team of scientists in London on Monday received the first government approval in the world to edit the genomes of human embryos for research purposes, opening a new front in genetics research.
The lead researcher, Kathy Niakan of the Francis Crick Institute, has proposed using the powerful gene editing technology CRISPR-Cas9 to alter the genomes of human embryos to better understand the first days of development after fertilization.
A regional ethics committee that reviews applications from the institute still needs to weigh in on Niakan’s proposal before she can begin the study. But the decision by the UK’s Human Fertilization and Embryology Authority represents a landmark in the broadening acceptance of the gene editing technique.
What is the significance of the decision?
CRISPR has been embraced by thousands of labs around the world, but most of the use to date has been in animals or in non-reproductive human cells. Editing human embryos, sperm, and eggs has been controversial because those “germline” changes could be passed on to descendants, raising the worry that scientists could directly alter the human population.
In this case, the embryos won’t be implanted to start a pregnancy. The researchers have pledged to destroy them within a week.
This is not the first time scientists have edited human embryos. Chinese researchers stunned the world when they reported in April 2015 that they had used CRISPR in embryos to repair a gene defect behind beta-thalassemia, an often fatal blood disorder. The researchers only had success in a handful of the embryos and encountered lots of “off-target” effects, meaning the editing affected a gene they hadn’t meant to disturb.
The researchers at Sun Yat-sen University were using nonviable embryos that were never going to be implanted. They had received approval from a university ethics board for their experiments, but not a government panel.
Beyond the ethical concerns, most scientists say CRISPR needs much more refinement before it could be used as a tool to fix disease-causing genetic mutations in embryos. But they hope that applying the technology in a research setting, as Niakan is proposing, could reveal new insights into human development.
What exactly will Niakan be doing?
Niakan, who submitted her application to the panel in September, studies the earliest stages of human development, when the embryo is just a few dozen or hundred cells and has not yet been embedded into the womb. She is focused on the genes involved in separating the 20 or so cells that eventually grow into the fetus from the cells that form the placenta and egg sac; understanding them could illuminate more about fertility and what promotes a successful pregnancy, she said.
“Miscarriages and infertility are extremely common, but they’re not very well understood,” Niakan said at a press conference in London in January.
Niakan plans to use CRISPR first to inactivate a gene called OCT4 to determine its role in development. She said she would like to study another two or three genes but it depends on the number of embryos she can get. She plans to study about 20 or 30 embryos for each gene her lab is examining.
Niakan’s lab has been altering genes in these cells in mouse models, but she said differences between mouse and human embryo development emerge from the first cell division. Some of the genes she wants to investigate are not even present in the mouse models.
“The only way we can understand really human biology at this early stage is by further studying human embryos directly,” she said.
Where are the embryos coming from? Would they be implanted?
Niakan will be using spare embryos from IVF clinics with consent from the donors. They will not be implanted. Niakan’s lab stops the embryos’ development about five days after fertilization, when they are comprised of between 64 and 256 cells, and performs gene and protein expression analyses.
Could this research be done in the United States? What about in other countries?
The research isn’t illegal in the US, but the National Institutes of Health won’t fund any human embryonic gene editing. Researchers in the US have discussed how they would go about doing studies in germ cells, but it’s unclear if or how many labs may be conducting studies using private funding.
As for the rest of the globe, it’s a bit of a hodgepodge and often unclear. Different countries have different policies, and they can vary depending if you’re looking at gene editing for research purposes or for efforts toward an actual pregnancy. A 2014 paper from Japanese researchers found 29 countries ban germline gene modification. But in some of those countries — including China, India, and Japan — the rules are more like guidelines and cannot be enforced like laws.
In a paper published last month in Science, researchers from the University of Miami and McGill University wrote that most of the countries they reviewed take an “intermediate” approach that outlaws editing embryos for a pregnancy but permits some relevant research. They also found that “considerable uncertainty” exists about whether laws preventing editing embryos, sperm, or eggs for a pregnancy apply to research as well.
What do scientists and bioethicists say?
If you have an opinion on germline editing, you can probably find a scientist that shares your view. A group called the Alliance for Regenerative Medicine supports research in somatic (or non-reproductive) human cells, but draws the line at germ cells and embryos, citing safety, ethical, and legal concerns. But plenty of others, including some of CRISPR’s pioneers, have been somewhat open to germline editing as long as it’s for research purposes and not intended for a pregnancy.
Others have said that if safety, ethical, and legal issues are taken care of — and don’t hold your breath that that happens any time soon — there may be certain cases when using gene editing in human reproduction is “morally acceptable.”