IRA FLATOW, host:
This is TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.
A little bit later in the hour, we'll be talking about Canadian beef imports and mad cow disease.
But up first: last week's announcement that human skin cells can be reprogram to behave like embryonic stem cells have scientists working in the field calling it a spectacular advance and groundbreaking brilliant work. This technique, if perfected, could mean an abundant source of human stem cells that don't require the destruction of days-old embryos and could one day provide specialized cells for treating disease.
This hour, we're going to look at this latest stem cell advance and whether it will settle the debate over research with human embryonic stem cells, or will it bring that debate to a whole new level. We'll also ask about comes next? What kinds of treatments will stem cells lead to? What has to happen to turn these big discoveries into treatments for patients with diseases like Parkinson's, diabetes, spinal chord injuries? And what can we learn from the stem cell themselves, what will they tell us about the diseases and progression of diseases as we study them right there in the laboratory?
If you'd like to get in on the conversation, our number is 1-800-989-8255, 1-800-989-TALK. Always, you can surf over to our Web site and you can join a discussion with the folks over in "Second Life" and look for folks with their SCIENCE FRIDAY T-shirts in Science School over there.
Let me introduce my guests. John Kessler. Dr. Kessler is the Davee professor of neurology, chair of the Department of Neurology and director of Northwestern University Stem Cell Institute at the Feinberg School of Medicine at Northwestern in Chicago. He joins us today from WBEZ in the Windy City.
Welcome to the program, Dr. Kessler.
Dr. JOHN KESSLER (Director, Northwestern University Stem Cell Institute, Feinberg School of Medicine): Thank you. Good afternoon, Ira.
FLATOW: You're welcome.
Kathy Hudson is the director of the Genetics and Public Policy Center at Johns Hopkins University. And she joins us today from our NPR studios in Washington.
Welcome to the program. Good to have you back, Dr. Hudson.
Dr. KATHY HUDSON (Director of the Genetics and Public Policy Center, Johns Hopkins University): Good to be here.
FLATOW: Let's talk about, Dr. Kessler, last week's researchers reporting that they could reprogram skin cells to behave like embryonic stem cell. They're not embryonic stem cells exactly, are they?
Dr. KESSLER: No, they're not. And that's something that seems to be lost in a lot of the press reports. It really was a very, very exciting breakthrough. It really taught us a lot about how we can take one type of cell and convert it into a cell with a lot of very different potentials. However, the authors of the studies were very careful to point out that their cells share characteristics of embryonic stem cells, but they are not precisely like embryonic stem cells. So we really have a lot of work to do before we understand exactly whether these cells will be safe to be human - used in human beings and, in fact, whether they can even be used in human beings.
FLATOW: Tell us what kind of work you're talking about. What do you mean being safe to be used?
Dr. KESSLER: To make these cells, what the researchers did was used viruses to take specific genes and they inserted those genes into the skin cells which converted the cells into cells that are very much like an embryonic stem cell. However, number one, any time you use a virus, you run the risk ultimately of that virus creating problems in the cells, some of the problems that we saw with viral gene therapy. Number two, even if we use techniques that don't involve viruses, if you insert new genes into cells and they disrupt the normal pattern of DNA in the cell, you run the risk of converting that cell into something that would be a cancer cell. So we have a long way to go before we learn how to put these genes in in a way that we don't disrupt the normal mechanisms of cell - of controlling cell division.
FLATOW: Mm-hmm. Now, the last time I heard such glowing things said by scientists about research was the human genome project a few years ago, in the deciphering of the human genome. Yeah, we haven't seen very much end up, in so many years, come out of that project yet. Are we getting a little too carried away or a little too ahead of ourselves here, do you think, Dr. Kessler?
Dr. KESSLER: Well, actually, I would say two things. First, with a respect to the human genome project, we actually, in the scientific world, have seen an enormous amount come out of it. It hasn't yet given us a lot of therapies because from the moment you discover something to the point where you can have it practical therapy for human beings, takes quite a few years.
Dr. KESSLER: But in fact, the human genome project was really a revolution for us because the sequences that were used, for example, to convert the skin cells came from the human genome project. That's how we knew the human sequences for these genes.
Dr. KESSLER: I don't think that this breakthrough has been overhyped in the sense that it really gives us a new way to look at the biology. I think it's a little bit overhyped in thinking that, well, suddenly we've replaced embryonic stem cells. The quote, unquote, "ethical wars" are all over and so forth because they most certainly are not.
FLATOW: Do you agree, Kathy Hudson?
Dr. HUDSON: Well, I think that the breathless excitement, in this case, is actually warranted because we have solved the very important fundamental problem, in being able to generate cells that are capable of turning into all sorts of cells. And if we can repeat this and have these cells go head to head with embryonic stem cells and they can prove themselves, we have solved an enormous problem in being able to provide the tools for the development of new therapeutics and regenerative medicine.
I want to come in for a minute about the sort of hype question, and you talked about the human genome and maybe stuff not really materializing out of all of that hype and promise. And I think, in fact, that we have seen quite a bit come about as a result of the human genome project. We have over 1,500 - 1,400 genetic tests that are now available, most of those were developed because of the understanding of the human genome that we gained from the human genome project.
I agree that therapeutics are much slower to come along. And I think for stem cells, for genomics, for most areas of biology, we need to sort of separate the enthusiasm about a new way of understanding biology and how it works from the time it takes to translate that into something that can be put in a pill and cure what ails you.
FLATOW: So you think similarly in this case that you first - real information will come out of studying the cells themselves instead of the therapeutic results?
Dr. HUDSON: You know, I'm a developmental biologist by training, and I think it's just completely remarkable that you can take four genes or actually maybe only two genes and put them in a fully differentiated skin cell and get them to behave like they're starting all anew. And so that's going to give us incredible insights into, you know, how cells know what they are and what they should become. And that's a basic biology that for, you know, scientist is really throwing.
FLATOW: Let me poke that a bit more. Why would we have genes that can turn our skin cell back into the equivalent of starting over again?
Dr. KESSLER: Well, I hope that this…
Dr. HUDSON: Well, they weren't put there for that reason.
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FLATOW: So why would we have - why would do they exist?
Dr. KESSLER: Those are the genes…
Dr. HUDSON: So, John, you want to take that.
Dr. KESSLER: Yeah, those are the genes that exist that enable us to develop an organism in the first place. I remember the embryonic stem cell is derived from very early embryos and then those genes that are expressed at that point in time that gives them the properties to allow the cells to go create a whole animal. So those genes exist for the developing embryo, not for the adult cells.
FLATOW: Mm-hmm. So they're there just, you know - once they've done their job, they are dormant.
Dr. KESSLER: So once they've done their job, they are largely turned off. And…
Dr. KESSLER: …the point of this was by turning those genes back on, you can make the cell look like it's a very early embryonic stem cell.
FLATOW: You intubate…
Dr. KESSLER: I think one of the comments…
FLATOW: I'm sorry. Go ahead.
Dr. KESSLER: …you've heard before is very important…
Dr. KESSLER: …about these cells have to go head to head now with the embryonic stem cell.
Dr. KESSLER: And I think we all agree with that. It's - this comparison is going to be very necessary, which means by a priori we can't stop working with the embryonic stem cell. Some people seem to believe that, now, we don't have to do anymore embryonic stem cell work. In fact, we do. We have - those will be the gold standard by which we examine these new cells.
FLATOW: Mm-hmm. And go - I'm sorry.
Dr. HUDSON: I was going to ask John. Do you think that we need to derive new embryonic stem cell lines in order to do that comparison?
Dr. KESSLER: Well, that will depend a little bit on how the field progresses. It will depend a little bit upon the characteristics of the cells which we're using for comparison. I…
Dr. HUDSON: Mm-hmm.
Dr. KESSLER: …would guess that there's no need immediately to be deriving new cell lines except from perhaps, from people, for example, who have various genetic diseases in which studying the embryonic stem cell with those various disorders might be very, very useful.
FLATOW: There - one of those advantages being talked about with this new technique is that you can use cells from the same person so that whatever cells are produced is not rejected by that person. Would that also be true of embryonic stem cells?
Dr. KESSLER: Well, the only way that that would have happened with the embryonic stem cell was to use what was the other major controversy in the field, something that was called therapeutic cloning or somatic cell nuclear transfer…
Dr. KESSLER: …where you took a nucleus, for example, from a person's skin cell and put it into an egg cell and then use that to derive new embryonic stem cell. This, of course, is very much more exciting because now we can think about taking, just taking the DNA directly, the skin cell, leave it with its nucleus in it and convert it to be embryonic stem cell.
So I do think that those of us who have been using quote, unquote, "therapeutic cloning, somatic cell nuclear transfer," will not be using that to derive cells for human therapeutics.
FLATOW: So you think that the money that would be going into that is now going - we'll be going into this new technique?
Dr. KESSLER: Yes, I do.
FLATOW: Mm-hmm. And supposedly from what I read, the University of Wisconsin is not going to claim patent rights to this or demand royalties from people who use it.
Dr. KESSLER: Well, first, I would like to point out that the really exciting paper in this field came out a year ago and it came out from Dr. Yamanaka's laboratory, where he proved in principle that you could convert these cells.
The excitement about the two papers that just came out now was that it was in human cells and his first paper was with the mouse cells., so it's not certainly clear to me that Wisconsin would be able to claim any kind of priority anyway.
FLATOW: So that would just like ignite.
Dr. KESSLER: Well, they also recently lost a patent dispute in court, which I'm sure they will appeal about the basic patent on embryonic stem cells. And they've created that this controversy because there are those people who have felt that those patents have helped to delay the field a bit. So I think there's been a lot of pressure for everyone to feel that this is a wide-open, exciting scientific discovery.
FLATOW: Kathy Hudson, you would agree?
Dr. HUDSON: Yes. You know, the important thing here - and John mentioned this -is both from somatic cell nuclear transfer, we have these very thorny ethical issues with both destroying embryos in order to get the stem cells, but also the issue of where did the oocytes come from and whether or not women would potentially be coerced in providing those oocytes. And that has consumed the attention of endless ethics committees around endless mahogany tables in Washington for the last several years and we can now basically do away with those discussions.
FLATOW: Okay, we're going to take a break, come back and then taking your phone calls: 1-800-989-8255, talking with Dr. John Kessler and Dr. Kathy Hudson. Also, you can surf over to our Web site at sciencefriday.com and join the folks over in "Second Life." We're talking about this and taking your questions. Stay with us, we'll be right back after the short break.
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FLATOW: I'm Ira Flatow. This is TALK OF THE NATION: SCIENCE FRIDAY from NPR News.
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FLATOW: You're listening to TALK OF THE NATION: SCIENCE FRIDAY. I'm Ira Flatow.
We're talking this hour about stem cell research and policy with Kathy Hudson, director of the genetics and public policy center at the Johns Hopkins University - this office is located in Washington; Dr. John Kessler, the Davee professor of neurology and director of Northwestern University Stem Cell Institute at Northwestern University.
Our number: 1-800-989-8255. I'm a little confused, and maybe my listeners are bit confused about it. Dr. Kessler, you're saying on one hand, we still have to do more research in the old-fashioned embryonic stem cell line, on the other hand, more - the money is not going there. Can you tweeze that out a little bit for me?
Dr. KESSLER: Well, first, you asked me the question, specifically, about so-called therapeutic cloning, and I think there's less money likely to go that route because this, I think, is a substitute for that. But with respect to the embryonic stem cell itself, it will be the gold standard by which we judge these new cells. We are going to have to compare them. And it - and, of course, we still have to find out whether these new cells do have all the capabilities of the embryonic stem cell and whether we will ultimately be able to use them.
I happen to believe they will. I happen to think that this will supplant deriving new embryonic stem cells from embryos, but of course that remains to be proven.
FLATOW: And how…
Dr. KESSLER: But there will be new - new ethical issues will arise.
FLATOW: Well, that's what I want to talk about. Yeah, go ahead.
Dr. KESSLER: Well, for example, there's reason to believe now that it may be possible to reprogram a skin cell so that it's identical to a fertilized egg. Well, then what do we have? And all those people who felt that a cell that had the capacity to generate a whole, you know, a whole animal by its splits equivalent to being a human being, have we, in fact, then created a human being simply by reprogramming a cell to be what a scientist would call totipotent, in other words, able to generate the whole animal. I don't know that that can be done, but these recent studies suggest, probably it can.
FLATOW: Kathy Hudson, do you agree?
Dr. HUDSON: I do. I think that these cells have enormous promise. I think we don't have to do a whole lot of more additional research in somatic cell nuclear transfer. But I think that there are very important issues, and this was mentioned early on with the viruses that are used in order to reprogram these cells, in at least the paper out of University of Wisconsin -specifically documented, I think, that there were over 20 different integration sites within the genome where these viruses sat down. Ultimately, the genes inside those viruses appeared to be silenced, so there, you know, the cell sort of knows its work is done and they can turn these genes off.
But the viruses where they insert is critically important, and we have seen from really tragic outcomes in gene therapy, where genes having sorted in critical, you know, genes that are added have inserted into important genes and resulted in serious illnesses and death in those patients. So we have to figure how to get around that. And I'm…
FLATOW: So it's an engineering problem, basically.
Dr. KESSLER: Yes, scientific engineering.
Dr. KESSLER: I think that's a fair description.
FLATOW: Mm-hmm. 1-800-989-8255. Hi, Emily in Louisville. Welcome to SCIENCE FRIDAY.
EMILY (Caller): Hi, I'm actually in the middle of writing a college essay on this exact topic. And I think that the research is very promising and has the potential of being very beneficial, but my question has to do with whether we, as a country or, like, the world, are ready for the possible immoral outcomes of the research, and maybe any current or future legislation or regulations about this. I was wondering if you could talk about that.
FLATOW: Tell me exactly - can you narrow it down what immoral outcomes you're talking about?
EMILY: Not really about the issue with the embryo or the possibility that you could be using a cell that could be a human being, but more with the issue of cloning or other outcomes that would not be - probably, weren't these exactly what you're looking for? I think that the genetic therapy has a very good outcome, but anything else…
FLATOW: Could be unintended, unintended consequences.
EMILY: Exactly. That's what I mean.
FLATOW: Okay, let's have - that's a good question. Dr. Kessler, you talked about that for just a little bit.
Dr. KESSLER: Right, well, I would say to the - I think the - what people are afraid of the most were the "abuse," quote, unquote, of the technology. It is the idea of cloning human beings, what's called reproductive cloning.
And I think virtually every stem cell biologists around the world favors making that illegal. I would point out, though, that virtually every technology can be abused. We learned on 9/11 that airplanes can bring down buildings. And you don't outlaw the technology, what you do is try to make certain that that technology is used in an appropriate way.
One of the exciting things about the use of the skin cells, as my colleague has pointed out, this really should make it so that we don't have to even utilize embryos, derive embryonic stem cells anymore; we don't have to do - use the cloning techniques. This really should be something that will enable us to use these cells to cure human disease and alleviate suffering.
Dr. KESSLER: So it's very hard for me to see any real downside in this.
FLATOW: Mm-hmm. Kathy, any comment?
Dr. HUDSON: Only one, which as the caller talked about, you know, cells that have the potential to become human beings. And what we really know now is that all cells, all cells that have a diploid nucleus, anyway, have the potential to become a human being.
And so I think that's sort of the notion of this fine, bright line in our minds or morally about that, I think we need to sort of, you know, reset our expectations there because of a skin cell can become a pluripotent cell, and if put inside and oocyte can become a, you know, a primate, as we saw last week.
You know, I think we need to sort - it's not about whether our cell has the potential of becoming a human being, because all cells have that potential.
FLATOW: Mm-hmm. John, let's talk a bit about basic research. Now, you have the ability to create these stem cells in your laboratory and possibly turn them in to let's say nerves, nerve cells.
Dr. KESSLER: Right.
FLATOW: What do you with that?
Dr. KESSLER: Well, there are many things we think about doing. We can convert them into nerve cells or cells, pancreatic islet cells to treat diabetes or myocardial cells to treat heart attack. My own particular interests in nerve cells are thinking about utilizing to help treat spinal cord injury. Probably, one of the earliest targets in the nervous system will be Parkinson's disease, a disease in which a very select group of neurons dies. And we can think about using these cells to replace that group of neurons that died.
There are many other targets in the nervous system where groups of cells are dying, for example, amyotrophic lateral sclerosis or Lou Gehrig's disease, which is a crippling disease where the motors - the cells that control all movement die. We can think about potentially replacing those with cells that do not die, and on and on and on.
The nervous system will be a much more complicated kind of organ to target then for example, the heart or the pancreas. But, really, we can think about ultimately cures for all these difference kinds of diseases.
FLATOW: You use a very interesting terminology. You said eventually replacing the damaged cells. And I understand that to mean that you're not talking about taking these stem cells and putting the raw cells into a body, but possibly growing the cells into that tissue that you want to replace. Is that right?
Dr. KESSLER: Exactly.
FLATOW: Because people think let's take the stem cells and throw them in there. And that's not what you're talking about immediately.
Dr. KESSLER: No, in fact, if you take a cell that's like embryonic stem cell and simply inject it into an animal, it will create a tumor called a teratoma. That's one of the tests of whether it is an embryonic stem cell.
So it's necessary for scientists to be able to pre-differentiate the cells along certain lines before we put them into the body. It may not be to a fully adult kind of cell. It may be that it wanted to be intermediate. In other words, on its way to becoming a heart cell or on its way to becoming a neuron, a cell in the nervous system.
But very clearly, we have to learn to do these things to the embryonic stem cells first before they're transplanted into human beings.
FLATOW: Mm-hmm. Dr. Hudson, where do you think the first results are going to show up in any of the research in the laboratory, which we know is going to come first?
Dr. HUDSON: You know, I think that the nervous system - I think that the targets have been fairly well, you know, the targets that we had for embryonic stem cells are the targets that we have now for these pluripotent cells. I think that the key issue really is going to be learning how to control the differentiation of these cells and then being able to set up good, clinical trials that can demonstrate not only that those cells are replacing or adding whatever is missing or needed…
Dr. HUDSON: …but also that they don't wander often and turn them into something that we don't want to see developing. So we don't want to see cancer as a substantial risk or side effect of stem cell treatments.
FLATOW: Are you going to be able to study some of the generative nerve diseases that take years and years to develop? I mean, you can take the cell, put them in a Petri dish and watch it over 70 years to see how an Alzheimer's might show up in the tangle of nerves there? Dr. Kessler.
Dr. KESSLER: Well, that's quite true. It's difficult to study aging in a culture dish. But what you can do is study some of the biochemistry and the molecular changes that are going on in cells as they age and try to reproduce those in cells in a culture dish to see how we could think about controlling what's happening to those cells as they age. The time course of changes of a cell in a culture dish are not the same as the time course of changes in the body. It happens at a very much more rapid rate in a tissue culture dish. So actually, it will be feasible and it is feasible to study those kinds of things in a culture.
FLATOW: 1-800-989-8255 is our number. Let's go to phones. Lots of people want to ask. Becky(ph) in San Francisco. Hi, Becky.
BECKY (Caller): Hi. How are you doing?
FLATOW: Hi, there.
BECKY: I'm trying to find out - well, first of all, I have diabetes. My father had diabetes. And I like to know, realistically speaking, how long a time we have to look at before we can find a cure for this.
FLATOW: Good question.
Dr. KESSLER: Well, that's a question, of course, that we are always asked and we all do our best to run away from that question because there is no firm answer. I can tell you that my estimate will be that it will be a time period measured in years but not decades. And that's really the best I could tell you. I think that we've made an enormous amount of progress over the last decade. I think we are getting close to understanding what has to be done but there are clearly still many years of research before we've reached the final point.
FLATOW: Theoretically, you could create the pancreatic islet cells, you know, taken - as we're talking about this technique - and put some back in, could you not?
Dr. KESSLER: Absolutely. But number one, no one has yet been able to take an embryonic stem cell and create a cell that's absolutely identical to the islet cell that people are beginning to get close. Number two, one of the problems that you face is when you transplant those cells into somebody who has diabetes, they may die. And they may die, number one, simply because the environment that you put them in into the pancreas or wherever you transplant them is not a very good one for supporting those cells.
And then, if you've actually derived these cells from the patient's own skin, diabetes - or at least juvenile diabetes, the one in young people - is what's called an autoimmune disease, where people make antibodies that kill their own cells, you then run the risk that the body would kill those cells all over again. So there are actually many technical hurdles to overcome. I'm quite optimistic that they will be overcome, but it can't be done in a week or a year.
FLATOW: Kathy Hudson, you agree that…
Dr. HUDSON: I think it's a dangerous thing to make…
FLATOW: We're always years - we're always years and not decades away. I mean…
(Soundbite of laughter)
FLATOW: …some sciences, like physics, were always 30 years away every year, you know? So…
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FLATOW: …are we really that close or are we going to be always years away ever year?
Dr. HUDSON: Well, I think we are years away. And I think that stem cells are not the only opportunity in diabetes. I think there has been lots of advances in genetics and in developing new therapeutics from other areas of research. And so I don't think we should put all of our hope for advances in diabetes in the stem cell basket. There are new understandings of adult-onset diabetes and a number of genes have been identified that contribute weekly to the development of adult diabetes. And we need to understand sort of who are all the actors, the molecular actors, and then, you know, what are their roles in this play and what's going wrong in order to be able to target therapeutics and new preventative strategies. So I think stem cells are one approach, but we have other areas that we can be optimistic about as well.
FLATOW: We're talking about stem cell research this hour in TALK OF THE NATION: SCIENCE FRIDAY from NPR News.
What would be a good lay terminology to describe the kind of technique we're talking about here?
Dr. HUDSON: Rebooting your computer.
(Soundbite of laughter)
FLATOW: Well, I mean if we - that's a good description of it. Would reprogramming - are we actually just using genes to reprogram cells now? Is it just like programming a computer? Yeah? Jack, yeah?
Dr. KESSLER: Yes, it's exactly - that's exactly what happens. Our genes are precisely what program our cells. And we have one program that run cells at the very early stages, as an embryo, and then different sets of genes, or the same genes used in different ways that then run the program in an adult cell. And what we've really - or what our colleagues have done - is turn on the set -back on the set of genes that normally would control the cell in an embryo, and made that cell more now like a cell in a developing organism.
FLATOW: Is the idea to develop cell lines of - like ageless cell lines of tissue that, you know - or is it for every individual, we want to pull out a skin cell and design something for each different person?
Dr. KESSLER: Well, the dream of this field, of course, would be for us to be able to have a designer stem cell line for every individual. If we use a stem cell line that's not derived from that individual, we will run into the same problems we've run into with organ transplantation. That is the body will reject it unless we give very powerful drugs which can be toxic to the individual.
If the stem cell line is derived directly from cells that came from the very individual who's getting the transplant back, then there'll be no rejection. So that is the - if you'll pardon the choice of words - holy grail for the field. But of course, I think it's likely that that will not be the very first way we do things. It's more likely that we will be able to use existing lines, learn how to convert them and use those first.
FLATOW: Mm-hmm. Let's go to Mike(ph) in St. Cloud, Minnesota. Hi, Mike.
MIKE (Caller): Hi. I just had a question. First, I wanted to say I really don't have problem using embryos that are going to be destroyed for research. They're going to die anyway. But my question was I haven't heard about any primate research or other mammal research into stem cell. And it almost seems like they want to round up a bunch of people that are desperately ill and do Frankensteinian research on them, you know, and that kind of thing. And I just wonder what's going on here? I mean, nobody's proved the stuff will even work in, say, a chimpanzee, which share, what, 99 percent of our DNA?
FLATOW: Let me get a quick…
MIKE: What's going on with that? Okay?
FLATOW: We've got about 40 seconds before the break. Who wants to tackle that one, quickly?
Dr. KESSLER: Well, that's actually just not accurate. Dr. Thompson, in fact, one of the scientists who just made this breakthrough, did all his original work with primates before moving to human cell. There's no Frankensteinian research being done. As physicians, as well as scientists, we're very, very carefully controlled in the things that we can do. And virtually every time, we're required to do studies in both small animals and large animals before we do it in human beings.
FLATOW: All right. I want to take both of you for taking time to be with us. Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University in Washington, D.C.; and John Kessler, the Davee professor of neurology, chair of the Department of Neurology at Northwestern University Stem Cell Institute.
Thank you both for taking time to be with us.
Dr. HUDSON: Thank you.
Dr. KESSLER: Thank you.
FLATOW: We're going to take a short break, switch gears and talk about cattle from Canada. Stay with us. We'll be right back.
I'm Ira Flatow, this is TALK OF THE NATION: SCIENCE FRIDAY from NPR News.
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