Science journalist, author and Nature editor Adam Rutherford talks about new book Creation: How Science Is Reinventing Life Itself, which looks at the science of the origin of life and at the emerging science of synthetic biology.
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Welcome to the Scientific American podcast, "Science Talk" posted on August 29, 2013. I'm Steve Mirsky.
On this episode, we finish up our conversation with Adam Rutherford about his new book, Creation: How Science is Inventing Life Itself. In Part 1, we talked about efforts to understand how life first came into being on earth; next, we talk about efforts to design and even create new forms of life. We spoke by phone on July 25.
Let's talk about the second part of the book. If the first part of the book disturbs some people, the second part is probably going to make even more people uncomfortable.
Adam Rutherford: What, you mean because I choose to start with a really fascinating chimera, the spider goat?
Steve Mirsky: Yes, which some people find this sort of thing really upsetting. I think it's great, but, you know, I also have told people how, you know, I'm mostly fish, so this kind of thing doesn't really bother me.
Adam Rutherford: Yeah, yeah. Well I think one of the—so I should say what the spider goat is. So spider goats—which isn't even that new technology, but this is based on a farm lab from the University of Utah, down in Logan in Utah. And what they've done is they've engineered some goats. They've genetically modified them so that they have a gene that encodes spider silk from the golden orb weaver spider. Drag line silk, which is the one that the spiders use when they swing.
And they've engineered that Jane into the goat—Freckles was the name of the goat—such that when the goat starts to lactate, produce milk, that also prompts the production of these threads of spider silk. And so you take the milk—you milk the goat, you take the milk, process it just to remove the fats really, and basically that's it. You then can lift out spider silk from the goat's milk. And so immediately, the question is, "Well why the hell would you do that?" and the answer is really because this is farming.
This is what we've been doing for 10,000 years and it's, in a sense, you can't farm spiders directly, because they're cannibalistic but spider silk is a really interesting material. It has such high tensile and elastic strength that it would be really useful for us to be able to produce in bulk quantities. So what we do with farming is we breed organisms so that they—we enhance their ability to produce things that we want. And that's what we've been doing for 10,000 years.
Steve Mirsky: Yeah, you point out in the book there's no such thing in nature as a Frisian cow or a, what is it—a savoy cabbage, either.
Adam Rutherford: Yeah, exactly. Exactly, in fact, I was—I spent quite a lot of time thinking if there's anything that we eat at all that could genuinely be considered natural and I couldn't really think of any. You know when I drive around the countryside in the UK and think about how beautiful the landscape is, how green and lush it is—even that is an entirely human designed landscape. There almost no parts of the UK that are, that could be genuinely considered to be wild and I think it's less the case in the 'States but, you know, if anyone does a daytime flyover from the East Coast to the West Coast, you can see quite how designed that great country is, just by the shape of the agriculture.
Steve Mirsky: A lot of rectangles.
Adam Rutherford: A lot of rectangles and there's weird round ones as well.
Steve Mirsky: Yeah.
Adam Rutherford: But you've got to go quite far on earth to find a place, which has since been profoundly affected and designed by our interaction with the environment. So, you know, apples are delicious because we bred them to be like that. We've been talking about creationists, well everyone loves the banana creationist ideas that, you know, only a deity would create something as delicious as that. Well, we know that's not true for a number of reasons but mostly because if you look at a naturally occurring wild banana, their stumpy, full of seeds, and totally inedible.
Steve Mirsky: Yeah, they'll break your teeth.
Adam Rutherford: Exactly, and bananas have been designed by a supreme power and that supreme power is banana farmers. Right? So my argument about the spider goat is that this is a way—just like we been doing for the last 10,000 years but in a more advanced and molecular level—this is a way of interacting with naturally occurring things in order to make things that we find useful. And like I said, it's, you know, Freckles, the spider goat is just a very visible example of genetic modification because it must happens and bacteria whereas this is something you can really see and feel and it is, it's very striking.
Steve Mirsky: Tell us about bio bricks.
Adam Rutherford: Yeah, I love this. I love this idea. So this is a—about seven or eight years ago, some of the people involved in this new form of genetic modification, that became known as synthetic biology, identified one of the problems which is that genetic modification is an artisan's skill, right? So I spent three years doing this for my PhD, doing a relatively simple form of genetic engineering and it took a lot of effort and a lot of skill and a lot of, you know, getting it wrong in order, ultimately, that it didn't work, okay?
So what that means is the entry-level for doing skillful genetic modification manipulation is very high. Now they identified this as a problem if you want this deal to expand and grow and so what they did is, is they effectively modeled what had happened in electrical engineering many, many decades ago, which is to standardize the parts so that every time you need a diode or a transistor or something like that, you don't have to invent that for the first time. You just go to the electrical engineering shop and buy a diode and you know it's going to fit. You know the opposite problem is if anyone, any of your listeners travel and they need a different plug socket adapter for every single country because they're not standardized.
So in genetic engineering, what bio bricks, the Bio Bricks Foundation, did is set up this repository where they would try and standardize and characterize these elements of DNA which were either genes are the bits that control genes and have them available so that anyone could use them. So you don't have to be a genetic engineer to do genetic engineering. So they call them bio bricks because they're kind of like Lego in that sense. Every Lego brick is precisely designed so that it will fit every other Lego brick, perfectly.
So that was the idea and we're beginning to see the fruits of the bio break endeavor, you know, over the last couple of years. I think, again, the high point was this sort of cancer assassins kits that came out of Ron Weiss' lab in MIT where they've taken a very complex set of bio bricks and put them together in such a way that—inserted them into a virus but a benign virus, so when the virus enters a cell, it effectively makes the calculation. It asks the cell five questions and makes a Boolean calculation. And if the answer to all of those five questions is positive, then it has correctly identified that that cell is a type of cancer cell, the HeLa cancer cell. I'm sure many of your listeners will know about HeLa cells from the brilliant book by Rebecca Skloot about Henrietta Lacks, right?
And when it does correctly identify this as a HeLa cell it then instigates, the cells cell death program. So it asks the cell to commit suicide. And this is only happening in cell culture at the moment, so it's a long way from the clinic, but if you think about the potential for that as a treatment for cancer, it's breathtaking. When we use radiotherapy and chemotherapy, you kill many, many healthy cells as well as the tumor us ones, whereas this is a way of dealing with cancer that will only and specifically with apparently 100 percent accuracy, it will only attack the cells that are known to be cancerous. So it's much more like a—the analogy I use is chemotherapy's kind of like a blunderbuss and this technique is like a sniper.
Steve Mirsky: Right. And just to go back to the goats for a second, the fact that you can take a gene from a spider and inserted into a goat and it works pretty much just fine, even after 700—what is it, about 700 million years of separation?
Adam Rutherford: Something like that, yeah.
Steve Mirsky: Yeah, between the last, you know, from the last common ancestor of those two organisms tells us so much about DNA and how conserved it is and about the fact that there really is one tree of life on earth.
Adam Rutherford: Yeah, that's kind of the link between the two halves of the book, really, because it's—it is exactly the fact that we have biology with all organisms because we're on this one tree of life, because we're all evolved from a single cell four billion years ago that we can do this. And it was only in the 70s that we invented this technology that, you know, farming has been limited for the last 10,000 years to mating two organisms that basically are capable of having sex with each other. And with the advent of genetic modification, we have breached the species barrier. We've, you know, obviously a spider and a goat can't have sex with each other, but they have the same underlying language that encodes them and the cell, the engineered cell, is oblivious to what species it comes from. It doesn't care. What it does is it reads the code and in the case of the spider goat, it reads the code, which says, "Produce milk here. Oh, and produce this protein here, which is spider silk," there you go. It's done.
Steve Mirsky: I mean bacteria can carry on lateral gene transfer where they just, you know, basically do a transgenic modification of each other and we have finally figured out how to do that at the multicellular level.
Adam Rutherford: Yeah, that's right. I think—yeah, I mean that's—the way the bacteria do that is basically the reason why they are, you know, the dominant type of organism on earth that we don't really, we don't pay enough attention to. But they've been around for four billion years and show no sign of going extinct and we're utterly dependent on them but a lot of that is to do with the fact that they don't have to pass their genes from parent to child. They can actually pass very useful genes from siblings. And that's, of course, the reason why we have superbugs in hospitals –they evolve very quickly and as soon as you establish—as soon as the bacteria emerges that is resistant to whatever antibiotic we're treating with them, they can pass on that resistance very quickly, whereas all other species that can do that have to wait until they actually have children. So yes, we should all bow down to our bacterial overlords.
Steve Mirsky: There's another fascinating discussion in the second part of the book. Let me get into it by asking you to explain why the James Joyce estate was suing Craig Venter.
Adam Rutherford: Yes, so this is—I guess synthetic biology really hit the headlines for the first time in 2010 when Craig Venter, who many of you'll know is a sort of big figure in the world of genetics. He's an amazing scientist but also very good at sort of getting his message out there, very good at the PR side of things. And they published this paper back in 2010 in which was effectively, the first cell whose parent was not another cell.
So what it was, they took a pathogen from a goat, a bacteria with a very small genome and they sequenced that genome. And then they got a computer and a DNA synthesizer to reproduce, to manufacture that genome artificially, and then they inserted it into the chassis of another closely related cell and booted it up. And all of a sudden, you've got a life, a cell, a living cell, which reproduced that didn't come directly from another cell.
In order to demonstrate that the DNA they put in there was definitely theirs and not naturally occurring, they put in a series of Easter eggs. Gamers call them Easter eggs. You know, little secrets hidden within the game which are there for fun, basically, or in Venter's case to show just how sophisticated our ability to manipulate DNA has become. And they were basically three. There was the names and addresses of all of the people that had worked on it. There was a code that explained how the code actually works—this is still written in DNA but just encoded in a completely different way—and the third one was three quotations.
So __________ quotations—hubristic, you might say a little bit pretentious. One might say—I'm not saying that, but you might say that. And one of them was from Robert Oppenheimer, the so-called father of the bomb, the atomic bomb, and one was the brilliant quotation from Richard Feynman, everyone's favorite bongo playing physicist which was, "What I cannot build a cannot understand." And the third one was from James Joyce from Portrait of the Artist, a beautiful quotation.
But the kind of funny thing about the last two is that what I just said—the Feynman quote, "I cannot build I cannot understand," was wrong. That isn't what Feynman said. He actually said, "What I cannot create I do not understand." Now they weren't a long way off, but you know, in genetics terms, accuracy is important. Changing one letter of DNA can be the difference between being healthy and being dad.
Steve Mirsky: Yeah, this should be a lethal mutation.
Adam Rutherford: Exactly. I did actually—I called him up. I called up the Craig Venter Institute and said, "What happened there?" And I got a rather curt response, which said, "Someone looked it up on the Internet." Full stop. Yeah.
Steve Mirsky: You would think before immortalizing the thing, and a life form, you might double check.
Adam Rutherford: Just check. Oh dear, it did make me laugh when that happened. And the second thing, which is I think equally funny is that they used this quotation from Portrait of the Artist As a Young Man and after about a week—a week after publication, someone had cracked the code. They didn't announce that it was in there, so it became a bit of a game for genetics geeks to try and crack it and, you know, after a few days it was cracked. And as soon as it was cracked, the James Joyce estate issued a cease-and-desist letter because they claimed that copyright was still in post on this quotation and that Craig Venter, this bacteria was breaching copyright.
And it actually turned out that it wasn't. It was out of copyright, but it still just kind of makes me laugh that, you know, someone in the Craig Venter Institute must've been seriously kicking themself that day.
Steve Mirsky: Especially if the—if any penalty was going to be determined by number of copies in print, within a few hours, they could've owed quite a lot of money.
Adam Rutherford: Yeah, absolutely. Although I think one of the interesting things about Venter's experiment is that it was—well two things really. One is that it was a lot harder than they thought and so while we can be a little bit hubristic about our ability to manipulate life, it actually took about $40 million and about 12 years, right? So much, much harder than we thought it was going to be. So, you know, we're doing this stuff, but it still, still really hard.
And the second thing is the bug that the ended up with wasn't very healthy, you know? It just wasn't—it would've been outcompeted in minutes, probably, in a natural environment. And so it showed that one of the principles was, the reason they used to such a small genome is that they were looking at the fewest number of genes possible that an organism could have in order to survive—not least because that makes it easier to recreate, but also so that the overall project that Venter's engaged in here is to have a sort of, a template genome, a basic living things on which you can add functions, add specific functions for engineering purposes.
Steve Mirsky: Right.
Adam Rutherford: But, you know, it wasn't particularly healthy. It wasn't like, you know, a vibrant thing that was going to grow out of a petri dish and take over the world. It was a pretty sickly bug.
Steve Mirsky: And the spider silk from the goat's milk is not quite up to the standards of the silk that comes from the actual spiders?
Adam Rutherford: Yeah, that's right, that's right. So the tensile strength is lower and the elasticity is lower and they can't quite get the threads as long as the spider can do. But then again, you know, spiders have had about 5 million—no 500 million year advantage on us in terms of evolving that ability so it's perhaps not surprising that we're not quite there, yet.
Steve Mirsky: Not surprising, maybe even a little reassuring.
Adam Rutherford: Absolutely. So Leslie Orgle, who was a very important chemist, who died in the '80s, I think, his second law has become known as, "Evolution is cleverer than you," and I think it's something that everyone in our line of work, chemistry, biochemistry, biology, genetic engineering—everyone should always, always remember Orgle's second rule.
Steve Mirsky: I don't think I'm giving anything away by discussing the ending of the book. This is just before the Afterword, which is also well worth reading, but the end of the book talks about the squeamishness of some people in the questions about, you know, "Should we be doing this?" "Shouldn't we be doing this?" And your response is—
Adam Rutherford: I think we have to be doing it. I think that for a number of reasons but primarily because we are looking at engineering solutions to some of the biggest crises that humanity and this planet faces, including feeding the ever increasing population, which is going to become more and more problematic as it grows.
In terms of climate change—dealing with the fact that our ways of producing fossil fuels, and indeed our use of fossil fuels is obviously extremely damaging to our continued life on earth, to the way we distribute and manufacture medicines. We're just at the stage where we are basically inventing new technologies that are going to be a serious part of addressing all of these things, all of our relationship between ourselves, each other, and the planet.
And so while some of these things, like the spider goat, like we talked, that's a bit weird—like many of these things feel a bit weird and possibly a bit wrong and generate a visceral reaction in people which is very emotive, I think we need to get over that, have sensible, mature, informed conversations in public between government, between scientists, between policymakers, and citizens—and crucially, citizens—in such a way that we can choose sensibly what technologies we invest in and invent in order that we get the best out of them. And I think in many examples, these conversations have been massively hamstrung in the past.
There's an interesting difference between this country, the UK, and yours when it comes to genetically modified food where we have none. There are no genetically modified ingredients in the food chain in Europe because that discussion never happened in the early 80s or over the last 20 or 30 years. It was won very quickly by people who opposed genetic modification ideologically and as a result of that, I have never eaten anything which has genetic modification in it.
Now, what is it, midday in New York for you? You've probably had some, you consumed some genetically modified products already today, twice. I think that something like 70 percent of foodstuffs in the 'States contains GM ingredients at some point in their generation.
As an experiment on whether they cause harm, I think there had been something like, I think it's like 12 trillion mils consumed containing GM foods in the 'States in the last couple years or something like that, and there is no—there is simply no evidence that eating genetically modified crops causes harm.
So that is an argument—and which is made as an argument in the UK and Europe, is clearly nonsense. Interestingly, in the last couple months in the UK, the government has begun to make statements that I think that they're basically saying we need to address this. We need to stop pratting around and actually seriously address whether GM crops are things that we should have.
And, you know, my stance is it is an opinion but I hope that it's an opinion based on the evidence and I think that's—that was one of the motivations for writing the book, just that this conversation can happen in public, sensibly, so that we can all make progress.
Steve Mirsky: We'll be right back after this word from Kerri Smith at the Nature Podcast.
Kerri Smith: On the nature podcast this week—tearing apart spacetime, growing a brain in the lab, metaphor and science, and the climate conundrum. More at nature.com/nature/podcast.
Steve Mirsky: That's it for this episode. Remember, you can get Adam Rutherford's new book Creation: How Science is Inventing Life Itself as your free audio book by taking advantage of the offer at www.audible.com/sciam.
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