AsianScientist (Apr. 24, 2015) – A team of Chinese scientists has caused worldwide controversy with the publication of their study on gene editing in human embryos. Their paper, published in the open access online journal Protein & Cell, detailed the modification of the gene responsible for β-thalassaemia—a potentially fatal blood disorder—using a gene-editing technique known as CRISPR-Cas9.
CRISPR-Cas9 has been previously used in gene-editing of human adult cells and animal embryos. However, there have been no published reports on its use in editing human embryos due the controversial nature of the topic and the feared implications of such research.
In their study, the research team, led by Dr. Huang Jinjiu from the Sun Yat-sen University in Guangzhou, attempted to edit the human β-globin (HBB) gene by cleaving it using CRISPR-Cas9. While the technique was successfully applied to the embryos, the results were dismal. Of the 86 embryos injected, 71 survived the initial cell multiplication stage and CRISPR-Cas9 technique. Of these, 54 were genetically tested and only 28 were found to be successfully spliced, with a small portion containing the replacement genetic material.
Although a landmark as the first report of human genome editing, the paper has stirred much debate on whether such an experimental technique should be used on human embryos. Even scientists like Dr. Edward Lanphier—who as President of Sangamo BioSciences is in favor of using gene-editing techniques on adult human cells—have cautioned against venturing into uncharted territory:
“It 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,” Lanphier told Nature News.
Due to the controversy surrounding human embryo editing, the paper found difficulties in being published. Huang, the lead author of the study, told Nature News that the paper was initially rejected by the journals Nature and Science on the grounds of ethical concerns.
The ethical considerations of human embryo editing
Last month, Lanphier was among scientists calling for a moratorium to restrict the use of CRISPR-Cas9 on the human germ line published in Nature. In his article, he pointed out the benefits of gene editing technologies to treat many human diseases such as HIV/AIDS, but cautioned against using it for other purposes. Using gene editing on sperm, eggs or human embryos constitutes an entirely different path with unknown effects, they argued.
One week later, Caltech’s Professor David Baltimore and colleagues published a perspective piece in Science, calling for greater discussion and dialogue to inform the rapid progress of CRISPR-Cas9 technologies. They emphasized the scientific, medical, legal and ethical implications of research using such technologies, as well as the steps that are needed to ensure that such research adheres to both safety and ethical guidelines.
However, the fact that the embryos used in the Protein & Cell study were non-viable due to genetic defects arguably makes this particular study ethically acceptable.
“The embryos they obtained from the fertility clinics had been created for use in in vitro fertilization but had an extra set of chromosomes, following fertilization by two sperm. This prevents the embryos from resulting in a live birth, though they do undergo the first stages of development,” according to Nature News.
Nonetheless, it is apparent that both the research technology and methodology lags behind the main objective—successfully editing out defective genes and eradicating diseases from the human race. As noted by the researchers, their findings included ‘off-target cleavage’ and ‘untoward mutations’, highlighting the inadequacy in knowledge for gene editing in human embryos and a far way from widespread use.
“If you want to do it in normal embryos, you need to be close to 100 percent,” Nature News quoted Huang as saying. “That’s why we stopped. We still think it’s too immature.”
Perhaps, for many, this study is a salutary warning and a timely reminder of the need for bioethical guidelines in scientific research.
“I believe this is the first report of CRISPR-Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” Professor George Daley, a stem-cell biologist at Harvard Medical School. “Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”
The article can be found at: Liang et al. (2015) CRISPR/Cas9-mediated Gene Editing In Human Tripronuclear Zygotes.
Copyright: Asian Scientist Magazine; Photo: Dr. Yorgos Nikas/SPL.
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