Human genome editing – the issues explored

By: Hayley Clissold, Policy Officer in the Wellcome Sanger Institute’s Legal, Ethical, and Governance Team
Date: 20.12.18

Recently, a Chinese scientist, He Jiankui, announced the birth of twin girls whose genomes he edited to provide resistance to HIV. The scientific community was left in a state of shock and there was an outcry from scientists all around the world condemning He’s actions. This revelation reinforced the need for an open, transparent and international debate on germline editing.

Here we explore the technology, what it is, how it might be used, the current regulations and the ethical issues surrounding it.

What is genome editing?

Genome editing is a technique used to modify a specific section of DNA. As all living things contain DNA, genome editing has an almost unlimited range of applications in organisms including bacteria, plants, animals and humans.

Genome editing is not a new technology. In fact, it has been around for decades. Genome editing has only recently taken the scientific world by storm because of the discovery of a new tool called CRISPR. CRISPR is simpler, faster, cheaper and much more efficient than any of its predecessor genome editing tools and because of its accessibility, CRISPR is now used in a vast spectrum of applications in labs all around the world.

CRISPR was originally discovered as a bacterial immune system. Some bacteria deploy CRISPR as a defence mechanism to chop up the DNA of an invading virus. Because of its ability to target and cut specific stretches of DNA, CRISPR is capable of removing any particular sequence – for example, disease-causing gene variants can be taken out of a genome. The technology also allows DNA sequences to be added or changed – so a disease-causing variant can be replaced with a ‘healthy’ one. Clearly, this technology offers almost limitless possibilities for science and in particular for healthcare.

Germline vs somatic editing

The sperm and egg are germline cells. The DNA they carry is passed on from generation to generation. Image credit: ScienceGenetics, Wikimedia Commons

Human cells are categorised as either a somatic cell or a germline cell. Germline cells are the reproductive cells (sperm or eggs) and somatic (body) cells are all the other ones (e.g. skin cells, liver cells, immune cells etc). Germline cells pass on their DNA to future generations.

Opinions towards genome editing differ depending upon whether the DNA modification occurs in a somatic cell or a germline cell. Editing DNA in somatic cells is more widely accepted largely because the modifications will only affect the treated individual and will not be inherited by future descendants. In fact, some cancer patients in the UK have already been treated by somatic genome editing and there are several ongoing clinical trials testing this technology for an array of other life-threatening and debilitating disorders. However, there are greater concerns over the use of genome editing in germline cells, because any modification to the genome could be irreversibly inherited by future generations.

Is germline editing illegal?

Genetic modification of human embryos for research purposes has been permitted since 2009, but only by using other genome editing tools. The world’s first licence for using CRISPR to edit human embryos was granted to Dr Kathy Niakan (Francis Crick Institute, London) in 2016 for studying embryonic development. Although it is legal in the UK to create and use genome edited human sperm, eggs or embryos up to 14 days old in research like Kathy’s, it is illegal to use genome editing for reproductive purposes. Therefore, embryos used in this type of research cannot be used to establish a pregnancy.

Despite this, in the future, there is hope that germline editing could offer a lifeline for people who are carriers of an inherited genetic disorder. If an individual is predisposed to a particular genetic disorder, CRISPR could be used to edit the genome of their sperm, eggs or resulting embryo itself to replace the disease-causing gene with a ‘healthy’ gene equivalent in order to prevent the child from being predisposed to the same disorder.

Is germline genome editing safe?

CRISPR is more efficient at precisely editing the genome at a specific location than other currently available genome editing tools, but there are still risks. CRISPR cuts the DNA once it recognises a specific DNA sequence, but the same (or very similar) string of A, T, C and G’s might be present in other sections of the genome too. This could lead to off-target effects where DNA modifications are made in the wrong place and potentially cause disruption elsewhere in the genome.

Structure of DNA in our genomes. Image credit: OpenStax, Wikimedia Commons
Structure of DNA in our genomes. Image credit: OpenStax, Wikimedia Commons

We also do not fully understand how all of our genes in our genome interact with each other. Therefore, would editing the function of one gene indirectly affect the behaviour of another? Although we can sometimes predict unintended consequences of genome editing, there is still a significant risk that unwanted knock-on effects might occur. As with all other medical interventions, we must weigh up the benefits and risks. For example, we know that chemotherapy causes nasty side effects and kills off healthy cells as well as cancerous cells, but we still administer it to cancer patients because the potential benefits of clearing the cancer outweigh the negatives. A similar risk-benefit assessment will be needed for germline editing. However, there is greater concern with germline editing because this medical intervention is irreversible and can be passed down to future generations.

This shouldn’t rule out the possibility of using this technology in the clinic to prevent genetic disorders, but it does reinforce the scientific consensus that germline genome editing should not be used clinically for reproductive purposes until the technology is deemed safe and effective through further research.

What are the ethical considerations?

There is no doubt that CRISPR offers a huge potential for preventing genetic disease, but we must carefully consider a number of ethical issues before the green light is given for its clinical use in embryos.

First and foremost are concerns that genetic modifications could be inherited by future generations. Currently, healthcare professionals obtain informed consent from patients for most medical interventions. However, for germline editing where the patient is an embryo (or indeed its future descendants), this consent can never be obtained and so permission can only ever be sought from the parents. Some people argue that parents make most decisions for their children anyway, particularly with regards to health, so why should this be considered any different? If the technology is available for preventing disease and suffering, then surely we have the moral responsibility to use it? Others argue that we do not have the right to permanently edit the genome of an individual who could then affect their respective descendants too.

Would germline editing increase social divides and reduce acceptance of disability? Image credit: Matt Arntz on

There is also the risk that germline editing to prevent genetic disorders could lead to a social divide. If we specifically edit genomes to remove any potential disabilities, would this reinforce prejudice towards disabled communities? Using genome editing technology would undoubtedly result in fewer people in society with disabilities. This could mean that there is less familiarity and social acceptance of disabled people in society and could result in less investment for research, treatment and social support services for these communities.

Not only could a potential social divide marginalise disabled communities, but also between socioeconomic groups. Would germline editing be available on the NHS? If not, expensive genome editing treatment could worsen existing health inequalities throughout the UK and the world.

We must also consider that genome editing seeks to improve physical health traits, but does not consider social or psychological well-being. Will genome edited humans be seen as superior, or indeed inferior, to others in society? Would their mental health be affected by knowing that their genome has been irreversibly edited?

Genome editing offers huge potential for healthcare, but we must consider when it is medically appropriate. There are concerns that permitting the use of genome editing for medical purposes is a slippery slope to its use for non-health-related enhancement purposes – it’s not a difficult leap to imagine the possibilities for enhancing athletic ability, improving intelligence, selecting eye colour or other physical traits. Although the scientific community condemns non-medical usage, there may occasionally be a grey line between traits associated with health versus enhancement. Therefore, there needs to be international legislation and regulation to ensure that the application of germline editing in humans is safe, responsible and ethical. 

There is consensus that all individuals should be entitled to human rights and that the use of genome editing should not increase disadvantage, discrimination or divisions in society.

Where are we at now?

It is currently illegal to edit embryos for a pregnancy in the UK and Europe. At the moment, our scientific understanding of using CRISPR for germline editing is too uncertain and the risks are too great to allow clinical trials to take place. There is widespread agreement that further research into safety and effectiveness needs to be undertaken as well as a public debate on its application. However, given the rate at which these technological advances are happening, it is important that we begin to think about how CRISPR could be used safely and responsibly within a clinical context. If germline editing were legalised, several criteria would first need to be met before it could be licenced for each clinical use. Such criteria would include an unmet clinical need, inability to use alternative treatment options, follow-up plans and a consideration of potential societal effects.

Germline genome editing is not an issue that can be debated in isolation. After all, irreversible modifications to DNA affects humanity and not just individual people or countries. The recent reports from China have placed genome editing in the limelight and we must use this opportunity to engage in an open and international discussion among scientists, healthcare professionals, ethicists, social scientists, religious groups, policymakers, regulators and the general public to consider the future potential of germline genome editing.

About the Author

Hayley Clissold is a Policy Officer in the Wellcome Sanger Institute’s Legal, Ethical, and Governance Team

Communications Team

From the Wellcome Sanger Institute, a charitably funded genomic research organisation

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