Research summary
Currently, there are three research teams working on the development of a synthetic human embryo model originated without sperm or egg: 1) that of Polish scientist Magdalena Zernicka-Goetz, who leads an international group of scientists from the University of Cambridge ( United Kingdom) and the California Institute of Technology (USA). This team published their results on June 27, 2023 in the journal Nature. 2) The laboratory of Berna Sozen, from Yale University, which also published its results in Nature and on June 27. And 3) The team of the Palestinian researcher at the Weizman Institute (Israel), Jacob Hanna, who on September 6, 2023 also published the results of his research in Nature.
The work of Jacob Hanna that circulated through the scientific community as a preprint following the announcement made by Magdalena Zernicka-Goetz on June 14 at the annual meeting of the International Society for Stem Cell Research in Boston about a similar advance, and which caused a general controversy, has been published with complete guarantee in the aforementioned prestigious scientific journal. This was a step that Hanna needed to take so that the community would give the necessary credibility to her research. On June 21 we published an article on the subject on our website, when there was still nothing published in Nature, and it was all communications from the researchers to the press. However, details of the model and its genesis can be learned from the article by Hanna and his collaborators.
The Israeli team started from the experimental models it had developed in mice. They repeated the experience with human cells. As on that occasion, the starting materials to build the synthetic model were neither fertilized eggs nor a uterus, but pluripotent stem cells. The researchers used Hanna’s newly developed method to reprogram pluripotent stem cells to further delay the clock: reverting these cells to an even earlier state, known as «naive,» in which they are able to specialize in any way. cell type. The synthetic embryos generated mimicked the 3D architecture and key developmental milestones of human embryos from 7 to 8 days post-fertilization to 13 to 14 days post-fertilization. The synthetic embryos had all the characteristic structures and compartments of the first few weeks, including the placenta, yolk sac, chorionic sac, and other external tissues that ensured their dynamic growth. «They are structurally similar to natural embryos, although they are not identical,» the authors summarize in their article.
How useful are these investigations?
These models open a key opportunity to generate valuable information on the processes that govern early human development (embryogenesis), especially the phenomenon of implantation, which would allow us to better understand the causes of spontaneous abortions in humans.
In addition, they provide the possibility of testing medications during this period of gestation, which the legislation of many countries prohibits doing on natural human embryos.
In general, the scientific community supports these investigations.
Are these embryonic models really human embryos?
Julio Tudela Cuenca and Lucía Gómez Tatay from the Bioethics Observatory comment on this important issue, as well as the bioethical implications of this type of experiments.
An article published on August 7 in the journal Cell, raises the need to assign a legal status to new embryonic models – human embryos – obtained from pluripotent cells, which in turn come from embryonic cells (Human Embryonic Stem Cells (HESCs). ) or reprogrammed somatic cells (Human Induced Pluripotent Stem Cells (hiPSCs)).
Its authors propose a redefinition of the human embryo, which could be applied to these new biological realities, the “embryo models, embryoids or blastoids”, to enable their legal treatment and protection.
In their conclusions, they launch the proposal of a new definition of the embryo that is applicable to these new biological realities similar to human embryos but obtained by manipulation in the laboratory other than the fertilization of gametes or somatic nuclear transfer (cloning). To do this, they define two characteristics on which whether it is considered a human embryo or not would depend.
The first characteristic would be its potential capacity to develop and form a fetus, thus defined from day 58 after fertilization. They call it the intrinsic capacity of cells to continue their development.
The second characteristic would consist of the existence of an external biological support, which the authors define as “elements that fulfill extraembryonic and uterine functions that, combined, have the potential to form a fetus.”
The evaluation of these two characteristics that would define the nature of the human embryo is, certainly, very complicated.
Firstly, evaluating the capacity of one of these embryonic models to continue its development beyond a certain maturation stage requires its transfer to a uterus, with the difficulties that this entails, both technical and legal, given that it is currently not permitted. the transfer of these “embryo models” into human wombs to continue pregnancy. On the other hand, the genetic manipulation to which they have been subjected to ensure that their cells proliferate as an embryo obtained naturally would, that is, after fertilization of the male and female gametes, can induce unknown changes in the genome. and difficult to control, given the complexity of its functioning and how little is known about the interactions between its genes, with unpredictable consequences.
Secondly, establishing as an essential requirement for the consideration of a human embryo the existence of extra-embryonic structures that provide biological support to the progression of this embryo means removing the consideration of a human embryo from the zygote or preimplantation blastocyst, which would mean going back to the -ya surpassed and abandoned as obsolete and far from the scientific evidence currently available – the concept of «pre-embryo», established in the 80s of the last century following the appearance of in vitro fertilization that allowed embryos to be obtained outside the womb.
The knowledge about the biological nature of the embryo that science contributes today, and that we have previously analyzed, defines it as a «continuum» in terms of its evolution, which does not allow us to define supposed evolutionary stages that imply substantial changes in its nature that justify modifying its biological status, considering it as something different from a human embryo in any of its evolutionary stages, even the initial ones. The authors recognize this undeniable biological continuum, but at the same time affirm that the legal protection of the embryo along this continuum must vary, since they focus on the characteristics of the embryo and not on its nature, avoiding at all times the concept of human dignity.
To overcome these difficulties, the authors of the aforementioned article propose that «human embryo models could be considered equivalent to embryos when: (1) they have shown the potential to develop efficiently and faithfully in vitro until a time to be decided based on ethical considerations and local regulations; (2) when equivalent models of animal embryos are shown to have the potential to form live, fertile animals in multiple species, including those most closely related to humans (eg, pigs, monkeys).»
Bioethical assessment
In our opinion, the authors’ approach is correct in that the origin is not what should determine whether an entity is a human embryo or not, but what it really is, regardless of how it was generated. However, the model defended by the authors to try to grant a defined biological status to the new embryonic models that allows their consideration and legal treatment, contains, according to our criteria, the same difficulties that motivated the failed position of the «Warnock commission». that in his report issued in 1984 in the United Kingdom, he laid the foundations for the acceptability of embryo research, establishing an arbitrary period of 14 days from conception – adopting the previous conclusions of the American EAB – in which the embryo would lack individual nature.
This means depriving the early embryo, specifically the preimplantation embryo, of the consideration of an individual of the human species, leaving it unprotected and being able to be manipulated and destroyed in research procedures that require it.
The attempt to establish criteria that can guide whether new embryonic structures obtained by procedures other than fertilization or somatic nuclear transfer (cloning) are considered human embryos or not, means excluding the early embryo from being considered human, either because Its ability to evolve until reaching the characteristics of a fetus cannot be demonstrated, or because it lacks the extraembryonic structures on which its subsequent development will depend.
The fact that an embryo, which has a human genome, even defective, cannot evolve beyond a certain point of complexity does not seem to be a sufficient criterion to rule out its human nature. Many human embryos obtained by natural fertilization have genetic defects that prevent their evolution until birth and this does not deprive them of their human status.
Finally, the fact that the embryo must possess the extra-embryonic structures, such as the uterus, that allow its development, in order to be considered a human embryo, does not constitute a solid argument. The existence or not of these extraembryonic support structures does not modify the intrinsic nature of the embryo, which has the potential for continuous development, without interruption, of increasing complexity and well structured, as long as it is provided with the biological support it needs to it. The fact that it does not have this support, as happens with embryos obtained in vitro or these new forms of embryonic models obtained in the laboratory, does not define its nature or its potential. Thus a neonate deprived of sustenance and condemned to die due to its total dependence on the environment is no less human than one who receives the necessary support and progresses to adulthood. Granting this support or not does not alter its nature, potentiality and, therefore, the treatment that should be offered.
The position of the scientists who subscribe to the proposal that we are analyzing seems to be directed -as it already happened in the 80s- to give the world of scientific research a margin of time to experiment with these embryos or embryoids, trying to redefine their status and thus avoiding the ethical difficulties involved in manipulating and destroying an individual of the human species in an embryonic state, more or less mature, which is not transcendent in its consideration as human.
On the other hand, it is also true that the recognition of embryoids as embryos may limit certain uses of these embryonic models, since they would also enjoy certain legal protection. However, it could also open it up to other purposes, such as reproductive purposes, since at the end of the day they would be recognized as embryos. The authors warn of the need to discuss and regulate these possibilities.
The attempt to establish the similarity of these products obtained in the laboratory with the embryos resulting from natural fertilization is extremely complex, having to proceed with their implantation in animal models first, to verify the degree of success or failure in their development. It cannot be ruled out that, in the event that these procedures were successful, they would be tried in humans later when this is allowed, putting at risk not only the individual who is trying to be evaluated, but also the pregnant woman who may suffer the consequences of genetic alterations that are difficult to predict.
The utilitarian criteria, on which the current proposed position is based, just as the aforementioned Warnock commission did in the last century, insist on justifying the means used, even though they are ethically unacceptable, depending on the end pursued, the research and the treatment of problems in embryogenesis and infertility.
It must be clarified that the ethical acceptability of every human act includes the legitimacy of the object, the means used and the end pursued. In this case, the destruction of human embryos, even of uncertain classification, is an illegal means that ethically disavows this type of research.
