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Slippery slope when gene editing advances outpace the law

Scientific development in human genome editing is progressing at a rapid rate, sparking hope and fear in equal measure, and raising the question: is manipulating genes to make designer babies the road to the future, or a recipe for monstrous disaster?

As hundreds of the world’s top scientific minds scientists arrived in London last month for the Third International Summit on Genome Editing, the ghost of 2018 loomed large, reports the Sunday Times.

That year, two days before the previous summit began, news leaked of an experiment by Chinese biophysicist He Jiankui. He and his team from the Southern University of Science and Technology in Shenzhen had created the world’s first gene-edited children.

Later to be named Lulu and Nana, the two in-vitro fertilisation embryos had their DNA deliberately altered before they were implanted in a surrogate mother.

Using Crispr technology – whereby scientists directly change genomes using specialised enzymes or “molecular scissors” to erase parts of the DNA in certain sites in cells and replace them – He had attempted to render the foetuses resistant to HIV.

Amid the international outcry Chinese authorities arrested the biophysicist. He and two colleagues were found guilty of “illegal medical practices” and jailed for three years.

The “firestorm”, as The New York Times called it, resulted from the fact that when you change the genes of an embryo, it changes the genes in every cell and this gets passed on down the generations.

He had disabled a perfectly normal gene to try to create resistance to certain diseases, but created high risks of other diseases in the process. Also, the technology still needs work (Crispr often alters the genes not intended to be altered), the research behind the experiment wasn’t sound, and the biological parents of the twins had not been properly informed.

The Chinese court said He “deliberately violated” medical regulations and had “rashly applied gene-editing technology to human assisted reproductive medicine”.

High price to pay

According to the Massachusetts Institute for Technology Review, which first reported on what he had been doing in his lab, “He Jiankui created the first gene-edited children, and the price was his career and his freedom”.

That scandal made the world sit up and question where it was all headed. Fast forward to 2023.

Michèle Ramsay, a professor of human genetics at Wits University, was in the audience in London as a woman named Victoria Gray stood up to speak.

Ramsay, director of the Sydney Brenner Institute for Molecular Bioscience and a member of the summit’s organising committee, was once again filled with the hope that her line of work inspires.

“Victoria Gray was one of the first people in the US to receive somatic genome editing for sickle-cell disease in a clinical trial,” Ramsay said. “She described how this had made it possible for her to live a ‘normal’ life. Somatic gene therapy (in Victoria’s case, removing bone marrow cells, editing them in a laboratory, and then returning them to her body) alters specific cells and are not passed on from generation to generation.”

Gray’s story illustrates the amazing potential of genome editing and what the future might hold if such work can be scaled up.

Ramsay emphasised that somatic human genome editing refers to the editing of non-reproductive cells, “and changes made in these cells affect only the person who receives the genome editing”.

Somatic cells are all those present in the tissues of the body, except for sperm and egg cells and their precursors.

“Remarkable progress has been made,” Ramsay said, “demonstrating it can cure once-incurable diseases.”

The more worrying branch is heritable human genome editing, “which refers to the editing of human embryos or gametes to be used for human reproduction”.

Such interventions are described as “germline” interventions and involve editing reproductive cells. This is the type that inspires fears of the advent of “designer babies”, tweaked to the specifications of the parents in a competitive world.

‘Still science fiction’

“Designer babies are still science fiction,” said Ramsay. “Currently, gene-editing is about treating and curing severe genetic disorders caused by single mutations in a single gene. When thinking about designer babies, people usually think about them being more intelligent, more beautiful (by which standards one may ask?), sportier, or resistant to infectious pathogens.

“We still do not fully understand the genetic contribution to these conditions, but we know they’re a combination of genetic (many different genetic variants across the genome) and environmental factors – so it would not even be clear what to edit, and the editing of hundreds of mutations at the same time is not on the cards.”

Hlonipha Mokoena, a professor of history at the Wits Institute for Social and Economic Research, said that, “ironically, most cultures already practise genetic selection”.

For example, “the preference for boy babies vs girl babies has already shaped the demography of countries where the preference is prevalent”.

Human beings “have always practised genetic selection based on what we know about genetic inheritance”.

“Many cultures have practised ‘colourism’, where light-skinned people are encouraged to marry other light-skinned people, and over time this can lead to the false impression that ‘dark skin’ only exists as a ‘racial’ characteristic, rather than a genetic one,” Mokoena said.

What can happen in a lab, then, is simply a technological expression of what unfolds over generations out in the world. However, one of the fiercest debates of our time is the gap between technical capacity and ethics.

ChatGPT and other artificial intelligence (AI) chatbots are a case in point, highlighting the fact that advances gather speed before ethical guidelines are in place.

“Since it seems we are already pulling away from some of the extreme consequences of AI, we will probably do the same with genetic coding and manipulation,” Mokoena said. “As with AI, the consequences cannot be fully understood and it is only when we experience dramatic and shocking changes that we begin to adopt more conservative and guarded policies and approaches.”

She said the vision for a “genetically modified child” might include high IQ, athletic ability, being musically gifted and so on, but that same child might “suffer from debilitating allergies as a direct result of being genetically modified”.

A problem introduced as a direct result of “designer genes” may “function as a caution against the belief that a ‘designer’ baby is better than an ‘ordinary’ baby”.

Professor Keymanthri Moodley, director of the Centre for Medical Ethics and Law at Stellenbosch University, said that as with any scientific advance or technology, both benefits and harms were associated with gene-editing.

“Ethical concerns depend on whether it is somatic cell gene-editing or germline gene-editing. The benefit of editing out specific diseases is widely supported, but concerns involve the clinical application of gene-editing and are based on the principle of non-maleficence.”

She said that safety and the potential for harm are major concerns due to the possibility of “off-target effects if edits occur in the wrong place, and of mosaicism, where some cells may carry the edit but not others”.

She described germline gene-editing as more contentious as any changes in the genome are transmitted to future generations, “for which they cannot provide consent”.

Terrifying scenario

Perhaps the most terrifying scenario is the kind of slippery slope Moodley describes: “There is a continuum and we can easily progress from gene-editing to prevent disease, to enhancement of embryos to create designer babies with specific characteristics. This raises concerns about eugenics.”

For Mokoena, we also need to take a long, hard look at our society and the forms of “enhancement” in which we’re already engaged. “Although I can appreciate the terror we feel at the thought of genetic manipulation that ‘selects’ for (certain) traits, I think in reality we are being hypocritical since we are already engaging in so much augmentation and plastic surgery that it is possible to create a ‘perfect’ human being by just tweaking the phenotype.”

So once the technology is available, “it won’t be possible to tell other human beings that they shouldn’t aspire to have ‘perfect’ children”.

But for Ramsay, a far more pressing issue is to do with access to somatic editing in an unequal world. “These procedures require specialised laboratories and transplant facilities, and this of course raises the issue of access and affordability.”

Gene therapy treatments currently cost about R18m-R54m and many low- and middle-income countries have no transplant facilities.

“This is especially relevant as the majority of people with sickle-cell disease (about 3m people) live in Africa,” Ramsay pointed out.

On the upside, “there is hope (and much research effort) that doing genome editing in the body (in vivo), without needing hi-tech laboratories and transplant infrastructure, will eventually be possible”.

Problems will arise when the advances outpace the guidelines and laws.

Ramsay said South African law prohibited heritable genome editing and human cloning for the purpose of initiating a pregnancy, “but we need more clarity on the legality of all forms of human genome editing”.

According to Moodley, “South Africa does not have specific laws relating to gene-editing. The National Health Act covers some aspects related to manipulation of genes that could be extrapolated to gene-editing. Some legal experts describe the law currently as ‘ambiguous’.”

Ramsay said “global governance for human genome editing” was an important focus at the London summit last month – not just who should use it, but who has access to it.

“How can we ensure it is responsibly and ethically used for good and will not be hijacked for harmful purposes? How do we address health inequities (within and between countries) to ensure that this technology will not just be available to the few who can afford it?”

The Lulu and Nana brouhaha resulted in two international committees being established to “develop recommendations to guide the international scientific and health-care communities toward responsible human genome editing”

Rigorous oversight

A statement released after the London gathering quoted one of these committees as finding that: “Heritable human genome editing should not be used unless, at a minimum, it meets reasonable standards for safety and efficacy, is legally sanctioned, and has been developed and tested under a system of rigorous oversight that is subject to responsible governance. At this time, these conditions have not been met.”

Ramsay imagines a future in which both “somatic and germline gene-editing are safe and effective options for patients and families with severe genetic conditions.”

She also imagines a world with “effective safeguards in place to prevent the exploitation of the vulnerable with promises of gene-editing cures, where this is not a reasonable option or expectation”.

As technology advances, so do hope and fear.

Ramsay said the science was becoming more accurate and off-target edits were fewer. “We are learning more about the behaviour of cells, and a group of scientists is working on gametes (sperm and egg) and how they could be edited before fertilisation to prevent severe disease.”

But, for a group of experts in Washington DC who wrote to Nature magazine in 2017, the year before He made headlines, we need to sit up and take notice before it’s too late.

What begins as disease control could end in the designer babies befitting Aldous Huxley’s dark vision of a “brave new world”.

They wrote: “Many oppose germline modification on the grounds that permitting even unambiguously therapeutic interventions could start us down a path towards non-therapeutic genetic enhancement. We share these concerns.”

 

Sunday Times article – Designer babies: hope or horror? (Restricted access)

 

See more from MedicalBrief archives:

 

Call for guidelines and ethical boundaries in genetic editing therapies

 

World’s first gene-edited babies’ creator relaunches career after prison release

 

Chinese declare that gene-editing scientist is breaking the law

 

 

 

 

 

 

 

 

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