Loren Williams: "The Original RNA World Model Is Dead"

"We know the abiotic world is very good at making amino acids. Abiotically produced amino acids are literally raining down on our heads, in meteors. It is difficult to imagine a primitive biological world of evolution, ultimately producing RNA and RNA precursors, that did not make use of amino acids, which were highly available from the get-go, and are so easy to combine to form wonder polymers. So the pure RNA World -- I don't accept it. There had to be many other molecules involved. And a dirty RNA World is a co-evolution world, with protein and RNA evolving together." -- Loren Williams

I met Loren Williams at the recent NASA-sponsored Origins of Life conference at Princeton. He was one of the liveliest questioners, always pitching with a relaxed focus. Williams is a professor of biochemistry at Georgia Institute of Technology and Principal Investigator of Georgia Tech's NASA Astrobiology Institute-funded center. Williams says his lab is looking to chemically rewind the "tape of life" to before the Last Universal Common Ancestor of organisms and is studying "the transition from nucleic acid-based life to protein-based life." He does not think we got to RNA abiotically, that is, it happened through biology.

Williams also said that between his Astrobiology center and Nick Hud's National Science Foundation-NASA funded center ($20 M grant from NSF)at Georgia Tech, they've got more people and resources devoted to Origin of Life than anywhere else in the US.

Williams thinks the Origins investigation is dominated by the United States, Europe, Canada and Japan but that the budget worldwide for research is still small, even though the public's interest is substantial and growing.

It is rumored that Japan is allocating $100 million to Origin of Life research.

"Sometimes when Japan does something, they do it big," Williams told me.

India is somewhat interested in Origins of Life research. The Russians are in disarray experimentally on Origins. Ever since Oparin, says Pier Luigi Luisi.

It is unclear what China is doing, says Williams.

Loren Williams' roots are in Seattle, Washington. He was born into a science family, his father, a PhD in marine biology, and his mother with a degree in microbiology.

"It was one big science project all the time," Williams laughs.

Loren Williams has a BSc in Chemistry from the University of Washington and a PhD in Physical Chemistry from Duke University. He was a postdoctoral fellow at Harvard, a National Institutes of Health postdoctoral fellow at MIT and a postdoctoral associate at Duke University. He's been a visiting professor to both the University of Sheffield, UK and the Tata Institute of Fundamental Research, India.

Williams has been the recipient of an NSF Career Award (1995-1998), the Sigma Xi Award (2009), and Petit Institute's "Above and Beyond" Award among other honors.

He is currently a member of the Executive Committee of the NASA Origin of Life Focus Group, has served on NASA's Exobiology Review Panel, and assisted with the development of NASA's Digital Learning Network. Other memberships include ISSOL (International Society for the Study of the Origin of Life), Biophysical Society, American Chemical Society.

He is the author of 100 scientific papers.

My interview with Loren Williams follows.

Suzan Mazur: Have we seen significant developments in the RNA world in recent years?

Loren Williams: The RNA World is evolving. If you look at how people presented it in the past compared to now, there have been significant changes. The 1986 paper by Wally Gilbert describes a pure RNA World, where you have RNA running all of metabolism and information transduction. It's all RNA, all the time, and nothing else. I don't think many people accept that as reasonable anymore. In that sense the original RNA World model is dead.

But what has happened is that people have adapted and modified the model. There are now dirty RNA World models in which RNA collaborates with other molecules. Most people now are assuming that amino acids, peptides and a variety of other molecules were involved along with RNA.

Suzan Mazur: So it's kind of what John Sutherland's been saying, it's important to integrate.

Loren Williams: Yes. That is definitely happening.

Suzan Mazur: Is it now happening as it is in Europe where you have different fields coming together?

Loren Williams: I think it's a global phenomenon. And I wouldn't call the RNA World a dead end. Most people would say it's a powerful model in part because it makes very specific predictions that can be tested. By testing those predictions it can be seen that the original RNA World has problems. The RNA World predicts that RNA can efficiently polymerize RNA, which seems problematic, biochemically. Another problem is related to the origin of RNA itself. Where did RNA come from? Where did RNA precursors come from?

Steve Benner and John Sutherland are working on trying to understand abiotic routes for production of RNA precursors.

However, Nick Hud just gave a really beautiful talk here at Princeton in which he showed data suggesting that RNA is a product of biology. In Hud's model there was an evolution of polymers - RNA was not the first informational polymer, but is the winner of an evolutionary process. To me this makes perfect sense. But broadly speaking, there are a variety of possible solutions on the horizon to the question of where RNA came from. Benner, Sutherland and Hud will work it out.

Benner and Sutherland hypothesize that abiotic systems made RNA precursors. Steve Benner suggests borate as a cofactor. Nick Hud would say no, RNA is a product of biology and you're never going to find an abiotic process to produce RNA or RNA precursors - it didn't happen that way.

The question of the origins of RNA is closely related to the nature of the RNA World. We know the abiotic world is very good at making amino acids. Abiotically produced amino acids are literally raining down on our heads, in meteors. It is difficult to imagine a primitive biological world of evolution, ultimately producing RNA and RNA precursors, that did not make use of amino acids, which were highly available from the get-go, and are so easy to combine to form wonder polymers.

So the pure RNA World -- I don't accept it. There had to be many other molecules involved. And a dirty RNA World is a co-evolution world, with protein and RNA evolving together.

Suzan Mazur: Do you think interest in the Origin of Life field is exploding or is it relatively static and viewed as esoteric?

Loren Williams: It has exploded for me! The public is interested, people are very interested. Origin of Life draws people to science.

Suzan Mazur: And the scientific community? Because I'm hearing a diversity of opinion on this.

Loren Williams: I think things are changing there. There used to be a sense that you shouldn't study Origin of Life because there was not a lot of funding for it and the questions were not answerable. For a young person to embark on Origin of Life research was considered professionally dangerous.

Suzan Mazur: It's not completely without clues. There's something tangible there.

Loren Williams: You're absolutely right. Yes, you're absolutely right. It is a solvable problem. It's a difficult problem. It's also not a binary thing where it's solved or not solved. It's going to be a long continuum. The solution to understanding the origin of life will never be a fully finished product. We understand much more about the origin of life now than we did 15 years ago. And we'll understand much more in 15 years than we do now.

Suzan Mazur: Are there more conferences coming up?

Loren Williams: There are lots of conferences coming up. One thing is that funding had changed so much. It's so much harder to get funding now for anything.

Suzan Mazur: For Origin of Life research?

Loren Williams: For anything.

Suzan Mazur: It appears that funding for Origin of Life research is increasing.

Loren Williams: Relatively, that's right. Compared to other things Origin of Life doesn't look so bad anymore.

Suzan Mazur: It's coming from the private sector.

Loren Williams: And from NASA and the NSF, there's money for Origin of Life. People should realize that funding for science, especially basic science is drying up. The NIH is funding grants at less than 10%. So the idea that it's foolish to study Origin of Life because you can't get funded is not as compelling an argument as it used to be.

Suzan Mazur: My understanding is that Templeton funding is a pain in the neck to try to get.

Loren Williams: That's small money, really.

Suzan Mazur: Some people are getting a fair amount of money but the process is so long and demanding. If you don't get it, it's a considerable investment of time wasted.

Loren Williams: All scientists spend a lot of time preparing grant proposals, most of which are denied. That is our life. Templeton is not like NSF or NASA's Exobiology or Astrobiology programs. Those are much bigger, more professional programs that are engaged in the sustained effort that is required. If the federal government isn't going to fund it, it's not going to get done. At Georgia Tech, between my NASA-funded center and Nick Hud's NSF-funded center, we may have more people working on origin of life than anywhere in the country.

Origin of Life is not independent of other areas of investigation. I can tell you that in my research, we are studying the ribosome and the role of the ribosome in ancient biolgy and the origin of life. What we're learning about the ribosome is going to allow us, I believe, to search more efficiently for antibiotics. Research in biomedicine and Origin of Life is intertwined.

Carl Woese is a good example. He was interested in the deepest and most profound questions in biology. His discovery of third branch of the tree of life obviously has profound implications for human health.

Suzan Mazur: Some people would go further. James Shapiro told me he considered Carl Woese the most important scientist of the last century.

Loren Williams: As a chemist I was taught to reserve that title for Linus Pauling. But Woese, well I am siding with Shapiro on this one. Carl Woese used to make the argument that you can't understand cancer without understanding deep biology. You can't understand things in isolation. And he rewrote the book of biology for all of us. Who can argue?

Suzan Mazur: Yes, I did probably the last feature interview with Carl Woese. Woese wanted to put the organism back into its environment and see the complex flow. It seemed almost like he was saying you can't separate life from nonlife.

There was all this discussion in the Princeton talks about LUCA (Last Universal Common Ancestor) as something material, but Woese was not thinking like this toward the end of his life. He saw LUCA as a process, not something material.

Loren Williams: But it was a population rapidly exchanging genetic components, a diverse population and -- this is my interpretation of his work -- as complexity rose the exchange levels slowed down. The exchange level got low enough and speciation took off.

Suzan Mazur: But toward the end of his life he was not thinking of LUCA as anything material. He was thinking about LUCA as a process. He and Nigel Goldenfeld were looking at rock formations in Yellowstone National Park.

Loren Williams: I don't know if I'm there.

Suzan Mazur: In my interview with Woese, he told me we don't know what life is.

Loren Williams: I agree. People talk about how we define life. You can't - well I can't.

Suzan Mazur: That's what he was investigating with his NASA research grant.

Loren Williams: Yes. Life is complicated chemistry.

Suzan Mazur: Woese was seeing it more as physical processes.

Loren Williams: If you were sitting in a plastic bubble, watching the origin of life on earth -- you'd never be able to say: Oh snap, life just started. There is no bright line. There is a smooth continuum between general chemistry and biochemistry.

Suzan Mazur: If you go to the website of Woese's collaborator Nigel Goldenfeld, you see this time lapse of formations in Yellowstone Park. What happens over a period of time, studying the processes.

But you think the public is interested in Origin of Life.

Loren Williams: Yes.

Suzan Mazur: NASA should help fund a series of roundtables on Charlie Rose. Get the message out there.

Loren Williams: I think they should.

Suzan Mazur: Who knows what ideas are out there, beyond the scientific establishment.

Loren Williams: It's a great way to sell science to the public.

Suzan Mazur: Right. You need funding. Here's the way to get it. Don't you think?

Loren Williams: Yes. But NASA is very good at selling science to the public.

Suzan Mazur: So you don't think Origin of Life is too esoteric a subject.

Loren Williams: No, it's not too esoteric. And I think you have to give NASA a lot of credit for its outreach. Other federal agencies don't do such a good a job at trying to foster public interest. The NSF tries, but they don't get to go to Mars.

Suzan Mazur: I think this information is so worth sharing. It's wonderful that Princeton and NASA streamed their Origins of Life conference over the Internet.

Loren Williams: Yes. And the Origin of Life is a solvable problem. Science, especially chemistry, is by nature indirect and inferential. Everything we know about chemistry we infer through indirect methods.

Suzan Mazur: Gunter von Kiedrowski, the father of systems chemistry, told me "we can't go back in time," we'll never know the exact history of the origin of life.

Loren Williams: That's BS. We can't see atoms with our eyes, yet we know there are atoms. We didn't witness the formation of the grand canyon. We have not seen a live dinosaur. We use inference. I am sorry, but "we can't go back in time" is nonsense. I guess the modifier 'exact' gives him an out.

Suzan Mazur: You mentioned something earlier about Stu Kauffman and autocatalytic sets and straw dog. Did you say straw dog or straw man?

Loren Williams: Well I want to be careful not to offend anyone. But please understand that I am a simple-minded biochemist. When theorists and physicists go off on emergence, complexity and coherence, I always say (very quietly) 'show me the molecules'. We have very powerful and well-developed concepts like free energy (G), enthalpy (H) and entropy (S). Those concepts explain and predict. Emergence, complexity and coherence don't mean anything to me.

Suzan Mazur is the author of The Altenberg 16: An Exposé of the Evolution Industry. Her interest in evolution began with a flight from Nairobi into Olduvai Gorge to interview the late paleoanthropologist Mary Leakey. Because of ideological struggles, the Kenyan-Tanzanian border was closed, and Leakey was the only reason authorities in Dar es Salaam agreed to give landing clearance. The meeting followed discovery by Leakey and her team of the 3.6 million-year-old hominid footprints at Laetoli. Suzan Mazur's reports have since appeared in the Financial Times, The Economist, Forbes, Newsday, Philadelphia Inquirer, Archaeology, Connoisseur, Omni and others, as well as on PBS, CBC and MBC. She has been a guest on McLaughlin, Charlie Rose and various Fox Television News programs. Email: sznmzr@aol.com

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