Radiolab - (So-Called) Life

Episode Date: April 7, 2008

In a world where biology and engineering intersect, how do you decide what's "natural"?

You're listening to Radio Lab. From New York Public Radio. Public Radio. W.N.Y. C. And NPR. It's alive. It's alive.

It's alive. It's alive. It's alive. It's alive. This is Radio Lab. I'm Chad up and Rod. Today we're in a Dr. Frankenstein sort of mood. So we figure where better to start? Death Test. Then at the museum? American Museum of...

Natural History. Where they have on a kind of Frankensteiny exhibit. Okay, I'm Laurel Kendall. I curate the American Museum of Natural History's exhibit, mythic creatures. We're standing in front of a dragon. Now, why would there be a dragon at the Museum of Natural History? Well, according to the curator Laurel Kendall, why not? The human mind loves to wonder, well, what would happen if we put wings on a horse or put a tail on a beautiful woman?

That is human. Justified however you want. That belongs in the museum. What you see before you is a hall of strange, twisting creatures dimly lit. And when you look more closely, you realize that they're all mashups.

From the natural world, for example. She takes us over to one corner points at a glass case where inside is this creepy little hybrid skeleton thing. Look at this beast and see how it really is a composite. Half of it is a monkey, the upper half. And the lower half? There's a fish tail.

Like some kind of trash. With some scales. The place is full of stuff like this. A lion with an eagle head, humans with snake tails, just about anything you can imagine. Very operatic. Oh, and I forgot to mention the most important part. Kids. Tons and tons of kids, completely in awe.

Oh, my gosh, a uniform. Oh. What are we standing under here? The Pegasus. Can you describe what we're seeing here? It's a horse. The body's like a horse. It has these really big wings.

like wings, like birds, like an eagle. Maybe somehow it's parents were a horse and a bird, and their genes formed together to make a pagocyst. It's just what I see, what I see, it just looks so exciting. I think that it just looks really cool. And when you ask these kids, is our producer Lulu Miller did? Why is it cool?

Like, why is it fun to see two animals mash together? Um. Well, they just look at you like you're dumb. It's a horse. What rings? Have wings? Yes. Birds, they're not mythical.

They're like regular. Every day you see them. Every time you just see a pigeon, you're like, oh, whatever. Maybe it's that simple. Yeah. Any case, the kids, sick of us and our dumb questions, ran off to this kiosk that the museum had set up around the corner where they could actually build their own creatures.

Okay, now can you describe your guy here? He has seven heads. And he has a tail with fire on it. Four legs. And he has a long body. And the thing is, what kind of legs are those? You can't help but wonder

if these same kids in about 30 or 40 years might actually be able to do this? For real. When they're grown up, those kids will be at home in the new world of biotechnology. They will be ready to put their skills to use. There will be do-it-yourself kits to breed new varieties of pigeons and parrots

and lizards and snakes. A body like a snake? rather than like a bird. Oh, can I do it? Because I never got to do it. Genetic engineering, once it gets into the hands of housewives and children, will give us an explosion of diversity of new living creatures. Without as physicists, Freeman Dyson, we'll hear more from him later.

Now, whether it's true or not what he's saying, it does seem to be the case that we are at this pivotal point now where the stuff that we used to only imagine might actually turn into reality. Which is why maybe you get an exhibit of fantasy creatures. at the Museum of Natural History. This is a celebration of the human imagination, human ingenuity, human art. It's a lion!

In the name of God, now I know what it feels like to be God. That's our show today, life, but not as we know it. Life as we might invent it, tweak it, augment it. Yes, but if you augment, tweak, and remake, people will quickly come to you and say, hey, don't fuss with this. It's not natural.

It's not right. Speaking of right, natural, and fussing. Who are you? Oh, I'm sorry. I'm Robert Krollowich, who was always right, always natural. And always fussing. In any case, that word you mentioned. Natural.

Yeah, that one, natural. What does it mean exactly? Let's just think about that. It usually means what's familiar. What we know. What we know. Let's just muck that up a bit. Because it turns out when you look in nature,

you will find things that are frankly very strange and not familiar. Like? Well, let me tell you a story. It's an amazing story. About a woman. Heard about it from a reporter, Sorin Wheeler. Hi, So, Soren.

Right. Hey. All right. Soren, tell me about Karen. Well, Karen is a mother of three. A middle-aged woman living outside of Boston in the suburbs of Boston. And she lives there with her husband Pete. The kids are out of the house now.

Tell me what you were thinking when you walked up to her door. Well, I was nervous. I was kind of strangely nervous about meeting her. Hi, Karen. But I got there and she was as friendly as can be. Well, come on, Ed. Bring in a couple cups of tea. She made me tea.

We sat in the living room and talked. And she was just normal, which is kind of weird, given the story that she was about to tell me. So let's start at the very beginning. Yeah. Well, in 1995, I was told that I needed a kidney transplant. immediately. What's that like? What are you going through?

It was frightening. The doctors told Karen they needed to act fast. They asked me who in my family might be willing to donate a kidney. So the two older boys, that's Matt and Jess, and Karen's husband Pete, they all went in to get what should have been a pretty routine DNA test. Yep, they had the blood work done. And they waited. A couple of weeks later, I got a phone call from the hospital.

And they said, Mrs. Keegan, this is a very unusual situation that we're going to explain to you. It's something that we've never seen before. But when the DNA testing was done on your sons, we found that they didn't match your DNA. Is that how they said it? They said they matched the father, but they're not a match. for you. What does that mean? They didn't match her DNA.

She's not their mother. Oh. Pretty much. Karen, this was crazy. Yeah. I mean, she told them, I was there. This could not possibly be. I gave birth to these kids.

I felt the pain. You know, you better do the test again because you're obviously wrong. And so they did do the test again. Same result. The read was correct. There was not a laboratory error. This is one of her doctors, Lynn Yule. We felt, particularly after the second time,

that it was real. And then they said, now we have had situations where the husband's DNA didn't match, but we've never had a mother whose DNA didn't match their children. So wait, if the DNA is saying she's not the mom, then what would explain that?

Well, the first thought was that there was some kind of mix-up. Some switch of babies or something. Oh, like a baby switch right after birth kind of a thing. Yeah, but the problem with that is that the dad is the dad. The father's right. So you have to figure it like, how could they have gotten the wrong kid but the right dad? So then what?

If that's the case. Here's the thing. At this point. As we got further involved with this. People are thinking maybe Karen's done something kind of fishy. Yeah. There must be something that you're not being told. Like maybe she implanted her womb with another woman's baby.

And then she just kind of lied about it? Yeah. That she lied about it. They said, well, could you tell us what hospital you had these children in? Exactly how? What would, I'm still confused? She's being accused of being some kind of monster. Somebody who maybe wished they had children or stolen a child or something had to be because obviously DNA is never wrong.

It's never wrong. Wow. So how does she talk to her family about this? What are those conversations like? I do remember some very, sort of sad moments with my sons. Yeah. You know, I told them.

I don't think they maybe even completely realized what I was saying. Lynn, Karen's doctor, couldn't get this out of her head. Something wasn't adding up. Didn't make sense. So she thought about the fact that they'd done all of the tests on Karen's blood. Only in her blood cells. So Lynn started thinking maybe they ought to look at some of the other parts. And to do that, we would need to...

To test other tissues. Scrape the inside of your mouth and get a little saliva and maybe a hair or two. Thyroid. Bladder and a skin biopsy. They're getting all sorts of parts of you. They're getting all parts, all kinds of parts from me. And that's when things started to get strange. When we got the results of the tissue studies, we identified two sets of DNA. Two people. Two what? Another person in Karen. She had another person inside her?

Well, sort of. She did have a separate set of DNA, so it was like she had another person with its own genetic identity in her body. Whoa. And the thing is, that other person, that was the mother of the boys. Well, how did he get there?

I mean, that's what the doctors were wondering. So they all sit down and put their heads together, try to figure it out, and then it hit them. You were a twin. You are a twin. She, I mean she had a twin? No, she's both twins. Here's what happened.

In Karen's mother's womb, originally there were two eggs. Two fertilized eggs. Twin girls, side by side. Developing in their own separate sacks. Then, after a couple days, something strange happens. Somehow the two embryos bump into each other. and they fuse into one unit. And that one became Karen.

Like a mixture of the two of them? Well, no. They didn't blend. According to Lynn, what happened is they kind of claimed different parts of her. They still had their own, what I want to say, boundaries. One twin claimed her blood, and the other twin claimed her thyroid and her bladder. So Karen is a plural. Yeah.

Is this, has this happened before? Well, supposedly it's pretty rare, but it does happen. In fact, there's a scientific word for this condition. Karen first heard that word from her doctor, Margo Crescoe. Margo came to my bedside, explained that I was a chimera, a term which I had never heard of before. Did she come and say, you're a chimera? Yes. Now, that was interesting because I called my son the English major and said, met, I found out I was a chimera. And he said, oh, you know what a chimera is, don't you? And I said, no. And he said, well, in the ancient Greek myths, a chimera is an animal that has

like a lion head, then a donkey's wolf, a goat tail, you know, it's a mixture. In Greek myths, the chimera was a monster. that the hero's supposed to slay. That didn't make me feel very good. Then Karen learned more about what chimera meant medically and what could have happened to her. If the eggs hadn't fused within four days, I would have become a Siamese twin.

When you hear that, you immediately have a more concrete vision of two selves, it brought home the reality that I really was a twin. She is a twin. One doctor said, do you think you have two souls? I think of myself as the union, but there is almost a sort of subtle sadness to think that that I would have had a sister.

Yeah. And so there is sort of a shadow feeling of loss. There could have been more. Thanks to reporter. Sorin Wheeler for that. Let's make things a little more disturbing now. Yeah. Because human beings, scientists are now capable of creating chimeras purposefully. And we talked to Lee Silver, who's a scientist at Prince.

Oh, Lee, okay, Lee, you have to say something. Okay. You know, my left ear is. receiving more than my right. And he told us about an intentional chimera, a creature created by a Danish embryologist named Steen Willitson. He took a goat embryo and a sheep embryo, and he pushed them together in his petri dish,

put that mixture of embryo back into a female. I don't remember which species. And then what was born was an animal that was part goat, part sheep. And he called that a geep. Was it visibly kind of goatee and kind of sheepy? Well, it was actually, yes, it was very visible. And what happened, because of the way development occurs, parts of its body look sheep-like and parts of its body look goat-like.

Which parts? Well, he did this multiple times. And so he actually got multiple geeps. And sometimes the animal would have a goat head, but then parts of its body would be sheep-like with wool. Other times it would have a sheep-head. How confusing it would be at the geop-ype. dance. You wouldn't know like who is supposed to dance with whom?

Could Geeps relate with one another in that way? I don't remember. He's not a deep. As he may look. With that little beard and everything in the hooves. Just to give you a visual, we've got a picture here of three geeps hanging out near a tree. Do you want to describe it? Well, the geep, one of them looks like a naked animal wearing a coat of shaggy. hair. It's got this streak of sheep wool running down its back,

but the rest of it looks kind of goatee. Do you find it cute? I kind of do find it cute. But now let's uncute it a bit. Suppose instead of talking about mixing sheep with goats, since you're not a sheep or a goat, let's make it more personal.

People are most worried about combining human embryonic cells and monkey or chimp embryonic cells. And so the idea is if you took a chimp embryo and a human embryo and you push them together, based on the deep results, based on lots of other data that scientists have accumulated, it's very likely that you'd have an organism born that was part chimp, part human. Well, there once was a creature like that because if you believe in evolution, you believe that

chimps eventually became humans. So somewhere in history, there is someone who is 10 chimp and 90% human. And that common ancestor evolved continuously and slowly from a chimp-like individual to a human. And in every point along the 100,000 generations, the children didn't look very different from their parents. But here's the very sad Hollywood movie. I go and I go and I create a creature a deep-like amalgamation, which is 50, 50% chimpanzee ape and 50% human homo sapiens. And he's the only one.

That's like creating a tragedy, it seems like, because you'd be creating someone who is isolated in his physiology. Yes, I mean, this is... No one could read with him, or maybe they could, but it would like... Well, I'm going to... It goes to you're taping this. Yeah, are you opening something.

I'm opening something for you. This is actually a play. Here, you can... Look at this. It's going to be performed next week. Sweet, sweet motherhood, is that it? Yes, that's it. So this is a play at the Guthrie Theater in Minneapolis.

Shelly McCann wants a baby, a human chimpanzee baby. Oh. Shelly's been spending too much time partying to build up a respectable grade point average. So she proposes the following senior thesis. Fertilize one of her eggs with the sperm from a chimpanzee. In her womb. It's an interesting term paper. So Professor Harry Stein must do everything he can to stop her.

The play is inspired by a true event. Really? This is your play. Yes. Jeremy Kerkin is the main playwright, and I've collaborated with him. What is the true event on which this is based? The true event is that about 10, 12 years ago now, I was talking in my usual flippant way to a bunch of students,

and a sequence information had just come. out showing that chimps and humans were almost 90% the same at the DNA level. And so I just threw out the idea, well, based on what we know about goats and sheep and everything else, you probably could have a hybrid developed between a chimpanzee and a human being. It was a thought experiment. What would it be? How would it develop? Which of its characteristics would be human? Which would be chimpanzee? The next day, a student, a junior, came to my office and said, She wanted to do the experiment inside her own womb. And so then, yes.

In real life, what did you do? Hit her on the head with a baseball bat or what? No, I had long. I was flabbergasted. She was absolutely serious because it is actually true. She was this student who partied a lot, and she needed, and the senior thesis of Princeton counts an enormous amount towards your final GPA.

So she wanted to do this unique experiment. hoping she'd get an A-plus in her senior thesis. She was very naive, obviously. Wow. That was the last time I saw her. You're going to put up this little chimpanzee for adoption as soon as it was born? Well, no, no. Worse than that.

I asked her, what would you do with this individual? I said, well, if it's a human being, you have to raise it like a human being and has rights like human being. If it's a chimpanzee, you put her in a zoo or you use it for experiments and what's it going to be? And her answer to that question was she would abort right before her. it came time to go into labor. She'd abort.

And so the whole idea of the senior thesis was to study the development of this hybrid inside of her womb. She really wanted to do this for real, not just on paper for a project, but actually to herself. Yes. Now, there are many, many, many, many problems.

Yeah. It gives me new meaning to be liberal arts education. It's got to be really liberal here. And we talked for about an hour. I dissuaded her. I never saw her again. Except in a way, in his play, the one he co-wrote, this is the play about the teacher at the fancy university

who happens just to be teaching a biology class. The human ovary within the mouse's body... Happens to have this notion about what would it be like if chimps and humans had babies together. Actually, in a number of ways, I am more similar to a male chimp than I am to my sister. Happens to have, in the play... Can we talk?

A student who comes up after class and says... I want to combine one of my eggs with chimpanzees. I don't want you to do this. Why not? Except, by the way, in the play, Shaxie goes through with it. I'm pregnant.

Well, you know, he wrote the play to keep a conversation going that wouldn't get out of his head. And the question is, what is a human being? If you look at it developmentally, evolutionarily, through these hybrids and chimeras,

where's the boundary between human being and non-human being? And at the end of my quest, I personally concluded that there is no boundary. No, no, no. It's fuzzy. So, in other words, if you look at the analogy I like to give is look at the color spectrum between green and blue.

When you go from green to blue along the color spectrum, it's a continuous gradual change from one to the other. There's no point at which you say, here's the boundary between green and blue. And if you take that analogy, which I did to human beings, you say during development, during evolution, in terms of a chimera, there's no boundary. But the social effect of having staked out that position is that you aren't going to defend our species against all kinds of amendments. There is a consequence to this kind of thinking, right?

I mean, you can't do a cold border anything goes, can you? No, no, I don't believe you can do anything goes. My purpose is to say not that anything goes, but that in theory, all these outrageous things could happen. And actually are happening. Here's an example. Since 1980, scientists have been taking human genes, genetic information, putting it into mice. I mean, this is sort of a routine procedure for people who do mouse molecular genetics.

And in fact, the really exciting thing that people are doing now is they're making cows that are engineered to produce human blood. and the idea is that you want to change all the genes in the cow that normally produce the proteins in cow blood. You want to make them all human. So you have a cow making human blood. I don't think most people would mind that. And then you could use it for blood transfusions. Wow. Could you make a cow with human blood and a human kidney so that you could use that too?

Well, actually, the Israeli scientists have already created a mouse that has a tiny little functioning human kidney. Get out. I could show you the picture. Yeah. So, I mean, and you know, and there are other people who are working with sheep and trying to make human livers inside sheep. And the whole idea is regenerative medicine. Sacrifice the animals to get a new kidney for you. Now, I actually think that as long as you don't play with the external features, I think society will accept it.

I mean, you know, people eat pigs. And if you can eat a pig, why not grow a pig to have a human liver, kidney, or heart? As long as it still looks like a pig, you're saying. That's right. As long as it still looks like a pig and it still behaves like a pig. You know, if you put a human arm onto a pig, I don't think people would like that. But you acknowledge that the distinctions you're drawing are emotional distinctions and not rational. Absolutely.

They're emotional. And I'm saying that sometimes emotional distinctions matter. I mean, I have no solutions. I mean, I don't know where to draw lines. Society has to draw lines. Radio Lab will continue in a moment. Message 1. Hi, this is Lee Silver.

Radio Lab is funded in part by the Alfred P. Sloan Foundation, the Corporation for Public Broadcasting and the National Science Foundation. Radio Lab is produced by WNYC, New York Public Radio, and distributed by NPR. National Public Radio. End of message. Hello, I'm Chad, Aboumrod. And I'm Robert Crowellwood. This is Radio Lab. Our topic today is, what is our topic today, Robert? Well, the topic today is making life that isn't there before you arrived in the room.

Okay, life, not as we know it, but as we might invent it or make it. Well, let's talk about life, you and I. Okay, so when you look around in the world at living things, and I say, look, Dad, there's a cat, and that's a dog, and that's a tree. And you notice that those things, of course, are different. Yes. And later when we go to school, we learn about phyelums and categories like kingdoms and stuff. So we learn about the nature of those differences, and then you're taught about struggle and competition.

and Darwin and species and all that. There is a new theory that's being talked about that turns all of that on its head. I heard it first from this guy. I'm Steve Strogatz. I'm an applied mathematician at Cornell. And the story he told me, which is based on analysis of DNA and very tiny organisms,

is that once upon a time he says, life began with a very primitive, very simple collection of cells. And these cells, said Steve, these cells like... It's a shape. It appears that when you go back far enough, there's a kind of rampant sharing of molecules. It's a kind of orgy in which there are no well-defined species or organisms, and I can give you my genes and you can pass.

We're a commune. It was a commune. What does that mean? It was a commune. What do you mean? What does it mean? I know what it means in the 60s free and love sense, but what does it really mean? What cells are exchanging is chemicals.

Chemicals that give them talents and traits. Jeans, here's what happens. I did this with Steve. In our ancient puddle, when Darwin thought that life might have begun in a warm puddle, let's say that you and I are both selves. Okay. So once upon a time there was you in a puddle, and I'm in the same puddle as you. And it gets a little colder in the puddle, so we should all get sick. But you don't get sick.

You have some kind of accidental talent. You can handle cold water. I'm shivering. Describe again what happens at this point, in the glorious old days. Well, my membrane, that is, I'm a cell, I've got a membrane, I've got my outer layer, maybe a little bit porous, and maybe... Whoops, some of my genes just leaked out. Okay, we're not talking sophisticated organisms.

And maybe you're porous too, and... Oh, whoa, you just absorbed some of those genes. So now we both have this... We both got it. We both got it. And if I've got this gene now, I can survive cold water because it's part of me. And if I bump into you... Now it's part of you.

So now this Steve gene has become a Robert gene, which has then become a bad gene, and we're doing this over and over and over. And we're getting really commune. It sounds so friendly. No, actually, don't think of cells like people. Shut up! All these exchanges, this gene swapping, was not intentional.

It's not purposeful sharing. That's Nigel Goldenfield. I'm a theoretical physicist at the University of Illinois. And he and his colleague, Carl Woz, did the science that led to some of these kind of goofy ideas. It's not me sort of saying, hey, I'm going to just help up my buddy over there. Here's a couple of jeans that I think you'll find handy. It's not something like that. Even still, if we're swapping genes so much and you know, you're giving me yours and I'm giving

me mine, what does it actually mean to be me? Yeah. If so much of me is spread around. Well, it would be very weird. Imagine a world in which for a while I have your nose, God forbid. And then I get my nose back. You'd have Steve's hair. Then Steve would get my ear. then he would get your nose. Once you start having a lot of exchange... I'll take your chin. Okay.

You can have my allergies. Then you start even asking, what does it mean to be a species? You can have my love affair with doubt. You may not even be able to talk about individuals. Yeah, if the mixing is good enough, we're all kind of indistinguishable. So identity would be very strange in this ancient world.

A lot of the concepts that we take for granted in in biology become more and more nebulous as you get further and further back to the root of the origin of life. Take, for instance, Charles Darwin. What Nigel's really saying is that for the first billion years of life, with a bee, with a bee, everything that Darwin teaches, all that stuff hasn't happened. There's no borders, no individuals, there's no species. That is Darwinism, evolution as we now understand it. That's an interlude in the real story of life. It's only what's happening now. What you got back at the very beginning was a whole bunch of cell swapping genes,

swapping advantages, swapping disadvantages, and it's kind of a wild time. A tremendous explosion of diversity in a way that life has not seen since then. Until... One dark and terrible day. Three billion years ago. As interpreted by Freeman Dyson. The famous physicist and delivered here now, by our friend the mathematician Steve Strogett.

Here's Steve. One evil day, a bacterium. anticipating Bill Gates by three billion years, refused to share. Refuse to share. The first bad guy is this cellular Bill Gates who decides that I've got an innovation that I don't feel like sharing,

or possibly I found a way to keep my membrane from leaking. That is, I'm not going to be a sharing soul anymore. And why? I mean, what made that one little cell decide to stop sharing? That's a good question. We don't really know. But what we do know? This was maybe the most dramatic moment in the history of life on earth.

This transition from the age of, if you want to call it, the age of sharing to the age of selfishness. And gradually, once one creature stopped sharing, pretty soon the others followed, and then more and more did the same thing. And now, for the first time in the history of life, finally we get Darwin. Now we get species. Now we see differences. Yes, it's the age of identity, of individualism. It's also the age of stasis. Things change, but they change much more slowly.

And any great thing, you know, like you are a bat and you figured out sonar? I don't have sonar. I can't get sonar. Be nice to have sonar like you're in a little electric fish that lives in the muddy waters of the Amazon. You don't care it's totally dark. You can see because you can see with electricity. I can't see with electricity. If I'm in the dark, I'm bumping my head.

Okay, so here's where we end up. Chapter 1. A great orgy of gene swole. Wapping. Chapter 2. The orgy ends. We pass genes now not to other guys, not randomly, but just to our own children. And finally, here comes. Chapter 3. As proposed by Freeman Dyson, the physicist. Freeman Dyson. After three billion years of life slowly evolving through random mutations, through bumps in the night, one species, Jad, human beings, you and me. We have become so smart, so, well, some of us, so technologically, advanced that we can swap genes. We now decide who gets what genes. And thanks to us, evolution as Darwin described it is beginning to end. And now we welcome evolution as described by Freeman

Dyson to the graduating class at the University of Michigan. I see a bright future for the biotech industry, becoming small and domesticated rather than big and centralized. Freeman thinks that in the future everybody, and he means everybody, they will all be creating new life forms. And why? Because they can. There will be do-it-yourself kits for gardeners who will use genetic engineering to breed new varieties of roses and orchids. Kits for lovers of pigeons and parrots and lizards and snakes to breed new varieties of pets. Genetic engineering, once it gets into the hands of housewives and children, will give us an explosion of diversity of new living creatures.

The final step in the domestication of biotechnology will be biotech games, designed like computer games for children down to kindergarten age, but played with real eggs and seeds rather than with images on a screen. Playing such games, kids will acquire an intimate feeling for the organisms that they're growing. The winner could be the kid whose seed grows the prickliest cactus, or the kid whose egg hatches the cutest dinosaur. So there's your future. I would like to make you. your future for the moment rather than my own foot. But it doesn't sound that bad. I mean, maybe a little sci-fi.

Well, actually, here's the interesting thing, is that what he's describing has already begun. There are kids doing this right now, or something very close to it. How old were you when you did this? I guess I was 20. I'm 21 right now. Okay. Who are you? What's your name? And what do you do? I'm Stephen Payne. I'm a senior in biological engineering at MIT. Now, here's the thing about Stephen. He, like most kids who are in the sciences and college, had to spend, and hours and hours and hours in the lab,

waiting for E. coli to slowly grow in a petri dish. E coli, like the stuff that gives you food poisoning? Well, yeah, it's the stuff that's common bacteria and it lives naturally in your gut, and it's, by the way, a big laboratory favorite. And the problem is, says Resch Messetti, who's a grad student at MIT, is E. coli in the raw?

Actually smell really bad. What does it smell like? I actually kind of smell, I guess, maybe like poo. I don't know. What do you think it smells like? Feses. Anyway, Stephen and his friends got it into their hands that they could make... Make E. coli that smell...

No, nicer. Yep. Nicer smelling. Like cinnamon or cherry. Or like minty fresh. We ended up deciding on wintergreen. Wintergreen? You got something against winter green?

No. In the real world, who has winter green? It's the petunia plant. Petunias have winter green? I have no idea. Yeah. A lot of folks study why plants make nice smell. So why do roses smell nice?

Why do petunias smell nice? So what we did was we requested from one of these folks, Natalia Duderava from Purdue University, we asked her to send us a sample of one of the genes she had studied that produces this winter green smell. She mailed it. Through the mail. They opened it up. We took it out. What were you taking out? A little bit of gunk? It's actually living cells, living dried cells.

Yeah, we pulled out the DNA, put it into a new cell. And once the new DNA had done its thing, Stephen called everybody into the lab. And we all came over and we're like, whoa, these, you know, this E. E. coli culture actually does smell like mint. And we were like, yay. That's crazy. Yay. So instead of smelling poo all day, they get to smell winter green.

Well, actually, there was more than that, because after their wintergreen success, Stephen and Reschman decided, you know, why should we stay in the lab all day, even though it smells nicer now? Because we have to sit there and watch these E. coli grow and grow until they're ready to be experimented on. We could be outside playing Frisbee. So they decided to put a little trigger inside the E. So when it's done growing, it switches from winnegreen to banana.

Banana? Yeah, the banana. So banana. You know, it smells like a banana milkshake. I mean, it smells more like a banana than a banana does. So winded green means it's still growing and banana means we're done. Yep. Wow.

That's kind of awesome. Awesome's a word. I want to discuss the awesome question here. Okay. Were you at all intrigued by the idea that as far as I know, and maybe as far as you know, maybe as far as anybody know, in the history of the E. coli creature, there has never been an E. coli that smelled like wintergreen. You made it yourself. Well, with the help of my team members, yes.

Did you feel a little spooked by the fact that you just created a life form new to creation? I mean, at least we're doing something that smells pleasant. But you didn't feel like Dr. Frankenstein or God or... Not at all. What does it feel like to make something that's never existed before? Just feels like basic engineering. Yeah. We're engineers.

I would say we're engineers. We're building stuff. Building stuff. Building stuff. Building stuff. Building stuff. Stuff. And not just stop.

Stop. Stop. I'm letting stop. The road ahead is bright and clear. Because we're bioengine. We'll fix the problems of today by building stuff with P&A. We're slicing genes with building creatures. Adding extra useful features.

No more waiting Darwin's done. Swapping genes is much more fun. Building stuff. Building stuff. The road at us. We're bioengineers. I'd rather be swapping gene. It's mankind's only fighting chance.

Designer genes, not dent in pants. We'll stop disease and green. Disease and greenhouse gases sequencing nucleic acids. Crack the cold, we've seen the light. We're building stuff. We're building lots. The road ahead is bright and clear because we're my... Thanks to Josh Kurs and Shane Winter for that music.

Radio Lab will continue in a moment. My name is Alyssa Hargrave and I'm calling from Shacopi, Minnesota, where it is currently negative 25 degrees Fahrenheit outside. Radio Lab is supported in part by the National Science Fund. and by the Alfred P. Sloan Foundation, enhancing public understanding of science and technology in the modern world. More information about Sloan at www.sloan.org. Hello, I'm Chad.

And I am Robert. This is Radio Lab, and today our topic is... Tinkering, I guess. Tinkering... With nature. Yeah. Or life. Yes, but down as we know it. Oh. Because before the break, we heard about some kids doing something that they call...

Yes, directed evolution. By sticking wintergreen into a place where winter... Green has never been before. Which definitely qualifies as life, not as we know. But now let's get into the true grid of this. Because those kids are looking at life in a fairly different way than most of us do. Yes. It's very interesting that the people who are creating these living systems are engineers.

This is Lee Silver from Princeton University. I mean, they really look at a living system as no different than a computational electronic device. And your hunch is they're right. My hunch is they're wrong. I don't know quite why. My hunch is they're right, but most of the world doesn't believe that. Which would include me, because I find it very hard to imagine that a life form something that's animate and lives for a span of years and then dies. You know, it's like when they die, the spirit kind of goes out.

It's hard for me to believe that that is just a chemical machine assembled from parts. Really? Yeah. Well, okay, I mean, I guess I can understand that. But let me introduce you to a guy now whose whole, admittedly young career is based on the idea that life is a machine that it's made of parts, parts that he can build and sell. Okay. So I'm Brian Baines. Brian, we met.

Actually, just down the street from those MIT kids. He is 31. That's right. Just 31. And he runs his own biotech company. I'm one of the founders of codon devices here. We make custom synthetic genes. scratch. And he's doing pretty well. The industry is basically doubling every two years at this point.

Just to give you a sense of what Brian does, you with me? Yep. Just take your example, those MIT kids. Let's say I'm one of those kids or someone else who's heard about them and I want to take my stinky bacteria and make it smell better. Or maybe I want to make it glow. All I have to do is call Brian. Sure. Because he'll sell me a simple gene like that for about $1,500. I just have to go online, look up the chemical recipe for How to glow in the dark. Yes, here it is. 1,200 letters.

A, G, C, A, C. These are letters of DNA. A, G, a T, and a C of four fundamental building blocks of DNA. Next step? Just list out those A's, G's, and T's and C. Yeah, just type them into an email. Generally, they're not typing it themselves. Imagine trying to type in 2,000 letters by hand without making a mistake.

Yeah, that would take too long. All right, just copy and paste them into an email. Send them to Brian. When we get that in-house, we, um, we, we, um, We're going to take that into our factory. Brian then plugs the string of letters into this machine, which is about the size of a desktop computer. We have a synthesis system where it literally has a bunch of little A's in a jar

and a bunch of Gs in a jar and T's and C's. Now mind you, these chemicals are inert. They are store-bought $100 a bottle. The machine they're all connected to reads all the letters that Brian plugs in. And when it's using A, the machine squirts out some... A dust. And when it sees a T, squirts out some T dust.

We can add an A or a G or a T or a C to a growing strand of DNA. And so we're literally adding one base at a time. So what starts as one letter pieces, then grows to 50, then grows to maybe 500, then grows to be 5,000. And at a certain point,

all of these inert chemicals hold hands. and that's literally how you make DNA chemically. That is how you go from dust to something that is not exactly alive, but if I take this little speck of DNA and stick it into my cell, amazingly, it will start to glow or smell better or whatever it is that I want it to do. It will do it. It's almost as if the cell is a computer.

And this little bit of DNA is a software program. I mean, that's the way synthetic biologists think about. And what synthetic biologists are hoping for is, like, is that the software, quote-unquote, will get standardized, it will come down in price, so that one day installing new features into organisms will be just as easy as when you install new software on your home PC. You put a word processor, you put a spreadsheet program. User-friendly. That's kind of the logic.

Yeah, but that's not that's, we're talking about life here. Life isn't like, you know, a game of Legos. What if it is? I mean, I know it's weird to think. It's wrong. Another word to describe it. It is. But what if it's not wrong?

Just imagine you can start to look at things in a completely new way. You can look at that creature over there and say, that creature right there has a talent that I really like. And that one over there, the second one, it also does something cool. Maybe if I take Talent 1 and Talent 2, stick them together, put them into a third creature, then I've got a little factory that can do really cool stuff. Create living things that have very important functional values.

As an example in our earlier conversation with Lee Silver, he brought up a guy named George Church. George Church is a scientist at Harvard Medical School. He's thought to be absolutely brilliant by everybody that knows him. Lee actually happened to have a picture of George on him, and he showed us. Oh, is that him? He does look like a radical. Let me see his face looks like.

Describe him. He's wearing an Army shirt of some kind. He's got a nice bushy beard and a spit curl. He could be Santa Claus played by Clark Gable. Well, we had to visit him. Hi. How are you? And George is.

unusual as scientists go. I'm George Church, professor's genetics at Harvard Medical School. For the last 20 years, he's been going further and further and further in terms of synthesizing life. Okay. I'll slide. You know what I'll do? I'll slide. He's stuffing some kind of big black rod up my nose. That would be the mic. The kind of creatures that George Church engineers are the same kind that those MIT kids use,

E. coli. By taking these little tiny E. coli and, you know. Adding a few genes from. other organisms and tweaking the internal chemistry. He has gotten the E. coli to suck in sugar, which is what they normally like to eat, but poop out. All kinds of things. Most notably, drum roll please. Diesel!

For real? Oh, yeah. The company I co-founded has produced hydrocarbons. That is just a fancy way of saying, among other things, diesel. Three different kinds to run in three types of engines. cars, trucks, and planes. I was curious to see how it all works, so he took me to a room at the back of his lab

where he's perfecting the process, and he pointed to a small container. So here's an example where we might grow up a large batch of cells in a fermenter. So this big vat right here, which is, I don't know, what's the size of a... This is a couple of liters. Pretty small. It's about the size of a Coke bottle,

and right now he can only make a few drops. So, there are some scale. issues to solve, but I asked him, you know, where does he imagine the stuff going? Project forward into the future, and he painted... Describe it for me. What would it look like? An amazing picture of huge bodies of water. Giant ponds or lakes. Of gas. I mean, just imagine we could take a boat, paddle around and be beautiful, birds chirping. Except under the surface, trillions of bacteria would be busily eating plant life, burping out diesel fuel.

which then float to the surface. As this kind of gassy foam. You can skim it off. Skim it off, throw it into a pipe. There you have it. I mean, this could be the oil refinery of the future. No more pumping it out of the ground and fighting wars. Forget that. That's old.

Now we're talking microbes, man, microbes. And this could be just the beginning. I mean, according to Lee Silver, people are hoping that this kind of bioengineering can produce all kinds of stuff. You know, a drug that cures malaria, something that makes plastic, I mean, anything.

Well, they would be good. Yeah, but there is part of it that makes it me a little uneasy. Why? Well, I want to introduce you to another bioengineer. He's often called the leader of the pack. Like the rat pack? Sort of like the rat pack. His name is Craig Venter.

And like the rat pack, folks, he's very talented. He's very ambitious. He's very driven. He's also working on a bug for fuel. He also thinks that the earth is in trouble. We're messing our nests, something terrible. And when we were at the 92nd Street Y in New York, he said to write out loud, bioengineering, creating new life, is our last hope.

It's probably our one major chance of having our species survive on this planet. I mean, this is the engineering of the rest of this century. And that's a little, I mean... Stand aside, young man. I'll rescue you now, with my magical scientific ability and my natural engineering skills. If he could save the world, I'd stand aside and throw him a parade. Well, except you don't realize just how ambitious. These guys are going for them.

What's wrong with ambition? Nothing, really, but what you don't know is just how bold this guy is. He not only wants to mix and match traits that already exist in life, to make new forms of life. He wants to do original design. He wants to think of things that life has never done before, things that are in his head that are entirely new. He even dreams of life from scratch. From scratch, completely like 4.1 billion years. ago kind of like in Genesis.

It would probably take a little longer, but I think there will be new life forms. You think it will be possible in your lifetime that someone will go into a store, buy dust, figure out what it is that they have to do with that dust so that what they make will be unmistakably alive. Not alive, then alive. Yes. Yes. But using the knowledge that we have from studying this four billion years of evolution

We know how to write it. This is the thing about, what if I told you that I thought, no. I don't know why, just no. I think you reviewed my grant. No, but there's a can-do-ness to scientists that puzzles me a little bit. Isn't there something that you think? And this would be really close to it, creating life, that just might be out of our grasp.

It might be forever mysterious. And yet you guys, like, is there anything in the way of engineering life? Is there anything that you think is not doable? Do you think it's never going to happen that you'll create a conscious life form from scratch? Or it will never happen that you will create a morally, you know, a creature with moral sense of right and wrong. But I don't know. I think you think that everything is possible. Everything.

I think you're right. Okay. I get that Craig and people like him might have a little bit of an attitude about what they can accomplish. But is that your problem? It's his attitude? No, no, no. No, it's a sense of life, I think, is wrong here.

I really appreciate, because of Darwin and Darwinian evolution, that it takes 100 million, 200 million, a billion years for creatures to figure out how to live in the neighborhood of life, how to know what to eat, what to avoid, how to fit in. You know, if you're going to sustain, you've got to learn how to live harmoniously with the rest of names. nature. It takes a while. But here come these engineers. Over some weekend, think, I have a new idea. Maybe they'll eat oil or I don't know. And then you stick it into the world and you've just

stuck something into a rich fabric of life and you have no idea of all the different consequences that could follow from that decision. Look at what happens right now with antibiotics. That scientist, Nigel Golden felt whom we heard from before. 50 years ago, we declared war on microbes. We fed antibiotics to cattle to kids when they had virus infections. We poured so much antibiotics into our bodies and into our food that the bacteria we were trying to kill, figured out a way to avoid our medicines, and now they're stronger than ever. Not smart. We didn't know.

There were things that we didn't really understand, that we didn't know that we didn't understand, and we're paying the price for that now. I am frightened that these people have so much ambition and so much certainty in them that, frankly, they don't fear what biologists don't know about life. It's really a Frankenstein story. That is there's so much hubris in this. And as Steve Strogatz will tell you, biologists, in fact, scientists in general know very,

we now know how much we don't know about life. If biology really is about collective behavior, the interaction of billions of molecules, billions of species, this network of life, we barely understand. You know, we keep being surprised about life. On the one hand, we can tinker in this engineering way,

like the MIT students do or like Ventor is doing. But on the other hand, the best biologists are still mystified that we only have about the same number of genes as a worm. We're really still missing 99% of the picture, literally. So it's a scary time to start playing Dr. Frankenstein, given how ignorant we are. Do you know that at Stony Brook University where your mom worked for all those years,

there was a scientist, maybe a few doors down from your mom who made from Stoneybrook University, From scratch using the dust particles we were talking about, the polio virus, which the whole world has been working to eliminate. He made a new polio virus. Why? I don't know why. There was a lot of controversy about it. But there is a guy, perhaps, in a cave somewhere in Afghanistan, who wants to make a polio virus and who will use it against this.

Yeah, yeah. You're right. You're right. You are right that there are some bad things that can happen. Very bad. So the question is, then what? Like, what do you do in the face of that risk? How do you proceed?

Do you say to these guys, stop? Would you have these guys stop doing what they're doing? Stop doing their experiments? Asking questions, being curious. That would be ridiculous to tell the science, not to do science? So what, then? I don't know. I don't know exactly.

But do I want them to not do experiments? No. I'm not saying don't. So I'm not going to be a troglodyte and say we shouldn't play with these. And Steve Struggets agrees. I think it's great. to play with them, but I'm scared too. I don't know.

I'm confused about it because we have to play. That's how we make all science, you know, they speak of homo-ludens, human beings, as the player. That we are what we are because we like to play with nature, with ideas, with language. This is how we learn things. So we're going to play. But we have to be very careful about how we play,

and we don't want to fall into the idea that we know more than we do. We have a vast ocean to discover before us. Okay, well, I guess that's all the time we have. Anything that you heard this hour that you want to hear again, more information. It's all on our website, RadioLab.org. Any creature you'd like to build or any design for a creature that you'd like to build or any monster that you have in your head that you'd like to make it real, living flesh. Send that to us too.

Yes. While you're on our site, send us an email as well. RadioLab at WNYC.org is our email address. I'm Chad Abumrod. I'm Robert Krollwich. Thanks for listening. Radio Lab is produced by Dad Avonride, Lulu Miller, Rob Christensen, Ellen Horn, Lauren Wheeler.

Production support by Sally Hership, Sarah Pellegrini, Ariel Lasky, Heather Radke, Linda Everett, Jonathan Miller, Josh Kurtz. And Shane Winter. Thanks to Nicholas Banticolk, Ben Maston, Priya George, Kate Hines, and Tom and Foster Hudson. Radio Lab's webmaster is Valentina Powers. Check out our website at RadioLab.org with a new design by Kevin Lohder, Jacob Smullion, Oates Richie Chai and Howard Parnell. End of mailbox.