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15 May 2016

Is this the end of sex?

A baby grown from a flake of skin or from the genes of three parents – the future of reproduction is mind-boggling.

By Philip Ball

Is it time to give up sex? Oh, it has plenty to recommend it; but as a way of making babies it leaves an awful lot to chance. I mean, you might have some pretty good genes, but – let’s face it – some of them aren’t so great. Male pattern baldness, phenylketonuria, enhanced risk of breast cancer: I’m not sure you really want those genetic conditions passed on in the haphazard shuffling of chromosomes after sperm meets egg.

It is already possible to avoid more than 250 grave genetic conditions by genetic screening of few-days-old embryos during in vitro fertilisation (IVF), so that embryos free from the genetic mutation responsible can be identified for implantation. But that usually works solely for diseases stemming from a single gene – of which there are many, though most are rare. The procedure is called pre-implantation genetic diagnosis (PGD), and it is generally used only by couples at risk of passing on a particularly nasty genetic disease. Otherwise, why go to all that discomfort, and possibly that expense, when the old-fashioned way of making babies is so simple and (on the whole) fun?

In The End of Sex, Henry Greely, a law professor and bioethicist at Stanford University, argues that this will change. Thanks to advances in reproductive and genetic technologies, he predicts that PGD will become the standard method of conception in a matter of several decades. (Recreational sex might nonetheless persist.)

If that doesn’t sound alarming enough, there will be all manner of other seemingly bizarre and alarming options on the menu for making children: using eggs and sperm both made from a single adult (the “uniparent”), or chromosomes tailor-made by chemistry, or IVF between siblings or pensioners, or IVF with the stolen biological detritus of celebrities.

Whether or not you buy Greely’s main contention (I don’t), The End of Sex is eye-opening about the prospects created by biomedical technology. Regardless of how we end up applying it, biotech has already transformed our view of what it means to be(come) human.

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Greely does a superb job in his book of explaining the science, as well as the law and politics (at least in the US context), that will make these things possible. At the root is the realisation that human tissue is far more malleable and protean than we had imagined. Every cell in your body – a flake of skin, say – could be a source not just of most or all other tissue types, but of other beings.

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Central to these scenarios is the culturing and manipulation of stem cells, the ur-cells from which all others develop. The most versatile are human embryonic stem cells. Because these are “pluripotent” – able to grow into any tissue type – they might be used for regeneration of damaged tissues such as nerves, heart muscle and bone.

But it was first shown in 2014 that they can also be used to generate “gametes”: eggs and sperm. So far, such “artificial sperm” consists of immature “spermatids”, which lack tails for swimming. That is no obstacle, however. Using methods developed for IVF, the cells can be injected directly into eggs to produce apparently healthy offspring – in mice, at least. If we want to make babies this way, we’ll generally want them to have the parental genes. It is possible to create embryonic stem cells containing the genes of an adult by using methods involved in cloning Dolly the sheep, in which genetic material is transferred from an adult body (somatic) cell into an egg that has had its own chromosomes removed. The egg can then be used to grow an embryo – a clone – from which stem cells can be cultured. When will that happen? Two years ago.

What’s more, in 2007 Japanese researchers reported that a cocktail of biochemical ingredients will convert body (somatic) cells like skin cells directly back into a pluripotent state like that of embryonic stem cells. It’s not yet clear if such “induced pluripotent stem cells” can be safely used to grow gametes and embryos. If they can, though, they could provide the most convenient route.

The point is that there are already several possible ways of making gametes starting from ordinary adult cells such as skin. And they will work for either sex. We can, in principle, make sperm from female tissue (which could only produce girls, as there is no Y chromosome) and eggs with a male’s genes. The techniques raise the prospect of a new, “easy” form of IVF, without the unpleasant procedure involved in harvesting eggs from the mother: a course of hormones to stimulate egg production, followed by painful invasive surgery to extract them. (Reimplanting the fertilised eggs is much less traumatic.) Instead of all that, eggs – and sperm, if you like – will simply be manufactured from somatic cells. It might be that all you have to do is spit into a bottle.

The other strand of Greely’s argument is the burgeoning of genetic testing and genome analysis. PGD was first performed as early as 1989, but at great cost and yielding very limited genetic information. But as gene sequencing continues its rapid
advance, we might be able before long to obtain a full genetic readout of an embryo in a day or so, for just a few hundred dollars.

Combine easy IVF with fast, comprehensive and cheap genetic screening, and you have “Easy PGD”. Hundreds, even thousands of embryos could be made and screened to find the “best” ones for implantation. The only limit on the choice is cost, but Greely is probably right that this will continue to fall precipitously.

He believes that, with the worst inconveniences of IVF banished, ever more parents will stump up a thousand dollars or so for the opportunity to choose the most promising child. These aren’t designer babies in the normal sense – their genomes aren’t edited cut-and-paste-style, although with the new precision gene-editing technique called CRISPR-Cas9, that might become possible. (It has already been done in human embryos but not for reproduction: the safety issues haven’t yet been resolved.) Rather, the embryos for Easy PGD are merely selected from what is available.

The catch is in choosing the best. Greely offers examples of the kind of embryo profile a couple might be given: female, dark eyes and hair, lower-than-average risk of schizophrenia and of breast cancer, higher-than-average risk of colon cancer, 55 per cent chance of top half in SAT tests, lower chance than average of being an athlete . . .

And there lies the problem. How do you weigh up those pros and cons and balance them against analogous outcomes for another ten, or hundred, embryos? You can’t.

There is another difficulty: it is not clear how much meaningful detail a genetic diagnosis will provide. Although, as Greely notes, it is already possible to determine characteristics such as eye and skin colour from the genome, personality traits are far more elusive. Intelligence – obviously likely to be high on parents’ priority list – exemplifies the problem. It is highly heritable: up to 60 per cent or so of the variations in intelligence in the population can be accounted for by genetic influences. But this doesn’t mean it is highly inheritable, because the genes responsible seem to be widely dispersed throughout the genome, and almost certainly have other functions, too. Intelligence runs in families, but there is no guarantee you’ll get a good dose. While putative “intelligence genes” have been sought for years, so far all we have found is a handful of genes that collectively account for less than two IQ points. Greely thinks this will improve as we get more adept at gene-hunting. I am not so sure.

Prospective new technologies fly only if they find a killer app. Aside from the desire to avoid certain serious but rare illnesses with a very tightly defined genetic component, I’m not convinced that Easy PGD will find one. The “choice” it will offer will be simultaneously overwhelming and ambiguous: no appreciable improvement over the alternative – which, after all, is free, private and rather pleasant.

Yet the important question that Greely’s book raises is not so much whether his vision of near-universal “sex-free conception” will come to pass, but how we will cope with what current biological technologies make (literally) conceivable. On two occasions he confesses that, despite having studied this field for many years, he was caught unawares by suggestions of how the technologies might be used. One is “uniparenting”, whereby a person (either male or female) has both eggs and sperm made from their somatic cells and used to create a child – who would, because of the recombination of chromosomes during conception, not then be a clone in the strict sense. “The other is “multiplex parenting”, in which two people make an embryo which then in effect conceives a child through IVF with another embryo, by mixing their gametes. It would, says Greely, allow a couple to have their “child” mate with someone else without even first being born, let alone reaching puberty.” Such ideas, he concludes, are “evidence of just how wide-ranging and non-intuitive the implications of new biological technologies may be for human reproduction”. Even the experts concede that their imagination is boggled by the possibilities.

I imagine most people will find these scenarios grotesque. But, safety issues aside, the ethical questions are not straightford, not least because no philosopher has yet resolved the rights and wrongs of bringing anyone into existence versus their not existing at all. (How are a person’s rights respected by denying them existence?) It seems unlikely that ethics committees will be required to rule on such cases in the foreseeable future, but there will surely be other, comparable conundrums we don’t yet anticipate. It is not going to be enough to follow the lead of the conservative bioethicist Leon Kass, the prime architect of the ban on federal funding for stem-cell research in the US under the George W Bush administration. Kass advocates what he calls the “wisdom of repugnance”, which is a fancy way of saying that we should be guided by gut instinct. Greely sets aside his otherwise cordial and considered demeanour to excoriate this position, and rightly so.

Kass was a master of the slippery-slope argument: had “uniparents” occurred to him, he would certainly have paraded them as evidence of where it all might lead the moment we start being permissive about research. The irony is – and this of course is fully consistent with the conservative position – that the stifling of stem-cell research in the US went hand in hand with an essentially unregulated, shockingly laissez-faire approach to the IVF business. By contrast, the liberal yet strict regulatory environment of the UK, administered by the Human Fertilisation and Embryology Authority (HFEA), has made ours a widely envied model of how to foster a productive and responsible research climate that can supply valuable benefits for human health.

Yet how would an organisation such as the HFEA even begin to navigate the ethics of “uniparents”? One thing seems clear: attempts to reach absolute judgements about rights and wrongs will probably just hamper serious debate while being outstripped by scientific advances anyway. The guiding question should be not “what?” but “why?” – with the welfare of a child born this way always paramount.

Greely’s book offers a balanced, informed and calm analysis of the legal, ethical and social frameworks within which we must resolve these dilemmas. It is a work neither of advocacy nor of outrage, but is humble and humane – a model of what good bioethics can be. It shows us how to think rather than telling us what to think.

The one factor that I could imagine, with great trepidation, helping techniques such as Greely’s Easy PGD to take off is one that the author doesn’t make much of: peer pressure. Goaded by the distorted agendas of our present education policies, we are encouraged to regard childrearing as a horse race, in which we are made to feel irresponsible if we don’t seize every advantage. If you’ll pay thousands on school fees, or to move to the right catchment area, why not a grand or so more for a spot of genetic tailoring at the outset, even if the benefits are small at best? The bullying by gene analysis companies has already begun. “Genetic testing is a responsibility if you’re having children,” says Anne Wojcicki, chief executive of the US-based 23andMe. And in 2008 the research director of another US firm warned: “If you had the chance to decrease your child’s risk of a disease like diabetes and you didn’t, society would blame you.”

Fear of “society’s blame” will make parents jump through hoops even if they know deep down that it won’t necessarily make their children any healthier, happier or brighter. And however unfair it may seem, it is hard to find compelling arguments for prohibiting the gaming of children’s opportunities by genetic selection. Greely anticipates the kind of sloganeering that will seek to capitalise on these pressures: “You want the best for your child; why not have the best child you can?” If we want to avoid this, we had better renegotiate, rather urgently, the priorities of childrearing, so that parents cease to feel a duty (whether they like it or not) to wring every presumed ounce of potential from their offspring.

If we do not, as Greely points out, a false promise of perfection could drive such expectations to pathological extremes. What if the child genetically selected for athletic ability or artistic talent fails to deliver? (“Do you know what that treatment cost?”) Beyond the valuable ability to avoid certain severely debilitating illnesses, genetic selection of embryos for a “better child” is no more likely to deliver than is the fantasy that cloning will somehow make us immortal. But what it would do is distract from the value of love and nurture, and of making the most of what you have, in favour of crude biological determinism. Which is why I hope that, in the end, most folks will look at themselves and think: “Well, sex never did me much harm.”

The End of Sex and the Future of Reproduction  by Henry T Greely is newly published by Harvard University Press

Philip Ball is most recently the author of Invisible: The History of the Unseen from Plato to Particle Physics (Vintage)

This article appears in the 11 May 2016 issue of the New Statesman, The anti-Trump