The creation of new organisms is the final goal of synthetic biology. This field of science emerged at the beginning of 21 st century and, since then, we have seen scientists 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 bounds of possibilities concerning new organisms. Are all biological structures we can imagine viable? If not, what are the limitations imposed and why? Scientists at the Complex Systems Lab at UPF have defined a space of known biological structures and propose the use of synthetic biology as a tool to investigate the paths unexplored by evolution.

The boundaries of the biologically possible

Advances in each of these disciplines, synthetic biology and tissue engineering, have been remarkable. Among them, it is worth highlighting the creation of the so-called organs-on-a-chip, devices at microscale that 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, with self-organization playing 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 designing complex cellular structures, but should consider the potential constraints associated to the organization of biological structures.

The morphospace

Many new biological structures and functions are a long way from the path marked out 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.

The team led by Ricard Solé has defined this organ and organoid morphospace with which to contemplate the universe of all 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 and already known threats and respond to all of them, represent two examples of the highest degree of cognitive complexity. The third axis of morphospace, physical condition, takes as reference the phases of inorganic matter and seeks to describe the mobility of the components of organs and organoid. Thus, we find the vast majority of biological structures in “solid” state, with some notable counterexamples like blood or microbiome, characterized by a greater mobility of their 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 thatcould be achievable using biological engineering strategies. In any case, the morphospace is a very useful tool to raise the chances of success new biological designs would have.

Work of reference: Aina Ollé-Vila, Salva Duran-Nebreda, Núria Conde-Pueyo, Raúl Montañez, Ricard Solé. A morphospace for synthetic organs and organoids: the possible and the actual. Integrative Biology, 2016, 8, 485 – 503. April 2016. DOI: 10.1039/C5IB00324E