By: Alissa Zhang
On January 14, 2016, the Human Fertilization & Embryology Authority (HFEA) approved a research license renewal for research project R0162. The application, submitted by Dr. Kathy Niakan of the Francis Crick Institute in London, proposed to study the roles of certain genes in the early development of human embryos, with promising potential implications for the treatment of infertility and genetic diseases (1). On the surface, this seems like a routine approval for the HFEA, which regulates all research on human embryos in the UK. However, the scientific community and the public have been strongly divided over the proposed research plan. Nine months before the request was approved, a group of scientists who had predicted such proposals called for a moratorium on experiments of this kind (2). Many fear this type of research could lead to the rise of so-called “designer babies” and other ethically questionable uses.
Dr. Niakan’s research focuses on the five-day process by which a fertilized egg matures into a blastocyst, which subsequently implants in the uterus. Dr. Niakan uses surplus human embryos from in vitro fertilization (IVF) procedures, which have been donated for research and are destroyed after seven days when the experiment is complete (3). IVF is a common source of human embryonic stem cells for research, and the seven-day limit provides a guarantee that the embryos will not develop past the blastocyst stage. So why has Dr. Niakan’s proposal caused so much controversy? One reason is that Dr. Niakan, in her license renewal, requested permission to use the CRISPR/ Cas-9 system to modify genes in these human embryos. When the HFEA approved her request, it was the first time that CRISPR had been approved for use in human embryos by a major scientific regulatory body.
According to the research proposal, Dr. Niakan plans to knock out OCT4, a gene that is activated in human embryonic stem cells that may play a role in pluripotency, giving cells the ability to differentiate into any kind of tissue. She will test this theory by knocking out the gene in day-old single-cell embryos, and analyzing the effect on the number of pluripotent cells that develop. If this pilot project is successful, Dr. Niakan will extend her study to other lesser-known genes that may be involved in early development, depending on embryo availability. CRISPR is crucial for this project because it allows researchers to selectively target and knock out one gene, and it is more efficient than other techniques, thus requiring less embryos (4).
The immediate goal of Dr. Niakan’s project is simply to gain a deeper understanding of the role of certain genes in blastocysts. Supporters of this research point out that the use of CRISPR in human embryos could lead to improved treatments for infertility and many congenital disorders (3). The HFEA strictly regulates experiments involving human embryos in the UK to ensure that any ethical concerns are satisfied. Since the embryos Dr. Niakan uses will be destroyed after seven days, there is no chance that any of them will reach viability.
Nevertheless, scientists as well as the public have raised legitimate ethical concerns about this kind of research. They argue that approving Dr. Niakan’s project may lead to dangerous and unpredictable consequences. There is simply not enough research on the topic of human genome editing to unravel all the potential scientific and ethical implications. Lanphier et al. warned that “genome editing in human embryos using current technologies could have unpredictable effects on future generations” (2). While the current motivation for such research is scientific and medical, gene-editing technology could be used for controversial non-therapeutic applications, such as allowing parents to select certain traits to create “designer babies,” instead of therapeutic applications, such as treating genetic diseases. Some scientists argue that this research is unnecessary, as alternative genome-editing techniques exist that could be applied to somatic cells rather than germline cells. While these methods could be less effective, they also carry less risk.
It is clear that the scientific community, regulatory bodies, and the public must carefully consider the potential implications before genome editing in human embryos can be approved – if it should be at all. However, there may not be time to do so. Although Dr. Niakan waited for approval from the HFEA, other researchers may not wait for regulatory approval. In April 2015, researchers at Sun Yat-sen University in Guangzhou, China attempted to use CRISPR to edit the hemoglobin-B gene in human embryos, with the goal of treating beta thalassemia. The embryos used in this case were nonviable, and the project was ultimately unsuccessful (5). Yet this experiment shows that scientists may not be willing to wait for approval from the scientific community or the public, and, in countries where research is less regulated, they may not have to.6 Due to the publication of this study, “CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes”, scientists around the globe began to advocate for a moratorium on human genome editing (2).
The HFEA approved Dr. Niakan’s project because it met the standards for research in human embryos – and rightly so. Other experiments which meet the same standards, and which ensure that genetically altered embryos will not reach viability, should be given the same level of scrutiny and approval. As long as the embryos are disposed of, CRISPR edits cannot accidentally pass on to any living human being. However, if scientists consider using genome editing for therapeutic purposes, then higher standards and more research will become necessary The Sun Yat-sen experiment demonstrates that stricter regulations on human embryo experimentation must be upheld. Before genome editing can be used on human embryos that will be implanted, scientists, bioethicists, regulators, and legislators must collaborate on an international scale to determine the scientific, ethical, and legal limits of this technology.
Alissa Zhang ‘16 is a senior in Currier House, concentrating in Chemical and Physical Biology.
 Human Fertilization & Embryology Authority. January 14, 2016. License Committee – minutes. http://guide.hfea.gov. uk/guide/ShowPDF. aspx?ID=5966.
 Lanphier, E., et al. Nature Comment [online], March 12, 2015. Don’t edit the human germ line. http://www. nature.com/news/ don-t-edit-the-human-germ-line-1.17111#/ (accessed February 20, 2016).
 Stokstad, E. Science News [online], January 13, 2016. U.K. researcher details proposal for CRISPR editing of human embryos. http://www.sciencemag.org/news/2016/01/uk-researcher-details-proposal-crispr-editing-human-embryos (accessed February 20, 2016).
 Callaway, E. Nature News [online], February 1, 2016. UK scientists gain licence to edit genes in human embryos. http://www.nature.com/news/uk-scientists-gain-licence-to-edit-genes-in-human-embryos-1.19270 (accessed February 6, 2016).
 Liang, P., et al. Protein & Cell 2015, 6(5), 363-72.
 Wade, N. The New York Times [online], February 1, 2016. British researcher gets permission to edit genes of human embryos. http://www. nytimes.com/2016/02/02/health/ crispr-gene-editing-human-embryos-kathy-niakan-britain.html (accessed February 6, 2016)