The year is 2073. A man walks into a coffee shop and sees his favourite footballer sipping a drink from a paper cup. He waits for the footballer to leave and steals the cup. He takes it to an unregulated laboratory where the superstar’s saliva cells are taken and turned into sperm and egg cells. When fused together, the footballer’s embryo grows inside the lab’s artificial womb. The thief returns to the lab nine months later to pick up his newborn future star striker. The footballer himself, the sole genetic parent, is none the wiser that he has a new baby.
It sounds like Frankenstein science, but experts think the future scenario is not so outlandish. They point to a newly emergent technology: in-vitro gametogenesis (IVG). In this method of reproduction, embryos are grown in a lab by reprogramming adult cells to become sperm and egg cells. As with in-vitro fertilisation (IVF), it does not require sex to take place and would help couples struggling to conceive naturally. But whereas the “egg harvesting” process in IVF is intrusive and risky, IVG only requires skin cells. For prospective parents it offers a far easier and safer procedure, with no side effects.
More radically still, IVG may remove the need for two biological parents, one female and one male. As with the light-fingered footballer fan, a baby could be created from one person’s genetic material alone. And because multiple eggs and sperm can be created in the lab, parents may be offered the possible “add-on” of embryo selection. This is a controversial process, where parents are invited to evaluate the “qualities” of various embryos and to choose which to grow. These nascent technologies, combined with progress in the development of artificial wombs, open a Pandora’s Box of scientific, moral and legal questions, which experts concede we are yet to fully grapple with.
Henry Greely is a Stanford University bioethicist and a professor of genetics. He is also the director at Stanford’s Center for Law and the Biosciences. “I’d say a lot is going to change in 30 years,” he says. “Sex will not remain the main method of reproduction. That will be revolutionary for many, but there may be some serious concerns.”
The birth of 'uni-children'
Test-tube babies have been around since 1978, when scientists first created an embryo in a laboratory and returned it into the female partner’s uterus to grow and develop. Since then, more than 390,000 IVF babies have been born in the UK. But there are several factors limiting the uptake of IVF. Eggs are collected when a woman is under sedation, and a needle is passed through the vagina and into each ovary. “It’s unpleasant, expensive and risky,” Greely says. It also requires two parents, to provide sperm and eggs.
In 2016, a ground-breaking experiment by two Japanese reproductive biologists pointed the way to a new reproductive method. Katsuhiko Hayashi and Mitinori Saitou took skin cells from a mouse’s tail and reprogrammed them into stem cells. From these, they produced eggs, which were fertilised by sperm and transferred into the uteruses of female mice. They each gave birth to mouse pups. It was the first time that gametes (egg or sperm cells) were made with non-reproductive cells – in this case, skin cells – outside a mammal’s body.
Women struggling to conceive, or women using a sperm donor, might choose to use IVG in future because it is safer and easier than in-vitro fertilisation. “With IVG you can take fibroblast cells, which are found in many parts of the body but are easy to get from the skin or hair,” Greely says. “You turn these fibroblasts into induced pluripotent stem cells (iPSCs), and turn these into eggs . . . Any baby made from them has half of your DNA and half of the DNA of whoever provided the sperm. They are your genetic kids.”
The new method also opens up the possibility of what Greely calls “uni-children” emerging within the next three decades. This is where one human’s non-reproductive cells are used to produce both eggs and sperm – which are fused together to produce an embryo, and ultimately a child. This could be appealing to both women and men who wish to be single parents, as well as to same-sex couples who would rather not use genetic material from outside their relationships. Scientists are edging closer to this, Greely says. “Earlier this year, both eggs and sperm were made from a male mouse’s skin cells [unlike in the Japanese experiment, when only eggs were produced]. Scientists haven’t managed to make sperm from a female mouse yet, but they’re working on it.”
In March, another piece of research was published in Nature. This time, it explained that scientists had discovered a way to create eggs from two male mice, and when fertilised with sperm they went on to grow into healthy offspring. “This is revolutionary because in the future it is likely that just skin cells will be used for reproduction. They can be taken from an 80-year-old woman, or an eight-year-old girl, from an embryo that miscarried at eight weeks, or from somebody who’s been dead for eight years but whose cells were frozen carefully,” says Greely.
“You can take skin cells from all of these scenarios, and reproduce from these. As a result, there will be many ethical questions we face in future. Say there is a mother and she has a young child who gets hit by a bus. It will be possible to create eggs and sperm from that toddler’s cells, and create another child from that. You can also attempt to clone humans and have an identical twin to the child who died. That’s a whole other set of questions.”
'Underground clinics could exist'
Dr Nicola Williams is a Wellcome Trust lecturer in the ethics of human reproduction at Lancaster University. “There are good things that can come from IVG,” she says. “It can be used by same-sex couples, trans people, single people, cancer survivors. It could give so many groups the opportunity to reproduce.” But she also agrees with Greely that there is some cause for concern. When IVG is a publicly accessible reproductive method, “any skin or hair cells that are available to others could be used to procreate,” she says. “The problem is, we can create laws, but there will always be people who won’t adhere to the law . . . For the most part, regulation and legislation is going to protect against the illicit use of people’s genetic material . . . but it is possible that unregulated underground clinics will exist. They could make a lot of money from this type of thing.”
Legal roadblocks might slow scientific progress. The speed at which IVG arrives could be restricted, for example, by the 14-day rule for embryo research. This limits research on human embryos to a maximum period of two weeks after creation. It was implemented into the UK’s Fertilisation and Embryology Act of 1990, but it is also an internationally recognised ethical limit. Williams said that if the 14-day rule cannot be extended – to at least 28 days – then this will significantly slow the progress of IVG. This may prove frustrating for people who might benefit from the new technology, but it may also give society time to prepare for these changes.
Another area of significant development involves embryo selection, where parents are able to order a test to screen their embryos for genetic disease, or potentially for both wanted and unwanted characteristics: the so-called Designer Baby effect. Increased use of lab fertilisation and IVG might also lead to more and different kinds of embryo selection and modification.
In 1997, Guy’s and St Thomas’ NHS Foundation Trust began using Pre-Implantation Genetic Testing (PGT): a screening test that can genetically analyse embryos for abnormalities. PGT is routinely used by NHS services to help couples who are at risk of conceiving a child with a serious genetic condition, like cystic fibrosis or sickle cell disease. In this context, PGT is typically used after a cycle of IVF, where an average of eight eggs can be harvested. They are fertilised by sperm and become embryos, and will be tested for genetic issues. After this analysis, only the healthiest embryos are chosen for reproduction.
Embryo selection and gene editing
Some warn that increased uptake of IVG could lead to more parents testing not just for genetic conditions, but also for cosmetic and behavioural traits. Rather than picking the best of eight eggs retrieved from IVF, parents will be able to produce hundreds of eggs, and as a result, more embryos – and pick what they consider to be the best. “Parents will go to a clinic and they will be asked – what would you like to know about these embryos?” says Greely. “They will be able to tell you about each embryo’s disease risk, and cosmetic details for each one – and you pick the one you want. That could lead to arguments if parents want different things in their children.” It could also lead to new inequalities, where those with higher incomes can afford to pick the characteristics of their children, while others must leave it to chance.
Some private clinics already offer forms of PGT as an “add-on” to IVF treatment. But when contacted, all said they do not currently test for cosmetic or behavioural traits, only for genetic abnormalities. “Right now, PGT can tell you whether hair, eye and skin colour will be light or dark. But it’s no more detailed than that,” says Greely. “That will improve and we’ll get better at predicting things like height, hair type, body shape, IQ, whether they’re an introvert or extrovert. That doesn’t mean it will be accurate to what happens though, because some of these things are a combination of environment and chance, as well as genes. But parents will be able to find out something,” he adds. “I do worry that there will be countries who say you have to use PGT, and the government will pick which embryos get implanted. They will be the ones that have the genes for love of the Dear Leader. There won’t be such genes. But the Dear Leader will think there are.”
The prospect of gene editing pushes these fears even further. Gene editing is different to PGT and involves altering genetic material by replacing, inserting or deleting a DNA sequence. Russian president Vladimir Putin has, for his part, warned of the dangers, suggesting that it could be used to create super-soldiers who feel no pain or fear. It seems he has acted on this concern – not to slow or stop research in his own country, but to accelerate it. Bloomberg reported in 2019 that Putin spent $2 billion on genetic research that would, in his words, “determine the future of the whole world”. The Kremlin declined to comment on the story.
Meanwhile, in China, scientist He Jiankui reportedly used the gene editing technique CRISPR to remove the CCR5 gene that enables HIV infection from an embryo. This resulted in the birth of what were argued to be HIV-resistant twin girls in 2018. Scientists have debated whether the genetic modification did result in the prevention of HIV, or whether the CCR5 modification – a gene that also relates to brain function – meant the two children were born with a better memory and higher IQ, but still vulnerable to HIV infection.
There is no evidence that the Chinese government or Jiankui intended to design a super-intelligent baby and used HIV prevention as a cover. We do know, however, that Jiankui was aware of a research paper, published two years before the gene-edited twins were born, showing a link between removing the CCR5 gene in mice and improved memory.
The moral line
Dr Katie Hasson is associate director at the Center for Genetics and Society in California. Asked whether dictators could use gene editing technology and PGT to attempt to create a perceived “super race”, or whether authoritarian regimes could use IVG to create thousands of their genetic children to populate countries, she said these scenarios were “potentially a risk”. But her more immediate fears echo those of Greely – that clinics will offer to analyse an embryo’s “risk scores” in years to come, and attempt to predict health and cosmetic outcomes for a baby, even though these scores may not be accurate.
“A lot of the money and research being invested in this area is connected to Silicon Valley start-ups, and that’s concerning because there will be a desire to commercialise these processes as quickly as possible,” says Dr Hasson. “The algorithms they will use [to make genetic predictions] are proprietary. We don’t know what’s going into determining these scores. There’s not a lot of evidence that these predictions will be accurate, but prospective parents don’t know that.”
Even if the predictions aren’t accurate, Dr Hasson worries gene editing could still lead to inequality. “It would reinforce this idea that some children are biologically superior to others because they were gene edited – even if in reality the edits didn’t make a big difference – and that could cause serious harm to society.”
Editing out genetic conditions for future generations, raises other questions: What should be deleted, and why? What is considered superior or inferior? The process may unwittingly leave children open to other dangers. One large study published by researchers from Ohio State University and New York University found that “the three most significantly associated [genetic] variants” for uveal melanoma, a rare type of cancer, “are correlated with [the genetic region] which determines eye-colour.” By modifying genetic material to enable certain eye colours, would parents be increasing a cancer risk in their offspring?
Dr Giulia Cavaliere is a lecturer in ethics at King’s College London. Her research focuses on novel reproductive technologies and the history of eugenics (the discredited belief that humans can be improved through selective breeding). “Some people would look at these technologies and think of eugenics,” she says. “But many of us think that selecting a certain partner, sending your children to a good school, living in a particular area – that’s a form of creating a certain person, and that is what eugenics is . . . Others draw a moral line between genome editing for a mutation that can cause, say, Huntington’s Disease, and doing this in future to ensure children are a certain height or they have a certain eye colour. An interesting question is, why is one seen as morally permissible and the other not? Labelling something as eugenics doesn’t bring us forward in understanding what is morally permissible.”
Modifying genes or picking certain embryos to reduce the risk of certain conditions and disabilities is “discriminatory in itself,” Dr Cavaliere adds. “It could be seen as saying ‘This type of person shouldn’t exist.’ There is an idea that if we lived in a more inclusive society, disabled people would have better lives. You could say, why not change society, rather than who is born? When you go to the idea of replacing people with certain conditions or disabilities – that is going to be fraught.”
A new era of womb transplants?
Not only are methods of reproduction likely to change in the next half century, but how a foetus gestates will also look different. In August this year, the first UK uterus transplant was successfully completed. After 25 years of research, a team at Oxford University Hospitals NHS Foundation Trust transferred a uterus into a woman, after it was donated by her sister. The operation took 18 hours. The procedure has potential to help the thousands of women in the UK who are born without a viable womb or have had it removed following cancer or other conditions, and trans women. About 100 such procedures have been performed globally, with around 50 babies born so far following the surgery.
However, despite the potential, experts have doubts over how widespread the procedure will be in future. John Appleby is a lecturer in medical ethics at Lancaster Medical School. “Ultimately, this is major surgery with very significant impacts on people’s health – and not just the recipient, the donor too,” he says. And “there’s the question of resourcing: who’s going to pay for these things?”
While some people hope to experience pregnancy and are willing to undergo surgery to achieve this, others – mainly in lower-income nations – do not have the more fundamental right to avoid pregnancy, and are still not safe when pregnant or giving birth. The World Health Organization says that 287,000 women worldwide died in pregnancy and childbirth in 2020.
Most of these deaths were preventable. More than 160 million women, mainly in sub-Saharan Africa and south Asia, are also unable to access contraception.
In this context, the right to be pregnant might seem like a privilege. “But that’s an all or nothing argument,” says Dr Appleby. “The same argument exists with cancer drugs. If everybody can’t access them, does that mean nobody should?”
Perhaps more transformational is the creation of artificial womb technology, which could help not only hopeful mothers but also the 13.4 million premature babies born in 2020 across the globe. There are two types of artificial womb technology, also known as ectogestation. Full ectogestation refers to a child being created from scratch outside of a human body, and the embryo being placed on an artificial placenta. Partial ectogestation would involve transferring a foetus from a pregnant mother to a machine, completing the latter part of the pregnancy.
Normal human pregnancy lasts 40 weeks, but 24 weeks is the border for viability. If a baby is born on or after this point, there is potential to keep them alive. According to NHS guidance – and most medical policies around the world – if a baby is born before this stage it would be considered a miscarriage and attempts to resuscitate would be unlikely. “Partial ectogestation could offer pregnant people the opportunity to opt out of pregnancy, if it’s threatening their health, and without having to worry about losing their baby,” says Dr Elizabeth Chloe Romanis, an expert at Durham University. “The machine could take over.”
In 2017 a team of researchers at the Children’s Hospital of Philadelphia in the US released a video of what looked like a lamb inside a bag filled with fluid. In fact, this was a premature lamb gestating inside an artificial womb. The scientists say this technology could help millions of premature babies born globally each year. They say they want to improve outcomes for babies born between 22 and 28 weeks, for whom survival prospects have improved but long-term health problems are frequent.
Yet if full ectogestation develops, Romanis warns this could be used as an “instrument of control” against women. “I think the pressure on people to use the machine might be a lot,” she says. “If you have a machine that can gestate but there’s no worry that it will fall over in the street or accidentally eat the wrong thing [as a pregnant woman might], that can be used to control. There might be this pressure in future, that this machine can do your job
better than you.”
It could also be used to keep women in the labour force, and as a justification not to provide maternity leave or support. As of 2020, almost one in five large US employers offered egg-freezing benefits to their employees. Advocates say it offers women more choice by covering the costs of an expensive medical procedure that many could not otherwise afford; but critics see it as a way for employers to encourage women to have children later. “In a similar way,” says Romanis, “there may be companies who think, ‘Let’s pay for women not to be pregnant and give birth because that way they’re away from work for less time.’”
When it comes to reproductive science half a century from now, the ethical and legal dilemmas could look very different from those of today. Some new technologies will undoubtedly benefit society, but there are growing fears that policy-makers will struggle to keep pace with or even understand progress being made in laboratories. We need to begin preparing today for these potential developments – to ensure that humanity benefits, that access is as equal as possible and that the possible health risks are foreseen and accounted for.
“There is a worry that we could see a world where the wealthy can afford to reproduce and never be pregnant, and yet for those who can’t afford it not a lot will change,” Romanis says. “We need to think about mitigating that.”