A step toward solving central mystery of life on Earth — Harvard Gazette
(A) Illustration showing the different stages of polymer vesicle growth leading to the action of expulsion of amphiphiles. (B) Illustration showing the formation of new vesicles from the reorganization through self-reproduction of amphiphiles expelled into the bulk.
The frequent creationist assertion that abiogenesis is impossible without invoking supernatural intervention has taken another significant blow with the recent open‑access publication in Proceedings of the National Academy of Sciences (PNAS). The study, Self‑reproduction as an autonomous process of growth and reorganization in fully abiotic, artificial and synthetic cells, demonstrates, for the first time, the successful laboratory creation of simple, non‑biochemical self‑reproducing vesicle‑like systems exhibiting Darwinian evolution: each generation varies slightly in traits that influence their ability to replicate.
This breakthrough indicates that such self‑sustaining systems could plausibly arise through natural processes, and gradually—through Darwinian mechanisms—evolve into the first simple biological life forms, from which all life subsequently diversified. It also lends empirical support to the principle that when self‑replication with small variation occurs in a selective environment, evolution in the direction of increased fitness is inevitable.
Glossary of Key Terms. AbiogenesisReflecting on such inevitability, Thomas Huxley remarked, upon first reading Darwin's Origin of Species, “How stupid not to have thought of it oneself!” That optimism remains well‑grounded—yet, sadly, some still lack the imagination or willingness to acknowledge how trivial it is to see that evolution is the inevitable outcome when environments change and selective pressures vary over time.
The natural process by which life arises from non-living matter, such as simple organic molecules assembling into more complex, life-like systems.
Amphiphile
A molecule with two contrasting regions: one hydrophilic (“water-loving”) and one hydrophobic (“water-repelling”). This dual nature allows them to self-assemble into structures like membranes.
Micelle
A spherical cluster of amphiphiles, with the hydrophilic ends facing outward towards water and the hydrophobic ends tucked safely inside. Micelles are considered primitive precursors to cell membranes.
Vesicle
A small, fluid-filled sac enclosed by a membrane of amphiphiles. Vesicles resemble simple cell-like compartments and can trap molecules inside, creating distinct internal environments.
Polymerisation
A chemical reaction in which small molecules (monomers) link together to form larger chains or networks (polymers). In origin-of-life research, this process is key to building complex structures.
Heritable Variation
Small differences that can be passed on from one generation to the next. In this study, variations in vesicle structure or composition influenced survival and reproduction—satisfying a core requirement of Darwinian evolution.
Milestones in Origin-of-Life Research
1953 – Miller–Urey Experiment
Stanley Miller and Harold Urey simulate early Earth’s atmosphere with water, methane, ammonia, and hydrogen. Electric sparks produce amino acids, showing that building blocks of life can form naturally.
1960s–1970s – Amphiphile and Vesicle Research
Scientists discover that simple amphiphilic molecules spontaneously self-assemble into micelles and vesicles, suggesting how primitive cell compartments could have arisen.
1982 – Discovery of Ribozymes
Thomas Cech and Sidney Altman show that RNA can act as a catalyst as well as a genetic material, sparking the “RNA World” hypothesis.
1990s – Laboratory Protocells
Researchers create artificial vesicles that can encapsulate molecules and, under certain conditions, grow and divide — early “protocell” models.
2009 – Synthetic Life Milestone
Craig Venter’s team builds a bacterial genome from scratch and uses it to “boot up” a cell, demonstrating the viability of fully synthetic biology.
2025 – Pérez-Mercader’s Abiotic Self-Replicators
Harvard researchers led by Juan Pérez-Mercader report the first entirely non-biological vesicles that grow, reproduce, and evolve via heritable variation — a key step toward solving the mystery of how life first emerged.
Predictably, creationists will argue that because this experiment was designed and carried out by scientists, it somehow supports Intelligent Design. But this confuses the role of the researchers with the natural processes they revealed. The scientists did not “design” the self-replicating system in the sense that a watchmaker designs a watch. They simply assembled the raw ingredients, provided energy in the form of light, and then observed what those molecules did under those conditions. The crucial point is that the formation of vesicles, their replication, and their Darwinian variation were not imposed by intelligence — they were the spontaneous outcome of chemistry.
By the same logic, one could claim that a physicist “designs” gravity by dropping a ball, or that a chemist “designs” rust when iron is left in water. Setting up conditions for a phenomenon to occur is not the same as creating the phenomenon itself. What Pérez-Mercader’s team has shown is that once the right environment exists, lifelike behaviour follows naturally. If it happens in a laboratory today, then it could equally have happened on the early Earth without anyone there to supervise it. Far from supporting Intelligent Design, this work demonstrates how little “intelligence” is required for the first steps toward life — none at all.
In the experimental system, a mixture of non‑amphiphilic molecules polymerises under green light. These polymers self‑assemble into micelles — spherical structures possessing both hydrophilic and hydrophobic characteristics — that trap fluid to form vesicle‑like sacs. These vesicles eventually either eject amphiphile‑laden fragments — akin to spores — or burst and release their contents. Crucially, the expelled progeny exhibit slight variations, and those more successful at survival and self‑replication become more prevalent, embodying what the researchers call a “mechanism of loose heritable variation”, a foundational element of Darwinian evolution.
The research team, led by Juan Pérez‑Mercader of Harvard’s Department of Earth and Planetary Sciences and the Origins of Life Initiative, designed this minimalistic, non‑biochemical system to reveal how life‑like properties might emerge from purely physical and chemical beginnings.
Kermit Pattison’s detailed article in the Harvard Gazette (published 22 July 2025) offers an accessible explanation of the work and its profound implications:
A step toward solving central mystery of life on Earth
Experiment with synthetic self-assembling materials suggests how it all might have begun
It is the ultimate mystery of biology: How did life begin?
A team of Harvard scientists has brought us closer to an answer by creating artificial cell-like chemical systems that simulate metabolism, reproduction, and evolution — the essential features of life. The results were published recently in the Proceedings of the National Academy of Sciences.
This is the first time, as far as I know, that anybody has done anything like this — generate a structure that has the properties of life from something, which is completely homogeneous at the chemical level and devoid of any similarity to natural life. I am super, super excited about this.
Juan Pérez-Mercader, senior author
Department of Earth and Planetary Sciences and the Origins of Life Initiative
Harvard University, Cambridge, MA, USA.
According to Dimitar Sasselov, director of the Origins of Life Initiative and Phillips Professor of Astronomy, the paper marks an important advance by demonstrating how a simple, self-creating system can be constructed from non-biochemical molecules.
As it mimics key aspects of life, it allows us insight into the origins and early evolution of living cells.
Professor Dimitar Sasselov (not involved in the study)
Director of the Origins of Life Initiative.
Harvard University, Cambridge, MA, USA.
The team sought to demonstrate how life might “boot up” from materials similar to those available in the interstellar medium.
The earliest known evidence of life are tiny fossils of ancient microbes about 3.8 billion years old. But their discovery hardly solved the mystery of just how or when life began. What simple biological molecules gave rise to complex cells? Was there a single origin or multiple events? Did life begin on Earth or on another planet?
These questions have puzzled biologists for centuries. Charles Darwin speculated that life began in a “warm little pond” and then diversified into varied forms.
In the 1950s, Stanley Miller and Nobel laureate Harold Urey conducted experiments at the University of Chicago in which they simulated the conditions of primordial Earth — an atmosphere of methane, ammonia, hydrogen, and water with electric arcs of lightning — and produced amino acids, the organic molecules that form the building blocks of proteins.
Into this debate stepped Pérez-Mercader, an energetic scientist who describes himself as a “77-year-old kid.” Trained as a theoretical physicist, he spent his earlier career investigating grand unified theories, super symmetry, super gravity, and super strings.
In the 1990s, he shifted into astrobiology and founded the Centro de Astrobiología in Madrid in collaboration with NASA, and oversaw Spain’s participation in NASA’s Mars Science Laboratory.
In 2010, he came to Harvard with another grand undertaking.
I’m trying to understand why life exists here.
Juan Pérez-Mercader.
All forms of life share a few basic attributes: They handle chemical information, metabolize some form of energy (such as consuming food or performing photosynthesis) to sustain themselves and build body parts, reproduce, and evolve in response to the environment.
Pérez-Mercader worked out mathematical equations for the basic physics and chemistry of biology and used their solutions as guidance to synthesize artificial life in a test tube.
For years, these efforts remained theoretical explorations without an experimental demonstration. Then came a laboratory breakthrough with the advent of polymerization-induced self-assembly, a process in which disordered nanoparticles are engineered to spontaneously emerge, self-organize, and assemble themselves into structured objects at scales of millionths or billionths of a meter.
At last, these tools enabled Pérez-Mercader and his colleagues to bring their theories to life — literally.
In the new study, the team sought to demonstrate how life might “boot up” from materials similar to those available in the interstellar medium — the clouds of gasses and solid particles left over from the evolution of stars in a galaxy — plus light energy from stars. A test tube served as the lab version of Darwin’s “warm little pond.”
The team mixed four non-biochemical (but carbon-based) molecules with water inside glass vials surrounded by green LED bulbs, similar to holiday lights. When the lights flashed on, the mixture reacted and formed amphiphiles, or molecules with hydrophobic (water-adverse) and hydrophilic (water-loving) parts.
The molecules self-assembled into ball-like structures called micelles. These structures trapped fluid inside, where it developed a different chemical composition and turned into cell-like “vesicles,” or fluid-filled sacs.
Eventually, the vesicles ejected more amphiphiles like spores, or they just burst open — and the loose components formed new generations of more cell-like structures. But the increasing numbers of expelled spores slightly differed from each other, with some proving more likely to survive and reproduce — thus modeling what the researchers called “a mechanism of loose heritable variation,” the basis of Darwinian evolution.
Stephen P. Fletcher, a professor of chemistry at the University of Oxford who was not involved in the new study but pursues similar research, said the PNAS study opens a new pathway for engineering synthetic, self-reproducing systems — an achievement that past experiments attained only with more complex methods.
The paper demonstrates that lifelike behavior can be observed from simple chemicals that aren’t relevant to biology more or less spontaneously when light energy is provided.
Professor Stephen P. Fletcher, (not involved in the study)
University of Oxford.
Pérez-Mercader characterizes the experiment in more animated terms. He thinks it provides a model for how life might have begun around 4 billion years ago. By his reckoning, such a system could have evolved chemically and given rise to the last universal common ancestor — the primordial form that begat all subsequent life.
What we’re seeing in this scenario is that you can easily start with molecules which are nothing special — not like the complex biochemical molecules associated today with living natural systems. That simple system is the best to start this business of life.
Juan Pérez-Mercader.
Publication:
Significance
Self-reproduction is one of the most fundamental features of natural life. This study introduces a biochemistry-free method for creating self-reproducing polymeric vesicles. In this process, nonamphiphilic molecules are mixed and illuminated with green light, initiating polymerization into amphiphiles that self-assemble into vesicles. These vesicles evolve through feedback between polymerization, degradation, and chemiosmotic gradients, resulting in self-reproduction. As vesicles grow, they polymerize their contents, leading to their partial release and their reproduction into new vesicles, exhibiting a loose form of heritable variation. This process mimics key aspects of living systems, offering a path for developing a broad class of abiotic, life-like systems.
Abstract
We investigate mechanisms for the observed nonlinear growth in the number of polymer vesicles generated during a photo-Reversible Addition-Fragmentation Chain Transfer-based polymerization-induced self-assembly (PISA) reaction. Our experimental results reveal the presence of a self-reproduction process during which chemically active polymer protocells are chemically and autonomously generated in a light-stimulated one-pot reaction that starts from a homogeneous blend of non-self-assembling molecules and which, as observed microscopically, form vesicular objects that grow and multiply (reproduce) during irradiation with green light (530 nm) as the reaction proceeds. By using a filtration-based protocol, our experiments demonstrate that the self-reproduction process occurs concomitantly with the PISA process and results in a nonlinear increase in the number of polymer vesicles during photopolymerization which can only be ascribed to their reproduction via polymeric spores ejected from previously existing first-generation vesicles. The second and subsequent generations’ vesicles also self-reproduce and continue the process of population growth.
Among the characteristics shared by all extant living systems (1–3), their chemically controlled self-reproduction ranks perhaps as one of the most spectacular and exclusive. Under the control of their internal chemical networks, and in tight relationship with their environment from where they harvest food, energy, and information, natural living systems spawn representations of themselves (reproductions) as fully functional systems which also autonomously and under sufficiently similar conditions to those of their progenitors are again capable of self-reproduction into new generations. Indeed, when living systems reproduce, their species continues to exist via their progeny and propagates as such into the future while also enabling fundamental aspects of their Darwinian evolution due to the generation by reproduction of populations which include heritable variation (4).
In extant, biochemistry-based life, even for the simpler single-celled living systems such as bacteria, the process of reproduction is complex and involves many complicated and coordinated steps. These take place within the cell under the precise control of biochemistry and collectively constitute the cell division cycle (CDC) (5). Like Virchow said in 1858 “omnes cellula e cellula” or “every cell comes from a pre-existent cell” (6–8).
However, we may ask: Is extant biochemistry (9) with its delicate and well-tuned complexity over billions of years of evolution on Earth necessary for a protocellular (10) chemical system to self-reproduce? Can one construct in the laboratory, nonbiochemical, compartmentalized chemical systems capable of autonomous self-assembly and self-reproduction? Answering these basic questions is important for systems chemistry, artificial life, for protocell research seeking to understand what life may have been like before the advent of biochemistry or Last Universal Common Ancestor (LUCA) during a so-called protocell era and for understanding the potential for life in the Universe, including exoplanets (11–13). During the protocell era, “life must have been simpler” (10, 12) and hundreds of millions of years could have elapsed evolving the transition from chemistry to some form of generalized life (14, 15), which eventually lead to LUCA. Finally, these questions are also central in the old, but nascent, field of synthetic artificial life based on nonbiochemical material implementations of fully synthetic chemical systems capable of mimicking natural living systems (10, 11, 13, 16–20).
In an effort to explore the answer to the above broad questions about the necessity of biochemistry, perhaps helping to trace back life’s origin to the “combination of carbon chemistry and the physics of self-organization,” (21, 22) and building upon the opportunities in precisely this direction offered by polymerization-induced self-assembly (PISA) (20, 23–29), we have designed a PISA batch reactor where in an aqueous solution and strictly avoiding any biochemical molecules, we synthesize amphiphiles that self-organize, self-assemble, and self-boot into chemically active micelles. (In this paper the term boot is used in the sense of computer science.) The micelles then develop into functional giant vesicular systems (GV) from just a few small (and low complexity) molecular species chosen ad hoc by us for implementing PISA. Starting from a homogeneous blend of several such simple molecules, our systems exclusively rely on chemical forces controlling the exchange of atoms among molecules, together with their physicochemical implications (30), and use light as a source of external energy. The aqueous thermostated and illuminated reaction mixture contains a hydrophilic polymer with a small, and slightly hydrophobic chain transfer agent molecule (CTA) bonded at its end (this can be further simplified if desired, cf. refs. 31 and 32), plus some selected monomers such as acrylonitrile or hydroxypropyl methacrylate (HPMA) that can be photopolymerized to the above hydrophilic polymer to yield amphiphilic block copolymer molecules. Finally, the PISA mixture also contains at least one photocatalyst or iniferter (a photocatalyst molecule that acts as initiator, chain transfer agent, and terminator of the polymerization reaction) (33) for the photopolymerization reaction. [Note that this very simplified out-of-equilibrium system can abstractly be (34) imagined as a laboratory version of a “warm little pond” where the notion of heterotrophic abiogenesis can be explored.]
After illumination is switched on, the chemical reactions start and the initially homogeneous blend produces amphiphile molecules in the bulk. As the concentration of this amphiphile increases beyond its Critical Micelle Concentration (CMC), the activity of the chemical reactions leads to liquid phase separation due to the ongoing polymerization process of the hydrophobic block in the amphiphiles, which eventually self-assemble and self-organize into micelles (35). During their self-assembly in the course of the living polymerization synthesis of the amphiphiles, these micelles entrap some of the current reaction medium, which guarantees the continuation of the polymerization reaction in their interior, although at a rate different from the one in the bulk which, consequently, generates and amplifies osmotic gradients (19, 36). In other words, by simultaneously changing the packing parameter value (30) of the living [in the sense of living polymerization (37)] amphiphile due to the increase in the length of its hydrophobic block, the ongoing internal photopolymerization reaction also powers the dynamical morphological evolution of the micelles which develop in time and eventually become micron scale vesicles (loosely called GVs). The crucial chemical difference between the materials and conditions inside the membrane and within the vesicle on the one hand, and on the other hand the bulk (environment) within which the vesicles booted-up and now exist, gives rise to a series of events which (for appropriate PISA formulations) manifest in the course of the optical microscopy observation of the giant vesicles undergoing this process.
Prominently among the above events is that during the photopolymerization (38) reaction under microscope illumination, a striking nonlinear increase in the number of self-assembled vesicular structures (19, 34, 39, 40) takes place. This immediately leads one to ask whether a) the observed increase in vesicle number is caused only by the inherent production of newer vesicles that once were smaller nano-scale micelles that developed into vesicles which are growing due to photopolymerization and consumption of chemicals during the polymerization reaction or b) if, in addition to the above, there is a contribution due to the self-reproduction of older vesicles that had previously been generated during the ongoing PISA process. We will study in this paper the details of this nonlinear increase in the number of vesicles during PISA and find b) to be the case.
S.K. Katla,C. Lin, & J. Pérez-Mercader (2025)
Self-reproduction as an autonomous process of growth and reorganization in fully abiotic, artificial and synthetic cells Proc. Natl. Acad. Sci. U.S.A. 122(22) e2412514122, https://doi.org/10.1073/pnas.2412514122.
Copyright: © 2025 The authors.
Published by the National Academy of Sciences of the USA. Open access.
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
What makes this research so devastating for creationist claims is that it strikes at the very heart of their favourite fallback position: the supposed impossibility of abiogenesis without divine intervention. Creationists insist that life could not have begun without “God-magic” because no natural mechanism could explain the transition from non-living matter to the first living cell. Yet here we see, in controlled laboratory conditions, a purely abiotic system assembling itself, reproducing, and even exhibiting Darwinian variation and selection. In other words, a central claim of creationism — that life cannot emerge without supernatural help — has been shown to be false in principle.
Of course, these vesicles are not alive in the full biological sense, but that is precisely the point. They are proof of concept that nature can, without guidance, generate the essential ingredients of evolution: replication, variation, and selection. Once that threshold is crossed, the rest of life’s history follows as a matter of inevitability. The “mystery gap” on which creationists have relied is steadily narrowing as science continues to fill in the details.
This also reveals a deeper problem for creationist thinking: their argument is rooted not in evidence but in ignorance. The history of science shows that appeals to “impossible without God” have repeatedly collapsed whenever new discoveries are made. Where once thunder, disease, and the motions of the planets were attributed to divine causes, we now have natural explanations. Abiogenesis research is doing the same for the origin of life. The Pérez-Mercader team’s achievement doesn’t claim to have solved the entire puzzle, but it proves the puzzle has a solution that does not require supernatural shortcuts.
In short, each advance like this reduces creationism further to irrelevance. The real lesson here is that science progresses by asking questions and testing ideas, while creationism stalls by declaring answers it cannot demonstrate. With every experiment that shows how lifelike properties emerge from chemistry, the creationist “God-of-the-gaps” shrinks yet again — and the story of life becomes more coherent, more natural, and more awe-inspiring.
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