Balancing innovation and ethics: Using human embryonic and foetal material for research

The use of human embryonic material in scientific research has opened new avenues for understanding the fundamental processes of human development, as well as the origins of disease and potential avenues for treatment. By studying these early stages of development, researchers can uncover mechanisms that are otherwise inaccessible, providing insights that are crucial for advancing human health. Nonetheless, this research also raises questions about the boundaries of scientific exploration and the responsibilities of researchers around the world.

As research continues to evolve, scientists are focussed on ensuring work with embryonic and foetal material is conducted within ethically sound and transparent frameworks. This blog explores the opportunities and challenges of using embryonic and foetal material in research, the regulations that have set standards for ethical use and how the Wellcome Sanger Institute is keeping at the forefront of this work and driving innovation whilst upholding these standards. It also touches upon associated work and where this field is heading in the future as the field increasingly integrates in silico models alongside experimental approaches.

Scientists use the term embryo to describe human development from fertilisation through the first eight weeks.¹ Beyond this stage, it is usually referred to as a foetus.¹ By studying embryos, we can uncover more about the early stages of human development when most of the cell types in the body are specified and organised. These processes are highly dynamic and occur in ways that cannot be fully replicated in other models. Understanding them is crucial for revealing fundamental biological mechanisms that underpin human fertility, congenital disorders and tissue regeneration. Insights gained at this stage can also provide foundations for developing therapies and interpreting how early developmental errors can lead to disease later in life.

In the UK, research using gametes – sperm and eggs – and live embryos up to 14 days of development is regulated by the Human Fertilisation and Embryology Authority (HFEA). This regulation is set out in the HFE Act 1990, which was amended in 2008. During this period, researchers can culture live embryos to discern what is going on during early development. While we do not conduct this type of research at the Institute, these studies provide crucial insights into fundamental developmental processes. The samples used are donated with informed consent in cases where an individual has had successful rounds of in vitro fertilisation (IVF) and more embryos have been created than needed, or the IVF embryo is not suitable for implantation. Other types of HFEA-licensed activities include creating human embryos in vitro, storage and use of human reproductive cells for human application, such as for IVF, and deriving stem cells from reproductive cells or embryos. When an embryo regulated under the HFEA is formalin fixed paraffin embedded (FFPE), the tissue becomes preserved for study. Although the embryo is no longer living, researchers can still extract genetic information for research. Once fixed, these samples are no longer regulated by the HFEA.

The period between weeks two to four of development is sometimes referred to by scientists as the ‘black box’ window.² To date, regulation requirements have made it difficult to understand more about what happens during this period.  Last year, the Progress Educational Trust (PET) – a small charity that educates and debates the responsible application of reproductive and genomic science – held their 2024 annual conference which some of our researchers at the Institute attended. At this meeting, HFEA announced the recommendation that the law should be changed to extend the day 14 limit on in vitro human embryo research to day 28.³ Research after day 14 would enable scientists to understand more about the ‘black box’ window, providing potential insights into congenital diseases and complications during early pregnancy. HFEA has made it clear that this would only be approved on a case-by-case basis and after extensive public engagement. Such an amendment would require a change to the law and therefore, has to be discussed by the UK Government.

As HFEA-regulated samples at present cannot be cultured in vitro beyond day 14, researchers seeking to examine material from later stages of early pregnancy cannot currently rely on these samples. Instead, such work is regulated by the Human Tissue Authority (HTA), which enforces the Human Tissue Act 2004 (HT Act). The HTA regulates activities concerning the removal, storage, use and disposal of human tissue including pregnancy remains such as embryonic and foetal tissue.

Samples from pregnancy remains can come following pregnancy loss or elective termination. These samples are classified as the mother’s tissue under the HT Act. Samples can include biopsies, tissues or FFPE material.

At the Sanger Institute, we do not hold HFEA or HTA licences as our work does not involve procedures, such as creating material, that require these licences. Instead, we receive non-living in vitro embryos such as FFPE samples as well as tissues, cells or extracted nucleic acids from pregnancy remains all under Research Ethics Committee (REC) approval. RECs carefully review research applications and only projects that receive a favourable opinion are permitted to proceed.

When wanting to obtain such samples from external sources with the relevant licences, researchers at the Institute work closely with colleagues in the Legal and Research Governance (LeGo) teams. The Legal team will review contractual obligations, and the Research Governance team support ethical and compliance considerations. Researchers at the Institute must complete a Human Materials Form Electronic (HuMFre), an internal ethical due diligence form reviewed and approved by the Research Governance team. The form captures key details such as sample responsibility, donor consent conditions, data sharing, ethical approvals, project use, handling of remaining samples and approval end dates. Samples cannot be received or used onsite until a contract, ethical approval and an approved HuMFre are in place.

One of the core aims of the Cellular Genomics programme at Sanger is to understand how human tissues develop in vivo, in order to reveal what goes wrong in disease and to inform the development of new diagnostics and treatments. The team aim to create models that mimic human biology and use them to test the effects of altering specific processes. However, to fully understand these processes, researchers need to draw on data derived directly from human tissues. The team specifically use these tissues to improve in vitro models – a cycle of refinement ensures their models recapitulate the complexity of human tissue architecture and can be easily scaled.

Model organisms such as mice, rabbits, pigs and even primates have long played an important role in research and continue to provide valuable insights. At the same time, some of their developmental mechanisms differ from those of humans at the molecular and cellular level. This means that the insights scientists obtain do not fully translate into humans. For example, unlike humans, mice lack the same degree of growth and folding of the outer layer of the brain, which limits how much we can learn about the origins of human brain complexity from studying mice alone. It is clear that to develop treatments for humans, we still need to use human biological resources.

At the Sanger Institute, Head of Cellular Genomics, Professor Muzz Haniffa and her team recently created a prenatal skin atlas – a comprehensive reference map describing how the skin develops before birth. Here, they sampled prenatal skin across different time points during the first and second trimesters of human development. The samples were provided by HDBR and the Cambridge BioResource. The data generated were further used for benchmarking a pluripotent stem cell (PSC) derived skin organoid model – a 3D, self-assembled cell culture system that mimics the structure and function of human skin in vitro.^4,5 This was to understand what the similarities and differences were in order to improve the model. They found that almost all major cell types in the skin were recapitulated in the skin organoids, aside from immune cells.  Now, there are multiple efforts within the team to build on this work by leveraging the existing skin organoid model and further enhancing it with specific immune cells, such as patient-derived macrophages, which they found to have a key role in skin development.

There are a lot of diseases that are the result of dysregulated endometrial cells, including endometriosis that affects roughly 10 per cent of women worldwide.⁶ Creating models of healthy and diseased states will allow the team to disrupt and understand how regulatory mechanisms are altered during disease progression.

Both of these approaches demonstrate the use of prenatal tissue to generate atlases that will act as ‘recipe books’ for researchers to then create in vitro models. Once we have these models, scientists can then fine tune them to better mimic in vivo tissues, bringing us even closer to replicating real human biology.