Genetically modified superhumans. Babies born with made-to-order characteristics. The idea has been explored in everything from academic journals to movies. CRISPR technology could make it a reality.
The ability to alter human genes in a way that can be passed onto offspring, called germline engineering, has long been possible. But until recently the methods available to genetically modify animals were so inefficient and crude that no sane biologist would dream of using them on humans. Tinkering with the genes inside people has been limited to gene therapy, where the changes don’t get passed to the next generation (see “Is a new dawn of widespread gene therapy on the horizon?“).
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Now the precision and efficiency of CRISPR has reopened the debate about human germline engineering. But why do it? The most compelling reason would be to prevent the inheritance of genetic diseases, yet this is already being done without gene editing.
Dialling out disease
One approach is prenatal testing, which involves screening for the disease-causing mutation during pregnancy, giving parents the option of abortion. Another is preimplantation genetic diagnosis (PGD), in which prospective parents who undergo IVF have their embryos screened. Only those that won’t develop the disease in question are then implanted. PGD can already be used to prevent thousands of serious genetic diseases.
But PGD is impractical if a child is at risk of inheriting two or more disorders. For two disorders, three-quarters of embryos might be unsuitable – and with couples getting only a handful of embryos per IVF cycle, rejecting three-quarters of them would make conceiving far less likely.
In fact, even with single disorders some couples get so few embryos that none of them would be free of the disease-causing mutation. In these instances gene editing could be used to fix their DNA – an option some regard as ethically preferable to discarding embryos, says of the Francis Crick Institute in London.
Similarly, while PGD is impractical for getting rid of the harmful gene variants that increase the risk of common conditions, such as heart disease, diabetes, Alzheimer’s or schizophrenia, it might be feasible with gene editing. Eliminating dozens of these harmful variants could make a huge difference, allowing people to live longer, healthier and even happier lives.
This has huge potential for reducing the disease burden, says , who studies the ethics of human enhancement at the University of Oxford.
But the technology isn’t there just yet. Nor do we know enough about the gene variants involved to start eradicating them. All this means that when it comes to reducing the risk of diseases, there is currently no compelling reason to attempt germline gene editing.
What about the far more controversial idea of enhancing children, by giving them gene variants both their parents lack? Many of the variants controlling skin, hair and eye colour have been identified, so in theory these kinds of cosmetic traits could be tweaked. But characteristics such as intelligence seem to be determined by hundreds of different gene variants, with each one having only a tiny effect. This means we are a long way from engineering intelligence into children, even if gene editing were safe enough to attempt it.
“Even if gene editing were safe, we are a long way from being able engineer intelligence”
And that isn’t yet clear. The most serious issue is that gene-edited embryos are often a mix of cells with the desired genetic change and cells without it – a phenomenon called mosaicism. The Chinese team observed this in their first attempt to edit human embryos.
Everyone in the field agrees it is far too soon to attempt to alter children. A few have gone much further and called for a voluntary worldwide ban on any work involving gene-editing of human embryos, even if there is no intention of allowing them to develop. “At this stage the question is whether to go ahead with research,” says Gyngell.
A ban appears unlikely. Several UK research organisations and funding bodies have declared their support for research in human embryos. So, too, has an international group of stem cell researchers and bioethicists, called , after holding one of the first meetings on it.
It concluded that not only should we leave the door open to germline gene editing, but there is much to be gained from research, including understanding embryonic development and finding out why some women miscarry. “We are all in agreement that this research has tremendous value,” says Debra Mathews of the Johns Hopkins Berman Institute of Bioethics, who was at the meeting.
But while germline editing is still decades away, it might not be that long before we start using CRISPR to tweak the genes of adults…
Read more: “CRISPR: The gene-editing revolution on our doorstep”
(Image: Paul Ryding)
This article appeared in print under the headline “Will this lead to designer babies?”
