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Science Talk

Your Inner Healers: Induced Pluripotent Stem Cells and More

Scientific American Editor in Chief Mariette DiChristina talks with podcast host Steve Mirsky about the contents of the May issue, including articles on induced pluripotent stem cells, high-speed and maglev trains, and blindsight. Plus, we'll test your knowledge of some recent science in the news

Scientific American Editor in Chief Mariette DiChristina talks with podcast host Steve Mirsky (pictured) about the contents of the May issue, including articles on induced pluripotent stem cells, high-speed and maglev trains, and blindsight. Plus, we'll test your knowledge of some recent science in the news.

Podcast Transcription

Welcome to Science Talk, the weekly podcast of Scientific American hosted on May 1st, 2010. I'm Steve Mirsky. This week on the podcast, we'll talk to Scientific American Editor in Chief Mariette DiChristina about the contents of the May issue of the magazine, and we'll test your knowledge about some recent science in the news. So without any further ado.

Steve:          The cover article of the May issue, Mariette, "Your Inner Healers": Reprogramming cells from your own body could give them the therapeutic power of embryonic stem cells without, hopefully, the political controversy. So let's talk about, you know, what's embryonic stem cells, what are these things and what is the potential?

DiChristina: Okay, so just to back up really quickly, embryonic stem cells which many [in the] listening audience I'm sure have heard of, have been exciting to people in theory because they could present a lot of potential for cures. The idea is this, at the embryonic stage, a cell could become any one of the 220 different types of cells in your body. So for instance, you have bad kidneys, maybe in theory, you could take an embryo's stem cells and they could become kidney tissue which then could be used for transplantation. That's one of the many intriguing things about embryonic stem cell therapy. [It] could be used to grow different kinds of other organ tissue, heart cells, nerve cells for diseases such as Parkinson's or ALS amyotrophic lateral sclerosis, Lou Gehrig's disease—many of these currently unsolvable diseases could be addressed in theory with embryonic stem cells that could be made to become any one of a number of 220 different kinds of cells that exist in your body. But you mentioned the controversies. Embryonic stem cells make numbers of people uncomfortable with the idea that even an embryo that's only a couple [of] hundred cells some people believe that destruction of that embryo is problematic. What's interesting about this article—and I want to talk about the other kinds of the stem cells too because they're directly relevant—what's interesting about this article is it describes a new technique that takes any cell in your body, lets say your skin cell, Steve, and you can reprogram it or restart the clock to get it to the stage where it acts like an embryonic stem cell again without having to have remove[d] that cell from a natural embryo. This is what is so intriguing. The term for this technique and what it does, it creates cells called induce[d] pluripotent stem cells, and now while induced I think you can guess, it means, we've made them become stem cells again; pluripotent refers to the ability of these cells to become any number of kinds of cells like an embryonic stem cell, any number of the 220 that your body could conceivably become.

Steve:          And if we could harvest my own cells and turn them into stem cells again for transplantation, there's no rejection possibilities, they're the perfect kind of modeling clay out of which I could make anything that I could then put back into an adult body for therapy.

DiChristina: Right, this is the really exciting potential about this technique. [Now] the question is, the scientists have been able to induce this pluripotency again, or induce the ability for the turning back the clock to get [it] to act like a stem cell that could become anything, but we don't yet know exactly how that happens. I can tell you how they induce it, but they don't yet know why that happens, and they will need to study this so they can figure out, can we really control this process as well as we'd like to? And are these induced pluripotent stem cells really as variable and powerful a tool as embryonic stem cells appear to be when it comes to developing disease therapies?

Steve:          Just as a proof of concept, there's a discussion in the article about what it really is [is] a cure in a mouse model for sickle cell disease, where adult cells from the mouse are reprogrammed to not have the specific genetic mutation that accounts for sickle cell disease—and sickle cell is in some ways the best kind of condition to test these therapies with because it is a single mutation, and so you know exactly what you're trying to fix; something like heart disease, you know, may be so multifactorial that it's not a good testing ground for this kind of thing, but sickle cell is perfect—and so they transplant these cells that have had the genetic error corrected back into the mouse, and the mouse, those cells grow and multiply and take their place in the mouse and the mouse is cured. I mean, that's actually a genetic therapy cure.

DiChristina: I think this is among [the wonderful] potentials of this, you know. I mean, one of the things I'm very intrigued by is the whole tissue engineering for replacement organs also because as you know so well Steve, we don't have enough organs to replace the organs people need, and if you're lucky enough to get a kidney that's been donated or some other organ or tissue, then you have to take antirejection drugs for the rest of your life, costing thousands and thousands of dollars. So if you could take your own skin cell and through lab techniques, restart the clock on that, like you said, their potential there to act as a kind of clay that you can mold into anything is really a powerful idea. As usual though, in science it's a little harder to do than one might think. You can express the idea really clearly, but the techniques that are all involved are very sensitive and subtle. The way we're talking about restarting the clock—how do they even do that? I haven't talked to you about that yet. They insert—they've identified a small number of genes and they started with mouse research, [but] it's since been replicated in some other cells—and they insert these genes into the cells because these are the genes that seem to be active in the embryonic stage, but not later, so they took not a guess, we'll call it, they had a hypothesis [that] perhaps these genes that were only active during the embryonic stage, would help revert the cell and indeed that's how it worked, it did revert the cell. Now why did it exactly work that way, what are the messages that these cells are conveying to each other, how is that actually different, if it is, from an embryonic stem cell? We don't yet know, but it's very intriguing, it's been replicated many times; so it does seem like a very fruitful potential to explore.

Steve:          That's really interesting, I mean, all they did was basically—it's like if you like it at a graphic equalizer, and you see where all the settings are, and there's another stereo in the room, you say, I don't really know what each individual thing there does, but I'm just gonna make this graphic equalizer look just like that one, and [adjust] all the dials and, son of a gun, the same sound comes out.

DiChristina: Right.

Steve:          And that's what they did with the genes. Lets have this gene on, this gene on, this gene on and these genes off, and what's happening when we do that? We have no idea, but we know that it works.

DiChristina: And you might also say to me, "Mariette, how do they get those genes in there?" And what they do is they use a kind of a retrovirus as the delivery mechanism because viruses, hey they know how to get into cells and deliver a payload, and the question then becomes are there any after effects from using it, from using a virus? [There] was one mouse experiment where the delivery of genetic components using retroviruses created some latent cancer problems later. So while we have a delivery method, and while we have an intriguing technique, there are certainly a lot of questions that still need to be resolved.

Steve:          One of the other things you can do with the induced pluripotent stem cells is create mouse models or tissue models, I should say, for disease. So you can take an adult cell and when you induce the pluripotency, you can give it whatever condition you're interested in studying, so that the tissue that [grow] out of that cell, which would only then remain tissue wouldn't be transplanting it, it would just be for lab work, all that tissue show would show all the symptoms of tissue, in for example, type 1 diabetes.

DiChristina: Right, this is an excellent point. This is very entreating although maybe it sounds less immediately obvious why it's a benefit. The pure fact is you can't just take human tissue out [willy-nilly] from patients who are suffering, and you can't just test you know put new pharmaceuticals or new drugs on cells and watch how the cells react in human tissue routinely. I mean, they're always to do that but it's expensive and you [have] to make sure that you acquire the materials and the tissue in certain prescribed ways. If you could have the flexibility to change the course of the disease in the Petri dish, so to speak, or take somebody take a small sample of somebody's tissue and then grow larger amounts of it so that you can then study it specifically, you would have the ability to explore lots of drugs in a faster timeframe and more efficiently and probably more cheaply.

Steve:          Let's talk about flying cars; no not flying cars there are no flying cars.

DiChristina: It's the next best thing.

Steve:          Well, actually there are flying cars but they're few and far between thank goodness. But the flying cars that the Jetsons had, [we really still don't have], but the magnetic levitation trains are really a comin'....

DiChristina: …They are really a comin', and there's an article in this issue called "High-Speed Rail" that tells all about how they are coming and why they are [coming]. If I could just digress for just one minute, one of the things that tickles me about this article is, I was reflecting on the first issue of Scientific American in 1845, and you know what's on the cover of the first issue of Scientific American in 1845?

Steve:          I've seen it many times but I can't conjure it up in my head right now.

DiChristina: The above the fold image, there's a new technology that's displayed, and this is an August issue, I am thinking of this because I just wanted to mention to everybody in August it's our 165th anniversary. It's an improved railroad car and one of the improvements about that railroad car, this latest technology in 1845 was that it was aerodynamically designed so that it would move more quickly through the atmosphere and burn less coal and here today 165 years later almost we're talking about ways to make trains move through—for us in general to burn less coal; now we call it carbon, where then we would call it coal—and save energy and save time and high-speed trains are one way to do it, and on the other way you mentioned maglev trains, a little more futuristic but really are a comin'.

Steve:          And so high speed trains, I mean really high speed, not like we have the Acela in the Northeast connecting Boston and D.C. and it's called the high-speed train but it's really not.

DiChristina: It isn't really. I mean the Acela would—I have to [say] I love that train; just rode it two weeks ago down to D.C.. It's a lovely trip with a nice feel—but the Acela, which could conceivably travel at up to 150 miles an hour or so, it's designed that way; actually it only averages about 70 miles an hour in the corridor between Boston and Washington because the tracks can't support faster speeds.

Steve:          And it's sharing the tracks with commuter trains, other Amtrak lines, and freight trains.

DiChristina: Right, of course.

Steve:           Which are just [doddling] along.

DiChristina: Right, and so for us that feels [nice and] fast but when we speak of high-speed trains, we speak of 150 miles an hour and faster, and there are none of those at those speeds in the U.S. Of [course] they are common, fairly common, in other countries. They exist in Japan and in China and in places in Europe where you can go, and I've ridden the bullet train from Osaka to Tokyo; it's a marvelous experience to be cruising along at 200 miles an hour and have a very smooth ride and watch the ground [whip by you], it's quite extraordinary.

Steve:          How [is it] so smooth?

DiChristina: Well one of the tricks of high speed trains and one of the big limitations certainly for us here in the U.S. is that they really can't tolerate very much variation in inclination. So for the trains driving at that speed, the rail has to be extremely straight and the gradients we have, particularly in the west part of the U.S., don't generally permit those kinds of speeds.

Steve:          So then we're talking about, like, it is perfectly flat…

DiChristina: It's perfectly flat.

Steve:          … the [bed] on which a high-speed train is running. And the trains in Japan have this army of inspectors that goes out on a daily basis.

DiChristina: The other problem with high speed train travel—thanks for bringing that up—is that it's murder on the hardware. It's that, if you're going a 150 to 200 miles an hour down the track with metal wheels against the metal track, you're abusing both parts. So you have problems with the track maintenance, which you mentioned in Japan. Every night this army of maintenance workers gets out and inspects and corrects about 12 miles of track.

Steve:          It's about 3,000 workers.

DiChristina: And it's an enormous investment, but they do that so that they can make sure all those trains are able to keep running. The other problem with it, we mentioned the track problem, is the problem on the wheels and hardware itself. Something simple like wet leaves in the fall can grind wheels to be flat on one side or even impede the train from moving forward.

Steve:          Yeah, I was on a train going from New York to Boston and we [hit] a patch of wet leaves in Rhode Island coming out of a scheduled stop, and we had to actually go backwards about three miles and the[n] work up a head of steam so that we could go over that patch of wet leaves, and that added about an hour to our four-hour trip. And that's because we were on a tiny upgrade, probably 1 percent or less.

DiChristina: And those, you know, things like wet leaves, they cause enormous maintenance problems as well. They can square off the sides of the wheels.

Steve:          And trains in general though have to be on a grade of usually 2 percent, maybe you could push it to 3 percent. But if you go to the maglev, you can really kick it up and you can go to a 10 percent grade and still have pretty good efficiency.

DiChristina: And maglev trains, which are much more expensive obviously to build, it's a big infrastructure investment, could solve the [grade] problem from if you wanted to, say, build a train from L.A. to Las Vegas, you will be able to negotiate that a lot better if you had a maglev option because it can take those higher steeper grades.

Steve:          And they are now concrete plans to build L.A. to Las Vegas high-speed trains, Tampa to Orlando, and L.A. to San Francisco.

DiChristina: The federal government set aside among the stimulus money, is I think a package of some $8 billion dedicated to funding high-speed trains in various quarters where train travel would really be helpful. Train travel has a sweet spot, as the article explains, between a 100 miles distance and 500 miles distance between two points. [So in] the case of going from, you know, L.A. to Las Vegas, you have an entertainment center on the one side and a population center on the other and it's right in that sweet spot [for] mileage distance. It seems like a great opportunity. And likewise the Orlando to Tampa route that you mentioned is just much easier to do that,  to have a train set up, than it is to either try to fly between locations or drive.

Steve:          We have a table in the article that compares the 320-mile stretch between Tokyo and Osaka and it has the comparison of the cost, train, plane, car, the time span and the CO2 emitted.

DiChristina: Yeah, it's amazing how the trains works for these particular distances that we're talking about, 100 to 500 miles. [It] just beats driving your car or taking an airplane ride on every one of those measures. The cost of the journey for that, to that distance by car, in the table you mentioned, is $200, the plane is a little bit more, $225, but the train is a lot less, $130. And you're going 200 miles an hour, so you get there pretty quickly. In fact, how fast do you get there? You get there in less than, let's say the car ride takes about six hours and 45 minutes, the train time is two hours and 25 minutes. It's an enormous improvement and it's cheaper.

Steve:          And it's actually quicker than the plane door to door because you're not counting all the time spent going through security.

DiChristina: And best of all from the planet's health standpoint, the carbon emitted, if you're driving your car that same distance it was 209 pounds of carbon emitted but the train ride is only 50 pounds. With this high-speed train, it's a pleasant ride, I have sort of taken it myself; it's a lovely ride and very quick.

Steve:          A hundred and fifty million passengers every year on the Japanese bullet train, so the trains we're talking about for the U.S., [there's] really no new technology that's being developed for this; it's just doing it.

DiChristina: Right, it's a matter of deciding that we can afford to make the investment for several billion dollars overall for the various routes around the United States. And the article also has a nice map that shows what routes are being planned and what the status is of each of them. Probably the earliest action we'll see is in California where it looks like there may be construction on a high speed line next year.

Steve:          Right, so we're going to see these trains. Speaking of seeing we've an article called "Uncanny Sight in the Blind" and there's a phenomenon called blind sight which I have never heard of until this article and [why don't] you explain what it is and how they think it works.

DiChristina: One of the things I just love about the brain, any brain, is that we all have these things and use them everyday and we have no idea how they work on many levels and how they continue to surprise. And here's a case where the brain, you know, it sounds stranger than fiction. How could you have something called blind sight, which I'll explain a second—how can you not be able to consciously see and yet see things?

Steve:          So blind sight is somebody says, "I don't see anything, I'm completely blind."

DiChristina: Right.

Steve:          And if [you] throw a ball at them and they catch it.

DiChristina: Right, but they can tell you why they caught it but what they detected because the visual centers are interfered with. Let me back up for a quick second. [And this is a] this rare condition and one of the, you know, one of the puzzling things about blind sight and one of the reasons why it's taken us awhile to figure it out is it doesn't happen that often. There's a patient who is mentioned in the article who, because of a couple of strokes, lost the power of using his visual cortex, the visual processing centers that you're consciously aware of. So I am looking across the table at Steve right now and visually I know I am looking at Steve. Somebody with blind sight would not see you Steve, would not know that you are you know two feet across, three feet across [from] me but could potentially detect the emotions. Right now you're looking very concentrated at me; earlier we were smiling or you know talking about other things a person with blind sight can actually sometimes detect that emotion. But they can't tell you why they saw it, they can't explain to you what it was they noticed or detected. [It] is not conscious it's unconscious perception of things in the visual environment.

Steve:          They can see the expression on my face with some part of their brain, but their visual sense does not see it.

DiChristina: Right so they have no conscious awareness. Let me give you an example, because I think this is instructive. There is this patient—and in many cases in this kind of literature they just name patients with initials. So the initials they used for this patient is TN who is mentioned in the article. And TN was a patient who I mentioned had a couple of strokes and lost his visual perception, he was blind. You know, he could not see anything, was not aware of seeing anything. The authors put TN in a hallway, in a corridor, and that corridor had a number of obstacles in it, and told TN that there was nothing in this corridor that was an open corridor just walk down it. And TN walked around or took a meandering path and walked around all of the obstacles in the corridor. At the end they asked him, "How did you navigate that corridor?" and TN had no knowledge of having taken a meandering path, he just [said,] "I just walked through the empty corridor." This is an amazing aspect of blind sight. He did not know there was anything there and yet some part of his brain perceived this and negotiated a course through this corridor filled with obstacles.

Steve:          So, is there anything we are learning from this that maybe can be applied for restoration or an appreciation of environment for blind people or any kind of other applications?

DiChristina: Well, I think this is early days for applications. Some of the things that people with blind sight have been able to detect—which is interesting in the sense that it shed some light on how the brain works—they have been able to detect colors, motion and, in addition to the things that I mentioned earlier, simple shapes, and as I mentioned emotions. So that they can tell they can't tell you why but they can tell somebody is upset in front of them. And one of the things that this does at least for brain scientists is it identifies what area of the brain might be perceiving things that we didn't know about and we don't yet know definitively with blindness what area of the brain is doing the detecting but a top candidate is an area called the superior colliculus which is located in the midbrain, quite far from the visual centers. It's an intriguing finding that will let us ask new questions about how the brain works; you know, if this area of the midbrain is doing perception what else is it perceiving and what else is it doing?

Steve:          So those are three of the articles. Also there's material in the issue on neutrinos and the amazing Cassava plant, which researchers are hoping can be a staple food for poor people around the world. And we always have our 50, 100 and 150 years ago column as complied by, of course, Daniel Schlenoff.

DiChristina: Thank you, Dan.

Steve:          Thank you, Dan. May 1860, a scant 150 years ago, we have an article, let me just read you this little snippet from this article that we ran in the May 1860 issue:

"We would yet advise to set a room apart in mansions with a tittle of 'laboratory'"—I'm sure they said la-BOR-atory—"or the more ancient one of still room. The amount of instruction that can be derived from a private laboratory is far more than at first sight can be conceived and the entertainment, changeable as a kaleidoscope, is intellectually considered immeasurably superior either to crochet or Berlin work"—which we explain is embroidery.—"The delicate manipulations of chemical experiments are well-, even better-suited to their physical powers than to the sterner sex and to the ladies, therefore we commend the charge of becoming the chefs of the modern still room."

And this was in an article apparently called the "Art of Perfumery" or perfumery. And so what we were telling the rich people out there was to basically have a chem lab in your house where you could entertain yourself in the evenings by mixing things together and watching them explode.

DiChristina: I got very excited when I read that. As a person who, of course, grew up with a chemistry set, my father probably would have preferred it if I had limited myself to perfumery [rather] than the other things that I created that stank up the house.

Steve:          Which room of your mansion did you do your experiments in?

DiChristina: So I was reading this and I was thinking, "Oh, very good, so we're recommending chem lab in the house in your mansion, and I saw [the sterner] sex and I thought, "Which one is that? Oh yes, that's the man." And then I got to the women and I thought, "Are we actually going to recommend that women have their own home chem lab? How neat that is for 1860." And I thought actually this was pretty close to that; limited to perfumes but okay and nice for women to have a chem lab in the house.

Steve:          Yes. In its own way it is a little bit progressive.

DiChristina: It's a little bit progressive but as somebody who had my own little chem set in the house, not in a mansion laboratory, but in the basement usually or "get outside" my mom would say, I was pleased to see that we were recommending some science in the home and I do believe in that.

(music)

Now it's time to play TOTALLY……. Y BOGUS. Here are four science stories but only three are true. See if you know which story is TOTALL……. Y BOGUS.

Story number 1: The Mont Blanc pen company is releasing a line of pens with one-of-a-kind ink that can be traced directly to the owner.

Story number 2: Half of all the people who have ever lived to the age of 65 are currently alive.

Story number 3: Gorillas at Disney's Animal Kingdom in Florida have been taught to take their own blood pressure.

And story number 4: An asteroid has been found to be coated in a thin layer of ice of the water variety.

And time's up.

Story number 1 is true. Mont Blanc is releasing a new pen line in which each pen will have its own personalized ink; they note that "the authenticity of Mont Blanc personal code ink will be verified by Mont Blanc upon the presentation of a document letter or memento bearing the owner's handwriting. A forensic test will then reliably prove if Mont Blanc personal code ink has indeed been utilized."  Of course you don't know whether he had a gun to his head when he wrote up that new will.

Story number 2 is true. Half of all the people in human history who have reached the age of 65 are currently alive, according to an article by our friends at New Scientist magazine, and half of those 65-and-overs are right now in a mall parking lot in Florida.

And story number 4 is true. Spectroscopic analysis shows that the big asteroid called 24 Themis is coated in a thin layer of frozen H2O, [which] lends credence to the idea that the water on Earth may have been brought here by many such bodies that crashed into the planet when it was young. For more check out the April 29th episode of the daily SciAm podcast, 60-Second Science.

All of which means that story number 3, about gorillas taking their own blood pressure is TOTALL……. Y BOGUS. But what is true is that the gorillas at Disney's Animal Kingdom do now actually assist in their own ultrasound heart exams. The gorillas used to be sedated to get medical tests like ultrasound but veterinarians have trained the primates to adopt and hold certain poses, allowing technicians to get ultrasound measurements of the animals' hearts from safe on the other side of the bars of enclosure. Training was simple positive reinforcement using food treats. Next up they are really going to try to teach gorillas how to help that take their blood pressures; the toughest part is teaching them to stop puffing up the blood pressure cuff before it explodes.

Well that's it for this episode. Get your science news at www.ScientificAmerican.com where you can read our In-Depth Report on the mother–baby bond. That's triple tax-free. And follow us on Twitter where you'll get a tweet every time a new article hits the Web site. Our Twitter name is @SciAm. For Science Talk, the podcast of Scientific American, I'm Steve Mirsky, which is also my Twitter handle. Thanks for clicking on us.

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