They generate human embryos without an egg or sperm: mysteries and ethical questions that this scientific milestone awakens

A scientific team has generated synthetic human embryos using stem cells, reports the British newspaper The Guardian. This represents a new step to the one already announced last summer with the creation in the laboratory of a model of synthetic mouse embryos..

This is the international group led by scientists from the University of Cambridge (United Kingdom) and the California Institute of Technology (USA) and directed by Magdalena Zernicka-Goetz, who published last August in the journal Nature how they had managed to reproduce outside from the uterus and without using eggs and sperm what happens in the early stages of development of a mouse.

Nine months later, yesterday, the authors announced the performance of the technique with human material during the annual meeting of the International Society for Stem Cell Research in Boston (United States).. They affirm that they have achieved model embryos, similar to those found in the early stages of human development, and that with this scientific advance they could find answers when investigating genetic disorders and the causes of spontaneous abortions.. However, the work is accompanied by ethical and legal problems..

It should be noted that, as collected by The Guardian, full details of the latest work, from the Cambridge-Caltech laboratory, have not yet been published in an article in a scientific journal.. But, in the breakthrough presentation, Zernicka-Goetz described culturing embryos to a stage just beyond the equivalent of 14 days of development for a natural embryo.. Currently, UK law allows human embryos to be studied in the laboratory only up to day 14 of development..

What is known about the progress of synthetic human embryos?

Without more information than the presentation at the congress, the scientific community does not dare to go into detail. Thus, Alfonso Martínez Arias, ICREA research professor and researcher in Bioengineering Systems-MELIS at Pompeu Fabra University, as collected by SMC, argues that “there is no information available beyond the articles in the press: neither scientific article nor preprint. Therefore, this work cannot yet be verified.. It may be an important scientific step, but again, we need to see the full report and data before we can make those claims.”.

Along the same lines, he agrees with James Briscoe, group leader and deputy director of research at the Francis Crick Institute, explaining to SMC UK that “without a detailed preprint or peer-reviewed article accompanying this press release, it is not possible comment in detail on the scientific importance of this news”. And he defends that “in more general terms, although it is very early, synthetic models of human embryos based on stem cells have great potential. They could provide fundamental knowledge about critical stages of human development. These are very difficult stages to study and in which many pregnancies fail. A new perspective could help to better understand the causes of miscarriages and the unique aspects of human development.”.

There is no information available beyond the articles in the press: neither a scientific article nor a preprint. Therefore, this work cannot yet be verified.

James Briscoe, group leader and deputy director of research at the Francis Crick Institute

It should be noted that, in August, regarding the possibility of replicating the experiment in humans, Zernicka-Goetz stated at a press conference that it was not possible at the moment.. “It's still science fiction,” Lluís Montoliu, a research professor at the National Center for Biotechnology (CNB-CSIC) and CIBERER-ISCIII, also agreed at the time, who nevertheless pointed out that the possibility raises new ethical dilemmas that will have to be addressed. “It is a chapter of ethics that has yet to be written if one considers reproducing these experiments in the human species”.

Photomicrograph of an isolated human embryo in the blastocyst phase. SHUTTERSTOCK

Another expert commenting to SMC on the matter, Roger Sturmey, Professor of Reproductive Medicine at Hull York Medical School and Principal Investigator for Maternal and Fetal Health at the University of Manchester, says that “work published in The Guardianse builds on a growing base of research showing that stem cells can, under highly specialized laboratory conditions, be engineered to form a structure resembling the embryonic stage called a blastocyst. In normal development, the blastocyst is an important structure, as it is around this time that the embryo begins the process of implantation in the uterus and pregnancy is established.”.

What can it contribute to the knowledge of research in the field of fertility?

We know very little about this stage of human development, “but it is a time when many pregnancies are lost, especially in the context of IVF [in vitro fertilization].. Therefore, models are urgently needed to allow us to study this period to help understand infertility and early pregnancy loss.. Today, we can say that these synthetic embryos share a number of characteristics with blastocysts, but it is important to recognize that the way synthetic embryos form is different from what happens when a normal embryo forms a blastocyst,” Sturmey said.

It is important to recognize that the way synthetic embryos form is different from what happens when a normal embryo forms a blastocyst.

Roger Sturmey, Professor of Reproductive Medicine at Hull York Medical School

In presenting the work on mouse models, Zernicka-Goetz, Professor of Stem Cell Biology in Cambridge's Department of Physiology, Development and Neuroscience, highlighted the achievement. “This has been the dream of our community for years and the main focus of our work for a decade and we have finally achieved it”.

Nine months ago, Zernicka-Goetz explained that for a human embryo to develop successfully, there must be a “dialogue” between the tissues that will become the embryo and the tissues that will connect the embryo to the mother.. In the first week after fertilization, three types of stem cells develop: one will eventually become the tissues of the body, and the other two will support the development of the embryo.. One of these types of extraembryonic stem cells will become the placenta, which connects the fetus to the mother and provides oxygen and nutrients; and the second is the yolk sac, where the embryo grows and from which it obtains its nutrients in early development..

Many pregnancies fail by the time the three types of stem cells begin to send mechanical and chemical signals to each other, telling the embryo how to develop properly.. “Many pregnancies fail at this stage, before most women realize they are pregnant,” said Zernicka-Goetz, who is also a professor of biology and biological engineering at Caltech.. “This period is the foundation for everything else that follows in the pregnancy. If it goes wrong, the pregnancy will fail.”.

What are the ethical implications of this work?

It is to be expected that deep ethical and legal questions will also be raised. Because when they announced this step in mice nine months ago, the scientific community was already putting it on the table. “While it is premature to talk about real-world impacts due to system inefficiency and developmental blockage, it is now within the reach of scientists to generate post-implantation synthetic human embryos with the formation of organs such as the brain and heart.” beating. Therefore, it is crucial to discuss the ethical and regulatory implications of such methods for studying human embryonic development,” Christophe Galichet, a scientist at the Francis Crick Institute, told SMC UK in August..

In in vitro fertilization there is an established legal framework, currently there is no clear regulation that regulates the models of human embryos derived from stem cells

James Briscoe, group leader and deputy director of research at the Francis Crick Institute

“Unlike human embryos from in vitro fertilization (IVF), where there is an established legal framework, there is currently no clear regulation governing human embryo models derived from stem cells.. There is an urgent need for regulations that establish a framework for the creation and use of human embryo models obtained from stem cells,” Briscoe claims..

In this regard, the head of the group and deputy director of research at the Francis Crick Institute states that “on the one hand, human embryo models obtained from stem cells could offer an ethical and more readily available alternative to the use of human embryos obtained by IVF. On the other hand, the more similar human embryonic stem cell models resemble human embryos, the more important it will be to have clear standards and guidelines on their use.. This poses challenges. How will the comparisons be made, given the difficulty of obtaining and studying human embryos at the appropriate stages”.

Montoliu commented nine months ago that the new technological revolution we are witnessing “is still very inefficient (it is very difficult to obtain stem cells to spontaneously generate a synthetic embryo), but it has enormous potential”. And he alluded to such spectacular scientific advances as the birth of Dolly the sheep, in 1997, reconstructing an embryo with the nucleus of a somatic cell, or the inducible pluripotent embryonic stem cells, iPS cells, described by Yamanaka in 2006, which led him to win the Nobel Prize in Physiology or Medicine in 2012, shared with John Gurdon, pioneer of animal cloning in amphibians.

“A revolution that naturally also raises new ethical dilemmas, if we ever think of transferring these experiments to the human species for the generation of synthetic human embryos, perhaps with the aim of using them to obtain new tissues or organs to repair or replace those that already exist.” they don't exist”, pointed out the CNB-CSIC professor at the time.

In summary, the experts call for prudence, as Briscoe points out. “It is important that research and researchers in this field proceed with caution, care and transparency. The danger is that missteps or unsubstantiated claims will have a chilling effect on the public and policy makers, resulting in a major setback for this field”.