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Changing the Human Genome: What Next for Germline Genome Editing?

19 July 2021
Appeared in BioNews 1104

The Progress Educational Trust (PET)'s latest online event 'Changing the Human Genome: What Next for Germline Genome Editing?' discussed the recently published reports from the World Health Organisation (WHO) on human genome editing.

Sarah Norcross, director of PET, began by presenting a brief scientific background on genome editing and its importance in scientific research. Recently two pioneers of the CRISPR approach to genome editing, Professors Jennifer Doudna and Emmanuelle Charpentier, were awarded the Nobel prize in chemistry (see BioNews 1067).

PET's event focused specifically on genome editing involving the germline (the heritable part of our biology). This could provide a wide range of benefits but also presents ethical and regulatory challenges, especially in a clinical setting.

The first speaker was Professor Robin Lovell-Badge, a member of the WHO's Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing (which was responsible for the new reports). He is also chair of trustees at PET, and a group leader in stem cell biology and developmental genetics at the Francis Crick Institute.

Professor Lovell-Badge provided a brief run through of the WHO reports published earlier in the week (see BioNews 1103). He discussed how the WHO publications are a first 'serious attempt' at discussing global governance for genome editing. The reports present appropriate frameworks for regulating scientific and clinical research and practice with thorough analyses and scenarios.

Professor Lovell-Badge spoke on the ethical issues that had to be considered in the report, and special challenges that had to be explored. He outlined the tools, institutions, and processes for human genome editing governance that currently exist, and how these reports provided guidance for future steps. Importantly, he highlighted that the international committee represented all WHO regions, to ensure that thoughts from around the globe were considered and reflected.

The second speaker was Dr Norah Fogarty, group leader at King's College London's Centre for Stem Cells and Regenerative Medicine. She was one of the first researchers to use genome editing in human embryos, researching early embryonic development.

Dr Fogarty spoke to the audience about her experiments researching the effects of the OCT4 gene and its role in healthy embryo development. Extensive work in animal models had demonstrated that OCT4 was essential for embryogenesis and pluripotency, and therefore Dr Fogarty used genome editing to perform a proof-of-principle experiment to establish whether OCT4 had a similar role in human embryo development.

Using videos from her experiment she showed how CRISPR/Cas9 components were introduced into a human embryo to disable OCT4. Although initially, the video footage showed that the human embryo was able to undergo healthy division and growth, the modification of the OCT4 gene caused the blastocyst to continually collapse in on itself and it was unable to expand, demonstrating the importance of the gene in human embryo development.

Dr Fogarty summarised the importance of genome editing as a way to study human gene function, with possible benefits for medical research. She noted that, at present, research has shown that CRISPR/Cas9 genome editing can cause large unintended deletions, and therefore emphasised the need for further research before moving to any clinical applications.

The following speaker was Dr Peter Mills, assistant director of the Nuffield Council on Bioethics and project lead for that organisation's report on human genome editing.

Dr Mills posed two questions to the audience: why do we need reproductive genome editing and how should we use it? The most discussed hypothetical purpose is for prospective parents to have a child that is genetically related to both. Although this is usually suggested as a way of avoiding certain genetic conditions that may be present in the parents, it could at some point be desired to include novel genetic traits that the prospective parents do not have. When considering how we should use reproductive genome editing, Dr Mills discussed two possible approaches: the biomedical approach and the entrepreneurial approach.

To illustrate the biomedical approach, he referred to the statement by the organising committee from the second international summit on human genome editing which said that germline genome editing should only be used when there is 'a compelling medical need, an absence of reasonable alternatives'. However, Dr Mills discussed how this is unclear when the application of genome editing is a medical need to the embryo or future person, as the main benefit of using genome editing is to allow prospective parents to have genetically related children. Although genetic relatedness may be important, it is not necessarily a medical need, and using reproductive genome editing is not equivalent to treating a condition in an existing person.

The second approach, the entrepreneurial approach, is the use of reproductive genome editing because it is 'technically achievable' and brings benefit – medical or otherwise – to the offspring. Dr Mills used Dr He Jiankui as an example of this entrepreneurial approach. Genome editing was used to alter the CCR5 genes in human embryos to make them HIV 'resistant' before transferring them to their genetic mother, resulting in the birth of twins (see BioNews 977). Dr Mills pointed out that the parents in this case (one of whom had HIV) could have conceived a healthy, genetically-related child (albeit a child without HIV 'resistance') using existing clinical techniques.

The final speaker was Professor Vardit Ravitsky, president of the International Association of Bioethics, professor of bioethics at the University of Montréal, Canada, and senior lecturer in global health and social medicine at Harvard University, Cambridge, Massachusetts.

Professor Ravitsky spoke on how bioethics must tackle the tricky task of balancing risks and potential benefits both in controlling and developing new technologies. She explained that new technologies bring the possibility of medical breakthroughs, and therefore there can be a cost to not exploring them.

Professor Ravitsky discussed previous publications in the field of germline genome editing to demonstrate how we are already considering how to 'pave the way' for reproductive uses of genome editing, and how the technology should be governed in a responsible way.

She considered some of the issues that genome editing may raise on a global scale: issues of justice, equity, access, and inclusion. Although reports have emphasised the importance of public outreach and inclusion, she questioned whether we are being inclusive and fair in the voices being heard and represented in debates. Additionally, it is unclear at present who will control access to the technology and whether it will be affordable globally, or whether access will be dependent on private interests. Moreover, who will be paying for the cost of developing the technology, or the possible medical issues that may emerge from its use?

Norcross thanked the speakers and opened the floor for questions from the audience.

The first question asked whether the WHO's Expert Advisory Committee had gathered much information about the twins whose genomes were edited by Dr He. Professor Lovell-Badge stated that the Committee gathered what information it could, but few details had been disclosed by the Chinese authorities.

Professor Ravitsky noted that after the Dr He incident there were many publications about 'rogue' scientists, yet there is often an emphasis in scientific research and funding on boldness and novelty. It is challenging to balance the message of pushing forward and innovating with a message of caution and responsibility.

Dr Fogarty added that scientists are often altruistic, and their work is undertaken to benefit other people. Inevitably though, there will be different personalities among scientists, and it is challenging to ensure that they all adhere to the same ethical standards. She suggested that it would be beneficial to emphasise the importance of incremental work, and that every experiment in which we learn more should be celebrated, not just the large innovative breakthroughs.

The next question concerned how, and by whom, it will be decided that the medical need for germline genome editing is sufficiently 'compelling'.

Professor Ravitsky discussed the difficulty in deciding this, and spoke of her recent paper exploring how a 'serious' disease can be defined. This has been a challenge in policy for decades. Although clinicians often prefer flexible definitions, more rigorous definitions may be required at a policy level.

Dr Mills stated that compelling medical needs may include a whole range of circumstantial conditions, as it is unknown what precisely will entail a 'good' reason for the technology. Professor Lovell-Badge agreed with Dr Mills that questions of risk and benefit are difficult to weight up in relation to a child that is not yet born, as distinct from an existing patient.

At present, Professor Lovell-Badge added, we may not not have enough knowledge about human genes and genetic variation to know exactly what 'a good target' for genome editing is.

A final question from the audience concerned whether the desire to have a genetically related child is important enough to warrant developing reproductive genome editing, a strongly debated question in the field. Dr Mills agreed that this question was incredibly important and must be dealt with when considering the regulation of these new technologies.

Professor Lovell-Badge added that the importance of having a genetic connection with children was not to be underestimated. Professor Ravitsky agreed, and discussed the significance that culture has placed on genetic relatedness, which continues to be encouraged in many contexts.

Overall, the event was a fascinating exploration of the questions raised by germline genome editing, and the speakers' presentations complimented one another well.


PET is grateful to the Association of Reproductive and Clinical Scientists and the Anne McLaren Memorial Trust Fund for supporting this event.

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