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What is life and what are the minimum ingredients necessary for life? Job Boekhoven, a researcher at the Technical University of Munich (TUM), Germany, believes that evolution can explain how life can emerge from non-living matter and provide answers to these questions. He and his team are seeking to build life from non-biological components using evolution. Together with the Niederholtmeyer Lab, they recently succeeded in engineering a cell-like system capable of producing offspring, a key prerequisite for Darwinian evolution.

Non-biological components, a pinch of evolution and then … life?

“The building of synthetic life deepens our understanding of life itself and allows us to explore the minimal ingredients necessary for life. Were these ingredients present on early Earth? What molecular signatures should space agencies be looking for in their quest for extraterrestrial life?” asked Job Boekhoven, Associate Professor at the Department of Bioscience, TUM School of Natural Sciences.

He and his team are seeking to demonstrate that life can emerge from non-living matter through evolution. To this end, and avoiding biomolecules such as DNA and proteins, they are working to assemble a self-sustaining, evolving synthetic cell.

What defines evolution: replication with mutation and selection pressure

To encapsulate evolution, as Darwin described it, the team is seeking to fulfil several prerequisites. The synthetic cells must be capable of replication, and not just of producing offspring, but copies of themselves in which the information and characteristics of the synthetic ‘mother’ cell are passed on to its ‘daughters’. Then, through random mutations, certain copies must display variations in these characteristics that can give them a survival advantage. Finally, natural selection must occur: under pressure, the weakest mutants decay while the best adapted survive, continue to replicate and become dominant.

“Over time, this leads to an ecosystem with ever-improving phenotypes. If this continues for long enough, you can expect synthetic cells to develop more and more beneficial traits, like the ability to move,” Job added.

Fuel-dependent synthetic cells: they grow, produce offspring and decay when energy runs out

The team has been working on selection pressure for several years and has developed “fuel-dependent synthetic cells”: these droplet systems need a constant supply of energy to maintain themselves and therefore only exist out of equilibrium.

Job explained, “Like life, they consume fuel molecules to emerge and grow. Like life, if they aren’t fuelled frequently, they decay and dissolve. This serves as a natural selection pressure. If we feed them periodically, they naturally compete for fuel.”

The team recently discovered that, under certain conditions, the fuel-dependent synthetic cells could also produce offspring – a prerequisite for Darwinian evolution. They published their results in the journal Chem in May 2025.

Led by first author Monika Wenish, the researchers formed these offspring-producing droplets from a mixture of polystyrene sulfonates (PSS), molecules carrying multiple negative charges.

“Monika figured out that if you mix long and short PSSs, during their short lifetimes, the fuel-dependent synthetic cells remodel and produce tiny speckles, like glassy domains with the long PSSs. When the droplets run out of fuel, they decompose and expel these tiny speckles, the ‘daughters’, which become the nucleus for the next generation. They ‘live’ for a few minutes, and if we apply fuel again, they grow and continue to ‘live’, and also produce offspring after a few minutes.”

The experiment was not without its challenges, particularly when it came to fuelling the system a second time and rescuing the offspring while visualising the entire reaction chain. Monika collaborated with Henrike Niederholtmeyer and her team, and together they developed a microfluidic device capable of periodically fuelling the system and thus rescuing the offspring.

“Monika is the brains behind this work. She’s very creative and has shown a lot of perseverance on this work.”

Next steps: Transmitting characteristics to offspring

“We now have systems that are undergoing natural selection and capable of producing offspring – a major milestone we’re very excited about. But these cells do not yet pass on any information to their offspring; their survival and reproduction remain stochastic,” Job said.

To enable evolution in synthetic cells, the Boekhoven Lab aims to introduce an information-carrying molecule—a genotype, a molecule that is replicated in the cell and passed on to the next generation, like DNA in biology.

“It is important that this genotype influences the phenotype of the synthetic cell, ideally by improving its ability to produce offspring or survive starvation. We are working actively and enthusiastically on this challenge and look forward to telling you more soon.”

Synthetic cells: the potential to re-imagine how nature can support us and reshape our society

“Our society relies on living systems: yeast to make bread, mould to make cheese, bacteria to produce life-saving insulin and antibiotics, and algae engineered to generate sustainable biofuels. While natural life is remarkably versatile, it also has limits. It depends on highly specialised enzymes that operate within a narrow range of pH, solvents, and temperatures. Synthetic life allows us to expand these boundaries,” Job explained.

Breaking down plastics, degrading PFAS, or synthesising complex drugs beyond the reach of natural enzymes, for Job, synthetic cells offer the possibility of applying the powerful principles of life – in particular evolution – outside the traditional biological context, to do things that living forms cannot do and find solutions that we could not have found ourselves.

The development of synthetic life must nevertheless be approached with care, because “like all transformative technologies, it comes with risks”. Job believes that researchers have a responsibility to study and anticipate potential risks. “Synthetic life has the potential to reshape science and society. We should pursue it with rigour, responsibility, and an eye to the common good,” he concluded.

Scientific article

Toward synthetic life—Emergence, growth, creation of offspring, decay, and rescue of fuel-dependent synthetic cells
Wenisch, Monika et al.
Chem, Volume 0, Issue 0, 102578