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JOE PALCA, host:

From NPR News this is Talk of the Nation Science Friday I'm Joe Palca. Up next this hour the science of Evo-Devo. Birds do it, bees do it, we do it. Turns out we all do it in a similar way. I'm talking about development. For years, scientists new very little about the process of development. They knew how it started with the meeting of sperm and egg; but how that one fertilized egg grew into a million celled or trillion celled organism was somewhat of a mystery, the black box of biology sort to speak.

Well, new technologies developed in the last 20 years or so have allowed scientists to see what's happening in that black box. And they found that development in wildly different organisms is remarkably similar. By looking at the relatively small number of genes that control development, biologists say they can learn a lot about evolution.

This new branch of biology even has the catchy title, which I've been using because I like to say it, Evo-Devo, for Evolutionary Developmental Biology. And joining me now to talk more about it is my guest Sean B. Carroll. He's an investigator with the Howard Hughes Medical Institute and a professor of molecular biology at the University of Wisconsin, Madison. He's the author of Endless Forms Most Beautiful; the new science of Evo-Devo published by W. W. Norton last year. Thanks for talking with me today Dr. Carroll.

Prof. SEAN B. CARROLL (Molecular Biology, University of Wisconsin):

Thanks for having me, Joe.

PALCA: So start me off. Did I kind of get it right about what Evo-Devo is?

Prof. CARROLL: Yeah, you're right on the button.

PALCA: Okay. Well, we can stop then, thanks very much. No I mean what's going on here? Why is this a new field of endeavor?

Prof. CARROLL: Well, as you mentioned in the last 20 years we finally got a peak inside the black box of embryos. And I guess let me start with an analogy. If you consider the construction of a building what would it look like to us if we didn't see the workers and the machinery putting that together? It would look as though the building assembled itself or was put there by some magical force.

Now that we can see the workers and the machinery, now we understand how things are put together. And now that we understand the making of an individual building, some particular species, we understand how differences in the way those workers and machinery put things together give you the different kinds of buildings that we see. In this case the different kinds of buildings that are different kinds of animals we see in the animal kingdom.

PALCA: Ah, now I meant to invite our listeners to join this conversation. The number is 800-989-8255; that's 800-989-TALK. So okay. So you talk about a molecular tool kit for building, I mean, what exactly are we talking about there?

Prof. CARROLL: Well, a small fraction of all the genes we have or any other animal has, are really devoted to organ building and body building. With the rest of the genes really carrying out basic physiological tasks like getting nutrients in and flushing things out or the specialized jobs of the types of cells we have, like those fore carrying oxygen or for fighting off invaders and things like this.

But the building, the putting your backbone in place, deciding the number of vertebrae, the number of ribs, where the hands are going to go, how many digits, where do the eyes go, how many there will be, the color of fur or skin or scales or feathers. These are the tool kit genes. They are shaping the size, the number and the color of bodies and body parts.

PALCA: So if these, if this idea that there's a relatively small tool kit that builds everything up from the same sort of set of principles. If that's the new idea what did people used to think?

Prof. CARROLL: They used to think that really there was entirely different genetic recipe for different forms of organisms. It was an intuitive bias that we just didn't see the connection between say something like a tiny fruit fly and a magnificent human. Our expectations were that there would be entirely different rules and entirely different materials being used in assembling the bodies of these different animals.

PALCA: So how does this idea square with you know what Darwin was talking about, about how different species evolve?

Prof. CARROLL: Well, Darwin and many of his followers understood the importance of embryology to understanding evolution. But it was, as you said, a black box for really more than a century. So while everyone could agree that what was going on in embryos was important and Darwin felt that embryology was the best evidence and support of the evolution of forms, understanding that changes in development lead to changes in form. They knew that at a conceptual level but they didn't have any material understanding of it whatsoever.

PALCA: So but this is the part that I always find I get a little confused at when I hear a description about something changing in the way we look at it. So okay, so if things didn't evolve independently but then these developmental genes have been sort of conserved all along from very simple organisms to more complex ones.

PALCA: You still have to have something that says, Okay, what's controlling the tool kit to come up with the different form?

Prof. CARROLL: Exactly, the operating instructions.

PALCA: Right.

Prof. CARROLL: So what we were expecting was that the genes themselves were changing. And we've been looking at genes and the genetic code for 40 years. And the expectation was with it sort of the inventory of tools used for building different animals would be different.

But really what makes animals different, what makes us different from apes and apes different from other mammals, etcetera, is how the tool kit is used. Those operating instructions are also encoded in DNA, but they've been in a part of the DNA that we haven't spent much time.

It is much harder to decode and decipher and this is really one of the current problems in biology is deciphering what I refer to as the dark matter of the gene gnome; the parts that have been harder to see but really have wired in there the instructions for how the tool kit is used.

PALCA: Right. And so it seems as if since this what you call dark matter has been a relatively new object of attention in the genetic world. In fact we don't really know very much about the control mechanisms yet.

Prof. CARROLL: No we don't. I don't want to say that we're you know lost, it's simply, it's much harder to study and we learn about it sort of piece by piece. The great thing about the genetic code is that we can read the genetic code of anything from a bacteria to a whale. It's the same code across all kingdoms. But the code for building bodies and how that's wired in is unique to each species. And so deciphering that code is a much tougher informational problem.

PALCA: Okay why don't we let our listeners join in on this, because I just find it, I find it an interesting concept and I wonder well before I ask, I mean is it gaining wide acceptance? Has everybody said, Oh yes of course this has got to be it or are there still people saying, No, no this Evo-Devo is a fad and it's going to pass away?

Prof. CARROLL: Well there maybe people who think it's a fad. I think everyone appreciate it. First of all understanding development was a huge quest for biology and it has great importance for example in the medical arena. So there has been tremendous solid progress in understanding the body building and organ building genes of everything from as I said fruit flies to humans.

Now in terms of evolution, it's a really simple connection. Remodeling development is what gives you the evolution of form. So if you want to understand diversity of form, you have to understand how development changes.

So Evo-Devo is here to stay. Understanding those subtle changes that take place in development that give us big brains or allow our posture to be upright or put our thumb where it is, these are things we're really going to want to understand.

PALCA: Okay let's invite the listeners into the conversation. Our number is 800-989-8255, that's 800-989-TALK. And why don't we try Chris in Dekalb, Illinois. Chris welcome to Science Friday.

CHRIS (Caller): Hi, Ira.

PALCA: Well it's somebody like Ira, its Joe Palca today.

CHRIS: Oh, I'm sorry.

PALCA: Okay.

CHRIS: My question is, okay in college in the early 90s when I was taking biology, we were taught the saying ontogeny recapitulates phylogeny. Which basically means that human embryos and higher mammal embryos go through stages which resemble the stages of evolution; is one point where the embryo (unintelligible) and it looks like fish gills.

There's other points where it looks very much like a chicken embryo and so you know they were saying that we kind of retraced the steps of evolution as we develop as embryos. And then I heard later that that had been totally disproven and they really weren't gill slits after all. So I wanted to see what Evo-Devo has to say about that debate.

PALCA: Cool question.

Prof. CARROLL: Great question. Well Evo-Devo gives us whole new ways of testing questions like that, because we have new ways of seeing the events that go on in embryos and asking, Well are there repertoires of genes that are being used that we know for example are used in fish in a particular way. How are they used in a mammal for example?

And the reason why ontogeny recapitulates phylogeny has been, it's such a catchy phrase but, and you then know there's a lot of sort of extra jeopardy words in there. But the reason why it has lost favor is we understand that evolution chucks all sorts of pieces of the developmental program. And that it's not a strict recapitulation of evolutionary history at all. There's a whole parts of development that are missing when one compares organisms, because as organisms change lifestyles and adapt to new habitats and, for example come to land versus water, things become dispensable and some things do disappear.

The other part of development that evolves a great deal are the very earliest steps in, for example, the making of eggs in the early events in an egg. That's also very closely tied to lifestyle. So it's misleading to think very strictly about ontogeny meaning development recapitulating phylogeny, meaning evolutionary history. We see bits and pieces of that which are very fascinating. The little while we have a tail or the features that we have that resemble those of our aquatic sis- our aquatic ancestors. But it's not a strict recapitulation so it's really something that we're urging not be taught.

PALCA, host: Okay, hey Chris thanks very much an interesting question.

CHRIS (Caller): All right. Thank you.

PALCA: Okay, you know that brings up the other question that I'm always perplexed by. Say you've got this little ball of cells that begins to grow and starts to take on shape and form. And obviously switches are switching on and off. If the, if the theory's right and there's this limited number of genes so there's some switch, switching going on. What makes the order work each time? I mean it seems like so much has to happen absolutely correctly to get from a two celled organism to an elephant. And you'd expect to have a lot of errors.

Prof. CARROLL: Yeah, a lot does have to work right but nature's been working on this for 600 million years. So, and, and really worked out a lot of it in the first hundred million. There's...

PALCA: It's a smart learner nature.

Prof. CARROLL: Yeah, nature's very good because it weeds out all the losers so only those genomes that do this really well get to play in the next round.

PALCA: Uh-hum.

Prof. CARROLL: There is some variation, and without variation, there would be no evolution. So we know that the size and shape and color of, of characters that come out in various species do vary. We can see that among ourselves most easily if you just look at human faces, you can see that cheek structure and eye color and all sorts of features of the head are different; but between us, of course, we all belong to the human species.

So all those differences are little variations in the process of development. So there is some tolerance in there. And the same sort of variation exists in other animal species. What natural selection plays with is that variation and if some of that variation is more useful than others, that's going to be favored as the form of those species and its descendants evolve. So you're right that there's an awful lot of switches, an awful lot of um, toggles that have to be thrown in the right order in the right timing so that things don't collapse. But that is what natural selection's really good at, which is preserving everything that works and allowing a little bit of tolerances into things to enable some variation.

PALCA: Okay well we'll probably want to ask you some more on that question but I'm going to invite out listeners to join in the conversation. Our number is 800-989-8255. That's 800-989-TALK and uh, let's take, let's take number three here, Jock, in Philadelphia. Welcome to the program.

JOCK (Caller): Uh, hello, I would like to make a quick comment and ask Sean Carroll a question.

PALCA: Go ahead.

JOCK: The, the comment is I want to thank you greatly for your wonderful book that I'm about halfway through; because it is, it's very understandable for someone not conversant with the field. And it's helping me understand what my daughter is doing, who recently changed her plans to go to medical school. And I learned two days ago has been accepted into the Evo-Devo Program at Washington University in St. Louis.

PALCA: Well there you go.

Prof. CARROLL: I want to point out that this is not a relative of mine making this call.

(Soundbite of Laughter)

PALCA: Okay.

JOCK: It's a great book and I recommend it to anybody interested in science and particularly interested in informing themselves about the debate over evolution. The question I have is, using you science as a foundation, what do you predict will be possible in the way of translating this into clinical application in the practice of medicine in the future?

PALCA: Okay great quest...

JOCK: Like Genomics and, and that field is emerging as a powerful new discipline looking ahead. Thank you very much.

PALCA: Great question Jock thanks. Quick answer?

Prof. CARROLL: Yeah, great question and it gives me a great opportunity to explain the, the intimate connection here between development and, and human medicine. And so understanding those genes that determine which cells are going to be of which types and how organs grow and the identity of organs. These are the genes that we're going want to, for example, want to manipulate in with stem cell technology. So I thing that one of the things we're going to look forward to is a greater expansion of our power to regenerate tissues and uh, this will all play into the role of transplantation to repair organ damage, to replace damaged sun types and things like that.

PALCA: Sean Carroll, I need to interrupt and say we're talking with Sean Carroll about the new science of Evo-Devo. I'm Joe Palca. And this is Talk of the Nation from NPR News. Okay let's take another call. Thanks for that answer. Let's go to Jeff in Jacksonville, Florida. Jeff welcome to the program.

JEFF (Caller): Well thank you Mr. Palca. Doctor, um, real quick question. I was a diver in the Navy, and one of the, one of the tenets was that everything in the body is driven by partial pressures of various chemistries within out blood. I just wanted to know if there's, if there's anything, and I've often thought that it would be similar to what, what triggered the development of genes and the expression of genes in the partial pressures within each cell of the chemistry that's found in the amniotic fluid in a developing embryo?

PALCA: Interesting.

JEFF: Is that, is that, am I completely off base or is that, is that...

Prof. CARROLL: Well development is going to run generally on different chemistry. It's really the chemistry of proteins interacting with DNA and the cells interacting with each other. So all of the things you mess, mention are physiologically important, but they don't drive the process of development per se.

JEFF: Okay.

PALCA: All Right. Thanks, thanks very much for that. Let's take one more quick call and go to uh, uh, Rhonda in Des Moines, Iowa. Rhonda go ahead. You're on the program.

RHONDA (Caller): Hello.

PALCA: Hi.

RHONDA: I have always been intrigued that cloned animals aren't the same color or don't look like the animal they're cloned from. And I'm wondering if this has anything to do with that.

PALCA: Huh, interesting. Rhonda thanks for that question. Sean Carroll?

Prof. CARROLL: Great question. Cloned, you're speaking of cloned animals, Rhonda?

PALCA: Yes.

Prof. CARROLL: So the, the major technique for cloning of animals is to take the nucleus out of cell out of a typical body cell. Now that nucleus has gotten to that body cell, or gotten to that place through a long journey originally descended from an egg. There are changes that are taking place through that process that may not be reversible.

And so while cloned animals can be generated for some species from individual body cells, there have been some irreversible changes taking place such that some of those body features don't come out the same way the next time around, from, from the cloned cell. That's why we see differences, for example in body size. We see some metabolic differences and some of the features determined by the sex of the animal are also variable. So it's a great question, a great observation and if I could extend that, this is why the scientific community is uniformly against the cloning of humans...

PALCA: Okay well...

Prof. CARROLL: ...way, shape or form because of this tremendous risk that we don't understand about between the identity of clones.

PALCA: Sean Carroll, Sean Carroll we have to take a short break. I'm Joe Palca and this is Talk of the Nation from NPR.

(sound bite of music)

PALCA: This from NPR News. This is Talk of the Nation Science Friday. I'm Joe Palca. We're talking with Sean Carroll. He's the author of Endless Forms Most Beautiful, the New Science of Evo-Devo. He's also an investigator with the Howard Hughes Medical Institute and a professor of molecular biology genetics and medical genetics at the University of Wisconsin at Madison. And he's one of, well as his book title suggests, he's very involved in this new science of Evo-Devo. And we have a lot of interesting callers. So let's take one more. Let's go to Leah in Mansfield, Minnesota. Did I get that right Leah?

LEAH (Caller): Mansfield, Massachusetts.

PALCA: Oh well, wrong state. Anyway welcome to the program. What's your question?

LEAH: My question is, there is so many holes in the theory of evolution. And part of all this theory was discarded, why don't we ask a question. Who created the whole mechanism to develop the one species not another?

PALCA: Ahh.

LEAH: My second question is, who made the possibility to evolve in our genes?

PALCA: Okay.

LEAH: And my third question, it's the last one.

PALCA: Okay.

LEAH: If there are so many holes and uncertainty about evolution, why scientist don't weigh the scientific question, and don't consider that uh, the possibility of the creation by intelligent, of intelligent creation?

PALCA: Yeah.

LEAH: And the possibility the world was not created on a random, but by design.

PALCA: Well, I, those are all interesting questions and I think Sean Carroll, I'm, I'm guessing you've thought about this quite a bit.

Prof. CARROLL: My credentials in theology are fairly thin, but let me go to the point about holes in the theory of, of evolution. I think it's really important to understand that as often as that phrase is repeated, um, there's not a lot of truth to it. The point being that for 150 years biologist, geologists, scientist of all sorts of stripes have been testing and expanding upon Darwin's picture of evolution and seeing it in more rich detail as the decade's past. What we see at the level of the DNA record. What we see in embryos. What we see with new fossil discoveries, is entirely consistent an independent lines of evidence of the fundamental truth that life evolved by natural processes. In terms of the beginning of life, scientists don't really understand the beginning of life. We have some ideas but there are many, many ideas and they're all pretty much wide open to testing. In terms of design at a higher level, I think I'll pass on that one, 'cause I think every citizen's entitled to, to concede their own idea of that. And science is generally silent on that point.

PALCA: But I mean in your theory uh, doesn't it, isn't tempting to say okay uh, you know God made it work. Wasn't he so smart. He didn't reinvent the wheel for every different organism?

Prof. CARROLL: Well, I, I see you can certainly, you know, you're entitled to that viewpoint. And if you look at the scientific evidence, you'll understand that the process of genetic variation and natural selection is sufficient to account for all the changes and forms that we see through three billion years of life's history on earth. And that the scientific community has no trouble understanding the connection between simple and complex. And that that process of going from simple to complex is repeated every time an egg is fertilized. And we don't think that you need any miraculous intervention to create a human from a single fertilized egg. We know that it's biochemistry and it's cells and it's a lot of processes that are entirely observable and experimentally accessible. And so we don't reach for the supernatural, when we think the natural is completely adequate.

PALCA: Okay let's take one more call and go to Charles in Boulder, Colorado. Charles welcome to Science Friday.

CHARLES (Caller): Hi.

PALCA: Hi.

CHARLES: I have a quick question.

PALCA: Okay.

CHARLES: I want to know the impact of this research of the classification of new organisms and species and if that applies or not? And I'll take my answer off the air.

PALCA: Okay. Thanks.

Prof. CARROLL: So um, Evo-Devo is allowing us to see some connections that we couldn't see before. And what it allows us to do, for example, is that tracing the origin of particular structures. And sometimes identifying some connection that were concealed by outward appearances being so different. So it is starting to have an impact on how we understand the relationships between members of the animal kingdom. And it's allowing us to see very deeply into the stuff that makes animals similar or different. So it's going to have a contribution and it's still a matter of time, 'til we understand maybe what some of the most dramatic uh, notions we overturn through this field are going to be.

PALCA: All right. Well we've run out of time for this segment. I've like to thank my guest Sean Carroll. He's an investigator with the Howard Hughes Medical Institute and a Professor of Molecular Biology at the University of Wisconsin, Madison. He's the author of Endless Forms Most Beautiful: The New Science of Evo-Devo.

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