This article is a preview from the Summer 2020 edition of New Humanist
In 2018, the Chinese biophysicist He Jiankui stunned the world when he announced that he had produced genetically modified human babies – a world first. Speaking at an international summit in Hong Kong, He revealed to researchers that he had edited genes in a number of viable human embryos using a technique known as Crispr-Cas9, before implanting them into the wombs of willing test subjects. One of the women gave birth to twin girls in November that year; a third child was born at an unknown date soon after. (The details have been shrouded in secrecy.)
He aimed to give the babies a genetic resistance to HIV, a disease suffered by their fathers. By disabling a gene called CCR5, he claimed to have reproduced a naturally occurring mutation that allows a small proportion of individuals to be born immune to the disease. But although his announcement seemed to mark a major scientific breakthrough, it was not at all well received. Ethical guidelines – first developed in the UK but now widely accepted around the world – limit experiments on human embryos to their first 14 days. A full-term baby, or three in fact, was a reckless leap into the unknown.
The conference’s organising committee made the unusual step of releasing a public statement condemning He’s experiment, describing it as “irresponsible” and “deeply disturbing”. He, who had seemed nervous during his presentation, returned to his home institution in Shenzen under a cloud, with his yet unpublished research under intense scrutiny.
In the face of unwelcome global attention, the Chinese authorities sprang into action and on 30 December 2019, He Jiankui was fined 3m yuan (£327,360) and sentenced to three years in prison for “illegal medical practices”, including the forging of documents from an ethics review panel and knowingly misleading couples who volunteered to take part. Two of his collaborators were also found guilty, fined and sentenced to prison. The case made headlines around the world, and has prompted high-level discussion over how to regulate this radical new realm of science that cuts to the very heart of what makes us who we are.
Reproductive technologies of all kinds have always been a source of public anxiety. He’s gene-edited babies are far from the first to have prompted widespread condemnation, even horror. The earliest successful instance of sperm donation, for example, itself took place under ethically dubious circumstances. William Pancoast, a doctor based in Philadelphia, met a Quaker couple who were struggling to conceive in 1884; having ascertained that the husband was unable to produce sperm, the doctor anaesthetised the wife with chloroform and – unknown to the patient – inseminated her with the sperm of his “best-looking student”. At the husband’s request, the woman was never informed. Some doctors considered Pancoast’s actions, not unreasonably, to be a form of rape (one called it “ridiculously criminal”). Others considered it to be a perversion of the laws of nature, or disobedience to God’s will.
In 1978, similar arguments bubbled up around the birth of the first “test tube” baby, Louise Brown. One Tory peer warned that the technique could “imperil the dignity of the human race”. A reproductive biologist speculated that in the not-distant future, a woman might browse a baby supermarket, making her selection from a range of “one day old, frozen embryos” with eye colour and genetic make-up detailed on the label. Professor Sir Robert Edwards, the pioneering scientist who developed in-vitro fertilisation (IVF) as a technique, later complained that the public had been soured to the concept by “science fiction fantasies” that imagined doctors as “white-coated, heartless men, breeding and rearing embryos in the laboratory to bring forth Frankenstein genetic monsters.” Since then, more than 8 million babies have been born as a result of IVF.
In 2015, the UK became the first country to pass laws approving “three-parent babies”, in which a baby conceived by IVF shares 0.2 per cent of its genetic material with a third party. This is achieved by transferring the DNA of the mother into a donor egg as a method of protecting future embryos from inheriting devastating mitochondrial disorders like the neurodegenerative Leigh’s Syndrome. The issue provoked vigorous debate, with the then prime minister David Cameron forced to deny that researchers were “playing God”.
As Philip Ball argued in his 2011 book Unnatural: The Heretical Idea of Making People, old myths of anthropoesis, or the creation of artificial people, deeply impact and undermine the way that we perceive modern techniques of assisted conception, cloning and embryo research. From Prometheus to golems (anthropomorphic figures in Jewish folklore), and the human manufacturing labs of Aldous Huxley’s Brave New World, we are primed to view every advance with suspicion. The genetic modification of humans, and in particular human embryos, is the latest focus of this anxiety.
There are a number of methods of gene editing, but the recent development of Crispr-Cas9 technology has revolutionised the field. A landmark 2012 paper by Jennifer Doudna, Emmanuelle Charpentier and Martin Jinek demonstrated that a then-obscure microbiological defence mechanism – used by bacteria to disarm viruses, by chopping up their DNA – might be repurposed to cut genomes of any kind relatively precisely.
Researchers have since found ways to combine Crispr-Cas9 DNA-cutting with other mechanisms that allow the editing of DNA, opening up new avenues of genetic modification. In humans, gene editing might be altered to “knock out” the genes responsible for certain inheritable diseases, like Huntington’s Disease, or – theoretically – to make other “enhancements”, such as altering eye colour or even improving memory or intelligence.
Aside from the He Jiankui case, gene editing in human embryos is currently confined to research. Our understanding of the genome can be greatly augmented by using Crispr-Cas9 to identify and clip out individual genes, then seeing what happens. This is similar to the way in which selective lesions are used to study the brain.
“If we are frightened, what is it we are afraid of?” asks Dr Sarah Chan, director of the Mason Institute for Medicine, Life Sciences and the Law at Edinburgh University. “Those who consider the human embryo to have the same moral status and rights as a full-grown human being will regard experiments on embryos as ethically problematic. [But] for those to whom embryo research is morally acceptable, genome editing research should be no different.”
This is not to say that He’s experiment was justified. “At the time He Jiankui announced his experiment, there was widespread consensus that genome editing technology was not yet ready for clinical reproductive applications, for reasons of safety and uncertainty,” she explains.
Gene editing in humans is still very new and untested, agrees Prof. Robert Klitzman, a bioethicist at Columbia University and author of the new book Designing Babies: How Technology Is Changing the Way We Make Children. “The risks are several-fold,” Klitzman says. Firstly, even if He’s experiment went perfectly, there could be unintended consequences. Disabling the CCR5 gene may protect you from HIV, but might confer an increased risk from other infections, such as influenza and West Nile virus.
There may also be other critical functions related to the CCR5 gene that may soon materialise in the babies’ ill health. “It may be that the gene is involved with mental development, the development of the heart, or the muscles,” Klitzman warns. “To give you more context: we have over 95 per cent of the same genes as a mouse. The reason is that genes are put to multiple uses. Think of all the houses in London or New York. They’re all built out of only maybe 20 ingredients” – brick, steel, glass and so on – “but they are all different, because different instructions are applied.” So, disabling or editing genes might alter the nature of the test subject in profound, unanticipated ways.
We might see selecting between embryos, as is already widely practised via genetic screening, as analogous to choosing a house to buy. It’s another thing altogether to start reconfiguring the layout of the house – knocking down walls and weight-supporting beams – without knowing what you’re doing. “It’s a far more invasive procedure.”
Perhaps even more worryingly, the Crispr-Cas9 technique is not precise enough to achieve what He Jiankui wanted it to achieve. “He took out too much DNA,” says Klitzman. “If we only wanted to clip from point A to point B, say, he ended up taking out point A to point Z, and we don’t yet know what the risks of that are.”
When the human genome was first sequenced in 2003, it was initially believed that by far the majority of the genetic material was so-called “junk DNA”. We now know most of this “junk” plays a significant biological role, but still have only a sketchy understanding of the ways in which many genes function and interact. The loss of the neighbouring genes mistakenly cut from the babies’ genomes does not appear to have stunted their foetal development and infancy, but the impact may only become obvious later in life. (Or worse: after several generations.) “Maybe it will lead to intellectual deficits, maybe it’ll lead to kidney failure, maybe heart failure,” warns Klitzman.
Since the babies’ birth another, stranger possibility has also been floated. Research into the alteration introduced into the babies’ DNA has shown links with improved cognition and memory. Experiments on genetically modified mice suggest that those missing the CCR5 gene perform better during memory trials. In February last year, two months after He Jiankui was jailed, a paper published in the journal Cell showed that patients born (naturally) without the CCR5 gene recover more quickly from strokes. It was also linked with more advanced academic qualifications.
There’s no suggestion that He Jiankui intended to confer improved cognitive abilities upon the genetically modified babies. However, these cutting-edge experiments offer the possibility that he may yet have done so inadvertently – raising the spectre of yet another longstanding debate in reproductive technology: the question of genetic “enhancement” and so-called “designer” babies.
Even in that first case of sperm donation in 1884, Pancoast’s choice to use the sperm of his “best-looking” student is a revealing one. Sperm donation is a simple method of selective human breeding, and has been viewed in this light from the off. When the details of Pancoast’s procedure finally came to light, 25 years later, one of his former students (perhaps the donor himself) argued that “artificial impregnation by carefully selected seed” might be used to improve the species: an early example of eugenic thought. (This could be, he wrote, the solution to the “half-witted, evil-inclined, disease-disposed” progeny of unhealthy couples.)
In 1979, an American entrepreneur called Robert Klark Graham opened the Repository for Germinal Choice, a sperm bank stocked with the seed of Nobel laureates. Graham’s plan to breed a generation of geniuses, and more specifically his reference to the “retrograde humans” he believed were swamping the United States, created a media storm. The subsequent revelation that one of the Nobel-winning donors was the physicist William Shockley, a man who had previously stated publicly that black people were less intelligent and that low-IQ individuals should be sterilised, quickly moved the story from entertaining scandal to a far darker debate.
Graham’s venture ultimately failed, but his approach coloured the entire practice of modern sperm donation. Couples visiting larger sperm banks are still able to select their donor from a catalogue; the London Sperm Bank, for example, a private practice on Harley Street, allows prospective customers to sort their online database by physical attributes (race, eye colour, height, hair colour), academic achievement and occupation. Current donors include a “musically gifted” doctor with an “angelic face”, a six-foot PhD student and a semi-professional rugby player. (Both available from £850, for an ampoule containing “5 to 10 motile sperm”.)
Nevertheless, as any farmer knows, selective breeding is powerful, but also slow and inexact, taking many generations. Genetic editing offers the tantalising possibility of tweaking the genetic makeup of one’s own biological children to fit your ideal: longer-legged, maybe. Blue-eyed, perhaps. We know that parents want to do everything they can for their children: will they soon be able to go so far as engineering them to be more intelligent?
“It’s going to be wealthy people who will be able to add genes associated with IQ to their children, or make their kids taller or, say, run faster, or avoid certain diseases,” says Klitzman. “This raises questions of what kind of society we want.” As well as the obvious questions of eugenics and race, he adds, another problem is the impossibility of consent. “The future child has no say in this. With gene editing, you’re shaping someone’s life. Let’s say you engineer a kid, you give them extra genes that will help with a certain kind of athletic ability. The parents might say, gee, we spent $50,000 to make you a sprinter. You have to be a sprinter. We’d like to give children an open future, right? Where kids don’t feel they’ve been engineered to be a certain thing.”
Whatever the implications, it’s true that these questions are some way down the line. The Chinese twins – now known as Nana and Lulu – may have improved cognition and memory, or they may not. The science is currently somewhat unclear: although CCR5 is thought to have a significant impact on the brain, it’s not yet understood why, or how, or whether deleting the CCR5 gene will always be positive. This is, say researchers, why He’s experimental babies should never have been allowed to come to term.
Still, the case has shone a very bright light upon a fast developing field, which is not in itself a bad thing. “While He’s experiment was unethical and unscientific, it has had the effect of propelling with more urgency the global discussion around how human genome editing technologies should be developed and regulated, and promoted a wider discourse over scientific responsibility,” says Chan, the Edinburgh-based bioethicist.
China, long considered a “Wild West” for embryo research, has tightened up its ethical guidelines, and He’s imprisonment acts as a salutary warning to other researchers in the country. However, in countries like Russia and Mexico, such research is less strictly policed. (The first three-parent baby was born in Mexico, explicitly for this reason. John Zhang, the American fertility specialist, told the press he chose the country to conduct the procedure in because in Mexico “there are no rules”.)
The Russian molecular biologist Denis Rebrikov has already declared his intention to produce genetically modified babies in Moscow, as soon as he can, to a chorus of censure from researchers around the world. It’s not clear how quickly his plans might come to fruition. What is clear is that reproductive science tends to progress, with or without our consent.