How did life arise on Earth? Steven Strogatz speaks with the Nobel Prize-winning biologist Jack Szostak and Betül Kaçar, a paleogeneticist and astrobiologist, to explore our best understanding of how we all got here.
How did life begin on Earth? It’s one of the greatest and most ancient mysteries in all of science — and the clues to solving it are all around us. Biologists have sometimes imagined evolutionary history as a recorded “tape of life” that might turn out differently if it were replayed again and again. In this episode, Steven Strogatz speaks with two researchers inspecting different parts of the tape. First, hear from the Nobel Prize-winning biologist Jack Szostak, who explores how a boiling pool laced with cyanide could have given rise to essential life elements like RNA and DNA. Then hear from Betül Kaçar, a paleogeneticist and astrobiologist who resurrects ancient genes to learn how they helped evolve the processes essential to modern life.
Portions of a transcript of the recorded interview follow:
Did life begin, as Charles Darwin once speculated, in a warm little pond somewhere? The kind of nurturing, supportive place where it’s easy to picture delicate biology taking shape? Or more counterintuitively, as some scientists have proposed, did life get started deep down in the ocean, near hydrothermal vents, a seemingly inhospitable place where the pressures are enormous, and the temperatures are scalding? And, wherever life began, what were the earliest building blocks of life? Were they the molecules that we hear so much about today — RNA and DNA, amino acids, lipids — or were there something much simpler? In the past few years, some important clues have turned up. The payoff to answering these kinds of questions would be huge, not just for understanding how life began on Earth, but also to help us look for life on other planets, and maybe to figure out if we are alone in the universe.
(01:17) Joining me to discuss all this is Jack Szostak. Jack is a professor of chemistry and chemical biology at Harvard University, a professor of genetics at Harvard Medical School, and an investigator in the department of molecular biology at Mass General Hospital. He shared a Nobel Prize in 2009 for his work on the discovery of telomerase, an enzyme that protects chromosomes from degrading.
Strogatz (01:55): Let me start with a question about the origin of life. As I say, it’s one of the greatest mysteries in all of science and the attempt to solve it seems like one of the greatest detective stories of all time. What would be your best guess for how life began on Earth?
Szostak (02:09): Okay, so, so I think we have to think about some environment on the surface of the Earth, some kind of shallow lake or pond where the building blocks of RNA were made and accumulated, along with lipids and other molecules relevant to biology. And then they self-assembled into lipid vesicles encapsulating RNA, under conditions where the RNA could start to replicate driven by energy from the sun. And that would allow Darwinian evolution to get started. So that the, some RNA sequences that did something useful for the protocell that they’re in would confer an advantage, those protocells would start to take over the population. And then you’re off and running, and life can gradually get more complex and evolve to spread to different environments, until you end up with what we see around us today.
Let me just stop the tape here for a moment. Even a Nobel Prize winning biologist, who we might think cares deeply about how nature actually works, uses phraseology in his “best guess for how life began on Earth” that carelessly ignores stupendous difficulties that completely undermine the abiogenesis hypothesis. He spins off these statements like overripe political campaign promises:
“blocks of RNA were made and accumulated, along with lipids and other molecules relevant to biology”
“And then they self-assembled into lipid vesicles encapsulating RNA, under conditions where the RNA could start to replicate driven by energy from the sun.”
“And that would allow Darwinian evolution to get started.”
“And then you’re off and running, and life can gradually get more complex and evolve to spread to different environments, until you end up with what we see around us today.”
Szostak (05:12): For decades, thinking about the origin of life was confused, because everything in modern life depends on everything else. So it’s, so you have the DNA encoding the sequence of RNA and proteins, but you need the proteins to replicate the DNA. And to transcribe DNA into RNA, you need RNA to make protein. So you need — all parts of the system need all the other parts. So it was kind of a logical conundrum. And the answer, the solution to that, came with the so-called RNA world idea, which was originally postulated by some very smart people, like Francis Crick, and Leslie Orgel in the late ’60s, with the idea that RNA maybe had the ability to act as an enzyme.
Szostak (06:40): Okay, so tRNA is short for transfer RNA. It’s a relatively short set of RNA molecules, around 70 or 80 nucleotides long, and they carry amino acids to the ribosome. And then the catalytic machinery of the ribosome takes the amino acids from the tRNA, and assembles them into a growing peptide chain. So there’s a lot of roles for RNA in making proteins. There’s the tRNA that brings in the amino acids, there’s the RNA components of the ribosome, that it turns out actually orchestrate everything, do the catalysis. And of course, there’s the messenger RNA, which, you know, I think now everybody knows about messenger RNA these days, don’t they?
Strogatz (09:14): Well, maybe we should talk about cyanide, since you brought it up. I’m sure many people listening to this will be horrified, thinking that cyanide is how you kill people.
Szostak (09:22): I think it’s one of the lovely ironies of the whole field, that the best starting material to build all of the molecules of life, turns out to be cyanide.
Strogatz (11:54): Hm. Incredible. So, maybe we should return then to this theme of, you know, now that we’ve got cyanide world, we can somehow go up to RNA world, except that, apparently, that’s a big mystery, still, right?
Szostak (12:51): Well, I think the pathway to getting to two of the four building blocks of RNA is maybe 90% worked out? And I’d say one of the biggest steps — we have all this energy from sunlight, right? But the question is, how do you transform that energy into energy that’s in a useful form, a kind of chemical energy that can drive these building blocks to condense into long RNA chains? I think we would all agree that that has not been solved.
Let’s pause the tape again. When will origin-of-life researchers (publicly) acknowledge that living systems require specified complexity. Even if it were easy to condense the building blocks of RNA to long chains, the missing key is getting the correct sequence. Random strings of letters are easy to produce (the typing monkey business), but getting a reproduction of a meaningful essay just won’t happen by chance in the spacetime history of our universe. Nor can the result come about by a law of nature (emergent or otherwise), since the forces holding the “letters” together are not discriminatory.
Szostak (15:47): Okay, I can tell you where we are. So, several years ago, we found ways of making these primitive membranes, fatty acid membranes, grow and divide. They’re easy to feed with more fatty acids. And it doesn’t take very much to make them divide. So, for example, gentle shaking will do it. On the other hand, getting RNA sequences to replicate is a much harder problem. And so, that’s why that’s — we’re really focusing on that in my lab at the moment. We’ve been getting better at copying RNA sequences. So that means if you have, say you have one strand of RNA, you can use it as a template to build up the complementary strand, and then you’ll get a double helix, sort of like the double helix of DNA, except an RNA double helix. But a big problem then is how do you get those strands apart and copy the copies, and then copy those copies. And we have ideas about how to do it, but we haven’t gotten there yet. That’s the big challenge for the next couple of years.Quanta
Obviously, there’s room for much interesting biochemical experimentation to be done, and we have much to learn. But let’s not pretend that nature can do what already-discovered limitations of nature say it can’t do.