And all that’s needed to spark this process are particular sequences of hydrophobic and polar components, which his model can predict. “Dill’s model shows you need only those two properties,” said Peter Schuster, a theoretical chemist and professor emeritus at the University of Vienna. “That’s a beautiful theoretical result.”

“It puts in doubt the vision of the origin of life that is based on the RNA world hypothesis,” said Andrew Pohorille, director of NASA’s Center for Computational Astrobiology and Fundamental Biology. To him and some other scientists, proteins seem like a “more natural starting point” because they are easier to make than nucleic acids. Pohorille posits that the information storage system found in the earliest rudiments of life would have been less advanced than the nucleic acid-based system in modern cells.

“People didn’t like the protein-first hypothesis because we don’t know how to replicate proteins,” he added. “This is an attempt to show that even though you cannot really replicate proteins the same way you can replicate RNA, you can still build and evolve a world without that kind of precise information storage.”

This fertile information-rich environment might then have become more welcoming for the emergence of RNA. Since RNA would have been better at autocatalysis, it would have been favored by natural selection in the long run. “If you begin with a simpler model [like Dill’s], something like RNA could appear later, and it would become a winner in the production game,” said Doron Lancet, a genomics researcher who has worked on his own simple chemistry-based model at the Weizmann Institute of Science in Israel.

Seeking Proof With Peptoids

Of course, the key to all this lies in actual experimentation. “Everything that goes back further than 2.5 to 3 billion years is speculation,” said Erich Bornberg-Bauer, a professor of molecular evolution at the Westfälische Wilhelms University of Münster in Germany. He described Dill’s work as “really a proof of concept.” The model still needs to be tested against other theoretical models and experimental research in the lab if it is truly to put up a good fight against the RNA world hypothesis. Otherwise, “it’s like the joke about physicists [assuming] cows are perfectly elastic spherical objects,” said Andrei Lupas, director of the department of protein evolution at the Max Planck Institute for Developmental Biology in Germany, who believes in an RNA-peptide world, in which the two coevolved. “Any significance ultimately comes from empirical approaches.”

That’s why Zuckermann, one of Dill’s co-authors on the PNAS paper, has begun working on a project that he hopes will confirm Dill’s hypothesis.

Twenty-five years ago, around the time that Dill proposed his HP protein-folding model, Zuckermann was developing a synthetic method to create artificial polymers called peptoids. He has used those nonbiological molecules to create protein-mimicking materials. Now he’s using peptoids to test the HP model’s predictions by examining how sequences fold and whether they would make good catalysts. In the course of this experiment, Zuckermann said, he and his colleagues will be testing thousands of sequences.

That’s sure to be messy and difficult. Dill’s HP model is highly simplified and doesn’t account for many of the complicated molecular details and chemical interactions that characterize real life. “This means we will run into atomic-level realities that the model is not capable of seeing,” Zuckermann said.

One such reality might be that a pair of foldamers would aggregate instead of catalyzing each other’s production. Skeptics of Dill’s hypothesis worry that it would be far easier for the hydrophobic patches to interact with one another instead of with other polymer chains. But according to Pohorille, the potential for aggregation doesn’t automatically mean Dill is wrong about needing those hydrophobic patches to get autocatalysis started. “Modern enzymes aren’t just smooth balls. Enzymes contain crevices that assist the process of catalysis,” he explained. If there’s aggregation between the foldamers through their landing pads, it’s possible that the resulting structure could possess such features, too.

“Even if it seems unlikely, science has to consider all the hypotheses,” Bornberg-Bauer added. “That’s what Dill is doing.”

For now, at least, the RNA world hypothesis reigns supreme. Nevertheless, Dill and Zuckermann remain optimistic about what further research will yield. Dill plans to use the model to examine other questions about the origins of life, including how and why the genetic code arose . And Zuckermann hopes that the research — in addition to confirming (or refuting) Dill’s computations — will also help him make foldamers that can act as vehicles for drug delivery, synthetic antibodies or diagnostic tools.

“This model gives experimentalists like me a starting point,” Zuckermann said. “It lays down the challenge to find these primitive catalysts, to show how they work, to say: This could have really happened.”

This article was reprinted on ScientificAmerican.com.