For many years, we have been promised that medical innovation will one day allow us to edit the human genetic code, to remove harmful mutations in our DNA, and wipe out genetic diseases. At last, CRISPR/Cas9 has been hailed as the hero that will finally allow us to do this. It has been dubbed the “universal scissors”, that effortlessly allows scientists to stop genetic diseases in their tracks. But there is also a dark side to our hero, with the media especially suggesting that the technology has put us on a slippery slope to “designer babies”, where parents will Pick & Mix traits for their children.

 It is easy to get lost in all of this controversy and ethical debate around CRISPR/Cas9, and not really understand what the technology is and what its actual benefits, risks, and limitations are. To counter this, Flóra took on the personal challenge to get to the bottom of the discussions and, in this blog, reports back a summary of her findings. 

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CRISPR/Cas9 is the latest technological development in a longline of genome editing techniques; previous tools have included meganucleases, zinc finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs). CRISPR/Cas9 is in fact an abbreviation of the mouthful ‘clustered regularly interspaced short palindromic repeat-associated nuclease Cas9’. It has greatly excited the scientific and research community as it is the cheapest and easiest to use of the genome editing tools, as well as being the most accurate in its ability to identify and cut very specific parts of the genetic code, or “genome”.

It should be noted at this point that the technology is not yet perfect. One of the main limitations of CRISPR/Cas9 is that while it is very accurate, its method for identifying the correct part of the genome to edit is not flawless.
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As our genome contains many similar sections of DNA (“homologous” sections), it can accidentally target and cut the wrong part of the DNA, resulting in what is known as “off-target” edits. This can mean healthy parts of the DNA are interrupted and could lead to severe medical consequences, including cancer.

So you might wonder why there has been so much hype around the technology. Well, firstly, it is an excellent step forward towards effective genome editing, and the researchers are rightly excited. But much of the media hype has been caused by one particular experiment, published in 2015 about a research group in China who first used the technology in human embryos. Again, please note, this was in a research setting, the embryos were donated from a local fertility clinic as they were non-viable – that is, unable to result in a live birth. However, this was the first recorded time CRISPR/Cas9 was used in human embryos and excited the prospect that we could eradicate human genetic conditions by editing embryos, or sperm and eggs (known as “germline” cells), and prevent the condition from being passed on for generations to come.

This potential has sparked a very large ethical debate about the use of genome editing and the circumstances in which it should be permitted – if at all. Many are concerned by the prospect of one-off genetic editing resulting in life-altering changes not only for that one individual, but for all of their future children, and grandchildren, and future generations. It is also argued that our understanding of the human genome is still quite basic, after all, it was only in the early 2000s that we mapped the first human genome. Now 15 years later, we are already looking at cutting bits and replacing them with other bits. It is questioned whether we have a deep enough grasp of genetics to safely make such changes. As previously mentioned, many also fear genetic editing will lead to a rise of eugenics and “designer babies” where parents select for height, skin colour, intelligence, and more.

Even if we do not consider germline cell editing, and look at editing cells that are not inheritable (“somatic” cells), the ethical debate continues. It is questioned what circumstances genetic editing should be used and who defines these circumstances. Who decides what is “genetically healthy”? Where is the line between editing for disease prevention and enhancement? Should genetic enhancement be allowed? How will we ensure equal access to the technology and who will pay for it? At what point do the risks outweigh the benefits?

These are the questions regulators and legal teams around the world are struggling with at the moment. The more articles I read, events I attend, discussions I participate in, the more I realise the current confusion around the issue. It is a case in which technology has sped ahead much faster than we have been able to keep up with, and it has been published this week that CRISPR/Cas9 has been used clinically for the first time in China. So it is crucial that these ethical debates occur, and legislation is updated soon, to allow the potential benefits in a safe and regulated environment.
As rare disease patients and advocates, it is critical you get involved in these conversations. As 80% of all rare diseases have a genetic component, rare diseases will be the first targets for this new technology to address. So you need to make sure your views on acceptable risk-benefit, acceptable uses, and inheritable changes are heard, so regulators appreciate your needs and account for them in legislation changes.

If you would like to find out more, please watch EURORDIS’s excellent webinar on the topic of genome editing. Genetic Alliance UK are also looking for patients and family members to get involved in a new project around how to best communication about genome editing, register to participate here.

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