A stride towards unraveling life’s central enigma on Earth

It remains the ultimate enigma of biology: How did life commence?

A group of Harvard researchers has brought us nearer to a response by developing synthetic cell-like chemical systems that emulate metabolism, reproduction, and evolution — the fundamental characteristics of life. The findings were recently published in the Proceedings of the National Academy of Sciences.

“This represents the first instance, as far as I’m aware, that anyone has achieved something of this nature — creating a structure that embodies the traits of life from a substance that is entirely uniform at the chemical level and lacks any resemblance to natural life,” stated Juan Pérez-Mercader, a prominent research fellow in the Department of Earth and Planetary Sciences and the Origins of Life Initiative, the lead author of the study. “I am extremely excited about this.”

As per Dimitar Sasselov, head of the Origins of Life Initiative and Phillips Professor of Astronomy, the manuscript signifies a significant progression by showcasing how a basic, self-producing system can be formed from non-biochemical compounds.

“By mimicking essential elements of life, it provides us insights into the origins and early development of living cells,” noted Sasselov, who was not part of the new research.

The earliest documented evidence of life consists of tiny remnants of ancient microbes approximately 3.8 billion years old. However, their discovery did little to clarify the mystery of how or when life originated. Which simple biological molecules led to intricate cells? Was there a singular origin or multiple occurrences? Did life commence on Earth or originate on a different planet?

These inquiries have intrigued biologists for centuries. Charles Darwin theorized that life began in a “warm little pond” and subsequently diversified into a multitude of forms.

In the 1950s, Stanley Miller and Nobel laureate Harold Urey conducted experiments at the University of Chicago, replicating the conditions of primordial Earth — an atmosphere of methane, ammonia, hydrogen, and water with electric arcs resembling lightning — producing amino acids, the organic molecules that constitute the building blocks of proteins.

Amidst this discourse entered Pérez-Mercader, a vivacious scientist who characterizes himself as a “77-year-old child.” Initially trained as a theoretical physicist, he dedicated earlier years to exploring grand unified theories, supersymmetry, supergravity, and superstrings.

During the 1990s, he transitioned to astrobiology, founding the Centro de Astrobiología in Madrid in partnership with NASA, and oversaw Spain’s involvement in NASA’s Mars Science Laboratory.

In 2010, he joined Harvard with another ambitious objective. “I seek to understand why life exists here,” he shared.

All forms of life exhibit a few fundamental characteristics: They process chemical information, derive some form of energy (such as ingesting food or engaging in photosynthesis) to sustain themselves and construct body parts, reproduce, and adapt over time to their surroundings.

Pérez-Mercader formulated mathematical equations for the foundational physics and chemistry of biology and used their results as a guide to synthesize artificial life in vitro.

For years, these undertakings remained theoretical pursuits without experimental confirmation. Then came a breakthrough in the laboratory with the inception of polymerization-induced self-assembly, a process where disordered nanoparticles are designed to spontaneously form, self-organize, and create structured objects at scales of millionths or billionths of a meter.

Finally, these tools allowed Pérez-Mercader and his colleagues
“`to realize their hypotheses into reality — in a literal sense.

In the recent investigation, the team aimed to showcase how life could potentially “ignite” from substances akin to those found in the interstellar medium — the clouds of gases and solid particles that remain post the formation of stars in a galaxy — as well as light energy emitted by stars. A test tube represented a laboratory version of Darwin’s “warm little pond.”

The researchers combined four non-biological (yet carbon-based) molecules with water within glass vials illuminated by green LED lights, reminiscent of festive decorations. Upon activation of the lights, the mixture reacted and yielded amphiphiles, or molecules possessing hydrophobic (water-repellent) and hydrophilic (water-attracting) properties.

The molecules spontaneously organized into spherical formations known as micelles. These formations captured liquid within, which subsequently underwent a different chemical transformation and evolved into cell-like “vesicles,” or fluid-filled sacs.

Eventually, the vesicles released additional amphiphiles akin to spores, or they simply ruptured — leading to the emergence of new generations of increasingly cell-like structures. The growing number of expelled spores exhibited slight variations, with some proving to be more resilient and capable of replication — thereby simulating what the researchers termed “a mechanism of loose heritable variation,” the foundation of Darwinian evolution.

Stephen P. Fletcher, a chemistry professor at the University of Oxford who was not part of the new research yet engages in similar inquiries, expressed that the PNAS study paves a novel route for crafting synthetic, self-replicating systems — a feat that earlier experiments accomplished solely through more intricate techniques.

“The research illustrates that lifelike actions can emerge from basic chemicals that aren’t typically biological, occurring more or less spontaneously when light energy is applied,” he noted.

Pérez-Mercader describes the experiment in even more vivid terms. He believes it serves as a model for how life may have originated roughly 4 billion years ago. In his view, such a system could have chemically evolved, ultimately leading to the last universal common ancestor — the primordial entity from which all subsequent life descended.

“In this portrayal, we observe that it is feasible to commence with molecules that are unremarkable — not resembling the complex biochemical entities associated with current living systems,” he stated. “This straightforward system represents the optimal foundation for initiating the essence of life.”