Standards and practice of embryo research

There are no standardised regulations on research with human embryos or human embryonic stem cells (hES cells) derived from them, either at United Nations or European level. At the same time, there are a number of statements and regulatory approaches that are relevant to the feasibility and possible objectives of research with human embryos.

In Germany, the Embryo Protection Act (ESchG) passed in 1990 prohibits research with early human embryos outside the body. Scientists in Germany are therefore unable to contribute much to the clarification of important research questions in early human developmental biology. The same law also prohibits the derivation of stem cells from human embryos (hES cells). The German Stem Cell Act (StZG), on the other hand, authorises - under certain conditions - the import of embryonic stem cells produced abroad and their use for high-level research purposes.

In countries such as the USA, Israel, Sweden, the UK, France and Japan, in vitro research on early human embryos is permitted within narrow limits. There, research may be carried out on so-called surplus embryos for 14 days after fertilisation, after which the embryos must be discarded. Surplus embryos are embryos that were originally created as part of artificial fertilisation but are no longer used for this purpose. In some of these countries, it is also possible to create embryos for research from gametes donated specifically for this purpose. As a rule, reasons must be given as to why the available surplus embryos are insufficient or unsuitable for the research project in question.

The 14-day time limit for in vitro research on embryos is based on the bioethical recommendations of the Warnock Report of 1984, which was drawn up under the direction of the British philosopher Mary Warnock. As early embryos often die before implantation in the uterus, even in the case of natural fertilisation, and as this is the point at which pregnancy actually begins, the proposal was accepted internationally at the time. In addition, in vitro embryos could not be cultivated in the laboratory for more than five to six days for a long time anyway. As it is increasingly possible to cultivate in vitro embryos beyond 14 days, an extension of the period to 28 days is being discussed internationally in order to better research the causes of spontaneous pregnancy losses or diseases, such as congenital heart defects and disorders of the central nervous system, and to develop therapies. Those in favour argue that the embryo lacks the prerequisites for any ability to feel up to this point, as no functional nerve connections or sensory systems are yet present.

Some research questions can only be answered with embryos created specifically from donated sperm and egg cells for research purposes. Here, the experimental approach is directly linked to the fertilisation process. With donated supernumerary embryos, on the other hand, certain processes have already been completed, such as fertilisation itself, the formation and migration of the pronuclei and the replication of the parental genomes in the pronuclei.

Many findings on embryonic development have so far only been derived from animal experiments, mostly with mice. However, reliable results on the development of human life, epigenetic, genetic and environmental causes of diseases and the targeted development of appropriate therapies cannot be obtained from animal models alone. It has been shown that many specific biological processes take place differently in humans, for example the fertilisation of the egg cell, cell division or the time of activation and regulation of certain genes.

Induced pluripotent stem cells (iPS cells) represent a potential alternative to obtaining human embryonic stem cells (hES cells). Around 15 years ago, researchers succeeded for the first time in converting body cells that are already differentiated in their function into pluripotent stem cells. The iPS cells can be obtained from adult skin or blood cells from donors through reprogramming. However, there are indications that iPS cells have genetic and epigenetic differences to hES cells: On the one hand, they can adopt epigenetic patterns of the adult cells from which they were derived. These differences and the question of the extent to which the differentiation of hES and iPS cells in vitro corresponds to embryonic development in vivo are the subject of embryo research. On the other hand, mutations that have accumulated in the adult cells of origin over the course of their lifetime are passed on to the iPS cells. In order to better understand such processes, the iPS cells would have to be compared with the corresponding stem cells in the embryo's cell cluster and with hES cells. Such investigations could also shed light on the potential of iPS and hES cells for research into diseases and the development of cell therapies.

In recent years, scientific progress has increasingly blurred the boundaries between somatic cells, germ cells and embryos. In the meantime, many different cell formations (embryoids) with embryo-like properties have been created in international stem cell research. It has been possible to generate various embryo-like structures from iPS cells, such as blastula-like formations (blastoids). In 2023, it was also possible for the first time to obtain more advanced stages of development from human embryonic stem cells (hES cells) without a fertilisation process taking place. These stages normally correspond to those that develop shortly after implantation of the embryo in the uterus. The further development potential of these cell formations is still open - particularly because their development in vitro ends by itself after a few days and it would not be ethically justifiable to implant them into a human organism. Here, too, comparative embryo research can provide information.

Published: May 2021, updated November 2023