Headlines have touted CRISPR-Cas9 as a technology with endless abilities for the future – from changing DNA, to introducing new genes and alter levels of gene expression. All culminate in either optimistic declarations of personalised medicine and new, climate-resistant foods or warnings that the new technology heralds an era of increased inequality, eugenics and “super-humans”.

Whether either – or both – of these alternate futures will materialise is of course uncertain. Nevertheless, they hint at the immense power of tools like CRISPR-Cas9. Such “disruptive technologies” have the potential to bring about rapid developments in fields such as drug design, food supply, green energy etc., but in doing so they will inevitably challenge social norms. Consequently, the extent to which we use CRISPR-Cas9 and related technologies to shape the future is as much a product of ethical consideration as it is technical feasibility.

One of the least controversial uses for CRISPR-Cas9 is its use in therapeutics – namely cancer therapy. The first instance of using genome-edited immune cells to treat cancer was reported in 2015, when a young girl suffering from acute lymphoblastic leukemia (ALL) received donor T cells ( universal chimeric antigen receptor T cells, or UCART cells) that had been edited using Transcription-Activator Like Effector Nucleases (TALENs) (Great Ormond Street Hospital for Children, 2015). The child is now in remission.

TALENs are an older form of genome-editing technology, and though effective in this instance, suffer in comparison with the CRISPR-Cas9 system. Though easier to designer than Zinc Finger Nucleases (ZFNs), their predecessor, CRISPR’s single guide RNA is easier to design again. Additionally, the entire CRISPR-Cas9 complex is smaller than the TALEN complex, making it easier to deliver to cells.

This brief recap of the recent history of genome editing brings another important point to light – whilst CRISPR is currently the foremost technology in the field, it may not remain so. Basic research constantly brings greater understanding to biological mechanisms, and may uncover an even better means of editing genomes. Already, further study of the CRISPR system in different prokaryotes has uncovered variants that cut RNA rather than DNA (Abudayyeh, 2016).

One of the biggest questions that remains surrounding gene editing is not one of technology, but rather ethics. Editing embryos – for research, therapeutically or otherwise – remains a highly contentious issue. As well as the usual arguments concerning the sanctity of life, the prospect of introducing perhaps-irreversible changes into the human gene pool also forces us to question our “right” to impose such changes onto future generations. This is especially true when considering non-fatal disabilities such as blindness or deafness. Many in these communities do not consider themselves “disabled”, but rather as living a life different from that lived by the majority. Editing genomes to remove the alleles that cause deafness, for example, would thus be akin to eugenics.

Already, researchers are using CRISPR to edit viable embryos in research settings – in 2016, it was announced that the Human Fertilisation and Embryology Authority (HFEA) approved the use of CRISPR-Cas9 to research the causes of infertility (Callaway, 2016). The application was made by Dr. Kathy Niakan, a researcher at the Francis Crick Institute in London. The team will be allowed to use the embryos for seven days, after which point they will be destroyed. The decision was generally welcomed by the scientific community, and may pave the way for less restrictive use of CRISPR-Cas9 in other countries around the world.

Ultimately, science cannot resolve the dispute between what is possible and what should be done: that must come through public discourse.

One of the more realistic – and more immediate – applications of CRISPR will be in gene drives, systems of modified inheritance in which one part of the genome is passed on to offspring at a higher frequency than other areas of the same genome (Burt, 2003). Complex regulation and technical issues prevented their implementation for years, though CRISPR-Cas9 has largely allayed the latter hurdle. However, it was recently announced that gene-edited mosquitoes will be released as part of a trial in Burkina Faso (Swetlitz, 2017). This will likely be the first of many trials in the region, and if successful could help lessen any opposition the drives still face.

By comparison with other genome-editing technologies, CRISPR’s relative ease of use cannot be understated. The fact that it is considerably cheaper and faster than other genome-editing technologies means that it is unsurprising that the technology has already been commercialised for use outside laboratories. Though the primary users will likely either be educators or civilian enthusiasts, there are some concerns regarding biosafety. Most uses will be benign, though the possibility of release of modified organisms – particularly viruses – poses an notable threat. Most countries have strict laws regarding the release of such organisms, though these could easily be touted in the new, unmonitored environments where CRISPR may now be used. The benefits of disseminating CRISPR to the masses and encouraging interest into a rapidly developing field must thus be balanced against the dangers such widespread use presents.

Despite still being in its infancy, CRISPR-Cas9 has brought unprecedented revolutions to the field of synthetic biology and genome engineering. Yet its applications have been even more far-reaching: its use in developing new therapeutics promises hope for those with otherwise incurable illnesses. Gene drives, once-theoretical models of disease control, are even-closer to release. Though to relish in the undisputedly beneficial applications of CRISPR-Cas9 would be to ignore the many complex issues we face through its use. When it is appropriate to edit human genomes – is it only in cases of fatal disability? What of diseases that are not fatal, but severely life-limiting? And will it ever be acceptable to edit for more frivolous traits such as hair colour? As the products of CRISPR genome editing become more widespread – and many likely coming from amateur users – these questions will become more pressing and shape the future use of the technology.

References:

Abudayyeh, O.O., Gootenberg, J.S., Konermann, S., Joung, J., Slaymaker, I.M., Cox, D.B.T., Shmakov, S., Makarova, K.S., Semenova, E., Minakhin, L., Severinov, K., Regev, A., Lander, E.S., Koonin, E.V. and Zhang, F. (2016). C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353:aaf5573

Burt, A. (2003). Site-specific selfish genes as tools for the control and genetic engineering of natural populations. Proceedings of the Royal Society Biology 270:921-928

Callaway, E. (2016). UK scientists gain licence to edit genes in human embryos. Nature 530: 18
Great Ormond Street Children’s Hospital (5th November 2015) World first use of gene-edited immune cells to treat ‘incurable’ leukemia Available at: http://www.gosh.nhs.uk/news/latest-press-releases/2015-press-release-archive/world-first-use-gene-edited-immune-cells-treat-incurable-leukaemia

Swetlitz, I. (14th March 2017). Experiment is planned for a West African village – if residents agree. Available at: https://www.scientificamerican.com/article/a-revolutionary-genetic-experiment-is-planned-for-a-west-african-village-if-residents-agree/

About the Author

Rachel Murray-Watson is currently pursuing a PhD in Cambridge University. Rachel obtained a first class honours (BSc) in Biological Sciences from Imperial College, London. Her thesis was on “Modelling the Spatial Spread of Gene Drives” and she won the Howarth Prize for excellence in plant sciences. Rachel won the Institute of Biology’s prize for 1st place in biology in the national examinations in Ireland. Her current area of research is mitigating the impact of communicable agriculural diseases by developing effective control strategies.