Biophysicist Dieter Braun: Origin of Life Investigation Renaissance

<strong>DIETER BRAUN</strong>
DIETER BRAUN

Redford-style good looks have not been enough to divert Dieter Braun from his research interest in nonequilibrium conditions on the microscale, and what is now a central role in the investigation into the origins of life. Braun---a professor of systems biophysics at Ludwig Maxmilians University in Munich, a Simons Foundation collaborator on the origins of life, and scientific coordinator of the OLIM initiative (Origin of Life Munich)---says a whole new breed of scientists, "experimentally driven,” have entered the field as funding opens up and that origins of life research is no longer a “side activity,” fishing expedition, or place for dreamy “pet theories.”

I first became aware of Dieter Braun several years ago when Rockefeller University physicist Albert Libchaber spoke to me of Braun’s star quality as an origins investigator in his lab (postdoctoral research 2000-2003). I next noticed Braun on the Simons origins page also featuring Jack Szostak, Dimitar Sasselov, John Sutherland and Matt Powner, and finally contacted him about a recent paper he coauthored on hairpin structures. Since Braun was not first author on the paper, he tossed his hat to postdoc Georg Urtel who was, and who agreed to be interviewed.

I couldn’t make it to the recent kickoff of the Dutch Origins Center, where Braun gave a talk on “transport phenomena and nucleic acid replication,” so I made another story pitch.

As our interview that follows reveals, Braun grew up in a village in the German countryside, was a computer geek by high school but saw physics as far more challenging. His diplomas are in physics from the University of Ulm and Technical University Munich, and his PhD, summa cum laude, from Max Planck Institute of Biochemistry, also in physics.

Following his years at Rockefeller University, Braun led the Munich-based independent Emmy Noether research group at LMU on biomolecule thermophoresis and thermal trapping. A spinoff company, NanoTemper Technologies (now with 100+ employees), was founded by two of the group’s students. Braun currently heads a new research group at LMU focused on “recreating the origin of life.”

Along the way he’s toyed with something he callsbookkeeping mechanics,” producing a paper: “Nonequilibrium Thermodynamics of Wealth Condensation”---which may have also caught Jim Simons’ attention.

Among Dieter Braun’s awards are---Deutscher Grunderpreis (2015, for NanoTemper); Simons Foundation Collaboration on the Origins of Life (2014, $1.5M); Prodekan (2012); Step Award (2012, for NanoTemper); Deutscher Innovationspreis (2012, for Nanotemper); Klung-Wilhelmy Weberbank Price (2011, Germany’s top award (€100,000) for physicists age 40 or younger); European Research Council’s Starting Grant (2010, €1.5M).

I was particularly impressed that Braun indicates on his CV--- “2005 Parental Leave: half time position for 1.5 years,” and as a committed parent has taken an active role (Chairman of the Board) in the running of the “midday care” school association in his alpine neighborhood outside Munich.

I reached Dieter Braun by phone last week at his lab at LMU for this conversation.

Suzan Mazur: You’ve recently said that you are not an artist but photos of you have a certain Redford aesthetic.

Dieter Braun: [Laughter]

Suzan Mazur: Your online biography is a bit sketchy. Do you come from an art family? A science family? An industrialist family? Are you possibly related to the motorcycle racer Dieter Braun?

Dieter Braun: Not that I know of. I came from a small village in the German countryside. My father played the organ. There are a lot of musicians in the family, although I am not one.

Suzan Mazur: But where does your color sense and style come from?

Dieter Braun: My father was into photography. He had a dark room and photography equipment. He was the guy who was kind of the official photographer of the village.

In science I think it matters a lot how you make a point so that people can grasp the message fast. It makes sense to take time to make pictures, graphs, and other images.

Suzan Mazur: I gather your family did not take an active role in your early science career by building a lab for you in the basement and providing chemicals like Jack Szostak’s did?

Dieter Braun: No. I did a lot of programming when I was a kid. I earned my first money selling program code to small journals. Back in the 1980s people bought small magazines and typed programs from them. I was a computer geek more than anything else.

Suzan Mazur: Your interest in science began when?

Dieter Braun: When I was 17 I made a decision that informatics was probably a little bit too boring so I chose physics. I was also inspired by my older brother who studied physics.

Suzan Mazur: Your wife, Veronica Egger, is a scientist too.

Dieter Braun: Yes, she’s involved with two-photon microscopy and a professor of neurophysiology at Regensburg University, about an hour and a half from here by train. She was previously at LMU’s Munich Center for Neurosciences---Brain & Mind, although it didn’t work out that we were at the same LMU location.

Suzan Mazur: Are you an athlete?

Dieter Braun: Not really. Where I grew up in southern Germany I did a lot of bike tours. We now live outside Munich in the Alps, Bavaria. We like to hike.

Suzan Mazur: You’re being funded, in part, by a Simons Origins Foundation grant of $1.5M. Aside from that research grant and your EU funding, are there European philanthropies supporting your origins investigation?

Dieter Braun: That would be interesting, but no, there is not the kind of philanthropic culture here in Germany to fund science as there is in the US. The universities here are very good, studies are free. But philanthropy, giving back to universities doesn’t exist here.

Suzan Mazur: Jim Simons told me this about research funding in Europe and the US:

“Philanthropy doesn’t happen in Europe very much period. . . . Philanthropy in the United States, per capita, is far greater than it is in Europe. We have a very old tradition of philanthropy. . . . Private enterprise used to do more of it [support research] in the United States, in particular. Big companies, most notable would be Bell Laboratories. . . .
When I got my PhD, the best place in the world to study what’s now called condensed matter physics, and in those days it was called solid state physics, was at the Bell Telephone Labs. That was a better place than Harvard or MIT or anyplace else. They did the best research. . . . It was a remarkable institution. But when the telephone company was broken up, when AT&T was broken up, none of the individual companies really had enough money to so generously support that kind of enterprise. . . .“ Jim Simons, The Origin of Life Circus: A How To Make Life Extravaganza

What do you think about the John Templeton Foundation funding origins of life research?

Dieter Braun: We’re getting a good corps of people now who are reshaping the field in a completely new way. It’s clearly a time to invest in origins research. We’ll see solid science back from these investments.

In the past, origins of life was a side activity for older, established scientists. Now young people are entering the field who are much more experimentally driven. They don’t write long papers about their pet theories without solid experimental proof. It becomes a real scientific exercise now, particularly as funding becomes more available.

Suzan Mazur: The Templeton Foundation is known for its coupling of science and religion and there’s a good deal of controversy about that. Would you accept Templeton funding for origins research?

Dieter Braun: I haven’t fully look into that. Professional funding now should be without strings attached.

For the Simons Foundation, for example---you make a proposal, two pages, saying roughly what you will do. The rest is mostly based on trust. Simons is bringing good professional practice to the field. . . .

Dieter Braun: Actually our university, LMU, includes a theological faculty. They’re very serious and down-to-earth people. If people are serious, I can imagine that serious research can be possible.

I would hesitate taking money from NASA though because it’s very often geared to engineering and space missions. That would inhibit our freedom in doing experiments much more than the Templeton Foundation, which seems to try to explore a little bit more on the right and left side of things or fund projects that normally are not funded by the science community.

Suzan Mazur: The Simon Foundation seems to have a continuing interest in origins research.

Dieter Braun: The Simons Foundation does a good job connecting the origins community and in structuring things so that people really are collaborating.

Suzan Mazur: Your current Simons Foundation grant expires in 2019. Will you be refunded?

Dieter Braun: There’s some hope. In parallel, I submitted an ERC Advanced proposal to EC for a five-year grant to pursue research, which I almost got last year. Let’s see. We try to secure funding from various sources to keep us independent. If we depended solely on the Simons Foundation, it could limit our freedom.

Suzan Mazur: One of the problems in funding origins research is that it still seems largely angled to Darwinian evolution, which has been seriously challenged over the last decade. A recent Spectator magazine article noted that Darwin’s “theory quickly outstripped his scientific data and instead became a grand narrative seemingly capable of explaining the entire history of life on earth.”

Eugene Koonin, who---like Nigel Goldenfeld and Carl Woese---thinks that biology is on its way to becoming the new condensed matter physics, has told me this:

“No one in the mainstream scientific community now takes selection literally.”

It appears that continued use of the term selection in scientific papers is seen as one factor preventing biology from becoming a hard science. Would you comment? Do you see biology as the “new condensed matter physics”?

Dieter Braun: That’s a long discussion. Basically, the term selection in biology is one that is used for already existing life, right? So we can study selection and evolution for example at the bacterial level and molecular level for things already replicating. But I do think it’s important in this field [origins] to be precise regarding the term selection.

Suzan Mazur: But who’s doing the selecting?

Dieter Braun: In our experiments, for example, we use tiny rock compartments as traps (mimicked by fluid-filled glass capillary tubes), driven solely by a heat flow. A physical mechanism, temperature difference, accounts for accumulation of molecules in one spot. It brings the molecules inside the compartments together. It chooses larger molecules over smaller ones, and oligonucleotides with similar sequences and binds them together. That physical mechanism of bringing molecules together has nothing to do with biological selection, but could be seen as a first step in physically selecting long molecules with similar sequences.

The idea is that you have porous or volcanic rock. If you walk over Iceland, you find conditions like this where hot water vapor comes out and volcanic fire and you think of what might be possible in these pores. For such experiments [thermophoresis], you only need temperature difference. I’m not saying this is a solution. We try to make something step-by-step (1) that we can do in the lab, and (2) might have had similar boundary conditions on early Earth.

Suzan Mazur: There seems to be a need for new terminology, new language in the field to describe this. Selection isn’t an accurate description.

Dieter Braun: That’s a big difficulty in the field, absolutely. Selection, if I say that to biologists, to physicists, to chemists, it has completely different meanings to each. In science we have trouble writing papers because we run into these ambiguities in different fields. That’s what’s going on right now in the origins field. Things are increasingly interdisciplinary. It would be a great advantage to have more precise language. We will find this as we continue to communicate across disciplines. In the end, experiments will be our common language.

Suzan Mazur: Do you see biology now as, or as becoming, the new condensed matter physics?

Dieter Braun: What do you mean by “the new condensed matter physics”?

Suzan Mazur: That biology is developing into a hard science. It’s not fuzzy Darwinian science anymore.

Dieter Braun: Biology isn’t about Darwinian evolution even if you just look at the cell as it is. Many solid, quantitative studies are now being done on this with serious modeling similar to, say, condensed matter physics. And if you look at how the cell evolves, how it varies, how extensive the mechanism is that’s going on---biology is relying increasingly on quantitative analysis. We have to push further toward an explanation that fully explains things from bottom up.

Suzan Mazur: How much of getting to the bottom of the origin of life depends on redefining what life is?

Dieter Braun: I think in a way quite a bit. What we try to do in the lab is start with a certain idea of life. We do an experiment and we think of all the things we might need for evolution. The result might be very primitive. We then go out to the scientific community for response. Other investigators might say: “You need to explain this and this and this.” We then go back to the lab and try to add that too. Does it work? It will be progress with a lot of feedback loops. Communicating with biologists as well as many other disciplines. Eventually we ask: “Look, is this life or not?”

I think what will be found is an experimental question. We hope we might even persuade biologists to say, “Oh, I can see a logical line from the early Earth all the way to the cell.” However, a lot of things still need to be shown experimentally.

Suzan Mazur: Do you think 4 billion years is enough time to take us from nucleic acid to Homo sapiens?

Dieter Braun: Absolutely yes. I’m optimistic. That is driving us because we think that if we have the right conditions, we can do the crucial steps in the lab. I would argue that if we needed to have a long time and very strange, not understandable processes for this to happen, then we couldn’t do the experiment in the lab. So, yes, I am optimistic.

Suzan Mazur: Do you think RNA may have been premixed in an Earth-bound meteorite?

Dieter Braun: All the data that’s in on what is coming from space, my rough idea---this should all be based on data---is that comets give up quite a number of complex molecules but from all that we’ve seen, it’s not yet giving us nucleic acid. It’s giving us amino acids, short peptides, but not nucleic acid. Part of the ingredients come from outside Earth, similar to where most of our water originated. Simple molecules came from outside Earth, but the evolutionary process probably happened on Earth.

Suzan Mazur: And you continue to favor the thermophoresis hypothesis regarding origin of life?

Dieter Braun: Everyone has a pet theory to push an experimental line as far as he/she can make progress with it. We do, still do, so we continue that route. Science is about making hypotheses and about being honest if the hypothesis is falsified by experiments. You can never prove a hypothesis.

Suzan Mazur: You’ve got Albert Libchaber as an ally. He told me this in his office at Rockefeller University:

“Yes, and my interest lately focuses more about life originating in thermal vents deep in the ocean. In thermal vents you have large temperature gradients because water comes out of the vents in a high temperature.
The little volcanoes that make thermal vents are full of porous material, and those pores hold all the temperature gradients you need. What was shown is that with this temperature gradient many nonequilibrium processes exist.
For example, we discovered that polymerase chain reaction (PCR) is possible under thermal convection. There’s nothing but thermal convection. In the center region of a convective cell double-stranded (DS) DNA melts and in the side single-stranded (SS) DNA is copied. We thus made the smallest PCR machine, centimeter in size. . . .
We did that when Dieter Braun was here as a postdoctoral fellow, about 10 years ago.
We also showed that if you have a very thin geometry, water cannot move because of friction to the wall but the suspension moves. So in a temperature gradient, you can accumulate the suspension.
There can be a huge accumulation. We saw that you can accumulate, you can amplify, you can even select length. So all those processes may have played a role at the origin.
This is one of the questions always asked. How do you reach a critical concentration? Well, temperature gradient can do that. It can also amplify, it can select size. It can select even some sequences.”---Albert Libchaber, The Origin of Life Circus: A How To Make Life Extravaganza

Dieter Braun: Being a postdoc in Albert’s lab was a great experience. He gives a lot of freedom to his researchers and freedom is important to do good science.

Suzan Mazur: How did you find living in New York?

Dieter Braun: This was a great experience. I am always happy when going back. Nevertheless, with kids, life is way more simple---and cheaper---here in Germany.

Suzan Mazur: How close are we to understanding the origin of life and/or making life in the lab?

Dieter Braun: We’re getting quite close. Jack Szostak and many other origins investigators are making fast progress. We will have replicating systems and see the evolution of these sequences probably within the next 5 - 10 years. Defining a very minimal way of life.

Suzan Mazur: There are now a half dozen or so origins centers in America, Europe and Japan. Is throwing more funding at the problem the way forward or do we need new “mindstorms,” as Pier Luigi Luisi has said. Are we really going to be there in 5 - 10 years or do we need new approaches?

Dieter Braun: In the past there was no money in this field at all. If we’d made our origins proposal 10 - 15 years ago, we would not have been funded. People now see that origins experiments can be solid. Even to the point that you get biotechnology from them.

We secured funding in the physics world by arguing that non-equilibrium effects are interesting. People agree on that. Meanwhile, we can say we produced new biotechnology.

Two former students of mine spun off their own nanotechnology company---NanoTemper Technologies, which now has more than 100 employees. They first studied the movement of molecules by a thermal gradient and developed the idea to measure how strong biological molecules bind. Pharmaceutical companies use the technique now to develop new drugs. More money is currently paid to Germany in taxes from this spin-off than was ever spent on our lab.

Suzan Mazur: So the origins investigation is no longer regarded as a fishing expedition?

Dieter Braun: Yes. That’s a big change of gears. Our lab experiments are interdisciplinary ones tackling core questions of how information in terms of sequences emerged in realistic Earth conditions.

Dieter Braun: It showed how many scientists representing many disciplines---far apart---can come together. Groningen is in a good position now to do what other Origins centers are doing, like Harvard, Scripps, ELSI, etc.---as well as the one we’re trying to create here in Munich---that is, securing funding to further grow the science. It’s important that there’s enough money. Serious experiments are not so cheap.

Compared to funding for other scientific disciplines and the overall funding of science---$2.5M for Origins research is not a lot of money---it is baby steps for getting this going as a real field.

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