Dimitar Sasselov: Generation II -- Let There Be Light

MUNICH, GERMANY - JANUARY 22:  Dimitar Sasselov of Harvard University speaks during the Digital Life Design conference (DLD)
MUNICH, GERMANY - JANUARY 22: Dimitar Sasselov of Harvard University speaks during the Digital Life Design conference (DLD) at HVB Forum on January 22, 2012 in Munich, Germany. DLD (Digital - Life - Design) is a global conference network on innovation, digital, science and culture which connects business, creative and social leaders, opinion-formers and investors for crossover conversation and inspiration. (Photo by Johannes Simon/Getty Images)

We told Harvard from the start [in 2006] that there is no such thing as an origins field. There is astrobiology, and there are individuals working on origins-of-life experiments, and what we want to do is not really fundable any other way. We told the provost committee, "We need you to share our vision and support our research because the federal agencies -- NASA, NSF, NIH -- won't." We added that we also couldn't predict whether it would work out. (Dimitar Sasselov in conversation with me)

Astrophysicist Dimitar Sasselov ("Di-mi-tar," as in Demetrius) is director of the Harvard Origins of Life Initiative -- a group of scientists that includes Jack Szostak, George Whitesides, Andrew Knoll, Martin Nowak et al. -- and co-director (with Jack Szostak) of the Simons Collaboration on the Origins of Life, which says a lot about the confidence that the scientific community has in Sasselov's leadership in this cutting-edge area. He's also a warm, engaging man with a talent for creative organizing in a field that astrophysicist Piet Hut once described to me as nomadic "herding-cat science." One of Sasselov's most important contributions in science could turn out to be his expertise in ultraviolet radiation: Sasselov is now designing the UV light in which the world's first synthesized protocell, which he calls "Generation II," is expected to emerge in roughly three years and begin a new tree of life.

Dimitar Sasselov was born into a prominent science family in Bulgaria during the years of Soviet influence and was raised in Nessebar, a town on the Black Sea coast founded by Greek colonists in antiquity and still rich in archaeological artifacts. In fact, Sasselov's father, also named Dimitar, was a dirt archaeologist (now retired and writing books), as well as an architect, with an interest in late antiquity and early antiquity (Thrace) through the late Roman Empire (Byzantium). His mother was a horticulturist responsible for the design of some of Bulgaria's parks.

Sasselov was very much encouraged professionally by his parents and might naturally have chosen a career in marine biology, since the family lived near the sea, "but life is a string of accidents along the way," he said, "so I ended up in physics and astronomy."

Sasselov told me he found living with all the political red tape in communist Bulgaria "very frustrating," saying further, "luckily, by the time I was in my early 20s, the whole political system was falling apart. It collapsed eventually in 1989."

I first met Dimitar Sasselov and his wife, an artist, last winter at the Manhattan apartment of mentalist Gerard Senehi, who likes to host intellectual salons. Sasselov was the guest speaker.

After about 10 to 15 minutes into Sasselov's talk about the origins of life and the search for "super-Earths," I, of course, wanted to know how Sasselov defines "life."

At the time he said there was no agreed-upon definition. He has since told me the following:

There is clearly the realm of atoms and small molecules to consider, which is chemistry, and there is also something that emerges under conditions we are still trying to figure out. This is also chemical but has a level of organization making it qualitatively different. Therein lies the challenge.

Where do we draw the line between those two extremes and generalize it, not just for microbial life on Earth, which I agree is the main representative of the life phenomenon, but also for other environments and with other combinations of molecules and chemicals? ... I'm investigating the phenomenon from the point of view of the cosmic large scale.

If we study the universe at large scale, we see the hierarchies that developed over the last 14 billion years, starting with very diffuse gas made entirely of protons, electrons and a small number of alpha particles, which will become helium. So it's hydrogen and helium, a certain amount of photons and gravitons, gravity waves, and other perturbations which are in the space-time matrix, the space-time that all this exists in and is expanding. From that early time to today, different objects form -- galaxies, and clusters of galaxies. Within galaxies stars form, and around the stars, planets. ... The point is: Where is the place of life in this whole hierarchy?

Dimitar Sasselov is a professor of astronomy at Harvard University. He did his undergraduate studies at Sofia University in Bulgaria, where he also received his Ph.D. in physics, and then received a second Ph.D. in astronomy from the University of Toronto. He was a post-doctoral fellow at the Harvard-Smithsonian Center.

Sasselov is the author of the recent book The Life of Super Earths and co-editor (with Mine Takeuti) of the books Stellar Pulsation and Pulsating Stars.

He is a frequent and lively lecturer and knows how to handle the media, greeting me at the Senehi salon by telling me that he loved my blog.

Excerpts of my interview with Dimitar Sasselov follow.

Suzan Mazur: You've identified three milestones of Homo sapiens in your book The Life of Super Earths: the Copernican revolution, globalization, and synthetic biology. You note that the first two of these are already done deals. Here's what you say about the third, synthetic biology:

For the first time in about 4 billion years a new species is not going to emerge from the set of processes that led to the diversity of life on this planet. Instead, one species is going to synthesize another -- a life-form that is unique, but not in the way that a new dog breed or a genetically modified corn plant is made unique by some cosmetic differences with its progenitor. It will be new in terms of its unique biochemistry, a new life-form that has no place on Earth's tree of life, a new life-form at the root of a new tree of life.

My question is why scientists have become intelligent designers of life. What is your goal in creating "Generation II," as you call it?

Dimitar Sasselov: One, it's a very practical thing. If we want to understand the phenomenon, if we want to understand and study its history and the possible ways it appears out there in the galaxy, the easiest way is to build proxies or actual toy models -- as we usually call them in science -- in the lab. If we want to understand generally what would be the sensitivity or the reaction of a simple living system to changing planetary conditions, we can't use existing life forms, because they are too sophisticated. Hopefully we'll be able to synthesize a simple synthetic cell and see the feedback from experimenting with it.

It's fascinating that we are now going to be able to synthesize life in the lab because we think we've understood what the molecular building blocks are for over half a century. But we still don't have a sense of what makes them work as a system. We can't figure that out any other way than to build a synthetic cell.

Suzan Mazur: What is the goal beyond figuring out the synthetic cell?

Dimitar Sasselov: If the project is successful and the synthetic cell functions and produces populations, then there is so much to do with it, with those populations and this new tree of life. It will open biology in a completely different way. It will transform the face of science altogether.

You have to see what you get. But I'm sure it will happen soon. For me it's feasible. I know it will work.

We're doing the bottom-up approach. Chemist John Sutherland is very much involved in this, working from his lab in Cambridge. We were collaborating with John even before the Simons Foundation funding. The ultimate goal is to go all the way from his pre-biotic chemistry, building the individual pieces of RNA and the other molecules needed, and then encapsulate them in Jack Szostak's lipid vesicles.

Suzan Mazur: In the various scientific collaborations now in progress on the origins of life, including the Harry Lonsdale-funded teams, would you say investigators are being cautious enough about the dangers of conspiring -- that is, making one person's research fit snugly into another's for a desired result? For example, if one had glycerine and the other had purines, then that would open the door to the monomers hypothesis, which could segue into your idea, etc., etc. Would you comment?

Dimitar Sasselov: I do think there are multiple pathways, but we can't make a statement in one direction or the other. One of our goals is to answer that question. Our approach is to look for possible pathways, not for the pathway. But even if we just find one, we'll be more than happy.

Suzan Mazur: So if we get a few more creation myths along the way, that's part of the process?

Dimitar Sasselov: Yes.

Suzan Mazur: Jack Szostak announced at the 2014 World Science Festival that we'll have life in the lab in three to five years -- closer to three. You said five years.

Dimitar Sasselov: I'm deferring to Jack here.

Suzan Mazur: You began to describe the synthetic cell you're making there at Harvard as a modest protocell.

Dimitar Sasselov: Modest, yes. It should be built from scratch in order to understand each piece and function, as opposed to using it as a black box, which works but you're not quite sure why it works.

Suzan Mazur: From your perspective, what's missing from the soufflé at this point?

Dimitar Sasselov: There are two steps missing out of the eight steps toward an RNA protocell that Jack and others are still working on. One of those steps not yet figured out is how to make RNA strands grow longer and grow generally in order for the individual pieces -- called RNA nucleotides -- to bond into a strand. The RNA nucleotides have to be chemically activated. This is easy to do in the lab but tricky for it to happen naturally. That's one of the issues.

The other one is enabling RNA to form -- without any initial templating -- in lipid vesicles that are floating in a clay-water solution containing the chemicals necessary to form nucleotides. Templating is using a strand chemically as a photocopier to make more copies.

These two things should come together in the next three years. That's why Jack said at WSF that in three years we hope to have all the components together and will have vesicles with activated nucleotides in them.

These components will follow the chemical steps we know from doing those steps individually in the lab. But now the components will be a system, and for the first time we'll have something similar to an evolution arms race -- Darwinian evolution -- between the individual vesicles with their particular selected RNA strands. Hopefully we'll see it go very quickly through several generations, see the selection process working.

Suzan Mazur: Thank you. I understand you're exploring the interaction of radiation and matter, that you're trying to recreate the light of prebiotic Earth in your lab. What was different about the light then? How far along are you with the experiment?

Dimitar Sasselov: All this interesting chemistry and biochemistry that we've been discussing, including and especially including the synthesis of the building blocks, is now increasingly well understood. John Sutherland and Jack Szostak and George Whitesides and others have managed to make a lot of progress in that direction. One pervasive aspect of the pathways -- it's not a single pathway but several pathways -- is that they always require ultraviolet light for different nontrivial steps in the chemical reactions which are involved.

That means that we have to model and actually recreate this UV-radiation environment in the lab in order to do the whole sequence properly. As it happens, this is my expertise. I'm building a small lab where we'll be doing all of that.

So technically the integration of all the different steps discussed above will eventually have to be done in the lab I'm putting together, where I'll be simulating conditions under UV radiation, either corresponding to the early Earth or to some of those exoplanets we're discovering and will be discovering and studying.

Suzan Mazur: The light of prebiotic Earth was stronger.

Dimitar Sasselov: Yes. There was not the oxygen there is today in the Earth's early atmosphere. Earth's oxygenation was subjected to harsher, stronger UV light.

Suzan Mazur: John Sutherland did say at last year's annual Lonsdale meeting that he doesn't have the proper light (and couldn't afford to get one). He said he's using 254 nanometers.

Dimitar Sasselov: Yes, chemists work with mercury lamps or other lamps which produce a spectrum of UV light completely diametrically opposed to what a star would produce in terms of UV light. It still works partly because what UV light does is simply deliver energy.

A lot of what the chemistry requires is the right kind of UV radiation as a source of energy. There are some subtleties there, particularly in terms of left-handed vs. right-handed, and that still unsolved problem of polymerization ( i.e., the activation and growing into a longer strand), which I think will be solved with the proper UV source.