What if editing genes could fight rare diseases? [Science and Technology Podcast]

Written by Mihalis Kritikos,

A new technique to simplify gene editing might herald a new era of genetic modification. What are the benefits and potential dangers of this technique, and how should policy-makers respond?

The capacity to engineer genomes in a specific, systematic and cost-effective way is a long-standing objective in the field of genomic studies. Several ‘gene editing’ technologies have recently been developed to improve gene targeting methods, including CRISPR-Cas systems, transcription activator-like effector nucleases (TALENs) and zinc-finger nucleases (ZFNs). The CRISPR-Cas9 system currently stands out as the fastest, cheapest and most reliable system for ‘editing’ genes. It is seen as the biggest game changer in the gene editing field, due to its high degree of reliability and effectiveness, as well as its low cost. This technological trajectory is expected to enhance our capacity to target and study particular DNA sequences in the vast expanse of a genome. CRISPR-Cas9 has the potential to cut the DNA of any genome at any desired location in many types of organisms, replace or add parts to the DNA sequence by introducing the cas9 protein, and appropriately guide DNA into a cell. This extremely powerful tool could help molecular biologists to explore how the genome works.

Potential impacts and developments

CRISPR-Cas9 has great potential as a tool for directly modifying or correcting fundamental disease-associated variations in the genome and for developing tissue-based treatments for cancer and other diseases by disrupting endogenous disease-causing genes, correcting disease-causing mutations or inserting new genes with protective functions. Researchers hope to use CRISPR-Cas9 to adjust human genes to eliminate diseases, fight constantly evolving microbes that could harm crops or wipe out pathogens, and even edit the genes of human embryos.

CRISPR-Cas9 can be used to alter the genes of a wide range of organisms with relative precision and ease, and also create animal models for fundamental research. Editing the genes of animals could improve disease resistance, control mosquito populations so as to mitigate or tackle malaria transmission, or even lead to the creation of ‘farmaceuticals’ — drugs created using domesticated animals — or better food production. The system could also facilitate the transplanting of animal organs into people by eliminating copies of retrovirus present in animal genomes that may harm human recipients.

Altering DNA in human embryos is also possible using CRISPR-Cas9 technology, which could eventually lead to transformative changes in human well-being, with consequences for people’s life span, identity and economic output. The technology can also be used to create a ‘gene drive’, which means that a particular selected gene will be preferentially handed down to the next generation, thereby rapidly spreading through entire populations.

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While CRISPR offers many fascinating prospects, the use of CRISPR has also triggered socio-ethical concerns over questions such as whether and how gene editing should be used to make inheritable changes to the human genome, lead to designer babies, generate potentially risky genome edits or disrupt entire ecosystems. The use of CRISPR-Cas9 raises social and ethical issues not only for humans, but also for other organisms and the environment, leading scientists to recommend a moratorium on making inheritable changes to the human genome. For instance, the application of CRISPR as a pest control technique may produce unintended effects and mutations, which may lead to the dispersion of gene drive, the disappearance of a whole animal population, accidental releases and/or the irreversible disturbance of entire ecosystems. In fact, research activities intended to modify the genetic heritage of human beings which could make such changes inheritable are not financed under Horizon 2020, the EU framework programme for research and innovation.

Taking the non-maleficence principle into account in risk assessment, and distinguishing the clinical and therapeutic aims of gene editing from its enhancement applications/uses, have also become major sources of concern. Another important problem is the efficient and safe delivery of CRISPR-Cas9 into cell types or tissues that are hard to transfect and/or infect. Further concerns include the prospect of irreversible harm to the health of future generations, and concerns about opening the door to new forms of social inequality, discrimination and conflict, as well as to a new era of eugenics.

Anticipatory law-making

The rapid pace of scientific developments in the field of gene editing makes regulatory oversight particularly challenging. Moreover, there is a debate over whether CRISPR-Cas9 should be regulated as a gene editing technique, or whether its products should rather be controlled ad hoc with a result-based approach. International discussion on the regulatory status of genome editing techniques has focused on whether current definitions of genetic engineering or genetically engineered organisms could also apply to these recently discovered genetic editing tools.

The European Commission is currently working on a legal interpretation of the regulatory status of products generated by new plant-breeding techniques, to minimise legal uncertainties in this area. Such an interpretation may pave the way for a decision on whether gene editing technologies should fall under the scope of the EU legislative framework on the contained and deliberate release of genetically engineered organisms.

Patenting CRISPR-Cas9 for therapeutic use in humans is also legally controversial. In February 2017, the US Patent and Trademark Office (USPTO) issued a decision on who should hold the patent on using CRISPR-Cas9 to edit genes, defining the terms and conditions for profit generation from this technology in the years to come.

The risks of hereditary, unpredictable genetic mutations raise questions regarding the safety of the technique and the attribution of liability in case of damages. In a recent report, the US National Academies of Sciences, Engineering and Medicine urged caution when releasing gene drives into the open environment and suggested ‘phased testing’, including special safeguards, given the high scientific uncertainties and potential ecological risks. Safety measures are necessary to avoid dissemination of organisms that may cause ecological damage or affect human health.

In fact, many scientists caution that there is much to do before CRISPR could be deployed safely and efficiently. In particular, CRISPR might create additional challenges from a risk assessment standpoint, in that organisms produced by these methods may contain more pervasive changes to the genomes of living organisms than traditional genetic modification techniques.

Read this At a glance on ‘What if editing genes could fight rare diseases?‘ on the Think Tank pages of the European Parliament.