March 16, 2006

How Does Chemistry Become Biology?

NASA -- How does chemistry become biology? Solving this question is important for research into life's origins, and also for the search for life elsewhere in the universe.

In this interview, Dimitar Sasselov, professor of astronomy at Harvard University, describes a new comprehensive study that will try to figure out how chemical systems cross over into the world of the living.


Interview with Dimitar Sasselov

Astrobiology Magazine (AM): Harvard University is funding a new study called the "Origins of Life in the Universe Initiative." Recent news reports implied this meant Harvard is entering the debate of intelligent design versus evolution.

Dimitar Sasselov (DS): That's the spin the Boston Globe put on it, but we would not describe it in terms of that debate. Instead, we are trying to understand the pathways that bring us from cosmochemistry, or chemistry in a completely inorganic sense, through the point where it becomes biology at the molecular level.

We want to find the essence of why certain molecules function in a biological sense. These large molecules somehow are capable of self-replicating themselves, and improve as they do so by the general rules of Darwinian evolution. Once we understand that process well, we may have a possible pathway to life and biology.

So we are just trying to widen our studies on the origins of life in the universe. The "s" is very important here. It's not the "origin" of life, but possible pathways to life. And "in the universe" is important as well. Not simply on the Earth, but generally, on any planet, given any of the conditions that we know exist in the observable universe.

We're looking beyond the solar system in order to understand possible initial conditions. The Earth and even the solar system are not general enough for us to do this. The Earth is marvelous to study complex life, because the diversity of life here helps you understand evolution -- how we started with very simple microbes and ended up with things like us. But the Earth is just one possible pathway for the emergence of viable biomolecules from chemistry. Are there multiple pathways? Do all chemical pathways converge to one or two or three possible ones to produce life?

Another reason to look at life's origin in the universe, rather than just on Earth, is because of upcoming NASA missions like Kepler or possible future missions like Terrestrial Planet Finder (TPF). I'm very concerned that, when we finally have spectra of other planets, we are not going to know enough about biologic activity in general to be able to say what is and is not a biosignature. When we talk about designing such telescopes now, we have to design them with some biosignatures in mind. The biosignatures we know now are based on life on Earth: oxygen, ozone, water. Is that exhausting the possibilities? So I want our experiments to assure me that what we are doing, in developing these missions, is not crazy.

We are already working on a project where we are compiling possible initial conditions of extrasolar planets. A major part of that will come from what we know about the Earth, and a large part will come from what we know about Mars. But probably 50 percent of that compilation will be initial conditions that are possible on planets that do not exist in the solar system, but could exist in other planetary systems.

AM:So you're creating a computer model to put in all the chemical conditions, to see if you can push chemistry into biology? You do this for an Earth model, a Mars model, and hypothetical world models as well?

DS: It's more than just a computer model. It is a combination of many things, including computer models and laboratory experiments.

AM:Such as Miller/Urey experiments?

DS: Yes, but that's only one aspect of constraining possible chemical initial conditions to see what kind of molecules could have existed, and in what concentrations. For example, say we want to know whether a particular molecule which is very similar to amino acid "“ methylene "“ could be prevalent on different types of terrestrial-type planets, or the moons of Jupiter, or Titan, or Jupiter itself. We know it exists in interstellar clouds; it's been detected.

So you go to our planetary scientists and ask, "How can we estimate the reservoirs of this molecule? If it was there, during which time period?"

Then you ask the cosmochemists, "Do meteorites and lunar samples contain that molecule? If so, what is the size of that reservoir?"

Then you go to astronomers and ask, "For planets like Venus, Earth, Mars, and then bigger Super-Earths which are not in our solar system, what are the models telling us about their surface conditions? Would this molecule survive in any of them, and by how much and during what time?"

So we put this all together, and that will be one single entry in a compilation table that is composed of all the molecules we're interested in.

AM:How many possibilities are there to test in this comprehensive way? Do you know how long the list is?

DS: We don't simply go blindly and try all the possible combinations. We have intuition about what could and could not work, from the chemical pathway point of view. Extensive work has been done on what, here on Earth, are the chemical compositions that correspond to different vital processes for microbial life.

AM:After all the lab experiments that have tested the conditions hypothesized for early Earth, and yet failed to generate "life," do you feel that you're missing some vital ingredient, so you're searching for what that might be?

DS: It's not that they've tried all the possible permutations and nothing worked. It's more that they have new ideas they are trying to run experiments on, but the set is too limited. Some of these new ideas have come from what we've learned from the other side of the story; what my chemist colleagues call the deconstruction side. That is, trying to understand how the molecules in simple systems like viruses and bacteria actually work.

You don't find any molecules like ribozymes in the open cosmos. You only find them in living organisms. So how did they come to work? Obviously there was a lot of improvement with time, but they're molecules. You can deconstruct them into individual atoms. The hope is that, as you clip a molecule and make it smaller and smaller and yet it still keeps its functionality, you will eventually understand what makes it work. That research has been going on for more than ten years now. People working on deconstruction, like Jack Szostak and Gerald Joyce, are exploring new pathways. They are able to manipulate individual molecules at a level we couldn't ten years ago, and so the chemists now have more insights into what is going on.

AM:Is this related to research into the RNA world?

DS: The RNA world idea was based on the fact that the ribozyme could self-catalyze its own self-replication. People like Walter Gilbert said, "Maybe that's how life originated on Earth." But there are other possibilities beyond the RNA world, so I prefer not to describe it in those terms. It's more about the deconstruction approach, about understanding how this particular molecule, which happens to be RNA on the planet Earth, manages to do what it does. If we understand what is at the core of that function, then we can hopefully imagine a completely different molecule that would be able to do the same thing. Then you can imagine a new paradigm to a completely different type of life. But at this point, that's all science fiction.

AM: Let's say you break life down to the barest essentials and it looks remarkably like a virus. Well, many people would argue a virus is not life, even though it does replicate, because it cannot live without a host. So is it just self-replication chemistry that you're looking for, or do you need to go beyond that in terms of complexity? When do you think you will have that "Eureka" moment?

DS: That will be a good question to ask to each of the team members, because I'm sure you'll get a different answer. To me, the big question is, "How can a molecule have the same number of atoms and seems to be similar to an RNA molecule, and yet it doesn't do anything biological?" You put a bunch of it in a solution and it just sits there and eventually decays. But if you put just a single strand of ribozyme in the solution, 20 minutes later the whole thing is teeming with copies of the molecule. And not only that, you've left it in the sun, so it got hot, and it's full of copies which are slightly different "“ they've evolved to degrade less under sunlight than the original molecule you put in.

So what is the difference between the two molecules? The way it looks now, discovering the difference will be accomplished in the lab. I once asked Gerald Joyce, "Why do you spend all this time in the lab, when we can build the molecule in the computer, atom by atom, and then run this computer program to see what the different possibilities are?" He convinced me that there was no computer on Earth big enough to do this. The molecular reactions in the lab, in just one second, are about a million times faster than what a computer can do. There won't be a computer capable of that for at least 50 years.

AM:There are a lot of hypotheses for the location of life's origin on Earth: hydrothermal vents, sunlit shallow pools, etc. Does your study address that question as well?

DS: That is the second step. Once we understand how simple molecules become polymers, and then how some of these polymers get to be like ribozymes and can do the things RNA can do, then we've achieved our goal as a team.

AM:So first you're looking for how chemistry becomes biology, and after that, you'll start to think about the kinds of environments that could happen in.

DS: Yes, exactly. There are many environments for life to emerge, but that is not the focus of our research. Other people are working on that, conducting experiments or going to different places on Earth. That's what the work on extremophiles to a great extent has been focused on in the last few years. But we are very interested in that research, because it's where we take some of our initial chemical conditions from.


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