The take-away

• 87% of in vitro fertilisations fail. CRISPR-Cas9 could help to better understand the function of genes that favour embryonic development.
• Some researchers think that society should have a discussion on how to use technologies like CRISPR-Cas9.

A barbaric short cut depicts the gene editing technology, which is advancing almost too quickly. In six years, CRISPR-Cas9 has revolutionised genome research and achieved a resounding success. And understandably so. “CRISPR Cas-9 is not the only gene editing tool out there, but it is much faster and simpler than other methods that have been developed since the early 2010s,” says French expert Hervé Chneiweiss.

Unlocking the mystery of the IVF

Research laboratories are starting to obtain authorisation to work on the genome of viable human embryos. This shift is viewed as exciting by some and frightening by others. The latest to do so is the Francis Crick Institute, a London-based biomedical research centre, which began studying in vitro fertilisation (IVF). Used since the 1970s, IVFs still fail 87% of the time. Medicine is struggling to explain why a fertilised egg develops properly. To answer that question, Crick researchers focused on the OCT4 gene, which plays a role in the initial stages of embryonic development, by suppressing its expression in a portion of the 58 viable human embryos donated and watching what happened next.

Reported in an article published at the end of 2017 in “Nature”, their research confirmed the importance of OCT4 in forming blastocysts, a sort of ball comprised of 200 to 300 cells formed in the early days of embryonic development. This phase is crucial, as the embryo must reach this stage before it can be successfully implanted in the uterus. “For now this work falls under fundamental research, with no foreseeable clinical applications in the medium term,” explained Dr Chneiweiss cautiously.

In 2015, a team of Chinese researchers had already broken the taboo by using CRISPR-Cas9 to modify the DNA of human embryos with beta thalassemia, a monogenic disorder which leads to anaemia resulting from the destruction of red blood cells. Another ground-breaking example was in August 2017, when a US team based in Portland, Oregon edited out a gene mutation that causes hypertrophic cardiomyopathy, after fertilising healthy donor eggs with sperm carrying the mutated gene responsible for the potentially deadly heart condition. Also published in “Nature”, these findings, although contentious, confirm an overall trend. The technology is progressing, becoming more precise, and opening up new opportunities.

Ethical debate and social implications

After settling for a while, the controversy surrounding the initial Chinese research is now back with even greater force. The emerging ethical and moral issues cannot be ignored, as they revive deep-seated fears of eugenic musings and Gattaca-style transhumanism, as portrayed in Andrew Niccol’s famous sci-fi thriller. Can we modify the genome of human embryos and therefore that of the next generations? “Deliberations about biotechnologies such as CRISPR-Cas9 should include a range of different stakeholders in society,” to discuss critically who makes decisions and who benefits from the technology and who does not, says Professor Ruth Müller from the Technical University of Munich.

Making matters even more difficult, its acceptance hinges heavily on political, cultural and social attitudes. “The dispute over GMOs has shown how complex debates over new technologies are,” the researcher says. “Different stakeholders approach the topic differently, based on their needs, values and the specific issues affecting them.” “The technology itself isn’t the problem,” Dr. Chneiweiss points out, “it’s what we do with it.” The fear that we have cracked open Pandora’s box is not about to subside. But one thing is sure, laws will eventually have to be passed.

Designer babies, and how to make them

Developed in 2012 by a team of two researchers, the French microbiologist Emmanuelle Charpentier and American biochemist Jennifer Doudna, CRISPR-Cas9 is easier, cheaper and above all more accurate than other techniques such as TALEN and ZFN. Rapidly adopted by thousands of laboratories around the world, the method is used to turn off or delete DNA sequences within formed cells in a two-step process. A piece of RNA (CRISPR) targets a specific sequence in the genome and uses the endonuclease enzyme Cas9 to cut the two DNA strands at a fixed position.

That is how CRISPR-Cas9 quickly earned the nickname ‘genetic scissors’. And the technology sparks all sorts of hopes and fears. Whether it is used on plants, animals or humans, CRISPR-Cas9 scales up the possible into realms as yet unexplored in the living world.