Biomedicine: embryos without egg, sperm and uterus

Development biologist Magdalena Zernicka-Goetz and her team at the California Institute for Technology and the University of Cambridge write in the journal Nature that this is a great advance in the future production of artificial organs for transplantation. However, research also raises a number of ethical questions – because the technology is, in principle, also applicable to humans.

Ambiguous classification

The tenor in the scientific world is suitably ambivalent – from euphoria to restraint. “These results will have far-reaching consequences for modern science,” comments German geneticist Malte Spielmann. The Spanish molecular biologist Lluis Montoliu speaks of a “technological revolution”. The discovery resembles the first cloned Dolly sheep in 1997, or the first description of stem cells that could be reprogrammed into an embryonic state derived from body cells (ipS cells) in 2006 and which were later awarded the Nobel Prize.

On the other hand, there are ethical questions. For example, bioethicist and Protestant theologian Ulrich Körtner insists on clarifying the question of “what are the ontological, legal and moral status of synthetic embryos compared to conventional embryos made from eggs and sperm”. Existing provisions, such as the Austrian Reproductive Medicine Act, did not cover them at all. The key question is, “Will the necessary ethical and social debate keep pace with the rapid pace of research,” said Körtner

Almost half of your pregnancy is achieved

The basis of artificial mouse embryos were not eggs and sperm cells, as in the natural variant, but three different types of stem cells – cells in the body that can differentiate into different types of cells or tissues. Scientists created a new biological structure from a mixture of these stem cells and allowed them to mature in an incubator. This artificial uterus was developed by stem cell researcher Jacob Hann of the Weizmann Institute in Israel, and his team recently reported similar experiments in Cell magazine.

Szymon Zernicki Glover

Magdalena Zernicka-Goetz in the laboratory

Zernicka-Goetz, Hanna and other experts mimicked the early stages of the natural development of mouse embryos for the first time. The artificial embryos have reached a stage equivalent to eight and a half days of natural pregnancy – almost half the gestation period in mice, or about 19 days. By that time, they had developed the brain, heart, yolk sac, and gut. Only then did they stop developing, which corresponds to the developmental stage of the human embryo at the end of the first trimester of pregnancy. “It is unbelievable that we have come this far,” says research leader Magdalena Zernicka-Goetz. “It has been a community dream for years and the result of a decade of hard work.”

Better research without animal testing

Thanks to artificial embryos, the early stages of natural pregnancy can be better investigated, emphasizes the development biologist. There is still faulty communication between the different types of stem cells and thus complications during pregnancy. “Many pregnancies fail by this time before women even know they are pregnant,” says Zernicka-Goetz. In the case of artificial embryos, individual genes can be deliberately switched off, which allows for better investigation of developmental disorders or disorders of organ formation. The same goes for brain development and the complications that come with it.

Natural and artificial embryos show almost no differences

Amadei and Handford

The synthetic and natural embryos show a comparable structure of the brain and heart

Artificial organs for transplantation

There remains the question of the ethical classification of scientific progress. On the one hand, artificial embryos can significantly reduce the number of controversial animal experiments. On the other hand, the purpose of the research is clearly therapeutic – i.e. one that wants to work with human cells. “Creating human embryos is many times more complicated,” comments human geneticist Malte Spielmann. Nevertheless, on the basis of current research, it is to be expected that “at least individual organs can be cultured synthetically”.

Study leader Zernicka-Goetz believes the long waiting lists for organ donors are a good case for her work. “The knowledge that comes out of it can lead to the creation of artificial organs that save lives.” Israeli-Palestinian stem cell researcher Jakob Hanna recently launched a new company to work in this direction.

14-day rule for embryonic research

The success rate for synthetic mouse embryos is still very low at 1-2 percent of viable embryos. Moreover, the development of synthetic human embryos in the laboratory has so far been contrary to the 14-day rule in many countries. According to this principle, human embryos obtained by artificial insemination can be grown in the laboratory for a maximum of 14 days after fertilization or until a primitive streak is formed.

However, in May 2021, the International Society for Stem Cell Research (ISSCR) recommended relaxing this 14-day rule in selected cases. In the light of experimental progress, the ISSCR suggested that research aimed at culturing human embryos above the two-week level in the laboratory should be subject to prior review by interdisciplinary committees on a case-by-case basis and subject to multi-level external review.

Unclear legal situation

In Austria, the Reproductive Medicine Act prohibits experiments on human embryos. However, the legal classification of artificial embryos is unclear everywhere in the world. In the future, it is likely to depend increasingly on the extent to which they resemble human beings capable of development and should be appropriately classified as human embryos.

Another phenomenon is pointed out by the embryologist Michele Boiani from the German Institute of Molecular Biomedicine. Max Planck. “ISSCR guidelines, by allowing the creation of synthetic human embryos, prohibit their transfer into the uterus, which has always been considered a major barrier to highly unethical experimentation.”

However, studies in mice show that transfer to the uterus is not necessary at all – the guidelines are therefore “toothless tiger”. He is concerned about the prospect that “synthetic embryos reconstructed from stem cells alone may enable reproductive cloning in humans.”

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