In 2015, Chinese scientists reported successfully editing the human genome using CRISPR technology, which drew awe and stirred ethical debates at the same time.
The gene editing tool – the bacterial protein-derived innovation that allows scientists to cut and paste certain portions of DNA – has even emerged as Science magazine’s 2015 Breakthrough of the Year.
The controversial gene splicing technique has taken a stab at a number of diseases and even spurred the experimental-phase gene drive, which is hoped to extinguish Zika-causing mosquito populations.
Last week, a separate team of scientists in China did it again: they said they have edited human embryonic genes to help make them resistant to HIV infections, the second published experiment of its kind.
The team from Guangzhou Medical University, led by stem cell scientist Yong Fan, reported collecting 213 fertilized human eggs from April to September 2014. Donated by 87 patients, the eggs were unfit for implantation via in vitro fertilization due to their extra set of chromosomes.
They employed CRISPR-Cas9 gene editing to cause a mutation into some embryos that crippled the immune cell gene CCR5. Some people naturally carry the mutation, which alters the protein in a way that blocks the virus from entering and infecting T-cells, and thus become resistant to HIV.
According to results, four out of 26 targeted human embryos were modified. Not all chromosomes, though, obtained the specific mutation, either containing unmodified CCR5 or harboring different forms of mutation.
Nature sought comment from Fan, who had not responded by the time of the report.
“This paper doesn’t look like it offers much more than anecdotal evidence that it works in human embryos … It’s certainly a long way from realizing the intended potential,” commented stem cell biologist George Daley. He added that the main takeaway in the paper is the use of CRISPR in introducing a precise genetic alteration.
For Daley, the experiment was far from achieving its goal of producing a human embryo with all copies of CCR5 rendered inactive.
On the other hand, the issues should be resolved in non-human primate studies first, if to ask Xiao-Jiang Li, a neuroscientist from the Emory University in Georgia.
In April 2015, a different team in China announced that it successfully modified a gene associated with a blood disease in human embryos. The modification done in this world-first was not viable and therefore, could not have led to a live birth.
Thus, both studies have pointed to results that are "comforting and disturbing" at the same time, according to Dr. Peter Donovan, a biological chemistry and developmental cell biology professor at the University of California.
“[T]his group of researchers also reproduced another finding described by the first group, namely that this type of gene editing also causes off-target effects," he said.
These failures have led to conclusions that CRISPR is not yet ready for use in human embryos, with much work needed to be done as long as researchers do not get to the point of implanting viable genetically engineered embryos into a living woman’s uterus.
At the International Summit on Human Gene Editing in 2015, scientists from the U.S., the UK and China were in agreement that viable human embryos can be used for research, but it would be unacceptable to alter the DNA of these embryos in clinical settings.
Fan’s team appeared to echo these sentiments, writing that attempts to generate genetically modified humans through early-embryo modification “needs to be strictly prohibited” until the ethical and scientific kinks are ironed out.
However, it looks like experiments on genetically altered embryos are forging ahead.
Early in 2016, British regulators green-lit experiments on viable embryos, with Francis Crick Institute researchers set to use CRISPR to snip out genes that hinder healthy fetal development.
The findings of this study were published in the Journal of Assisted Reproduction and Genetics.
Photo: Caroline Davis | Flickr