Xavier Guchet
University Professor
University of Technology of Compiègne

Biofabrication refers to the manufacturing of hybrid and highly organised 3D structures combining biomaterials, living cells and various elements necessary for cell life in an extracorporeal environment (for example, growth factors or nutrients). Biofabrication is the very type of a technology with a broad spectrum which can serve as a basis for many applications.

In the medical field, the current trend is to probe the ethical issues of this type of technology along a whole process called "translational": these issues are indeed examined at each stage of the design and validation of the technology, from the research laboratory to the patient's bedside, including preclinical studies (in vitro or in animal models) and clinical trials involving the human person. This global point of view on the whole biofabrication value chain implies a very strong ethical requirement: that is to ensure that all the actors involved never lose sight of the overall purpose of their respective work, namely to bring a real benefit to the patient.

Each stage of the translational process of biofabrication raises specific ethical issues.

An essential ethical issue in research is the need for researchers, scientists or engineers not to forget that their devices will be used by flesh and blood patients who are vulnerable and likely to have a bad experience with them. The organisation of the translational process does not always allow to put researchers in direct contact with patients, far from it, resulting potentially in a more or less abstract perception of the latter by the former. In these conditions, how to bring them to better understand the requirements, not only to provide medical treatment in the sense of seeking technical efficiency (cure), but also to look after the patients with the moral concern due to them (care)? How could technologies conceived far from the worlds of care, and in ignorance of what care really is, contribute not only to improve the technical aspect of the medical treatments per se, but also to satisfy the moral vocation of taking care that defines the professional work of caregivers?

Other important ethical issues raised by biofabrication should be considered at the stage of laboratory research, well before developments and applications. In addition to the question of toxicological risks, there is also that of the possible use of non-human cells for the biofabrication of tissues or organs intended to be implanted in the human body. If authorised by law, this possibility would raise specific ethical questions – related to interspecific hybridisation, i.e. the blurring of the boundaries between living species, and ultimately the experience of patients who have received this type of device - that the use of human cells would not.

At the stage of preclinical studies, the most debated ethical question relates to animal testing. In that regard biofabrication can provide promising prospects. As an example, the development of research aiming at manufacturing organoids (that is to say simplified and miniaturised versions of human organs) raises the hope that eventually animals will no longer be needed for pharmacotoxicology tests. There is no doubt that this field of application benefits from a very positive ethical consideration.

When reaching the clinical trial stage, i.e. the testing of devices on cohorts of human subjects, questions must be raised that are not specific to biofabrication. These questions revolve in particular around the informed consent of trial participants, the inherent uncertainty in the results of the trial and participant education (in particular on the risks involved), the criteria for inclusion in the trial and, correspondingly, the equal access to innovative protocols.

A broader ethical issue in biofabrication concerns the understanding of this technology by the general public. The term used, biofabrication, can indeed be misleading since it is not about creating life. Biofabrication consists instead in letting the cells do their work, by placing them in adequate environmental conditions. A tissue or an organ is not manufactured, instead cells are provided with everything they need to rebuild the tissue or organ of interest themselves. Biofabrication is not manufacturing strictly speaking, at least if the term manufacturing alludes to the conventional engineer who combines materials according to a pre-established plan, and who therefore has complete control of the whole process which leads to the final structure. In this sense, biofabrication is less a fabrication than a more or less well-controlled management of living processes, guided by imagery and modeling.

This clarification is important insofar as any misunderstanding should be avoided: the bioengineer does not create life, instead he lets himself be led by life. The word biofabrication should not be understood as the fabrication of bios (life in Greek) but rather as the fabrication by life, that is to say by cells that have been recruited to do what engineers cannot do in a purely artificial way.

Most of the time, the bioengineer can convey in the public the image of an engineer animated by what the ancient Greeks called hubris: the absence of any fair measure and discernment in technical activity, shutting down any capacity to know what to do or not to do and where to place the limits. Most often the bioengineer is regarded as a tinkerer of life, seeking to submit all the processes of life to his rule. He (or she) would be the ultimate champion of the Cartesian maxim : to become "as master and possessor of nature" - except that he (or she) would have simplified the formula by forgetting the "as". Bioengineering would thus be the acme of the will to master nature and life. Ethically, the cursor is inevitably in the red.

However, biofabrication precisely does not espouse this image of an engineer carried away by his hubris. His attitude is less mastery than modesty and, let's say, care. Cells demand care, otherwise they die. Furthermore, they never behave exactly in the manner that is expected of them, they are recalcitrant: it is impossible to control them. The bioengineer above all pays attention to the cells and their needs.

An artificial heart is made without the assistance of cells. In this field, the engineer can consider having full control of his trade: isn't the heart a pump? We know how to make pumps. However, a liver cannot be fabricated; it must be biofabricated, that is to say made by life itself. In this case the engineer can only go along processes that he (or she) does not control.

Therefore, the transversal ethical issue of biofabrication is huge. Indeed, these new engineering methods do not only add to the plethora of existing methods, they lead us to wonder about the very meaning of engineering as a whole: are we ready to admit that our technical course of action, in a high-tech context included, may be subject to another imperative than the desire to master nature in order to exploit it without limits - that it may even be the complete opposite: a search for efficiency obtained above all by an attitude of caution and care?

Biofabrication could suggest a fallback strategy: we cannot manufacture a liver using conventional engineering approaches; therefore we are obliged to entrust the task to cells. In short, this would be an acknowledgement of helplessness, in other words a negative view of biofabrication seen as a makeshift solution for engineers who do not know how to proceed. Yet, it is possible to have a much more positive view: biofabrication could indeed lead us to ponder on what it can mean today, for engineering as a whole, to take care of nature and living beings. In essence, it could introduce a new image of the contemporary engineer: that of a manipulator taking care of what he manipulates.