Steve Benner: Let's Discuss Origin of Life on Charlie Rose

"If you don't have a theory of life, you can't find aliens, unless they shoot you with a ray gun." -- Steve Benner

Steve Benner describes himself as a "crackpot synthetic biologist to some extent" (i.e., he thinks outside the box). Benner pioneered synthetic biology, for example, and in 1984, generated the first synthetic gene to encode an enzyme. He is credited with establishing paleomolecular biology involving research into extinct organisms, as well as inventing "dynamic combinatorial chemistry," and is one of the founders of evolutionary bioinformatics. Benner currently directs the Florida-based Westheimer Institute at the Foundation for Applied Molecular Evolution, and is an inventor with at least 22 patents. But he's also highly entertaining, and if he's ever ousted from the scientific establishment for crackpot science, he could easily replace any of the late night television talk show hosts (except Craig Ferguson). Sadly, I missed Benner's AAAS lecture this past week on "the interaction between primates and alcohol."

I first encountered Steve Benner at World Science Festival 2008. He fielded a question I had about Antonio Lima-de- Faria, the 90-year-old cytogeneticist who lives on top of a fiord in Sweden and has vivid ideas about the role of crystals in evolution.

Benner has a way of lifting people up, describing Lima-de-Faria as "my distinguished colleague from Lund."

He did it again recently at an Origins of Life conference at Princeton, this time in an electric talk titled "Is the RNA World Passe'?" inspired, he said, by my story, "Princeton Powwow: RNA World's Last Hurrah?" in which he referred to Italian Origin of Life investigator Pier Luigi Luisi as "my friend Luigi" and explained for all (Princeton and NASA streamed the Origins event over the Internet) just why Luigi told me that the RNA world is a baseless fantasy. Benner said it's because ribose decomposes, it is unstable.

Benner further engaged the Princeton gathering, moving so rapidly that he appeared to be simultaneously at the power point and chalk board. He managed to resuscitate the crowd after a technical and somewhat inaudible presentation by chemist John Sutherland, winner of the Harry Lonsdale Origin of Life prize.

Said Benner, working the room: "All those people who are awake raise their hand."

ISSOl (International Society for the Study of the Origin of Life) president Dave Deamer, one of the grand masters of Origin of Life, was first to reach up high, shouting "Yes!"

Steve Benner received both his BS and MS degrees from Yale in Molecular Biophysics and Biochemistry the same year, 1976, and in 1979, a PhD in Chemistry from Harvard.

Benner told me that his father was also an inventor, and an engineer. His mother is a musician and homemaker.

His interest in science he said began in childhood as a rockhound and a bit later as a pyromaniac.

Steve Benner is the author of the book, Life, the Universe, and the Scientific Method as well as 300 scientific papers.

Some of his awards include: Anniversary Prize, Federation of European Biochemical Societies; B.R. Baker Award; Arun Gunthikonda Memorial Award; Sigma Xi Senior Faculty Award.

My interview with Steve Benner follows.

Steve Benner: I'm running my own non-profit research institute. The Foundation for Applied Molecular Evolution is the corporation in which is embedded the Westheimer Institute for Science and Technology.

Suzan Mazur: I occasionally send you my stories.

Steve Benner: I look at you frequently because you always have a bit of an edge, which I love. You also wrote this book, The Altenberg 16: An Expose' of the Evolution Industry, which I thought was entertaining.

Suzan Mazur: I was just stepping into the discussion about Origin of Life in 2008. I thought it was important to talk to a diversity of people, including amateurs and mavericks, because who knows where the great idea comes from.

Steve Benner: Exactly. As I mentioned and you quoted me, none of us are experts and we don't really know what we're doing with this.

Suzan Mazur: Since the Princeton conference is about the RNA world, would you comment as to whether you think things in the RNA world have moved significantly forward in the last few years?

Steve Benner: Yes. They really have. In part, because there's been a swing back and forth between two major themes. One theme emerged in the 1980s, the discovery of catalytic RNA, which led the community, myself included -- I was just a pup at the time -- to think the problem was a lot simpler. The discovery by Sid Altman, Tom Cech, Norm Pace and various people, that there was a potential for RNA being a catalytic molecule was certainly something.

It went back a lot earlier. Carl Woese had this on his mind. You can go all the way back to Alex Rich in 1962. As far as I know, Rich was the first person to actually suggest RNA could perform both the catalytic and genetic roles.

I thought it would be a much easier process. By the 1990s it was quite clear -- as evidenced by Stanley Miller's paper from 1995 or 1996 -- that it was going to be a hard slog to get RNA in its oligomeric form because of the instability of its various pieces. Again, a downer from the 1960s when people were finding prebiotic ways, all sorts of things based on Stanley Miller's earlier work.

Leslie Orgel was one scientist. Juan Oro. All these people found lots of these things going on quite quickly. But in the 1990s we hit another wall with the research. And by the year 2000 scientists were saying -- like my good friend Pier Luigi Luisi, who you've noted has referred to the RNA world as a baseless fantasy. Luigi and I were colleagues at the ETH in Zurich for 10 years, by the way. In the 1995-2000 period, scientists were in despair.

Suzan Mazur: But Luisi is up to date about developments in the RNA world.

Steve Benner: The way he states the case is probably a bit stronger than he actually himself believes. All of us do this in speaking to the Fourth Estate.

Suzan Mazur: He told me something even worse.

Steve Benner: Even worse?!

Suzan Mazur: I asked Luisi if funding was the issue slowing down progress in the Origin of Life field. He said that is not the problem. Luisi said there are no new ideas, we need "mindstorms."

Steve Benner: There is a shortage of ideas plus there's a shortage of funding to pursue the ideas that we do have. It's an interesting question whether putting more money in will result in more substantial ideas. It's a cycle you can't anticipate, you have to try.

You saw the lecture here at Princeton from John Sutherland, who has lots of ideas. John is trying to explore possibility space. He's reasonably well funded, as British scientists go, because he's at the MRC in Cambridge.

Have you spoken with Matthew Powner, who is a student of his now at Imperial College?

Suzan Mazur: Sutherland left for the airport following his talk, cancelling our interview.

Steve Benner: Have you spoken with Powner, his collaborator? Powner is also looking at the process of making DNA.

Suzan Mazur: I have not, although I've mentioned both of them in my reporting, as winners of the Lonsdale prize.

Steve Benner: That's right. They were winners of the Lonsdale Orign of Life Challenge.

Suzan Mazur: But I don't know where they are with that experiment, with that research. That's what I was really hoping to find out from Sutherland.

Steve Benner: I don't know at all.

Suzan Mazur: Sutherland told me he was not talking about it in his Princeton address, but I did think I'd get a little something during our scheduled lunch interview.

Steve Benner: I've been in contact with Harry Lonsdale. He's a chemist. Ran for the US Senate.

Suzan Mazur: Yes. I did an interview with Lonsdale.

Steve Benner: We'd like to host a session with all of the Lonsdale research award winners at the 2014 Gordon Origin of Life conference.

[Note: Steve Benner is Chair of the upcoming Gordon conference.]

Two and a half years after the award should be enough time to see some results. I've invited Harry. He said he might come and see what his investment hath wrought.

Suzan Mazur: I would love to attend as well.

Steve Benner: Well you're allowed to come. It's January 12 - 17, 2014 in Galveston, Texas. Again, it's a great place to be because the discussion really is unfettered and unconstrained.

Suzan Mazur: Lonsdale wanted to go really public with the Origin of Life message. He saw that I'd been on the Charlie Rose Show and asked if I could introduce him. I told him what I knew in terms of doing science roundtables these days on the program, which is what Paul Nurse told me in 2008 at his Rockefeller University Evolution symposium. That is, if you want to do a science roundtable on Charlie Rose, you need a corporate sponsor like Pzifer, which is who Nurse brought in for his 13-part series.

Steve Benner: I didn't know that.

Suzan Mazur: Some think Orign of Life is too esoteric a subject for a public discussion, but Princeton and NASA made the wise decision to stream the Princeton conference over the Internet. I think Lonsdale is right. There should be a series of Charlie Rose Origin of Life roundtables.

Steve Benner: I agree.

Suzan Mazur: Luisi says there are no new ideas. Why not widen the discussion circle? Freeman Dyson was on Charlie Rose talking briefly about origin of life. Why not bring Freeman Dyson in again and many others for an in-depth conversation?

Steve Benner: Science, to the public, is at one level the memorization of facts based on an authority -- your teacher, who has the cosmic authority of the expert. You'll see this all over -- "four out of five dentists agree". The appeal to authority and consensus of opinion.

But science is also the opposite. I'm a great fan of Richard Feynman who comments that science begins with a denial of the opinion of experts Science begins when you say NO. The perceived wisdom is wrong. Feynman's opinion is exactly the opposite of what many people think science is, the memorization of facts taught to you by an authority.

Suzan Mazur: That was the view of the late science and technology historian David F. Noble, who told me, "A consensus of scientists. Well, when you have a consensus of scientists, that should set off alarms."

Steve Benner: Scientists must be trained. This is a problem. Feynman goes on to point out that there's an enormous amount of what goes on in the public sphere in term of science that is mostly not scientific at all. He also says there's an enormous amount of intellectual tyranny in the name of science.

Suzan Mazur: Noble thought that peer review was at the heart of the problem. He considered it censorship.

Steve Benner: Well, it's a big problem. I'm a very soft peer reviewer. I think if you want to publish something that makes you look like a fool -- go ahead. Be my guest.

Suzan Mazur: Yes. You have a right to put it up there. Lynn Margulis courageously fought PNAS over its system of anonymous peer review.

Steve Benner: Exactly. This is how I don't get asked to review very often.

Suzan Mazur: Some scientists say, well peer review is good because other scientists will add a piece here and there.

Steve Benner: In a good peer review that will happen.

Suzan Mazur: Why not just get the story as right as possible and put it up?

Steve Benner: In point of fact there is some good that comes from peer review.

Suzan Mazur: Plus scientists have to pay to be published. They pay for their articles to appear in peer-reviewed journals. And pay even more if they want the articles open access.

Steve Benner: It's conceivable that the next generation of scientists will go to entirely web-based publication. The reason peer review exists now is that when you print a journal and put it in the mail, you then have a limited resource to meter in some sort of rational way. On the Internet nothing has to be metered.

Suzan Mazur: So is the Origin of Life field exploding within the scientific community?

Steve Benner: We now have the ability to address most if not all of the 1990s objections to the RNA World. That means we have ways to get ribose directly. We have ways to get ribose and its nucleotides indirectly. Some of that progress is due to the work of Sanchez and Orgel. Some of these are very old ideas. John Sutherland has amplified these splendidly. There is essentially nothing from the 1995 critique of the RNA world that does not have an answer.

Suzan Mazur: But it will be a creation scenario that COULD have happened. Not what did, in fact, happen.

Steve Benner: There is this general question when the science experiment ends. Peter Galison has written a book, How Experiments End. Nothing is ever proven in science. At some point the community decides this is no longer the most pressing problem. That's it. The investigation moves on from this to that.

It's is a matter of opinion as to whether the solutions to the 1990s' objections regarding the RNA world are sufficiently robust to allow people to move on from them to something else. It is a little early to say that. Right now what's emerging in the RNA world, which Iren Chen talked about here at Princeton, is that we don't know how useful function is distributed among sequence spaces.

You have 4 raised to the power 100 different sequences of RNA 100 nucleotides long. We don't know how productive function is distributed there compared to destructive function.

One of the things about the model of autocatalysis is that we have many molecules and this increases the chance of having one that does something productively but it also increases the chance of doing something else destructively.

Suzan Mazur: You said something about straw dog regarding autocatalysis.

Steve Benner: Straw man, I think I said. The modelers had come up with four objections to the model. But none of them are the objections that come to mind first to the chemist… The first thing that a chemist says is that if I start adding components to a mixture which is working, the first thing I do is prevent it from working because by adding a component it inhibits an interaction between two spaces. The easiest way a chemist can see this is by crystallization.

If you decide crystallization is what you are going to look for. You go into a laboratory and get an A grade in your organic chemistry laboratory -- as in Breaking Bad, the fictional television episode -- trying to do a high-quality methamphetamine product. The first thing you discover is that you must go a long way towards purification of typical organic compounds before they will crystallize. That's because impurities inhibit molecular organization that is necessary for crystallization.

There are a few exceptions. Louis Pasteur is famous for having tripped across one in the tartrate series where you could crystallize spontaneously the left-handed molecule and the right-handed molecule and then pick them apart by tweezers. Very important result in the history of chemistry. If tartaric acid had not been so well behaved, science would have waited another decade or so to get that point clarified.

John Sutherland made a comment about a conglomerate, that is the failure to spontaneously resolve two mirror image molecules by crystallization

When you present these models -- say Stuart Kauffman's collectively autocatalytic sets (CAS) model, one of the earliest, and he's been very influential. I think Stuart would agree with this. The first thing that you see when you're a chemist is an objection. Hey Stuart, you're adding things and thinking it's all good.

Well, very often when you add things, it's bad. It destroys interaction. It inhibits interaction. It catalyzes undesirable side reactions. It depletes material.

[Note: Stu Kauffman says he agrees.]

Suzan Mazur: Are you involved in making a protocell?

Steve Benner: We're not. There are a lot of very bright people in that business. A lot of them are in Europe.

Suzan Mazur: Are scientific fields here in the US integrating as they are in Europe?

Steve Benner: I saw a piece of yours a while back about the CERN meeting coming up. Partly because of the European funding structure, which we got a taste of in Antonio Lazcano's talk regarding Mexico. Lazcano said that if you are a professor, you have a chair which has an endowment associated with it so you have a certain amount of research without having to go outside. It makes people lazy and that's one of the criticisms Americans will direct at the European system. But it also permits imagination and broad-based interest.

If you go to France, you see people coming up with cutting-edge advances in sort of this evolution fringe.

Suzan Mazur: This is good.

Steve Benner: Of course it's good.

Suzan Mazur: Well there could be more public interest and more funding in the US. How do you get the public enthused? Do a 13-part series on Origin of Life on Charlie Rose.

Steve Benner: All of this is coming from Europe. I had 10 years in Europe where I had the ability to do crackpot things. It is because of the funding structure in Europe.

I worked for 10 years in Switzerland at the Swiss Federal Institute of Technology, and I was the beneficiary of the European funding system, for which I'm eternally grateful, and for which major advances came out which would not have been conceivable at all in the United States.

You heard Eric Goucher's talk here at Princeton, where he was resurrecting ancient enzymes. We were the first people to do that, we did that in Europe. We would never have done that in the US. I proposed that to the NIH when I was just a pup in the mid 1980s, but the NIH panelist reviews were scathing. And I've kept them.

The second thing is that we reinvented the genetic alphabet. Put 12 letters into DNA and the four ACTG. But go around the world and ask where has synthetic biology expanded on the notion of what might constitute a genetic system. Well in Belgium there's Peter Herdwijn. You go to Albert Eschenmoser at ETH in Zurich, my former laboratory. This is all coming from Europe. There is nothing of this power originating in the United States.

Suzan Mazur: But you're a synthetic biologist now in America.

Steve Benner: That's right. A crackpot synthetic biologist to some extent. Synthetic biology is now mainstream. It was certainly not mainstream in the early 1980s. Or in the 1990s when Pete Herdwijn was getting started in Belgium.

It was only because of the funding structure of Europe where you were allowed to bring together -- you were mentioning this in the protocell area, but this is 20 years ago -- the molecular biology needed to do this, the synthetic organic chemistry needed to do this, the physical chemistry, the biophysics, this concept about origins of life to inspire. You didn't see that anywhere in the United States until after Europe took the lead. That is a direct assignment, you can attribute that directly to funding.

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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