NYU chemist Robert Shapiro decries RNA-first possibility

Back in the depths of time, an event almost miraculously improbable happened, creating a long, unlikely molecule. And life arose on Earth.

Or, if you prefer, back in the depths of time, in a soup of small, relatively common molecules, an unknown chemical reaction occurred, sustained itself, replicated … and life arose on Earth.

A talk by New York University chemist Robert Shapiro brought the scientific debate over the first chemical stirrings of life to the Biological Laboratories lecture hall Wednesday afternoon (Oct. 15) in the first talk in this year’s Harvard Origins of Life Initiative annual lecture series.

Shapiro, chemistry professor emeritus, delivered the talk “A Simpler Origin for Life,” a presentation based on his well-publicized opinions on the likeliest ways life can begin. Shapiro, who received his doctorate from Harvard, was introduced by Origins of Life Director and Professor of Astronomy Dimitar Sasselov. Sasselov welcomed Shapiro back to Harvard and described him as one of the most well-known scholars on life’s earliest spark.

Shapiro traced the history of thinking on the origin of life on Earth. The discovery of DNA in 1953 brought speculation that life might have arisen with the first spontaneous assembly of the long, coiled molecule. Holding the blueprint for life, DNA could have begun replicating itself and passing on its genetic information, making the transition from nonliving to living for the first time.

DNA fell out of favor as more became known about the elaborate processes needed to make proteins from DNA’s instructions, however. Some thought that a simpler but related molecule, ribonucleic acid (RNA), which also carries genetic information, would be a good alternative candidate.

As more people jumped on the RNA-as-first-molecule-of-life bandwagon, which Shapiro termed “RNA-first,” Shapiro found himself more frequently criticizing the idea. He decried what he saw as the extreme improbability that such a long, complex molecule would or could arise spontaneously and become the first step in the long chain of life that followed.

“It started out with the idea that life itself had to begin with such a replicator [of genetic information],” Shapiro said. “The odds against [RNA forming on its own] are astronomical.”

While chemists have succeeded in making the molecules of life — or their components — in the lab out of simpler molecules, Shapiro said the tightly controlled processes in a chemistry lab can’t be mistaken for what would have happened on the early Earth.

“Any abiotically prepared replicator before the start of life is a fantasy,” Shapiro said.

Eventually, Shapiro said, his students gave him the nickname “Dr. No” because of his criticism of theories of how life began. He thought it appropriate to offer an alternative theory in an effort to become “Dr. Yes.”

Why search for ways that the highly improbable might have happened, Shapiro asked, when an alternative explanation using more common and simpler compounds has been relatively unexplored? Instead of the “RNA-first,” he asked, why not “metabolism first”?

Shapiro said life could have arisen in a completely different way from the spontaneous assembly of a long molecule holding genetic information. It could have started as a self-sustaining reaction involving simpler molecules that grew more complex, replicated, and eventually led to the creation of genetic material like RNA or DNA.

If true, this “metabolism first” scenario would mean that life in the universe is potentially quite common, because it doesn’t rely on an extraordinarily rare event to get the process started, Shapiro said.

“There’s nothing freaky about life; it’s a normal consequence of the laws of the universe,” Shapiro said.

Shapiro said such a metabolismlike reaction would require five things: some sort of a boundary to keep the ingredients together, such as a rock-bound compartment; a supply of energy; a coupling of the energy to a “driver reaction”; a chemical network that would permit adaptation and evolution; and reproduction.

Though such a model would have no single molecule holding the genetic information, like modern cells do, Shapiro said that wouldn’t necessarily preclude replication. If a reaction grew, obtaining or producing more of its chemical constituents until it split, it could still replicate the reaction perfectly each time even without a master molecule.

During a spirited question-and-answer session after the talk, audience members said that most people today realize how unlikely the RNA-first scenario is. Others said that over vast stretches of time, even unlikely events can become near-certainties. And still others said that things that seem impossibly complex can turn out to be elegantly simple once we figure them out.

Shapiro urged today’s scientists and students to explore the metabolism-first idea, saying that it has drawn little experimental attention. With modern instruments and talented chemists, it might be possible to figure out the details of such a reaction — a proof of concept — in just a year.

“I think a good organic chemist like you have here, with the equipment you have here, could solve this within a year,” Shapiro said. “You won’t have solved everything, but you’ll have cracked a portion of the walnut open.”