Understanding life and finding its origins remains one of the great enigmas of our times. Some people go looking for answers in outer space, retracing the history of the earth, others, such as Prof. Job Boekhoven, Associate Professor of Supramolecular Chemistry, and his team, try to synthesize life in the lab using simple molecules and chemical reactions.
Why are scientists trying to synthesize life?
The use of different life forms, such as yeast strains and bacteria, has long been part of our food production, including traditional Bavarian products such as pretzels (Brezen) and beer. Nowadays, genetic modification of such life forms has become an accepted method for producing life-saving medications, such as antibiotics and insulin, from fungi and bacteria, as well as sustainable biofuels from algae. Yet, despite disposing of a vast array of genetic tools, we still rely on highly specialized enzymes that operate in a relatively narrow window of pH, solvents, and temperature. On the other hand, using synthetic life, we could work outside of the classical operation window of life, potentially revolutionizing biotechnology, medicine, and materials science. Thus, we could envisage a life form capable of converting plastics into useful monomers at 250°C in an organic solvent, or a life form capable of degrading PFAS, a persistent ‘forever chemical’ currently polluting our soils and surface waters. These are just a few examples. However, before going into the scientific approach taken by the Boekhoven lab, synthetic life, and indeed life itself need to be clearly defined.
“Such is life”, a well-known phrase used on a daily basis. But what exactly is life, how do we define it, how did it arise, and can we mimic it?
How did life arise from non-living matter? The Big Bang Theory explains how sub-atomic particles and atoms first arose. Subsequently, it is thought that simple organic molecules arose, whether in the early Earth’s oceans, skies, or primordial soup, through a series of chemical reactions and processes. These molecules then replicated and evolved through natural (Darwinian) selection, eventually leading to the complexity of life. So, life did not originate from nothing, but what is it, when do we speak about (synthetic) life?
During the two-week workshop “Engineering Life” organized by the Origins Cluster in 2023, 57 scientists from over 14 countries debated at length not just the technical challenges of synthesizing life, but also the social and philosophical challenges1. Four criteria were defined as the fundamental prerequisites of life: self-sustaining, self-replicating, (randomly) mutating and open-endedly improving through a selection of the fittest. Hallmarks associated with life are compartments, growth and development, metabolism, reproduction, responding to stimuli, and adaptation through evolution. Only if these criteria are fully met do we speak of (synthetic) life.
The Boekhoven lab has chosen a so-called bottom-up approach to create synthetic life, that is, starting with a few (simple) molecules and using chemical reactions they continually build up the complexity of their system to eventually meet the above criteria. The model system they use consists of coacervates, liquid droplets with a high density dispersed in a dilute phase, similar to oil or gelatin droplets dispersed in water. These droplets form spontaneously from aqueous mixtures and, despite not having a membrane, provide stable compartmentalization. Without a membrane, reactants can move in and out of these droplets. Hence, the droplets could function as a “replacement cells”, putatively reflecting what took place on early Earth. However, these droplets are typically stable in equilibrium, whereas life constantly requires energy and nutrients to maintain its non-equilibrium state.
Hence to mimic biological traits, the Boekhoven lab engineered fuel-dependent droplets2. Specifically, under conditions that normally do not allow the spontaneous formation of coacervate droplets, a fuel was added, inducing a chemical reaction whereby the corresponding electrostatic changes in turn induce the formation of droplets. Importantly, the droplets grow in the presence of fuel, but decay (dissolve) without it. Moreover, the system can be tweaked such that large droplets can fragment to form offspring, resembling the way certain bacteria can sporulate. The offspring, in turn, inherit material from their “parent”. When fuel is supplied periodically (i.e., starvation cycles), some droplets dissolve, and others survive until the next round of fuel.
The next step undertaken by the Boekhoven lab was to add some form of a genetic/hereditary component to the system3. In living organisms, so-called genotype-phenotype coupling is observed, whereby the genotype is the complete genetic information of the organism, and the phenotype its “appearance” or observable traits and functions. A spontaneous mutation or change of the genetic information that benefits the organism’s survival and/or reproduction will provide a positive selection for organisms with this mutation at the expense of others without it. Hence, natural selection or the “survival of the fittest” as already described in the fifth edition of “On the Origin of Species” by Charles Darwin in 1869, occurs.
To add this component to the fuel-dependent droplets or synthetic cells, an autocatalytic replicator was used. This is not a piece of DNA or RNA, but rather a chemical reaction capable of catalyzing its own production from building blocks. The fidelity of the autocatalytic reaction is determined by the selective use of the right building blocks for its production. Their experiments identified an autocatalytic replicator named KR3 (= genotype) benefitting from encapsulation into fuel-dependent droplets (synthetic cells), as filtering of the appropriate building blocks by the droplets (i.e. differential partitioning) ensured a decreased error rate concomitant with an increased KR3 production. Conversely, droplets containing the replicator genotype displayed a different morphology and their lifespan (= phenotype) was increased more than 3-fold. Importantly, this mutual relationship between genotype and phenotype was maintained over multiple cycles of fueling and starvation. These experiments are a demonstration of reciprocal support of genotype and phenotype, capturing a fundamental aspect of life whereby, on a very primitive level, an organism functions as a survival machine for its genes, ensuring their continued replication and evolution.
The coacervate droplets and replicators used by the Boekhoven lab are still far removed from “living in a bubble” and showing Darwinian evolution, yet they bring us a step closer to understanding the fundamental principles underlying life. Future experiments will explore improved molecular recognition mechanisms to enhance selective replication and incorporate aspects such as synthetic cell division and metabolism. Ultimately, the Boekhoven lab aims not just to explore the boundaries of science but to offer a tangible and useful real-life application.
Publications
A roadmap toward the synthesis of life. Kriebisch, Christine M.E. et al. Chem, Volume 11, Issue 3, 102399 https://doi.org/10.1016/j.chempr.2024.102399
Toward synthetic life—Emergence, growth, creation of offspring, decay, and rescue of fuel-dependent synthetic cells Wenisch, Monika et al. Chem, Volume 11, Issue 9, 102578 https://doi.org/10.1016/j.chempr.2025.102578
- Primitive genotype-phenotype coupling in fuel-dependent synthetic cells with an autocatalyst. Soria-Carrera, Héctor et al. Chem, Volume 12, 102816 https://doi.org/10.1016/j.chempr.2025.102816
More links and information
- Prof. Boekhoven’s profile: https://www.professoren.tum.de/en/boekhoven-job
- BoekhovenLab https://boekhovenlab.com
- Department of Bioscience in the TUM School of Natural Sciences https://www.bio.nat.tum.de/en/bio/homepage/
Press contact
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