Steve Benner is a natural-born synthesizer. He has devoted much of his career to synthetic biology, trying to create a system that looks and acts like life in a test tube. He left a tenure-track job at the University of Florida in 2005 to establish the Foundation for Applied Molecular Evolution (FfAME), where he works with biologists, chemists, geologists, and astronomers to answer the “big questions”: Where did we come from? Are we alone?
Benner wrote a popular book on the subject, Life, the Universe, and the Scientific Method, due in bookstores in 2009. He suggests a four-pronged approach to the quest for understanding life: hunting for life in outer space; resurrecting ancient, simpler forms of terrestrial life in the lab; investigating how it sprung from inanimate chemicals; or building it from scratch. All these approaches need a theory of life: The methods we use to study life depend on what we think it is. “If you don't have a theory of life, you can't find aliens unless they shoot you with a ray gun,” Benner says. But scientists quibble on the best definition.
At the 2009 meeting of the American Association for the Advancement of Science in Chicago, Benner announced the latest breakthrough in his quest for artificial life: a new form of DNA that mutates and evolves. He also spoke in a symposium called “Weird Life” about how synthetic biology will aid in the search for life as we don’t know it.
Let’s start small: What is life?
The NASA definition is “a self-sustaining chemical system capable of Darwinian evolution.” It means that you have kids. There’s replication with error. Errors have to be themselves replicated.
You’ve grown rock crystals, right? That’s replication: You seed the growth and get more crystals that look just like it. Crystal replication is imperfect, there are defects in those crystals. Why is that not life? Because those defects are not replicatable. You can’t get a new crystal out of the old one with the same defects, or close to the same defects.
Same thing with fire. There’s this Star Trek episode where Crusher and Data are trying to decide what’s life. So fire, it grows, it metabolizes...
It consumes fuel, produces waste…
(Laughs) Right. But the NASA committee focused on Darwinian evolution. It’s a theory of life. It's a statement that, when you go to Venus and look in the sulfur clouds, or you go to Titan and look at the methane oceans, there will be a chemical system that supports Darwinian evolution. That's actually quite useful.
How is it useful?
Because we can come up with structures that do support Darwinian evolution, and those that do not. We're not going to go to Titan, look at it and say "Hmm, let's wait a million years and see if it evolves," right? So it's not a very good operational definition. But we can look for molecules that we believe from chemical theory would support replication with error, with the errors themselves replicated. That's why it's useful. There are only certain chemical systems that can support that, and there are many chemical systems that cannot.
"Synthesis drags scientists kicking and screaming across uncharted territory. We want to understand life in some essential way, and the way to figure out if you really do understand it is to try to make it."
What we have published is that you cannot have a real molecular system that does genetics in the Darwinian sense without having on it a repeating charge [like the molecules that make up the backbone of DNA, each of which has a positive charge associated with it]. If [the molecule has] a repeating dipole, that is a plus-minus, it's like putting north-south magnets on a string. It will not be a genetic molecule. It will not support Darwinian evolution.
Why?
Because if you think about it, [a molecule with the charge] minus-minus-minus-minus can't fold. Monopoles repel. But plus-minus-plus-minus: I don't know if you've ever done this yourself, but if you put a series of magnets on a string, you haul it out and (crunching noise) it collapses! A genetic molecule has to stretch out [in order to make copies of itself].
That's what we would look for if we were trying to recognize extraterrestrial life?
Yes. Go to Mars and look for a polymer with a repeating charge. It makes no difference what letters are in the alphabet, but the repeating charge is something that does not arise easily naturally.
What made you want to create artificial life?
There is this idea that if you understand something, you can synthesize it. If you understand an automobile, you can make one. In this process of trying to do something synthetic, and failing, that is where you learn the reality about your understanding. Synthesis is a research strategy that drags scientists kicking and screaming across uncharted territory, where they’re forced to confront unscripted questions. If they fail, they have to confront their failure. If you fail to synthesize something, that means you don’t understand it. We want to understand life in some essential or broad way, and the way to figure out if you really do understand it or if you’re just fooling yourself is to try to make it.
You've been working on this synthetic molecule for 20 years. How did this get started?
Back when I was a tyke, I was interested in these questions: artificial life, universal life, all the rest of it. But assistant professors go through a process called tenure. So after about 8 years as an assistant professor at Harvard, I was offered a job at the Swiss Federal Institute of Technology in Zurich, Switzerland, where the funding was not done by peer review. In 1986, peers would not have any of this. This was crackpot chemistry, to recreate the genetic alphabet.
What exactly did you do?
It's like cooking. Most organic chemists are also good cooks. You know that you want to get a souffle that will rise, so you mix a certain amount of baking powder or yeast in the right ratios, and then you'll cook them for a period of time at the right temperature, not too hot, not too cold. You don't actually see any of these molecules, they're too small. You don't have tweezers to actually put groups of atoms on and off of these things. There are ways of adding, like in cooking, reagents to a mix.
And then there's the question of after you've cooked, what have you made? How do you know? If you're a cook, you just taste it. But with chemists, we do spectroscopy, all sorts of fancy things to make sure we made a molecule that has those atoms arranged in that way.
What were the major milestones along the way?
The chemists will tell you the major milestone is the making of the molecules. There are several levels, though. Making the molecules as pieces, as building blocks, is a big step. Sometimes the molecules work, sometimes they don't.
What's the difference between working and not working?
Just whether they're stable, if they fall apart. We had molecules that if you put them in the atmosphere they start to burn. So we had a number of these extra letters in the genetic alphabet that were not stable. Then you go back with a new theory, you put another atom or two in, and you make them more stable. The major breakthroughs, if you look at the publications—we've had about 100 papers published in this series!—you'll see steps where another atom or group of atoms finally gets the thing to not fall apart. And we're tired of it, I guess. Progress is incremental. It is embedded in much more failure than progress. A good part of the discipline of science, and training as a scientist, is to learn how to deal with repeated frustration.
Tell me more about the new base pairs [the molecules that pair up to form DNA’s double helix] you created.
They're similar to the Watson and Crick base pairs [of ordinary DNA], in the sense that they have roughly the same size and roughly the same geometries. They have different arrangement of hydrogen bonding groups.
Will these bond with regular DNA?
Nope. This is what we call orthogonal—you can have a molecular recognition system built from the new non-standard bases that doesn't react with the standard bases.
What's the state of things right now?
We have these made; we have them in genes. There are now enzymes that will copy those genes, and will copy the copies of the genes, and will copy the copies of the copies of the genes. There are children derived from a single parent that have six letters in the genetic alphabet. The molecules then are able to suffer mutations. This is a chemical system, not self-sustaining, but it's capable of Darwinian evolution, as long as someone's sitting there feeding it. It's not life. We have a dozen different theories of life. Some people will not be satisfied until every one of the criteria is met.
Lots of people asked questions after your talk about what the minimum definition of life would be.
It's a sliding scale, and it's a personal thing. What makes what we have done not artificial life is that it's not self-sustaining. So suppose it's self-sustaining. Then you can say, "Well, ah, but it doesn't have a cell." So you put a cell around it. Then you can say, "It has a cell, that's fine, Steve, but it doesn't do metabolism." So you get something that does metabolism. Then you can say, "Well, that's fine, but you haven't shown it to evolve in response to a real environmental stress." So you show that. "But it doesn't make proteins!"
What you're doing here is adding to your theory of life a cell theory of life, an evolutionary theory of life, a metabolism theory of life, a protein theory of life. At some point, if you have something that is in a cell, does do genetics, does have kids, does have kids that are mutants and evolve, does do metabolism, does make proteins, okay. Pretty much you'll get the entire community at this point. But we’re many, many years away from that.Lisa Grossman, a graduate student in the Science Communication Program at UC Santa Cruz, earned a B.A. in astronomy from Cornell University. She has worked as a reporting intern at the Santa Cruz Sentinel, the news office of the SLAC National Accelerator Laboratory, and the science unit of Wired.com. She will complete a summer internship as a science writing intern at New Scientist in Boston.
© 2009 Lisa Grossman
