There is no doubting the importance of biomedical research carried out by Juan Carlos Izpisúa and his team (1). Their work is focused mainly on:

  • a) the production of hybrids or human-animal chimeras;
  • b) the development of methods to make the CRISPR technique more efficient (see HERE), and
  • c) in vivo cellular reprogramming to prevent aging (see HERE). Now, however, the group has expanded its research objectives to the production of human embryoids for use in biomedical research.

While all these research fields have undeniable importance, both medical and social, they also raise objective bioethical concerns.

Human-animal chimeras bioethical implications

The group’s experiments for creating hybrids or chimeras were first published in May 2015, in an article in Nature. Essentially, they consisted of injecting human embryonic stem cells into mouse embryos so that they could generate quasi-human organs, which could be used for transplantation in human clinical practice. However, given the difficulty posed by the size of these organs, since they were experiments in mice, in 2017 they produced human-animal chimeras with larger animals – pigs and cattle (read HERE).

Organs for human tissues transplantation

Obtaining human-animal chimeras [read more HERE], i.e. animals that house human cells, and possibly in the future also tissues and organs, has great potential for biomedical research, but above all for the production of organs for transplantation.

Nevertheless, irrespective of their biomedical interest, these experiments present objective bioethical issues, which can be summarized as:

  • a) some of these experiments use stem cells from human embryos, which must be destroyed in order to obtain them;
  • b) the potential for the human cells implanted in the animal to colonize organs other than the one they are intended to produce is not fully controlled;
  • c) such colonization could even reach the brain or reproductive organs of the animal receiving the transplant (see more HERE), which would add a further bioethical difficulty;
  • d) the threat to the conceptual, social and moral boundaries that distinguish human beings from other creatures; and
  • e) biosafety and animal welfare issues.

These ethical problems have led to an international consensus calling for the termination of pregnancy of the chimeric animals at 14 days, as was done in the experiments mentioned here. However, Japan has disassociated from this consensus, having approved new rules in March this year allowing the implantation of chimeric embryos in animal mothers, their gestation and subsequent birth.

Continuing on with their research, Izpisúa’s group has now published an article in the journal Cell, in which they describe a method for obtaining “blastoids” in vitro; these are embryonic structures in the blastocyst stage that can simulate the early stages of embryonic development in vitro. In this paper, it should be noted that the blastoids were obtained from stem cells derived from adult cells.

Whether or not these embryoids may be considered as human. Embryoids’ anthropological status and animal chimera status are the centers of bioethical concerns.  Genetic differences between embryoids and human embryos do not provide a well-defined boundary.

Bioethical approach.

Concerns about human embryoids anthropological status

From a bioethical point of view, the possibility of obtaining in vitro models to study embryonic development, without having to use a real human embryo, is attractive.

In the study (see HERE), some blastoids obtained were implanted in the uterus of mice, resulting in the generation of tissues — albeit disorganized — but never managed to produce a viable embryo. Nevertheless, the authors note that his work “pave[s] the way to creating viable synthetic embryos by using cultured cells”.

From a bioethical point of view, we believe that the genetic differences that separate these embryoids from human embryos resulting from fertilization do not provide a well-defined boundary for consideration as humans or not (embryoids anthropological status), so their manipulation or destruction could lead to an attack on their intrinsic dignity if they are considered as individuals of the human species.

Accordingly, we are of the opinion that the principle of bioethical prudence should be applied to this research. This recommends a moratorium until it can be clearly established whether or not these embryoids may be considered as human embryos and, consequently, that human lives are not being manipulated in these experiments.

(1) In this sense, our Observatory has published two Special Reports: Ethical reflections of biomedical experiments by Juan Carlos Izpisua and New advances and challenges in the production of human-animal chimeras

Justo Aznar, Lucía Gómez-Tatay and Julio Tudela

Bioethics Observatory – Institute of Life Sciences

Catholic University of Valencia