We must face the ethical challenges of engineering life
Scientists have a duty to initiate a dialogue with the public on cellular engineering, says Daniel Müller. The discussion must be held now – before complex engineered cellular systems are ready for widespread use in humans.
Gene therapy is at long last becoming available for the treatment of human disease. There are now approved gene therapeutic treatments for conditions as diverse as inherited blindness, childhood spinal muscular atrophy and some types of blood cancer. These therapies typically compensate for defects in a single gene by delivering the properly functioning gene to a patient either using viruses or cells as vehicles.
Meanwhile, in the laboratory, the engineering of cells is going far beyond this relatively simple strategy. Researchers are also using non-human genes and are engineering cellular systems with complex functions, including some that are entirely new to humans (known as “de novo” functions). All of this leads to ethical questions that we must now address.
“Societal discussion should happen in a meaningful way that brings representatives of many schools of thought to the table.”Daniel Müller
One example of such advanced approaches is a new therapy for congenital blindness, a disease in which photoreceptors in the retina degenerate. Very recently, researchers succeeded in restoring the visual function of a blind patient using a light-sensitive protein from an alga.1 At least in a thought experiment, we needn’t stop there, since light-sensitive proteins exist not only in the light spectrum visible to humans. Snakes for instance have proteins that respond to infrared light. Recently, such proteins were used to engineer infrared vision in laboratory mice.2
blood sugar levels3 and secrete a blood sugar-lowering hormone in response to high sugar levels. In a related project, the cells secrete the hormone in response to coffee consumption, thus linking diabetes control to an activity that is part of a normal lifestyle for many people.4
Even though it will be a while before such engineered molecular and cellular systems are used in humans, it is very likely that one day this will be the case. Compared to conventional drugs, these therapies may have the advantage that their effect is gentler and more similar to human physiology.
Participating in decision-making
If we want to bring these new technologies to the people, caution and conservatism is the most prudent path forward. Perhaps most importantly, the general public must be both empowered and invited to become an active player on par with researchers in the decision-making process.
Some of the issues raised by synthetic cellular constructs are already known from stem cell and gene therapy: these treatments will be extremely expensive and therefore exacerbate the pre-existing gulf between those who can afford cutting-edge treatments and those who cannot. Another point to consider: since they could be curative as one-time treatments and remain in the body for life, how do we ensure shut-off mechanisms in case something goes wrong and the intervention exacerbates the disease?
Impact on human identity
But even more fundamentally, there must be a broad societal discussion about whether we should put engineered cellular or molecular constructs into human bodies at all. And if we do, we need to ask ourselves which functions should be engineered and how to prevent them from getting out of control in ways we cannot even imagine.
Furthermore, would a person with bioengineered functions be fully accountable for their own behaviour? If not, who would ultimately bear responsibility? Similarly, do we as a society accept persons having new or considerably improved de novo capabilities such as infrared vision or immunological enhancement? Certainly, once we start engineering basic and enhanced functions of life, this will challenge our current concepts of human identity, personhood and the conditio humana per se.
Time to seek and find consensus
It is not up to scientists alone to decide whether this is a path we should take. We should not reach the stage of clinical translation of complex engineered cellular or molecular constructs without deciding, as a global society, whether we can accept the deliberate engineering of human beings – and if so, for what purpose and with which limits.
Considering the rapid advances that these approaches are making in animal models and the precedents set by gene therapy, the time to seek a societal consensus on engineered cellular systems is now. While it is easy to call for broad societal discussion, it is difficult to say how this should happen in a meaningful way – that is, in a way that brings to the table representatives of many schools of thought – societal, cultural or religious – but also in a context that can actually influence policy.
A cross-cultural, cross-disciplinary dialogue
As scientists, we do not claim to know how best to carry out this gargantuan task. But we do have a responsibility to bring the subject of cellular engineering to the attention of the public and to facilitate open discussion by providing a framework where true dialogue can take place.
Our own efforts in this direction include an ethics think tank5 established in 2017 that comprises our National Centre of Competence in Molecular Systems Engineering as well as the Pontifical Academy for Life, the Bambino Gesù Hospital and the Istituto Superiore di Sanità, all in Rome. Next week, this group will hold a conference on the Ethics of Engineering Life,6 with express support for young attendees and delegates from countries outside of Western Europe and the United States.
In bringing together experts and laypersons from different nations, cultures, world religions and disciplines, this conference hopes to host a discussion in which all stakeholders participate on equal footing. We need a broad dialogue on the unique potential and risks of molecular and cellular systems engineering in order to reach a consensus between divergent views and values.
Daniel Müller discussed and wrote this article together with Natalie de Souza, Scientific Officer and Lecturer at the Institute of Molecular Systems Biology at ETH Zurich.
1 Sahel JA et al.: Partial recovery of visual function in a blind patient after optogenetic therapy. Nature Medicine 2021, doi: external page 10.1038/s41591-021-01351-4
2 Nelidova D et al.: Restoring light sensitivity using tunable near-infrared sensors. Science 2020, doi: external page 10.1126/science.aaz5887
3 Xie M, et al.: Beta-cell-mimetic designer cells provide closed-loop glycemic control. Science 2016, doi: external page 10.1126/science.aaf4006
4 Bojar D, Scheller L, Hamri GC, Xie M, Fussenegger M. Caffeine-inducible gene switches controlling experimental diabetes. Nature communications 2018, doi: external page 10.1038/s41467-018-04744-1
5 external page Ethics Think Tank
6 external page International Conference Ethics of Engineering Life