrap the exposed axons with the insulation called myelin that they need to work again. ALDA: So, nerves that don't work anymore simply because they've lost their myelin-- you can get them to work again. Right-- if we can just simply replace that then we can get important recovery of function such as recovering bowel and bladder control or improved movement of a hand. Now, to you and I, that might not sound like a lot... Oh, it's gigantic if you're missing that. Exactly. The gains in the level of independence for a person to be able to control their own bowel and bladder function or now to use a hand are the difference between living in an institution and living at home. You know, if I was trying to figure out how to do this I'd say, well, get some cells and stick them in there. You know, get some fully grown cells and stick them in. You... you put them in at the right stage so they'll respond to signals and actually grow on their own and grow into the necessary kinds of cells. Yeah, I think we've taken advantage of the power of development and said, "Jeez, you know "we don't know the myriad of signals. "Let's put them in at an early stage "where we can just throw a few switches "and get them going and let the body and the nervous system do the rest. " ALDA: Remyelination of existing axons using stem cell transplants is a tremendous breakthrough. But for a complete cure, new axons need to grow as well so as to reconnect severed nerves. ALDA: How do they know where to go? How do they know where to grow to? Why don't they just grow in every direction? That's the most difficult question now. It's interesting that if you put in cells they'll tend to migrate towards the injury site because the injury site gives signals to get them to go there. The most difficult thing right now is to get these neurons to make the appropriate connections over long distances. That has not been achieved yet. ALDA: Several hundred thousand Americans could benefit from spinal cord therapy and the pace of research is quickening. Encouraged by Christopher Reeve, eight centers around the world have formed a consortium to swap ideas and results. Everyone is feeling optimistic but here at the University of Miami, a consortium member Mary Bunge doesn't underestimate the challenges ahead. BUNGE: There are many different types of nerve cells. There are millions of fibers in the spinal cord. They are traveling in two different directions. They are ending in different areas of the spinal cord. It's a very complex problem. ALDA: Here they're developing a completely different transplant approach using not stem cells but what are called Schwann cells from peripheral nerves-- the ones found in arms and legs. Unlike spinal cords, peripheral nerves can repair themselves. The Schwann cells are cultured and then soaked up into little plastic fiber cylinders. The cylinders are used to take on the biggest challenge of all-- to make a living bridge between completely severed parts of a spinal cord. A section of cylinder containing about six million Schwann cells is placed across the gap in this lab animal test. The extraordinary result is that new axons-- nerve fibers-- are attracted to grow into the bridge. There the transplanted Schwann cells wrap the new axons with the vital myelin. Once again, the body has been coaxed into doing its own thing. The Schwann cells manage to give the right signals for new axons to grow and then make new myelin as well even though repair doesn't normally happen in the spinal cord. BUNGE: One, two, three, four, five, six. What has happened here is that the fibers grew into the bridge and then the Schwann cells that had been transplanted there then formed myelin around the axon. This is the outline of the Schwann cell here. Here is its nucleus. The Schwann cell became related to this axon. The myelin sheath appears as a dark ring. ALDA: They can get new nerves to grow into the bridge but not out again. BUNGE: A challenge now is to improve the amount of growth of axons from the bridge into the cord. ALDA: The latest approach is to take cells from the nose-- the nose of a lab animal again. In all mammals the nose constantly renews its nerve connections to the brain so the nose cells are injected into the spinal cord close to the bridge. The hope is that the nose nerve cells will somehow attract the new nerves out of the bridge so they can make new connections in the spinal cord. And that's in part what the nose cells did with new axons showing up an inch away from each end of the bridge. But right now, we don't know if there were new connections and disappointingly there was no significant improvement in the experimental animals' function. So, what does all this add up to for people? There's no doubt that practical treatments for injured spinal cords are still years away. But at the same time you won't find a scientist in the field who'll say we're not going to win this battle before long. ALDA: I've come to see Christopher Reeve

				I Might Walk! Christopher Reeve talks with Alan Alda about his 'realistic optimism' that he may walk again.
		Select text to jump ahead in the clip: at his house not far from New York City. It used to be woods. ALDA: Chris is now quadriplegic and confined to a wheelchair. He breathes with the aid of a ventilator. In 1995, Chris suffered a severe fall from his horse during a competitive jumping event in Culpeper, Virginia. With an injury at what's called the C-2 level he lost control of his body below the neck. REEVE: I was injured at the second vertebrae level but my spinal cord was not cut. What happened was I had a hemorrhage right in the middle of the cord at C-2. And then it caused atrophy. So right at C-2 the cord is one-quarter of its normal size. So think of it as a kinked garden hose. ALDA: Chris Reeve, seen here with his wife, Dana, and son Will prepared for a lifetime of paralysis. But soon he was to discover that for the first time, there was hope that science could tackle spinal cord injuries. ALDA: Were you encouraged to have this kind of hope when you first had the accident when you, say, were in rehab? Or were you encouraged to accept and adjust to, uh...? No, at first I was encouraged to accept and adjust. And in fact, I remember one researcher saying that, uh, "Well, in the beginning, one always hopes but over time, hope ebbs. " You know, and this is a researcher who now is at the forefront of the solution to the problem. Now we're at a stage where leaders in the field have discovered that exercise is absolutely essential. Now, for what? Exercise is essential to get you ready for the time when your nerves may be able to be regenerated? Or just in general, just...? Well, there's of course just immediate benefit in that you avoid infections, antibiotics, et cetera. And the other is think of it as the transcontinental railroad-- that the patient starts on the East Coast by doing his exercise and improving and heading west while the scientists start from the west and go from the Petri dish to the monkey or the rat and then into the human and hopefully they meet in the same place, in Utah or wherever. ALDA: Chris exercises three to four hours a day using specialized equipment-- equipment he wants insurance companies to provide for all patients, by the way. There's a bicycle used in conjunction with electrical muscle stimulation and a table that tilts upright. REEVE: We loosen the straps and somebody stands in front of me so that I don't fall over-- but actually I have good equilibrium-- and what we do is I mentally think, "Lean to the right" and my body does it. Wow. And then I mentally think "Lean to the left" and I go left and put all my weight on my left foot. And that is something where the brain is telling the cord to shift weight. ALDA: Work on a treadmill is intended to stimulate the spinal cord's own memory of walking patterns. We'll have a story about this idea later on. Overall, the point is to use to the full the few remaining spinal connections so he's ready to meet the scientists when they get to "Utah. " One short-term goal is simply to breathe naturally. He can already do this half an hour at a time. REEVE: What I'm trying to do is get off the vent and I do that with certain breathing exercises but also the treadmill therapy is helping that. What's the connection? How does that help? Well, you're activating the cord, you're taking advantage. You take advantage of an automatic breathing response? Of what's left. I'm not yet able to breathe automatically. Is your diaphragm working? My diaphragm works which is really a miracle because I'm injured at a level way above the diaphragm but by exercising very hard over the last five years I've improved, so I'm going up rather than down. Now, psychologically and emotionally that makes a tremendous difference. Oh, I can imagine. You know, this old saying: Give me the strength to do something about what I can do something about and to accept what I can't do anything about and the wisdom to know the difference. Your recent life has been kind of a vivid example of how hard it is to strike that balance, to find that wisdom. How do you do it? I mean, you must have to accept a certain amount. I don't buy into it at all. You don't accept any of it? No. Who knows what the horizon is? Yeah. You know, who knows how far we're going to go? Why should we put limits on it? You know, you know that pigs aren't going to fly... but I might walk, you know? ( Alda laughing ) ALDA: Chris Reeve's accident had compromised a highly successful acting career. And he decided that he should use his celebrity for all it was worth to further the cause of research into spinal cord treatments. REEVE: The main idea is to put a vision out there and then I even went so far as to do a commercial last year. I didn't see the commercial. Well, what happens in the commercial is that I'm seen walking to give a prize to scientists who, sometime in the future, had cured spinal cord injuries. And it was very upsetting to some people very uplifting to others but five months after the commercial was on the air people are still talking about it. So that's great. You want that debate you want that controversy, you want people to be agitated. But I checked with all the major scientists in the country that I, you know, have a relationship with and they said, "No, there's no reason "not to put that vision before the public because it will happen. " ANNOUNCER: And in the years since the new millennium the world has seen such progress. In 2004, the tide was turned against AIDS two years later, great strides against cancer and tonight-- tonight we celebrate a remarkable breakthrough in spinal cord injuries made possible by countless researchers and contributors. And to present this award, we have some very special guests. In the future so many amazing things will happen in the world. What amazing things can you make happen? What do you think your main contribution is? Is it raising money? Is it focusing attention? Being the person who gets everybody in the boat to row together? What do you think... what do you think of as your main contribution? Well, my responsibility is all of the above. You know, I'm president of a club I didn't want to join but, uh, nevertheless I have to take some responsibility. Not to do so would be really immoral. And I have the chance to speak up for a lot of people you know, who could never get to a congressman or never testify before a Senate committee or influence a budget. So, I actually... You know, I can't say it's my favorite thing to do but nevertheless, uh, psychologically, emotionally it really helps me that, you know, I can be of some use. ALDA: And when he does get back to work he's still trying to be of some use. In this remake of the Hitchcock classic Rear Window he wanted to help change the widespread stereotype of disabled people as isolated and embittered to something different-- to an image of people who could be, in fact, of some use. Achilles... bring up telephone. Dial 911. OPERATOR: 911 operator. I need to report a domestic altercation. OPERATOR: Can you describe what's happening, sir? ALDA: Christopher Reeve could hardly get much further from the stereotype. He set up a foundation which helps fund and coordinate the world's best research in spinal cord injury and he's a tireless advocate. What was an immensely creative life before the accident only seems to have become more so since in both public and private life. REEVE: You find alternate ways to accomplish and to express... your needs, your desires, et cetera. For example, I taught, when I was on my feet my big kids how to ride a bike and, you know, taking the training wheels off. But my young son, Will, was a little afraid to take the training wheels off. But I actually sat out in our driveway in a wheelchair. Somebody took the training wheels off and I talked him through how to do it. Now, isn't that cool? And who would have thought? It's great, you're relentless. I mean, you really don't give up. No, because now we need a way to connect. Yeah, yeah. And so many ways of connecting have been taken away. You know, I haven't been able to give him a hug since he was two years old, and he's almost eight. But he's got to hear it through my voice and through my eyes and just from being there. So I have to find ways to give him what he needs. And one of my jobs-- and this is the paradox of having a debilitating injury or disease-- is that you have to find a way to be more generous than you ever were before when you were on your feet. And what I mean by that is that you have to set people free so they don't spend their life worrying about you. Do you think about... do you let yourself think about how long it will take before they'll be able to get to the point where you can walk again? No, I don't... I don't measure it in terms of months, days or years. I measure it in terms of how hard people are working. So sometimes if I see a scientist at, you know, too many dinners... or, you know, out at too many meetings I say, "Go back to the lab," you know? "Get out of here. "Go put the white coat on, get to work. " You know, so I have a reputation as sort of an amiable pest. ALDA: We're back at the University of Miami to look at a remarkable study that's just getting under way. Rudolfo Stecco has been partially paralyzed

				Moving Memories Going through the motions sparks remarkable progress in paralyzed patients.
		Select text to jump ahead in the clip: since a car accident two years ago. He's one of 200 patients who, over the next five years will test the effects of intensive exercise but exercise during which only about one-third of the body's weight has to be supported by the legs. Put it at 88. 88? ALDA: There's a fascinating story behind this study. It all began six years ago with a patient who was exercising hard in an attempt to improve his walking which was very limited. Blair Calancie, the study director, takes up the story. CALANCIE: He could walk about 75 feet in one 45-minute session. Clearly it was nonfunctional with such small distances. The fourth year he'd come down, he decided he was going to go all out. He was going to embark on a very strenuous physical conditioning program under his own direction and worked out for four hours on the Monday four hours on the Tuesday standing, exercising, a lot of strenuous work. On Wednesday he comes in and says to one of our therapists "I'm getting these weird spasms when I lie down; it's like I'm walking. " She then responded, as was her way "You're a spinal cord injury, you have spasticity. Get used to it. " ALDA: Fortunately, Blair Calancie decided to take a look for himself anyway and what he found was a completely unknown phenomenon. CALANCIE: Just as he had described to us the moment we took him from his wheelchair and he laid out flat on his back his legs began an involuntary stepping pattern. What was intriguing was and what really set us out on this whole area of research is that at the same time the involuntary stepping started at night his ability to walk in the daytime, volitionally improved by an order of ten. So he went within a week from walking 75 feet in a session to 500 and 600 and 700 feet in one session. ALDA: Conventional therapy after a spinal cord injury is something like this-- mild stretching and gentle movement. But suddenly here was the possibility that intensive exercise would dramatically improve walking even 17 years after the injury in this case. CALANCIE: An important consideration for this study is that everybody has to be at least one year post-injury. And under today's current approach with managed care it's not at all unusual for an individual with an acute-- they've just had a recent spinal cord injury-- to be discharged from hospital at six weeks, seven weeks, eight weeks. Maybe they'll get rehab for another month to six weeks after that and beyond that, it's over. ALDA: Ida Fisher, for example, has been partially paralyzed for four years. CALANCIE: Ready to fire up? Let's go. ALDA: She's testing the treadmill and like all the subjects, she's partially suspended. She'd barely be able to move at all otherwise. Christopher Reeve does his treadmill workout regularly by the way. Nice, smooth steps. ALDA: After six weeks in the study Ida's seen a dramatic improvement. FISHER: Before, I walk less; I walk only half an hour. Now I walk an hour. ALDA: The study is recording many such improvements. The intriguing possibility is that the spinal column itself contains some of the instructions for walking. This central pattern generator, as it's called is known in animals but has never been seen before in humans. Hard exercise-- only possible with these subjects when partially suspended-- somehow restimulates the central pattern generator. CALANCIE: We're seeing dramatic improvements in individuals who are at least one year post-injury and often cases five, six, ten years post-injury which suggests that there's a great deal of untapped potential in these individuals. It's a very strong argument to the managed-care companies, to physicians that the common phrase of "Whatever you have at one year post-injury is what you've got for the rest of your life" needs to be rethought. ALDA: And it's an unexpected new source of hope for people with spinal cord injuries. ALDA: Don Crago is paralyzed from the waist down.

				Nerves of Steel Artificial electric stimulation helps the paralyzed stand, walk, and use their hands.
		Select text to jump ahead in the clip: But using artificial electrical muscle stimulation, he can walk. Dr. Byron Marsolais started this project. MARSOLAIS: He has absolutely no control of his legs at all. He is totally and completely paralyzed and every bit of motion that happens is coming through the electrical stim. Don, do you get all your balance from holding on to this walker? Yes, I do, Yes, I do. Does that put a lot of pressure on your arms? No, not really. Most of the pressure's on my legs. Actually, I prefer to let my legs do the work because if I did it with my arms, I would be tired out. Yeah. How tiring is it to take it... uh, every step? Uh, not too bad. It's comfortable, you know? But after the end of the walk, I will breathe heavy. Yeah. Standing takes a lot of energy because you have to stimulate the muscles for a prolonged period? Right-- he is standing by stimulating the flexors and the extensors, the antagonistic muscles, all at the same time. So he's stiff as a board. And that charge just has to be constant. It's constant... If you let up on it, he's liable to tip one way or another. Oh, he would, for sure. And so he looks good standing tall and stiff... ALDA: But you feel the strain? MARSOLAIS: But he's got strain. Yeah, I feel strain. ALDA: My introduction to the functional electrical stimulation or FES, program was eight years ago. What I'm trying to get to is his gluteus maximus muscle-- the big seat muscle. ALDA: Dr. Marsolais showed me how he implants wire electrodes. What you're inserting into the muscle is... that's not the electrode itself? No, this is just a little probe... Right. A very tiny probe. And the reason you're doing this is to see if you can get the muscle to react to give its greatest response? Exactly. And I want just the right muscle. That's the muscle that we want-- it goes right down here into the femur which is the big leg bone. And you see how it's beginning to jump there? It's starting to do what we want. I think I can do better... And in order to do better I have to get it right beside the nerve. ALDA: Dan Kemp, paralyzed in a car accident is on the table. Now, Dr. Marsolais looks like he's found the spot here. That looks pretty good here, yup. That's getting a pretty good, tight... I can see it. See how that... jerks things together there. It looks like about an inch and a half from where you were first searching for it. Yes, that's right, although we're angled a bit down. We started about here, and now we're about here so we were a good inch away. ALDA: Once he's found the best stimulation point for the muscle a hair-thin, permanent wire implant is slid into place. Dan was one of many experimental subjects who volunteered for the program. In his case, he received eight electrodes in each leg. Now we just bring this down to exactly the position that we were before. ALDA: The patients and Dr. Marsolais were literally stepping into the unknown. How do you feel going through this? Do you feel like a guinea pig? KEMP: Yeah, I do, but it's well worth it. You know, down the road, people will be able to look back and say if it wasn't for people like me that they wouldn't have got as far as they've got in the new procedures. So, you know, it goes down the line. Everybody helps everybody else, whether they realize it or not. ALDA: Eric Bellamy, paralyzed in a motorbike accident agreed with Dan that it was worth being a guinea pig. He saw simple, basic ambitions for himself and for the program. BELLAMY: I see being in a chair always but I see being able to go up steps and knock on a friend's door and say, "Hey, I'm down here! " instead of running around the house and screaming, "Hey, I'm here, I'm here! " I see being in a convenience store as one step, you know? Uh, so... Being able to get up and go through a narrow door to go get into the bathroom-- just for them answers. And if they can come up with that right there... Your life's in a chair but being able to overcome difficulties would be a tremendous step and that's what we're working on right now. ALDA: Eric was one of five volunteers who received the most complex of the experimental systems, with a total of 40 implanted and eight external electrodes. The computerized control box could handle 48 electrodes simultaneously with connections made through the skin on his thigh. One big goal was to establish how many muscles needed to be stimulated for effective standing and walking. Working out how to sequence the firing of the electrodes was another challenge. Okay, go ahead and stand up. ALDA: In this trial, 20 muscles per leg were being stimulated compared to the 50 per side that are involved in natural walking. Eric was able to walk relatively smoothly although he still needed to use his arms to balance. Developing an artificial balance mechanism is still one of the goals, but they have been able to reduce the number of muscles needed for walking to only eight per side-- as in the latest system we saw Don Crago using earlier. But Eric's muscles had to work constantly at full blast. MAN: They're using tremendous amounts of muscle mass. Their quadriceps are on 100% their gluteal muscles are on 100% their hamstring muscles are on 100% their back muscles-- everything's just blasted. Whenever they do something they're using 100% of all their strength. Whether it's one step, two steps they're using everything they got. Like when you stand, everything goes right into it, 100%, bam! Okay? ALDA: With tough, motivated subjects like Eric they were eventually able to work out how to reduce the high levels of muscle stimulation and they also figured out the best design philosophy. It's that simpler is better. They realized that even the most complex systems were going to get tripped up by the real world sometimes. Stop! Stop altogether. ALDA: Better instead to go for simpler standard systems that can bring basic benefits to the largest number of people quickly. Many of the pioneers in FES research have now dropped out. Eric got a bad infection. Dan couldn't keep up the long commutes to the hospital. But today, many people with spinal cord injuries have good reason to be thankful for the pioneers' efforts. This is an easy introduction to the real world, I guess you could say. ALDA: Jen Penko is one of the beneficiaries. She's showing me a rehab area at Cleveland Metro Medical Center-- the first of three centers around the country to be working with the simplified standard systems. PENKO: For instance, there's curb cuts and those types of things. It takes a little extra energy to get up that, doesn't it? A little bit, but you'll get curbs in the real world that are a lot more difficult than that. You can just set it right there because I'll get myself set up. ALDA: Jen has a simplified system th just does one thing-- allows her to stand. PENKO: So, the light by the "stand" means that it's ready to stand and all I need to do is press this button to go and