I am both delighted and honored in posting this piece by my good friend Fernando Baquero, whose insights and deep thinking have inspired me for decades. It is particularly exciting to start our Monday posts of 2025 with his thought-provoking essay on the origin of life. This is the ideal example of what I'm hoping to provide more of in STC's future, as I mentioned in my post from last Monday. – Roberto
by Fernando Baquero
We are commemorating the centennial of the first significant scientific hypothesis aimed at understanding the origin of life, published in 1924 by Alexander Ivánovich Oparin (1894-1980). The implicit message in this wonderful-to-read publication, but not expressed as such in the text, is that life arises in a kind of primordial soup of organic and inorganic molecules dissolved in hot water. In such a soup, these molecules interact, eventually evolving to form complex colloids that are then trapped as coagulates or precipitates, "strikingly reminiscent of that of protoplasm." However, Oparin didn't write a single word about the origin of organs or functions. Interestingly, his basic view on the origin of life based on molecular assembly and evolution has not been seriously challenged in a century, just slightly modified. For example, in more recent times the concept of compartmentalization via Oparin coagulates has been replaced by the concept that pre-biotic molecules may be captured by spontaneous self-assembled vesicles.
My recently published heterodox approach is based on the possibility that organs, organelles in bacteria, could have preceded organisms as independent bodies in the primordial soup. In other words, functions associated with assemblies of molecules forming proto-organs could have existed before the existence of cells, functioning and evolving for their own persistence. These proto-organs are (re)produced by iteration of the same chemical assembly. This produces an equivalent to reproduction, a condition for Darwinian selection.
Organs before cells?
In our view, the possibility that a limited ensemble of molecules inside a vesicle could give rise to a vital organization, based on the local development of the right association of organs, is extremely low. Certainly, much lower than if the vesicle captures not just separate molecules but pre-formed, already functional, extra-vesical proto-organs (See Figure). Different assemblies of proto-organs in a vesicle might have coevolved, first for self-maintenance, then for replication. The fittest of these ensembles of proto-organs gave rise to the first microorganisms. Just a week after our publication, another Spanish team working with a Miller’s like technology presented evidence of concomitant formation of protocells and prebiotic compounds. Of course, most of the successful molecular assemblies in the primitive microbial protocells disappeared by natural Darwinian selection over billions of years and only the ones structuring modern microorganisms survived. This reinterpretation of Oparin's proposal might offer an innovative way to test the possibility of extracellular functions associated with proto-organs. Of course, it implies that microbial life might have evolved in different places of the Universe according to the local conditions. In turn, this casts doubt on our ability to recognize life outside our planet, if it does not conform with the image we have of life on Earth.
Legend of Figure. A highly simplified scheme showing how vesicles in light blue capture simple entities or more complex pre-formed ensembles red and green small circles that should have emerged from molecules with lower levels of complexity. In the upper panel, in different prebiotic environments squares, some of these entities composed of 1, 2, or 3 members represented by numbers and letters will become part of self-constructed, more complex and 6-membered shaped ensembles combining numbers and letters. Such ensembles might acquire some primitive functions, such as ensuring their permanence in time or modifying the environment, and are considered proto-organs red and green rectangles. The possibility that, by capturing only simpler entities, a proto-organ will develop inside a vesicle should be extremely low. In the center of the upper panel, a vesicle captures with the same probability various simple molecules or relatively complex proto-organs. The larger the number of captured components of proto-organs, the higher the probability for the emergence inside a vesicle of a 6-member proto-organ. The possibility of having two or more different proto-organs in the same vesicle, and the resulting interactions between them, will contribute to the organ functional maturation and the vesicle will evolve as a proto-organism. In the lower panel, the larger associations of proto-organs tend to cluster in space and time, depending on their stability in particular environments, in such a way that they increase their possibility of being captured by the same vesicle forming big red or green circles, proto-organisms. The probabilities shown apply only to the number of elements in this schematic figure, and are presented exclusively as an example: in the natural world, the differences in probability should be much higher in favor of the capture of proto-organs by vesicles, thus facilitating the origin of proto-organisms. Source
Fernando Baquero MD, PhD, is a Professor in the Area of Biology and Evolution of Microorganisms at the Ramón y Cajal Institute for Health Research, Carlos III National Institute of Health, Ramón y Cajal University Hospital, 28034 Madrid, Spain.
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