Fluorescent images showing gene expression in early human embryos, where blue is each cell of the embryo, green is the OCT4 gene, red is the NANOG gene and yellow is overlapping expression showing cells that eventually give rise to the embryo proper or fetus. The embryo on the right has been edited to prevent the OCT4 gene from functioning.
The Human Fertilisation and Embryology Authority (HFEA) has renewed Crick group leader Kathy Niakan’s licence to edit human embryos, allowing her team to continue their research into early human development. The team have also received approval from an independent Research Ethics Committee under the Health Research Authority, the part of the NHS that oversees research involving patients.
The renewal builds on the existing licence and will allow for a broader range of research activity including creating embryos from donated sperm and eggs. Being able to introduce edits at the point of fertilisation will allow the team to study the earliest stages of embryo development and achieve reliable results using fewer embryos.
Kathy’s research focuses on the first 14 days of embryo development, looking at the key genes and factors that tell the cells in the embryo what to do. In the early human embryo, most cells will go on to form the placenta or yolk sac while a small number of cells will eventually form the foetus. These ‘pluripotent’ cells multiply and will eventually go on to form the entire human body, so each one is capable of becoming any other type of human cell.
By studying human embryos from the earliest stages, the team aims to understand how these cells become and remain pluripotent, and how they lose their pluripotency when they specialise. They hope to use this knowledge to establish pluripotent stem cell lines that can be taken out of the embryo and multiplied in the laboratory for many years. These pluripotent stem cell lines could help scientists to study and better understand human diseases at a cellular level and potentially develop new therapies.
“Pluripotent stem cells have huge potential for science and medicine, but at the moment we have a very limited understanding of how they are established and maintained,” says Kathy. “We are trying to improve our understanding of these unique cells by studying the precursors of these cells in their natural environment, the human embryo. Our hope is that this will lead to more efficient ways to create, maintain and use stem cells for both research and treatments for patients.”
Under the existing licence, patients at fertility clinics can choose to donate their surplus embryos to the research. In a typical in-vitro fertilisation (IVF) treatment, approximately a dozen eggs from the woman are mixed with sperm in the lab to create embryos. Doctors create multiple embryos to increase the chances of producing a viable embryo, as they do not all develop correctly. The most promising-looking embryos are selected for transfer into the womb while others are frozen in storage.
Most embryos donated under the current licence come from couples who have successfully completed IVF and want their stored embryos to be used for research. This will continue under the renewed licence, but couples will also be able to donate eggs and sperm stored before fertilisation.
“Creating embryos from donated sperm and eggs is an important next step in our research,” explains Kathy. “Donated embryos remain vital to our work, but to study the very earliest stages of development we need to start at day zero. Creating embryos will also allow us to fine-tune the timing of our edits and optimise our techniques to increase efficiency. As a result, we will be able to get reliable results using fewer embryos.
“While the couples who donate to our research are unlikely to benefit directly, we hope that their generosity will lead to findings that could help future couples. At the moment, around half of embryos fail to develop beyond the first week but we don’t know why. If we could identify the key factors for successful development, we could use this to improve IVF treatments.
“For example, we could look for markers of success that could be tested in the clinic, to help doctors select the best embryos. We could also look at improving the culture media, which contains nutrients to help the embryos grow. We may be able to tailor culture conditions for human embryos to help them develop successfully.”
Kate Brian, Chair of the HFEA’s Licence Committee, says: “We’re pleased to renew the license for Dr Kathy Niakan of the Francis Crick Institute for her ‘Derivation of stem cells from human embryos’ research.
“The research carried out so far has already produced important findings, revealing the differences between mouse and human embryos and demonstrated the importance of studying the role of genes directly in human embryos.
“We have granted the licence to allow the research to continue work developing treatments for serious disease or other serious medical conditions, promoting advances in the treatment of infertility and increasing knowledge about the development of embryos.
“To ensure that the research is ethical, approval from an independent Research Ethics Committee was needed as part of the license renewal and we’re delighted that this was granted.”