Is Stem Cell Research Making Progress?

Scientists working with mice are reporting success in using stem cells to regrow cells related to hearing loss. Three researchers join host Ira Flatow to discuss the latest adult and embryonic stem cell research news, and explain how the research may be used in humans.

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IRA FLATOW, host:

You're listening to SCIENCE FRIDAY from NPR. I'm Ira Flatow.

Up next this hour, the latest news on stem cell research. It's been, wow, it's been more than 10 years time flies since the first human stem cells were isolated by biologists at Johns Hopkins and the University of Wisconsin. And those cells, some of which were isolated from embryos, can potentially, the hope is, turn into any cell in the body. And hope was and still is that stem cells would one day be used to treat all kinds of diseases like Alzheimer's or diabetes, heart disease or cancer.

But the road has not been a smooth one. There have been some pebbles in it for stem cell researchers. Many people were, and are still, opposed to destroying embryos to get to the cells, and that has translated into less funding for those doing this research.

A new way to derive the stem cells using adult stem cells seemed to offer a way around the ethical dilemma of using embryos, but just how good a substitute they are for embryonic cells is still not clear.

So we thought we'd take a look at the state of stem cell research now. We'll look at embryonic and adult stem cell research together, what diseases can now be treated with stem cells, what diseases might we one day hope to cure.

Is it still more promise, more potential than reality? Where do we go from here? You can join our discussion. You can tweet us @scifri, @-S-C-I-F-R-I, or give us a call, our number 1-800-989-8255. And we'll be happy to bring you in as part of our discussion.

Let me introduce my guests. George Q. Daley is the associate director of the Stem Cell Program and director of stem cell transplantation at Children's Hospital Boston. He's also a Howard Hughes Medical Institute investigator and associate professor of biological chemistry and molecular pharmacology at Harvard Med School. Welcome back to SCIENCE FRIDAY, Dr. Daley.

Dr. GEORGE Q. DALEY (Associate Director, Stem Cell Program, Director of Stem Cell Transplantation, Children's Hospital Boston): It's good to be here, Ira, thank you.

FLATOW: You're welcome. Hans Keirstead is associate professor of anatomy and neurobiology at the University of California's Reeve-Irvine Research Center. He's also founded the Sue & Bill Gross Stem Cell Center there. Thanks for being with us today.

Dr. HANS KEIRSTEAD (Associate Professor of Anatomy & Neurobiology, Reeve-Irvine Research Center): Pleasure to be here.

FLATOW: Dr. Daley, after President Obama took office, if you recall, he ended the restrictions on using federal funding on embryonic stem cells. Remember, President Bush had put that restriction in. Did that lifting of those restrictions, did that result in a new flood of new research with those stem cell lines?

Dr. DALEY: Well, it certainly helped a lot, but we're still waiting to see the full implementation of this new policy. Under the Bush policy, we were severely restricted. There were 22 lines that were available to federally funded researchers. In fact, only about a half dozen were really widely available.

But in the last 10 years or so, there's been over 1,000 new lines made worldwide, and the new Obama policy promises to give access to researchers to a much larger chunk of those lines.

FLATOW: You say promises. Does that mean it's not happening yet?

Dr. DALEY: Well, it's slow. It's government.

FLATOW: What's the roadblock here? Come on, spit it out.

(Soundbite of laughter)

Dr. DALEY: Any you know, the policy was announced in March. In July, the National Institutes of Health announced a very detailed vetting process for the new lines, and in December, the first lines were approved.

We're now a little more than a year later. We've got some 64 lines, which is about three times as much as we had under the old policy, but there's still some issues.

Many of the lines that are approved carry restrictions. Not all of the former Bush lines have been accepted under the new policy. So scientists who have been working with the old lines are frustrated to some extent because they are not yet able to use the new ones or use their funding for these lines.

So we think we're getting there. There's been a little bit of a time lag for implementation, and we're all hopeful that the promise will ultimately be realized.

FLATOW: Any day now. Tell us the difference in a nutshell between the two kinds of stem cells, the embryonic and the non-embryonic lines.

Dr. DALEY: Yeah, it's very fundamental. The embryonic stem cells are really the master seeds of the body. They are the precursors of any tissue, and it's that versatility which makes them so valuable to biomedical research.

The alternative are stems cells in the adult body stem cells in the blood, stem cells in the skin, the gut and the like and these stem cells make only the cells in the tissue in which they reside.

So they're extremely valuable. We use blood stem cells to cure patients with leukemia and various genetic diseases of the blood.

But blood stem cells, for instance, won't make neurons, and they won't make liver cells. So if you really want to study the range of tissues, the embryonic stem cells have advantages.

FLATOW: Dr. Keirstead, which type of cells do you work with?

Dr. KEIRSTEAD: I work with human embryonic stem cells because of their ability to amplify at this time and form, as Dr. Daley has said, most of the cells in the body.

FLATOW: Well, we've been hearing over the years that taking cells of the adult stem cells are getting almost as good as the embryonic stem cells. Do you agree with that?

Dr. KEIRSTEAD: I think that the new methods of making stem cells from an adult, inducible pluripotent stem cells, or IPS technology, is one of the great advances of the stem cell field. Right now, it can be used for research and not for a clinical setting to treat humans, but it's getting there.

FLATOW: Is there some limitation on them for that, or...

Dr. KEIRSTEAD: Well, the methods in which they're made render them incompatible with human use right now. There's other methods that are being explored - that I'm sure will come to fruition - that will allow that technology to be used in the clinical setting. It's not there now, which means that we are still using human embryonic stem cells in order to really put into humans what we're playing with in - or we're experimenting with, in animals right now.

FLATOW: Dr. Keirstead, you were involved in the first human trial of embryonic stem cells in humans. The treatment is for a spinal cord injury. Can you tell us a little bit more about that?

Dr. KEIRSTEAD: It's been a very exciting road. What we did was take human embryonic stem cells and direct them to become not a hodge-podge of every human tissue type but rather one particular spinal cord cell type that's lost after spinal cord injury.

Having made this high-purity population of cells, we then put it into spinal-cord-injured rodents and restored their ability largely to walk. We've then walked the path of translating these discoveries, showing that they work in broader animal models, that they're safe, building the clinical teams and building the manufacturing capabilities with Geron Corporation to move it towards the clinic and obtain FDA approval to do so.

FLATOW: The Geron was set to begin clinical trials, but they were halted, were they not?

Dr. KEIRSTEAD: Yes. The bar is extremely high, and it should be for the first clinical trial in the world using this cell population. So we all agree that we've got to have a tremendous amount of diligence. In being diligent Geron (technical difficulty) recently, about a year ago, that there was a contaminant within the transplant population, a contaminant that wasn't necessarily dangerous, but it (technical difficulty) have been there.

So they found the problem, and then they found a way to get rid of the problem and presented that to the FDA actually after they had been FDA-approved, which I think really speaks to the integrity.

But in any case, having found a problem, having solved the problem, they presented the work to the FDA and they decided together to run one more experiment just to be doubly, triply sure. That experiment's ongoing right now. Should it have the results that we all anticipate, the hold will, again, be lifted.

FLATOW: 1-800-989-8255 is our number. Let's go to Jason(ph) in West Bloomfield, Michigan. Hi, Jason.

JASON (Caller): Hey, how are you doing? Thanks for having me on.

FLATOW: You're welcome.

JASON: I just wanted to say that I am a receiver of adult stem cells for idiopathic cardiomyopathy. I received the stem cells five years ago, and I had an injection fraction of eight and 10 back then.

FLATOW: Wait, wait, wait, where could you get them? They're not in...

JASON: Thailand.

FLATOW: You went to Thailand?

JASON: Yes, sir. And I went there, and they did the procedure, and my injection fraction now is close to 30.

FLATOW: Dr. Daley, how do you is this a safe thing he's done?

Dr. DALEY: Well, this is yeah, this is a growing trend, where patients who feel they have no options here in the United States are traveling overseas to receive these treatments. I'm very pleased that Jason has had a beneficial effect.

My concern is that many of these treatments are not based on very sound, pre-clinical evidence that they work. We don't understand the full range of safety issues involved in these approaches, and I'm very concerned that many of these clinics are not really operating under any kind of regulatory framework.

And so the kinds of patient protections aren't in place. Once again, I'm pleased that Jason had a good outcome, but I'm I think there's a growing number of patients who have had unfortunate outcomes at the hands of these types of stem cell tourism-type treatments.

FLATOW: Jason, did you know the risks before you went in to this?

JASON: Oh, yeah. Yeah, we were well aware of it, but we've - I've talked to another lady who had it done and it helped her. And then now there's thousands of us who have had it done. And one of the surgeons was actually from the University of the Minnesota, so - and now there's in Costa Rica, and they have surgeons from Florida and so...

FLATOW: If you do it, they will come.

JASON: Well, yeah. But you know, the point is, is that there is help out there for people, you know, that want to get it done.

FLATOW: All right.

JASON: I've received phone calls, emails from all over the world, and...

FLATOW: Well, good luck to you. Thanks for calling.

JASON: Well, thank you for taking my call.

FLATOW: You're welcome. 1-800-989-8255. I want to bring on my next guest as we move a little further into possibility of getting results from stem cell research. My next guest became interested in studying the hair cells in the inner ear. You know what those hair cells are. Lots of people tried to warn him that he might be heading down the wrong path. Those hair cells, which can be easily damaged and lead to hearing loss, they're notoriously hard to get to and hard to harvest. You can't work on them in the tiny confines of your ear. They're difficult to study in there. So he said, well, instead of harvesting them from animals, why -why don't we grow our own? And that's what he did. He used stem cells from mice and he coaxed the cells to grow into the same hair cells found in the inner ear.

And joining me now to talk about it is Stefan Heller. He's professor of otolaryngology at Stanford University in California. Welcome to SCIENCE FRIDAY.

Dr. STEFAN HELLER (Stanford University): Thank you. Thank you.

FLATOW: Your idea is to grow the stem cell, the hairy cells. Those are the cells that get damaged in hearing loss, correct?

Dr. HELLER: That's right. Yup. We - I mean, two motivations for doing that. One is just simple scientific curiosity, because we want to learn how the process of hearing works. And that is one of the last senses of the human senses that we haven't really elucidated. We don't know how it - how we really hear, what are the molecules and the genes that are involved in that. So it's a very basic scientific curiosity that drove us initially to do that.

And of course there are more than 300 million people worldwide that have debilitating hearing loss. So there's a huge population out there that could actually benefit from any kind of regenerative approach that we might discover on the way when making these cells.

FLATOW: Mm-hmm. This is SCIENCE FRIDAY from NPR. I'm Ira Flatow.

We're talking about, right now, stem cells and the hair cells in ears. So you didn't harvest them to actually say I'm just going to transplant them back into people. You wanted to learn how they grow and see physically what you couldn't see inside of a person.

Dr. HELLER: Right. I mean, the transplantation is the same. These cells that regenerate come from embryonic stem cells as well as from induced pluripotent stem cells. And the cells that regenerate have the same kind of issues that any other stem cell, embryonic stem cell transplant would have, which is we need to get them to a stage where they are incredibly pure before we can - before we're able to transplant them. As well as when translating this to human, we need to translate all the research that we are doing from mouse to human, which is actually underway. But again, the transplantation into the ear is a very difficult task to do.

And if you ask an inner ear surgeon, this is a compartment of the body that is so well-protected that a surgery on this compartment is only -can only be done in a high trained - with a highly trained professional. It's really difficult.

FLATOW: Yeah. I understand that in some animals the hair cells are able to regenerate.

Dr. HELLER: Right.

FLATOW: Well, I guess if you could figure out how to do that in a dish, maybe you could find some ways to get them to do that in our ears.

Dr. HELLER: Right. And that's, I think, the major push now. I think we are not using these cells primarily for transplantation, but our goal is to actually create - use these cells to generate an ear in a test tube for that sake to screen for drugs that are potentially able to induce, regenerate - regeneration in the inner ear.

And this regeneration is not a science fiction kind of thought. It actually happens in a lot of animals. In fact, only mammalian mammals like humans and mice and guinea pigs have lost this ability. If you use a chicken or a bird or a frog, all these animals, whenever they turn deaf, within weeks they can hear again.

FLATOW: So if you could find what promotes the regrowth...

Dr. HELLER: Right.

FLATOW: ...some sort of chemical signal, right, that might promote the regrowth of them.

Dr. HELLER: Exactly, right. And this will hopefully lead to a drug in the future. Not saying this will happen within the next 10 years, but...

FLATOW: Right.

Dr. HELLER: ...at some point we might reap the fruit of that.

FLATOW: And how big a colony of hair cells do you have? And are you getting close to that point where you can actually understand what they do?

Dr. HELLER: I would think we're trying to get a bucket load.

(Soundbite of laughter)

Dr. HELLER: And right now, we have a couple of thousands that we can generate within - about three weeks. So getting that up from a couple of thousand to a bucket load, whatever that means, is the next goal, yeah.

FLATOW: Mm-hmm. And then do you need to study them to genetically or just tease them out with different chemicals to see how they work?

Dr. HELLER: I mean theoretically what you can do is, for example, you can take a skin cell from a human patient - and we do this right now with mice - that have a defined or undefined defect in the ear. And it's very difficult - it's impossible in humans to sample that and to take a biopsy. But we would be able to generate the sensory cell type - the sensory hair cell in a culture dish, and then we can assess what is actually wrong with that cell. It will help in diagnosis, although that wouldn't help in treatment, but that's certainly a possibility.

FLATOW: From an individual who has a problem.

Dr. HELLER: Right.

FLATOW: Wow. Well, good luck to you. I hope - how far along - you only have a few thousand. You need a whole bucketful.

Dr. HELLER: I hope we are there in a couple of years. That would be really nice, yeah. Mm-hmm.

FLATOW: Well, we'll have you back when you can show us that bucket.

Dr. HELLER: Definitely. Yup.

FLATOW: Thanks a lot, Dr. Heller.

Dr. HELLER: Thank you.

FLATOW: Stefan Heller is a professor of otolaryngology at Stanford University in California. We're going to take a short break. And when we come back, we're going to continue to talk about stem cells. If you have any questions, give us a call. Our number is 1-800-989-8255. You can tweet us @scifri, at S-C-I-F-R-I. And go to our website at sciencefriday.com, where there's a discussion going on, and you can exchange comments about the program. Stay with us. We'll be right back after this break.

(Soundbite of music)

FLATOW: You're listening to SCIENCE FRIDAY from NPR. I'm Ira Flatow. We're talking this hour about stem cell research. My guests are George Q. Daley, associate director of the Stem Cell Program and director of stem cell transplantation at Children's Hospital in Boston; Hans Keirstead, associate professor of anatomy and neurobiology at the University of California Irvine. Our number: 1-800-989-8255 is our number.

Let me ask you, Dr. Daley, about something I was reading earlier this month about treating Parkinson's disease in mice using cells taken from a woman's uterus, and they seem to be very successful in this. Do you know anything about that?

Dr. DALEY: Yes. Yeah, there was a paper from Hugh Taylor. It's interesting. Many different tissues, including the lining of the uterus, harbor a kind of stem cell. It's an adult stem cell related to wound healing and regeneration called a mesenchymal stem cell. And under conditions in the Petri dish, you can coax those cells to become the dopamine-producing cells that are missing in Parkinson's patients.

Now, they may not be natural or fully normal neurons the way you might derive from a brain source, but they are enough to provide dopamine into these animal models, and you see a therapeutic effect. The future may be finding a safe and reliable source of dopamine-producing cells that we can transplant into patients in the future.

FLATOW: 1-800-989-8255. John in Bethesda, Maryland. Hi, John.

JOHN (Caller): Hi. Good afternoon.

FLATOW: Hi there. Go ahead.

JOHN: Oh, sorry. Go on.

FLATOW: Yeah, go ahead.

JOHN: So my question - and after Dr. Heller, I have one comment - but my question is, do adult stem cells have shortened telomeres like adult somatic cells, and therefore would that somehow or another limit their life span as compared to embryonic stem cells?

Dr. HELLER: Well, we do know that telomeres, to which John is referring, are these little tips at the ends of chromosomes. They're akin to the little plastic on the end of your shoelace that keeps it from fraying. And with adult tissues, as the cells reproduce, the chromosomes tend to shorten, these telomeres tend to decay. What we do know is that the embryonic or induced pluripotent stem cells have reactivated the enzymatic machinery to maintain those telomeres. And so in a sense those embryonic sources of cells are immortal. The adult sources of cells are and tend to be more susceptible to the aging process, so it is a relative but not an absolute advantage of the embryonic types of cells that they do seem to sustain the telomeres better.

FLATOW: So they're not identical then? Even though we'd like to say that the adult stem cells may be identical in function to the embryonic cells.

Dr. HELLER: Well, it's very important to realize that there are critical distinctions. And I want to make the point that it's not that one is better than the other. Clinically, at the Children's Hospital, I'm involved in bone marrow transplantation. That's the life-saving use of adult blood stem cells to cure leukemia. So in that context the adult stem cells are essential. So it's not one or the other, both are valuable, but they do have different biological properties. And the way they treat the telomeres is one such difference.

FLATOW: Okay, John. Thanks for you call.

JOHN: Can I...

FLATOW: Whoop. We lost him there. 1-800-989-8255 is our number. Let's see if we can get a couple more calls in. Joey in Tucson. Hi, Joey.

JOEY (Caller): Hi there. I'm love the show, Ira, and good afternoon, Dr. Daley. I'm a kidney patient here in Tucson on dialysis, and apparently a good transplant candidate, but terrified by the prospect of anti-rejection drugs and what have you. I've looked into stem cell trials for kidney regeneration, but I don't think I've seen anything outside of mouse trials being done in Mexico and Japan. And my question is, why the hell are these not being done in the United States?

Dr. DALEY: Well, there's a couple points there, Joey. First of all, the kidney is a very anatomically complex organ. And it's not clear - in fact, I think most kidney specialists believe that there isn't a stem cell that's going to regrow the entire kidney. The kidney is formed during embryonic development. And by the time you get to an adult, that - the cells that gave rise to it have already taken on a different shape.

What we do know is that there are tissues within the kidney that do regenerate. And there are scientists who are attempting to develop transplantation therapies that might enhance kidney repair. The reason that things aren't going on in the United States is not because we're reluctant or conservative. The science just does not sustain doing clinical work in humans for kidney disease.

And I want to revisit some of the comments that Jason made earlier. I think it's very important to realize that we're working aggressively, very hard, but under very scrupulous and rigorous regulatory frameworks here in the United States to translate this very promising area of science into new therapies. I have to be suspicious of many of the projects that are going on overseas, especially when many of these clinics are actually charging patients for what, today, are unproven therapies.

And so I want to direct people to the Children's Hospital website, Children's Hospital Boston, and to also keep an eye out for the International Society for Stem Cell Research, because we want to equip patients with the kind of information that allows them to make informed decisions about where they need to seek out their kinds of treatments.

FLATOW: Thank you, Joey.

JOEY: All right. Thank you very much.

FLATOW: 1-800-989-8255 is our number. Dr. Daley, you created adult stem cell lines for 10 human diseases, I understand. Can you give us an idea why you did that and what diseases you're aiming at?

Dr. DALEY: Yes. I mean, one of the ambitions of stem cell biology for many years has been to create disease models, patient-specific stem cells, for instance. And so embryonic stem cells - which come from typically generic embryos - don't really model human diseases. There are some which can be made from embryos that have undergone genetic testing. And if they are found to carry genetic diseases, they can model a disease.

But with this new approach of induced pluripotency, we can actually take any patient - whether it's diabetes or heart disease or Parkinson's or any number of conditions - we can move their cells into the Petri dish. That allows us to capture all of the genetic predispositions of that disease - and then coaxing these patient-specific cells to become the tissues that are affected by disease, scientists can study the disease process as it unfolds and develop new drugs to reverse the disease process.

One day, we may even be able to use a patient's own cells by repairing the genetic defects to give them back healthy tissues.

FLATOW: Well, why is that...

Dr. DALEY: So there's an enormous opportunity.

FLATOW: Well, why is that day so far away? What are the major hurdles to doing that? It would just seem so simple.

Dr. DALEY: It's very much in its infancy.

FLATOW: You know, you could take the cells out, put them back, they work. They know what to do.

Dr. DALEY: Well, we're still learning an enormous amount about how these cells behave. We have to know that they're safe. Current methods for generating these stem cells involve infecting them with multiple viruses, and the viruses and can sometimes activate cancer genes in the cells, which is obviously not safe. So we're learning how to make these cells without viruses, which would make them more clinically acceptable. We're learning how to coax them to become pure populations of tissues. And then, of course, there are all the challenges of actually engrafting patients. We've got to be able to take the cells, get them to the diseased area of the patient and hope that they function normally.

FLATOW: Now, Dr. Keirstead, you're also working on creating a different kind of spinal tissue, motor neurons. Tell us about that one.

Dr. KEIRSTEAD: Well, having succeeded in making one human cell population of the spinal cord from stem cells, we decided to try again and succeeded in making very high-purity populations of spinal cord cell type called a motor neuron that's lost in diseases like ALS, or Lou Gehrig's disease. And it's also lost in an infant disease called spinal muscular atrophy and a particular flavor of that disease that is very, very devastating on infants, manifesting a couple of months after birth and usually resulting in their death within a year.

FLATOW: Mm-hmm. And what kind of diseases could you - might be able to help treat or cure with this kind of neuron?

Dr. KEIRSTEAD: Having made very large populations of these motor neurons, we can then replace then in diseases of motor neuron loss, like ALS and this disease, spinal muscular atrophy.

FLATOW: Mm-hmm. Are you going to actually be able to try this out in any humans?

Dr. KEIRSTEAD: We are very, very close to beginning a phase one, clinical trial on babies with spinal muscular atrophy. It's a partnership that University of California Irvine has had with an industry player, California Stem Cell, with foundation players, Families of Spinal Muscular Atrophy, and many, many other families around the nation that have all pitched in their brains, their money, their resources to move this treatment from the bench to the bedside.

FLATOW: Mm-hmm. Dr. Daley, any trials for you that you're involved in that might be coming up soon, or that you know about?

Dr. DALEY: Well, the first clinical trial of an embryonic stem cell product is the one that Dr. Keirstead has described. I think others in the future may be in the area of treatment of particular kinds of blindness.

FLATOW: Mm-hmm.

Dr. DALEY: We can make the retinal pigment epithelium from the use of pluripotent cells. We can make photo receptors, and I think it's a very promising prospect for the future being able to restore vision. We're particularly interested in blood diseases. My lab has been able to generate blood from embryonic and these induced pluripotent cells in mice and to treat diseases in mice like immune deficiency and sickle cell anemia and the like. And we hope one day to be able to translate that into human patients.

FLATOW: Mm-hmm.

Dr. DALEY: But it's a slow, painstaking process. There's a lot of discovery that remains, and it's not something that's going to happen overnight.

FLATOW: Mm-hmm. We've heard that the body has its own storehouse. We've had scientists who've come on who were involved in diabetes research who find that if they're able to stop the body from attacking itself for a while, the stem cells can come back and actually, you know, try to recreate a pancreas. And it's a matter of just, you know, figuring out what the - caused this at the beginning.

Dr. DALEY: Well, you mentioned diabetes. This is a particularly controversial area as to whether or not the insulin-producing cells, the beta cells, actually will regenerate. We do know that the process in diabetes is - in particular, the autoimmune variety of so-called insulin-dependent or juvenile or type 1 diabetes - does involve the destruction of those insulin-producing cells.

In fact, I think that the data supports a model where there's very little regenerative reserve once that disease process has run its course, which is one of the reasons why my colleague Doug Melton here at Harvard is particularly interested in generating these insulin-producing cells from embryonic and induced pluripotent stem cells.

FLATOW: Mm-hmm.

Dr. DALEY: It'll give us, essentially, an inexhaustible supply to replace the missing cells in those patients.

FLATOW: Gentlemen, I want to thank you for taking time to be with us, and good luck to you. George...

Dr. DALEY: Well, it's my pleasure.

FLATOW: You're welcome. George Q. Daley, associate director of the Stem Cell Program and director of Stem Cell Transplantation at Children's Hospital at Boston. Hans Keirsted, associate professor at Reeve-Irvine Research Center at the University of California Irvine. Thank you both for being with us today.

Dr. KEIRSTED: Thank you very much.

Dr. DALEY: Thank you.

FLATOW: I'm Ira Flatow. This is SCIENCE FRIDAY, from NPR.

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