Human genome engineering has long sounded like a concept out of a Sci-Fi movie; believed to be possible sometime soon, but difficult to imagine happening right now. While engineering of the human genome might appear an implausible feat, over the last 20 years technological advancements have been turning this concept into a concrete reality. Among these leading innovations, the most crucial has been the development of CRISPR-Cas9 gene editing, which granted Jennifer Doudna and Emmanuele Charpentier’s Nobel prize last year.
The CRISPR-Cas system is a bacterial defence against viruses. When bacteria survive a viral infection, they save a small snippet of DNA from the virus and store it in their genome. If the same virus tries to reinfect the cells, the bacteria employ the CRISPR system to recognise the viral DNA and cut it up, destroying the virus. Professors Charpentier and Doudna learned how to use CRISPR outside of bacteria to seek out and modify any portion of a genome, opening up endless editing possibilities.
Following this discovery, patients affected by genetic conditions such as Beta Thalassemia and congenital blindness have been given access to curative drugs for the first time. This new form of treatment has been named “gene therapy”, as it can correct the mutated genes at the source.
While these are incredible achievements, human genome editing has been pushed even further with attempts to treat non-genetic disorders. For example, Cancer therapy is experiencing a revolution due to the invention of CAR-T cells, a modified form of regular T-cells, which make up our immune system and take care of eliminating foreign pathogens. In the case of cancers, however, regular T-cells lack the correct receptors to recognise the cancer cells as being a threat. To make CAR-T cells, T-cells from the patient are taken from their body and genetically engineered to possess a receptor specific to the patient’s cancer. The CAR-T cells are then re-inserted to eliminate the cancer cells, resulting in a high precision cancer treatment which provides a key alternative to chemotherapy.
However, there is another side of the story. While these advancements demonstrate the value of genome editing, recent research has presented many associated ethical problems.
On the 28th November 2018, He Jiankui, a researcher from the Southern University of Science and Technology in Shenzhen, uploaded a series of Youtube videos unveiling the first gene edited babies. Dr He revealed that he had altered two embryos by partially deleting a gene involved in the transmission of HIV into cells. He had embarked on this project with the goal of generating humans with an innate resistance to the virus, as an effort to ‘control the HIV epidemic’.
The experiment, carried out on several fertilised embryos from seven couples, resulted in one pair of twins, Lulu and Nana. While the partial deletion of this gene might, in theory, stop some variants of HIV, other forms of the virus do not access our cells by the same route. Therefore, the editing cannot ensure complete immunity against HIV, invalidating the final objective of the experiment.
The experiment was criticised as an example of scientific negligence and ethical oversight, and led to Dr He’s imprisonment. In fact, the extreme measures taken to protect the twins from HIV infections might have also lead to significant biological issues, with the potential to impact their quality of life. As a result, this event has not only provided proof of the important research steps that are still needed to optimise genetic engineering, but acted as a reminder of what uncontrolled human genome editing can cause.
Gene therapies and gene edited babies, although both applications of human genome editing, have received very different responses. The key distinction that makes one practice ethically acceptable compared to the other is the type of edited cells. Gene therapies have focused on editing only somatic (body) cells, which can carry mutations but do not pass our genetic code to the next generation.
Germline cells, on the other hand, transfer genetic information from parent to offspring. Gene edited babies are edited at the embryonic stage, meaning that all the cells in their bodies, somatic and germline, contain changes that could be passed on to their offspring. This is a very important distinction, as there is a suggestion that such modifications might spread in the population before revealing significant negative health impacts many years down the line.
The CRISPR-Cas9 system has been found to occasionally miss its genetic target, resulting in other genes being mutated. These “off-target” mutations can sometimes even cause large changes in the genome, such as chromosomal deletions. If a human somatic cell is mutated in such a harmful way, the mutations would not be able to spread into the population as the germline cells have not been affected. This is not the case with gene edited babies. to complicate matters further mutations do not always have a clear negative effect, as they can lie silent until the right genetic combination produces a nasty disease. Overall, this means gene editing babies could be very dangerous indeed.
Genome engineering of humans is now a reality. But while gene editing is shaping up to be an incredibly useful tool, its careless application can be equally destructive. It should therefore be obvious that we need strong controls on its practice. However, while tempting, a blanket ban would only result in illegal and uncontrolled genome editing, as was the case with Dr He. Instead, through cooperative and transparent research, the regulated application of human genome engineering could be a potent ally in our next steps of human development.
- Jinek, Martin, Krzysztof Chylinski, Ines Fonfara, Michael Hauer, Jennifer A. Doudna, and Emmanuelle Charpentier. 2012. “A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity.” Science 337 (6096): 816–21.
- Cyranoski, David. 2019. “The CRISPR-Baby Scandal: What’s next for Human Gene-Editing.” Nature 566 (7745): 440–42.
- Cyranoski, David. 2020. “What CRISPR-Baby Prison Sentences Mean for Research.” Nature 577 (7789): 154–55.
- Burgess, Darren J. 2014. “Characterizing CRISPR off-Target Effects.” Nature Reviews. Genetics 15 (1): 5–5.https://www.nature.com/articles/d41586-020-01906-4