Crossing ethical red lines in gene editing
There is more support for genome alteration for serious diseases than for ‘enhancement’
Here is a name to look out for in 2020: Denis Rebrikov. The combative Russian biologist wants to edit the genes of human embryos to cure deafness. If his ambition sounds familiar, it is because a scientist has already trodden a similar heretical path.
At the end of 2018, Chinese biophysicist He Jiankui created the world’s first gene-edited babies, disabling a gene called CCR5 in an attempt to make twin girls immune to HIV. That Mr He experimented with human pregnancies sparked global outrage, given the possibility that the infants could suffer unpredictable genetic side-effects.
The backlash has not quashed the enthusiasm of mavericks like Mr Rebrikov, from the Pirogov Russian National Research Medical University in Moscow, who awaits approval for the work from Russian authorities. The Pandora’s box that opened at the end of this decade — the idea of genetically editing the human race out of disease and perhaps towards an ideal — may well define science in the next. One expert has even speculated that humans may need to change their genes to survive global warming.
Diving into genomes in order to tweak them has become possible — and cheap and easy — thanks to a technique known as Crispr/Cas9. This method, one of the outstanding breakthroughs of the past decade, sends a targeted enzyme into a genome to edit the DNA. Think of it as the molecular equivalent of sat-nav and scissors: disease-causing genes can be deactivated, stripped out, amended, even replaced.
The catch is that the technique is not foolproof. It can cause unintended changes in other parts of the genome. Such “off-target effects” have been observed in edited animal embryos.
Tinkering at a very early embryonic stage, as Mr He did, also means the edits affect germ cells, which are involved in generating eggs and sperm. Such “germ line” changes affect not only that embryo but its descendants via genetic inheritance. That is why the germ line editing of human embryos, also called heritable genome editing, has been deemed unthinkable.
Mr He’s willingness to cross that ethical red line is chilling. The twin girls will need lifetime monitoring, their futures destined to follow an uncertain genetic script. It is not even clear that the promised immunity, against a preventable and treatable virus, has been achieved. If it has, this narrow triumph may have a price. Genes associated with one disease sometimes protect against others. Mutations in the CCR5 gene are also linked to a shorter lifespan.
Many have called for a moratorium on heritable genome editing. That has not materialised, to the relief of Robin Lovell-Badge, from the Francis Crick Institute in London. Professor Lovell-Badge chaired the 2018 conference session in Hong Kong at which Mr He dropped his bombshell revelation. Prof Lovell-Badge also sits on the World Health Organization’s advisory committee on the governance of the technology, which will issue a report next year on how nations should regulate it.
“Some people will want to never allow germ line genome editing because they think it’s bad for humanity,” he told me. “That scares me. I don’t like closing and locking doors. Take global warming — we might need to modify ourselves.”
By targeting deafness, a non-lethal condition, Mr Rebrikov is in danger of attracting the same criticism as Mr He. Why edit genes to fix an issue that can be treated at birth using cochlear implants?
Moreover, the gene in question causes only mild hearing loss in some people. This gets to the heart of a delicate conversation society is failing to have: will genetic technologies eradicate disease or erase human difference? Public opinion tends to support genome editing for serious or lethal diseases; less so for what we might consider enhancement. There is dismay that, in the many initiatives set up in the wake of the He scandal, people with disabilities are not represented in the decision-making.
All the while, avenues to genetic enhancement are proliferating. A Harvard geneticist is designing a dating app to match singles based on their DNA, with the aim of banishing inherited diseases. A fertility start-up offers IVF along with “report cards” on the resulting embryos, predicting their health and intelligence using a technique called polygenic scoring. Both have been condemned as eugenics.
Who, we should ask, would covet perfect human specimens? The two countries rattling the cage on heritable genome editing seem to be China and Russia. President Vladimir Putin has spoken of how the technique may one day create super-soldiers, incapable of pain, fear or regret.
Perhaps that is the trend we should look out for when it comes to genome editing: not pushy parents pursuing the perfect prince or princess but nation states assembling armies of loyal, optimised citizens.