In exploring the possible surfaces of encounter between human action and the complexity of living things, the gaze can rest on an infinite number of places, from patterns on design objects to the search for life beyond planet Earth. In the next articles, our focus will be on a particular category of technological constructs: biohybrid systems.
(The photo shows the blood-brain barrier on a chip. The blue dye shows where the brain cells would go, and the red dye shows the path for blood circulation.)
Biohybrid systems merge biology and engineering to replicate the functions of living systems or to develop components with life-like behavior, improved biocompatibility, and better sustainability. They are designed and developed for industrial, clinical, environmental purposes, but also for basic research in robotics and biology.
In particular, by defining these systems as a category of their own, a difficult question arises: where is the boundary between the artificial component and the biological component?
The hybrid nature of these entities embodies the encounter between two worlds that, when kept separate, can define themselves by negating the other, but when they meet, they highlight the incomplete definition of their domains.
For example, to generalize, a biohybrid system is composed of an artificial part and a natural part. The artificial component of the system is directly opposed to the natural one, in this definition, and is said to be obtained with art. Where does human art end and nature begin in a biohybrid system? If humans are a biological system, is human art and technology, in fact, artificial? And is a natural system used skillfully to perform a technological function not itself artificial?
These questions arise from the meeting of two worlds, which biohybrid systems realize, and highlight the limited scope of the definitions present in our language. Wanting to name things, a strategy to build a coherent, appropriate, and complete definition of what composes the biohybrid is to start from the definition of the isolated components.
The artificial component often has "negative" definitions: everything that is not natural, the reproduction of something natural but made by humans, the artifact. The theme of human design of the artificial product recurs, the implementation of a project decided a priori, as opposed to the uncontrolled flow of nature.
Wanting to define what is natural, instead, in the context of the study of biology we find ourselves asking what the definition of a biological system is. This question directly refers to a far-reaching question: what is life, and what is alive? It is interesting to note how this question has taken shape in the field of exobiology, a branch of biology that investigates the possibilities of extraterrestrial life. To be able to
recognize life outside the environment in which we are used to experiencing it, it is necessary to define it.
In 2010, S. Benner explores this question with the article Defining Life in the journal Astrobiology. The first point he starts from is clarifying the difference between the two definitions: "alive" and "life." Something that is alive may not have all the characteristics necessary to define life. For example, a cell from our skin is alive, but it is not life.
Benner cites one of the attempts to provide a universal definition of life, that of Koshland (2002): the seven pillars of life, or the "PICERAS" definition, where PICERAS is an acronym for programming, improvisation, compartmentalization, energy, regeneration, adaptability and seclusion.
Programming An organized plan that describes both the ingredients themselves and the interactions between the ingredients, so that the living system persists over time. In natural life as known on Earth, the program operates through the mechanisms of nucleic acids and amino acids, but the concept of a program can apply to other mechanisms imagined or not yet discovered.
Improvisation The ability of the living system to modify its own program in response to the broader environment in which it exists. For example, evolutionary processes and their impact on the genome of species.
Compartmentalization The separation of spaces that make up a biological system that allows the separation of environments in which different chemical processes take place. Compartmentalization is necessary to create a chemical environment protected from the outside in which reactions can consume and produce chemicals in the right quantities.
Energy Since living systems necessarily move, and this corresponds to an increase in entropy and an expenditure of energy, the latter is necessary for a living system to exist.
Regeneration The general compensation of losses and degradation of the various components and processes of the system: thermodynamic loss in chemical reactions, wear of structural components, and decline due to aging. Living systems compensate for these losses by importing molecules from the external environment, synthesizing new molecules and components, or giving rise to new generations of organisms.
Adaptability The ability of a living system to respond to needs, dangers, or changes. It differs from improvisation because the response is timely and does not involve a change in the program. Adaptability occurs from a molecular level to a
behavioral level through systems that react to events in the environment. For example, an animal that sees a predator might respond to the danger with hormonal changes and an escape behavior.
Seclusion The separation of chemical pathways and the specificity of the effect of molecules ensures that processes can function separately within the same living system. In organisms on Earth, each protein has a precise structural conformation, which is specific to its function, so that it can act selectively on its targets without affecting other parts of the system.
These are the characteristics that according to Koshland define life. However, according to this definition, a rabbit considered individually would not be life, even if it itself has all the listed characteristics. Life, instead, would be a pair of rabbits able to reproduce. Moreover, the list captures the thermodynamic, genetic, physiological, metabolic, and cellular characteristics of terrestrial life as we know it. However, it does not offer theoretical foundations to support that these characteristics should be generalized to possible forms of life that we have not yet observed.
Other definitions of life that attempt to offer such theoretical foundations have been proposed. For example, in 1994, Joyce summarized the discussion of a committee convened by NASA, at the suggestion of Carl Sagan, in these terms: life is a self-sustaining chemical system capable of Darwinian evolution.
The term "system" emphasizes the notion that, returning to the distinction mentioned above, entities can be alive (a cell, a virus, or a single rabbit) without individually exemplifying life. The expression "self-sustaining" is meant to imply that a living system does not require intervention by another entity to continue to be life.
Darwin's theory of evolution gathers his observations that groups of organisms of the same species gradually evolve over time through the process of natural selection. In this context, the expression "Darwinian evolution" refers to the process, developed from this theory over the last 150 years. This is based on a molecular genetic system (DNA, in terrestrial life) that can be replicated, sometimes imperfectly. The errors resulting from imperfect replication can themselves be replicated, and the organisms resulting from the variety of these replications are more or less well adapted to the environment. Depending on their degree of adaptation, the probability of passing on genetic information to subsequent generations changes. And so, with generational cycles, the genetic heritage of each species also evolves, reflecting its changes and adaptations to the environment.
In principle, current technology allows us to artificially modify the genome of offspring: our species in this way can bypass and modify Darwinian processes. How then does the reference to "Darwinian evolution" fit into Joyce's theoretical definition? Is it enough to include a new mode of evolution: a self-sustaining chemical system capable of Darwinian or supra-Darwinian evolution?
The questions about the relationship between what is natural and what is artificial, instead of being resolved, multiply.
In 2019, Vitas and Dobovisek published the article Towards a General Definition of Life to modify and extend the definition proposed by NASA in 1994: life is a chemical system far from equilibrium that maintains itself in equilibrium, capable of processing, transforming, and accumulating information acquired from the environment.
The novelty in this definition is the attention given to the thermodynamic aspects of living systems. Thermodynamics is a branch of physics that deals with heat, work, and temperature, and their relationship with energy, radiation, and the physical properties of matter. In practice, the authors define life as a system far from equilibrium.
When a system is in equilibrium, there are no flows of matter or energy, neither within it nor with the environment. In systems that are, on the contrary, in a state far from equilibrium, there are flows of matter or energy. This definition of life therefore places great importance on the flow of information from the environment to the living system. The new proposed definition of life is independent of how genetic information evolves, and therefore includes, from the previous one, both Darwinian and supra-Darwinian processes, making it more easily extendable to other, now unknown, processes of information exchange between biological systems and the environment.
According to these definitions of what is alive and what is life, is a biohybrid system alive? Is it life? Where is the boundary between life and artifice? Sometimes, one of the best ways to explore these questions is to build the system under analysis. In the next articles, various biohybrid systems will be described, to continue exploring the blurred and shifting boundary between what is and is not called life.
Roberta Bardini is a researcher in the field of computational biology and systems. She currently works at the Sysbio Group, Politecnico di Torino, where she obtained her PhD. She works on the development of multicellular organisms, and their valorization in the entrepreneurial field.
