In addition to producing human-animal organs, these experiences seek to study the first stages of embryonic development, and even be used to deepen the knowledge of some diseases and their treatment.
An article in the journal Cell (April 15, 2021), was the first work describing the chimera production human-ape (read HERE). The authors said that Monkey (Macaca fascicularis) embryos were injected with a particular type of human stem cells, expanded stem cells (hEPSCs), which were developed in 2017 (see more HERE) and have enhanced chimeric potential, i.e. greater capacity to develop in the host animal embryo. In the work we are discussing, hEPSCs have been shown to survive, proliferate, and generate various cell lines in the monkey embryo in vitro. Until now, Izpisua’s group and other groups had demonstrated the production of chimeric human-animal embryos, such as mice, pigs or cows (read HERE), but despite the efforts of different research groups, they have not been able to produce chimeras in that a sufficient number of human cells are generated to think that these can be the basis for creating tissues and organs in animals with a human component. This, apparently, could be due to the fact that the distance of the evolutionary line of the animals used is very far from the human evolutionary line. To overcome this difficulty, the authors use monkeys here, whose evolutionary line is much closer to humans.
Referring especially to the results, the authors verify the development of the chimeras produced up to the gastrula phase. At this point, they eliminate the zona pellucida in the chimera produced, and from it they obtain human-animal cells, which, when transferred to an external disk, continue to develop. By this means they obtain 132 cell lines of which 3 survived 19 days.
The fact that these experiences raise ethical problems is undoubted, since the same authors, in the discussion of their article, begin by stating that they have consulted with institutions and experts in bioethics at the international level, who apparently have approved their work. In relation to this, it would be necessary to know, first of all, which bioethical experts have been consulted, since as will be commented later, in our opinion, these experiences have an evident utilitarian nature, therefore, if the experts navigate this way, it is natural that they do not encounter ethical difficulties. But apart from this, in our opinion, the ethical difficulties that this work presents are clear.
In the first place, and essentially, due to the ethical difficulties that are linked to the production of human-animal chimeras, which we have dealt with previously, and which can be summarized by saying that it is difficult to determine what degree of humanization the chimeric embryo produced reaches. As a function of this, it may not be ethical to generate and manipulate these embryos, much less destroy them.
In relation to this, last April, the American National Academy of Sciences, Engineering and Medicine, issued a report concerning the experiences that we are commenting on, in which it is stated that human cells transplanted to the animal embryo could enter into their brain and alter their mental capacity, although they also add that this concern may be debatable because the chimeras produced do not yet have the nervous system constituted. However, we add to this that, if the main purpose of these experiences is to produce organs for transplantation, it will be necessary to allow that embryo to develop into an adult animal, so that its organs can be clinically useful and naturally. At that time, his brain is already constituted, so it could be colonized by an indeterminate number of human cells. As Katrien Devolder, an expert in bioethics from the University of Oxford, states in the same article, if the human-ape chimeras were allowed to develop into an adult animal, «the story would be very different.»
As in previous reports already commented by us, in the chimeric tissues and organs produced there may be a colonization of human cells of different degrees, with the possibility that said colonization extends beyond the organ that is to be produced and may even reach the brain, which It can certainly raise ethical problems that are difficult to solve.
In some of the previous works, the authors try to solve this problem by producing transgenic animals in which the gene-generating gene to be produced would have been deleted, for which, in their opinion, this organ would only be colonized with human cells, without that there was the option of colonizing other organs, including the brain, but this is far from being reliably proven. In any case, in the article that is being discussed, the monkeys used had not been genetically modified, so the colonization of human cells from different organs remains feasible.
On the other hand, in addition to producing human-animal organs, another purpose of these experiences, according to their authors, is to be able to study the first stages of embryonic development, and even be used to deepen the greater knowledge of some diseases and their treatment. To achieve this, it would possibly be enough to use embryos of monkeys, whose use does not present any ethical difficulties, but if with these experiences they want to approach the human, creating the chimeras that are being discussed, these ethical difficulties do not seem to be obviated.
In previous works by the Izpisua group, an additional bioethical difficulty was raised, since they used human embryos, which seems to have been solved here, since the hEPSCs used come from adult humans.
Elaborating on all previously commented concerning the bioethical evaluation of the use of human-animal chimeras, in a book dedicated especially to this topic (David Albert Jones. Chimera’s Children. Ethical, Philosophical and Religious Perspectives on Human-Nonhuman Experimentation. Edited by Calum MacKellar and David Albert Jones. London 2012), it is stated that “the experiences that combine human and non-human elements determine that the cells used can affect the brain and the reproductive capacity, that is: those organs that particularly affect the identity of the species and human unity ”, thus highlighting “ the serious danger of the production of human-animal hybrids, since we are faced with a monster in the broadest sense of the word, which is something unfair to do ”.
In summary, it seems to us that these experiences, since it is not possible to determine the degree of colonization with human cells of the tissues and organs produced, may not be ethically acceptable.
Despite all the above, the authors of this work justify its ethics by stating that their technique can create organs that can be used in clinical transplants. Given that at the present time there is an evident lack of human organs for transplantation, the possibility that is enlightened here of creating them could be thought to be biotically acceptable. However, this bioethical foundation is based on criteria that could be considered utilitarian, by making the end of the act carried out prevail over the means used to achieve it, with which we undoubtedly do not agree, since our line of thought coincides with bioethics personalist, according to which the principle of prudence must prevail when the means used in an investigation do not guarantee scrupulous respect for human dignity in any of the evolutionary phases of an individual, from fertilization to natural death. The unpredictable consequences that can result from the production of human-animal chimeras do not guarantee this.
1er link https://www.sciencedirect.com/science/article/pii/S0092867421003056
2do link https://www.cell.com/cell/fulltext/S0092-8674(17)30183-6?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867417301836%3Fshowall%3Dtrue
3er link https://bioethicsobservatory.org/2017/04/new-advances-in-the-production-human-animal-chimeras/20652/
Justo Aznar MED PhD y Julio Tudela Pharm PhD
Bioethics Observatory – Institute of Life Sciences
Catholic University of Valencia – Spain