Genome of Human Embryos Edited for the First Time
By Marc Tawfik, Biochemistry, 2018
A follow up to “Engineering the Next Human Generation” by Marc Tawfik, NUSci Issue 24
A group of scientists in China recently used the gene-editing technology known as CRISPR/cas9 to modify the genome of human embryos for the first time despite stern warnings by a number of prominent scientists, including one of the co-developers of the CRISPR/cas9 technology. The research team’s work is detailed in a paper published in Protein & Cell in April 2015. The paper was rejected from both Nature and Science on account of ethical objections as well as critiques regarding the quality of the results generated by the team.
CRISPR/cas9 is a gene-editing tool employing the capabilities of a particular protein known as Cas9. Cas9, derived from a part of the bacterial immune system known as CRISPR, has the powerful ability to cut strands of DNA in pre-specified regions. By taking advantage of this capability, the CRISPR/cas9 technology can be used to add or delete bits of genetic code to a user’s specifications.
The team of scientists, led by Junjiu Huang of Sun Yat-sen University in Guangzhou, used this technology to attempt to modify the gene responsible for β-thalassaemia, a blood disorder, in “non-viable” human embryos that were culled from local fertility clinics. The group hoped to minimize criticism by performing their experiment on these “non-viable” embryos whose fertilizations by two sperm had rendered them incapable of producing a live birth.
The goal was to edit the “hemoglobin beta”, or “HBB” gene, whose irregularity is the underlying cause of β-thalassaemia. The team injected 86 embryos with CRISPR/cas9 and waited 48 hours to allow the CRISPR/cas9 system to run its course. Only 71 embryos survived. 54 of those were genetically tested, revealing that only 28 had actually been spliced, while only 4 these showed the desired modification to the HBB gene. Furthermore, the team detected a significant number of “off-target,” or unintended, modifications to the embryonic genomes that were presumed to have been introduced by the CRISPR/cas9 system.
According to stem-cell biologist George Daley of Harvard Medical School, the study is “a landmark, as well as a cautionary tale” and “a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.” Critics claim that the less-than ideal outcomes of this study are due to complications stemming from the abnormal nature of the embryos used. Huang has acknowledged the critiques but maintains that in the absence of data from studies on normal human embryos, these embryos serve as meaningful models.
Next, Huang plans to continue the work from the original study, concentrating on reducing the number of “off-target” mutations produced by CRISPR/cas9, In future research, he will use far less controversial human adult cells — or animal cells — rather than human embryonic cells. However, it is rumored that four other groups of scientists in China are working to modify human embryos despite continued calls for a moratorium until an in-depth conversation regarding the ethical implications of such work occurs.
The ethical considerations for modifying human embryonic cells are substantial.
Modifications made to embryonic cells can be passed on to future generations, creating potential for the abuse of gene-editing technologies. As illustrated by this study, the technology still has a long way to go before it could be successfully employed in clinical practice, but once these tools are mastered, they may have the ability to completely eradicate illnesses like β-thalassaemia from the gene pool. However, it’s clear that a large-scale discussion to establish ethical guidelines and boundaries should take place prior to further development of powerful gene-editing technologies such as CRISPR/cas9 so as to minimize the potential for abuse of these tools in the future.
