Artificial organs: where are the limits?

Artificial organs: where are the limits?

The creation of new organisms is the final objective of synthetic biology. Ref. Art.: Ollé-Vila, S.; Duran-Nebreda, S.; Conde-Pueyo, N.; Montañez, R.; Solé, R. (2016). A morphospace for synthetic organs and organoids: the possible and the actual. Integrative Biology



Ronyó bioimprès amb impressora 3DThe creation of new organisms is the final objective of synthetic biology. This field of science appeared at the beginning of XXI century and, since then, we have seen scientist genetically modifying bacteria in order to degrade plastic polymers or even produce human kidneys using 3D printers. 

As synthetic biology and tissue engineering progress, it becomes necessary to know the bound of possible concerning to new organisms. Are all biological structures we can imagine viable? If not, what are the limitations imposed and why? Scientists at the Laboratory of Complex Systems from UPF have defined a space of known biological structures and propose the use of synthetic biology as a tool to investigate those paths unexplored by evolution.

The boundaries of the biologically possible 

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Advances in each of these disciplines, synthetic biology and tissue engineering, have been notorious. Among them, it is worth highlighting the creation of the so-called organs-on-a-chip, devices that microscale reproduce functions of a real organ and allow its study, or the creation of organoids in 3D cultures, that carry out development processes creating a structure which is similar to natural organs, having autoorganization a critical role. However, these examples are based in the imiatation of organs or functions that already exist in nature. As the authors propose, " there is no reason to only build organs and tissues as they exist in nature. We could think of, and design, novel organs that can still perform, but also expand, the functions of their natural counterparts." Such enhanced physiology could entail including completely new functions or even the capacity to diagnose and cure diseases. A striking example is the bioprinted bionic ear integrating chondrocytes in alginate along with printed silver nanoparticles in the form of an inductive coil antenna (cyborg organs). 
But, when talking about synthetic biology and tissue engineering, certain restrictions exist. This does not mean that we are necessarily limited in engineering complex cellular structures, but should consider the potential constraints associated to the system and organ-level of organisation.

The morphospace

Many new biological structures and functions are far from the path set by evolution. "Freed from the constraints of developmental processes, new rules of engineering biological matter can be found." Scientists have categorized known structures according to a set of variables. These variables define the morphospace in which the structures are arranged, showing those regions forgotten by evolution.

Morfoespai dissenyat per Laboratori de Sistemes Complexos UPF

The team led by Ricard Solé has defined this organ and organoid morphospace with which contemplating the unverse of all the possible biological structures. The three axes that make it up are: developmental complexity, cognitive complexity and physical state. The developmental complexity levels range from simple mixtures of unrelated cells to fully developed organs with interacting cells that perform a common function, as would be, for example, the liver. Underdeveloped systems would be the so-called chemostats, bacterial cultures commonly used in industry for the production of certain substances, such as some antibiotics. Regarding the degree of cognitive complexity, it is defined as the ability of organs to receive and process information. Thus, the brain, with its many neural connections and its plasticity, or the immune system, with the ability to detect new threats as both the familiar and respond to all of them, represent two examples of the highest degree of cognitive complexity. The third axis of morphospace, physical condition, taking as reference the phases of inorganic matter and is intended to describe the mobility of the components of organs and organelles. Thus, we find the vast majority of biological structures in the "solid", with some notable counterexamples like blood or microbiome, characterized by greater mobility of its elements.

Taking these three axes, the research team has made a snapshot of the current landscape of possible biological structures. One of the most interesting features of morphospace is the presence of an empty space that can have two meanings. The first is that the proposed combination in that region is not possible. The second, more encouraging, is that it is an inaccessible design for evolution under natural conditions but that it could be achievable using biological engineering strategies. In any case, the morphospace is a very useful tool to raise the chances of success would have new biological designs.


Reference article: Ollé-Vila, S.; Duran-Nebreda, S.; Conde-Pueyo, N.; Montañez, R.; Solé, R. (2016). A morphospace for synthetic organs and organoids: the possible and the actual . Integrative Biology 8:485 – 503. April 2016. DOI: 10.1039/C5IB00324E