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PETBioNewsReviewsEvent Review: Modifying Humans – Is global governance of genome editing possible?

BioNews

Event Review: Modifying Humans – Is global governance of genome editing possible?

Published 3 September 2021 posted in Reviews and appears in BioNews 1128

Author

Isobel Steer

Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the sequencing output from an automated DNA sequencing machine.

The Centre for Bioethics and Harvard Medical School, Massachusetts, presented a fascinating talk on the opportunities for great medical advancements, and grave harm, presented to researchers by CRISPR/Cas9 and other apporaches to genome editing...

The Centre for Bioethics and Harvard Medical School, Massachusetts, presented a fascinating talk on the opportunities for great medical advancements, and grave harm, presented to researchers by CRISPR/Cas9 and other approaches to genome editing. Is the global governance of human genome editing desirable? Is it possible? This is part of a monthly series, with other recent talks including titles such as 'Racism, Inclusion and Justice: Interrogating Bioethics'. You can find out more on Twitter using #HarvardBioethics.

The 90 minute event, Modifying Humans – Is global governance of genome editing possible?, was presented by Professor Robin Lovell-Badge, senior group leader at the Francis Crick Institute in London and chair of trustees at the Progress Educational Trust (PET) and moderated by Professor Insoo Hyun, director of research ethics at the Centre for Bioethics, and professor of bioethics at Harvard Medical School. Professor Hyun also recently spoke at PET's annual conference (see BioNews 1126).

Professor Lovell-Badge is known for co-discovering the SRY gene on the Y chromosome, which determines sex in mammals. Nowadays he is head of the division of stem cell biology and developmental genetics at the Crick Institute, as well as being on two important committees advising on human genome editing – the International Society for Stem Cell Research (ISSCR) and the World Health Organisation (WHO). If you think that a typical day in the life of Professor Lovell-Badge sounds stressful, I imagine his days now are a tranquil oasis compared to one particular November day in 2018, when he was moderating at the human genome editing summit as Dr He Jiankui (since jailed) stood up and announced that he had created the world's first genome-edited babies (see BioNews 1029). This, he said, was 'one of the biggest challenges in my life', as he had to subdue 100 journalists whilst trying to get Dr He to 'spill the beans on what he'd actually done'. The listener could have no doubt that Professor Lovell-Badge has plenty of experience with the topic!

In the first 40 minutes Professor Lovell-Badge talked through the science of genome editing, applications and 'technical problems', then in the second half tackled the issue of governance, legality and ethics. The last 30 minutes was a Q&A. Due to length and rapid pace of information (I listened at 0.75 speed!), I'd recommend taking a break between the two talks, or even just choosing the talk you are more interested in.

The genome-editing field exploded in 2012 with the work of Professors Jennifer Doudna and Emmanuelle Charpentier, and the technique is now used in research centres around the world. In short, genome editing usually requires: a protein or RNA to recognise specific DNA sequences, a nuclease enzyme to cut the DNA, and a DNA template to allow repair. To do all of this it hijacks methods that are already present in our cells. Currently, the most practical version of this is the simple, easy and inexpensive CRISPR/Cas9 approach. A less extreme version of genome editing uses a 'dead' nuclease to conduct epigenetic modification – altering gene expression without cutting DNA.

'Base-editing' is a very precise technique developed by Professor David Liu, where scientists can swap a single base pair for another. This is important because around 50 percent of inherited diseases are due to a single base pair mutation! Professor Lovell-Badge said that base editing and prime editing are currently under-used, but hold huge promise for future genome-editing therapies.

Traditional gene therapy does not use genome editing but inserts a functional copy of the gene at random in the genome, hoping that it will be expressed at sufficient levels in the right tissue. But it could have unwanted effects, such as activating cancer-causing oncogenes.

Both traditional gene therapies and somatic therapies using genome editing would aim to fix a genetic disease in the body of a living person, which can be achieved in two main ways. The first is outside of the body (eg, removing blood cells, treating them and then reinserting them to treat sickle-cell disease or cancer (CAR-T cells)). This technique was successfully used on children with leukaemia at Great Ormond Street Hospital (see BioNews 886). The second way is to deliver the genetic change inside the body, either through viral vectors nanoparticles or lipid droplets. ' But it could have unwanted effects, such as activating cancer-causing oncogenes.

Heritable genome editing is highly controversial but could be used to prevent transmission of genetic diseases. I was glad that Professor Lovell-Badge pointed out that there are already methods that don't involve genome editing, ie, adoption, gamete/embryo donation, preimplantation genetic diagnosis (PGD) or prenatal genetic testing with selective termination. However, PGD is not always possible, and it is inefficient. It would be desirable to many people to be able to efficiently 'rescue' embryos from genetic disease using genome editing.

Heritable genome editing could be done in two ways. The first method is removing and editing stem cells that give rise to eggs and sperm. This allows verification of the edits before the embryos are made. The second method, used by the notorious Dr He, is to edit the fertilised egg (zygote). This technique makes it harder to verify the edits (including potential off-target effects), and carries a risk of mosaicism (where not all the cells in the body carry the edited gene). Professor Lovell-Badge warns heritable genome editing is currently too risky and 'not sufficiently efficient to use in humans'. This brings us to his work at the WHO.

The WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing published two reports in July 2021: 'Human Genome Editing: A framework for governance' and 'Human Genome Editing: Recommendations' (see BioNews 1103). Seventeen experts on the committee from around the globe considered three categories of human genome editing – somatic (body cells), germline (egg/sperm/embryo cells not for reproduction), and heritable (germline cells for reproduction). Their outputs included a global clinical trials registry, a governance framework for human genome editing, and nine recommendations for governance. Much like the rest of us over the past two years, this involved 'lots and lots of zoom calls'.

I was interested to hear that Professor Lovell-Badge cited the unscrupulous practices of stem cell companies (see BioNews 1031) as one of the major influences in the committee's considerations: 'The huge risk for me is that the unscrupulous practitioners of IVF may say "we could simply edit some embryos while doing IVF – pay a little bit more money and we can try and get you with whatever trait you want"'.

I also enjoyed the Q&A session at the end, which was an opinionated discussion covering many topics. One that sparked my interest was the cost: gene therapies currently cost upwards of half a million dollars per patient, to which Professor Lovell-Badge commented: 'That is ridiculous. You cannot possibly have that cost for countries which are poorer'. To avoid this issue in the future, he strongly argued against leaving gene therapy to companies that are based in North America and Europe.

This was a comprehensive technical talk from a world-renowned expert, which essentially consists of two lectures spliced together (pun intended!). I'd recommend it to any biology or genetics student.

Sources and References

  • 17/09/2021
    Harvard Medical School Center for Bioethics
    Modifying Humans: Is Global Governance of Genome Editing Possible?

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