A team of Chinese researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, have for the first time genetically altered a human embryo, according to research quietly published earlier this month in the journal Protein & Cell.
The research, which Science explained, went largely unnoticed until it was the subject of an April 22 article by Nature News that confirmed rumors such research was underway. It has now led to a renewed debate over the ethical implications of editing the genomes of human embryos.
Huang’s team emphasized their experiments used “non-viable” embryos obtained from local fertility clinics and which could not result in a live birth, their announcement nonetheless ignited what Science dubbed “a firestorm of controversy around the world and renewed recent calls for a moratorium on any attempt to establish a pregnancy with such an engineered embryo.”
What the controversial research entailed
In their study, Huang and his colleagues explained that, while genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) had previously been used to modify genes in animal zygots, human cells and other model systems (and showed “tremendous promise” for both basic research and clinical applications), there was a “serious knowledge gap” when it comes to human embryonic DNA repair mechanisms.
To rectify that, as well as to learn more about the efficiency and potential off-target effects of this type of technology in human pre-implantation embryos, they used tripronuclear zygotes to probe the use of CRISPR/Cas9-mediated gene editing in human cells. They said they were able to successfully use CRISPR/Cas9 to cleave the endogenous β-globin gene (HBB), but that the efficiency of homologous recombination directed repair (HDR) of HBB was low.
They added that “off-target cleavage was also apparent” in the tripronuclear zygotes “as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway.”
Debating the ethics and value of human embryo modification
Huang’s team said their work highlighted “the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform,” demonstrating there are serious obstacles to overcome before these techniques can be used in medical applications.
However, Nature News explained that it has also led to a debate about whether or not using human embryos for this type of experiment is safe and/or ethical.
In the study, the Chinese researchers wanted to use the procedures to replace a gene in a single-cell fertilized human embryo, the website explained. If successful, this would have theoretically caused all cells produced as the embryo developed to have the altered gene. Due to the nature of the research, Huang claimed that the paper was rejected by Nature and Science. Neither of those publications responded to Nature News’ request for comment on the issue.
Last month, Edward Lanphier, president of Sangamo BioSciences in Richmond, California, and his colleagues published a study in Nature arguing that genetic modifications to human embryos crossed an ethical line-in-the-sand, noting that since changes are heritable, they could well have an unpredictable impact on future generations. Lanphier told Nature News that the new Chinese study “underlines what we said before: we need to pause this research and make sure we have a broad based discussion about which direction we’re going here.”
However, Guo-Qiang Chen, a microbiologist at Tsinghua University in Beijing, told Science that in China, “most scientists are more positive” about the value of research that involves genetically modifying human embryos.” Harvard Medical School stem cell biologist George Daley agreed, stating that he “personally would defend the fundamental scientific value of research into gene editing” in human embryos to explore the risks associated with its potential clinical use.