Embryo 78 – male
• No serious early onset diseases, but a carrier for phenylketonuria (a metabolic malfunction that can cause behavioural and mental disorders. Carriers just have one copy of the gene, so don’t get the condition themselves).
• Higher than average risk of type 2 diabetes and colon cancer.
• Lower than average risk of asthma and autism.
• Dark eyes, light brown hair, male pattern baldness.
• 40% chance of coming in the top half in SAT tests.
There are 200 of these embryos to choose from, all made by in vitro fertilisation (IVF) from you and your partner’s eggs and sperm. So, over to you. Which will you choose?
If there’s any kind of future for “designer babies”, it might look something like this. It’s a long way from the image conjured up when artificial conception, and perhaps even artificial gestation, were first mooted as a serious scientific possibility. Inspired by predictions about the future of reproductive technology by the biologists JBS Haldane and Julian Huxley in the 1920s, Huxley’s brother Aldous wrote a satirical novel about it.
That book was, of course, Brave New World, published in 1932. Set in the year 2540, it describes a society whose population is grown in vats in an impersonal central hatchery, graded into five tiers of different intelligence by chemical treatment of the embryos. There are no parents as such – families are considered obscene. Instead, the gestating fetuses and babies are tended by workers in white overalls, “their hands gloved with a pale corpse‑coloured rubber”, under white, dead lights.
Brave New World has become the inevitable reference point for all media discussion of new advances in reproductive technology. Whether it’s Newsweek reporting in 1978 on the birth of Louise Brown, the first “test-tube baby” (the inaccurate phrase speaks volumes) as a “cry round the brave new world”, or the New York Times announcing “The brave new world of three-parent IVF” in 2014, the message is that we are heading towards Huxley’s hatchery with its racks of tailor-made babies in their “numbered test tubes”.
The spectre of a harsh, impersonal and authoritarian dystopia always looms in these discussions of reproductive control and selection. Novelist Kazuo Ishiguro, whose 2005 novel, Never Let Me Go, described children produced and reared as organ donors, last month warned that thanks to advances in gene editing, “we’re coming close to the point where we can, objectively in some sense, create people who are superior to others”.
But the prospect of genetic portraits of IVF embryos paints a rather different picture. If it happens at all, the aim will be not to engineer societies but to attract consumers. Should we allow that? Even if we do, would a list of dozens or even hundreds of embryos with diverse yet sketchy genetic endowments be of any use to anyone?
“I don’t think we are going to see superman or a split in the species any time soon, because we just don’t know enough,” says Henry Greely, bioethicist.
The shadow of Frankenstein’s monster haunted the fraught discussion of IVF in the 1970s and 80s, and the misleading term “three-parent baby” to refer to embryos made by the technique of mitochondrial transfer – moving healthy versions of the energy-generating cell compartments called mitochondria from a donor cell to an egg with faulty, potentially fatal versions – insinuates that there must be something “unnatural” about the procedure.
Every new advance puts a fresh spark of life into Huxley’s monstrous vision. Ishiguro’s dire forecast was spurred by the gene-editing method called Crispr-Cas9, developed in 2012, which uses natural enzymes to target and snip genes with pinpoint accuracy. Thanks to Crispr-Cas9, it seems likely that gene therapies – eliminating mutant genes that cause some severe, mostly very rare diseases – might finally bear fruit, if they can be shown to be safe for human use. Clinical trials are now under way.
But modified babies? Crispr-Cas9 has already been used to genetically modify (nonviable) human embryos in China, to see if it is possible in principle – the results were mixed. And Kathy Niakan of the Francis Crick Institute in the UK has been granted a licence by the Human Fertilisation and Embryology Authority (HFEA) to use Crispr-Cas9 on embryos a few days old to find out more about problems in these early stages of development that can lead to miscarriage and other reproductive problems.
Most countries have not yet legislated on genetic modification in human reproduction, but of those that have, all have banned it. The idea of using Crispr-Cas9 for human reproduction is largely rejected in principle by the medical research community. A team of scientists warned in Nature less than two years ago that genetic manipulation of the germ line (sperm and egg cells) by methods like Crispr-Cas9, even if focused initially on improving health, “could start us down a path towards non-therapeutic genetic enhancement”.
Besides, there seems to be little need for gene editing in reproduction. It would be a difficult, expensive and uncertain way to achieve what can mostly be achieved already in other ways, particularly by just selecting an embryo that has or lacks the gene in question. “Almost everything you can accomplish by gene editing, you can accomplish by embryo selection,” says bioethicist Henry Greely of Stanford University in California.
Because of unknown health risks and widespread public distrust of gene editing, bioethicist Ronald Green of Dartmouth College in New Hampshire says he does not foresee widespread use of Crispr-Cas9 in the next two decades, even for the prevention of genetic disease, let alone for designer babies. However, Green does see gene editing appearing on the menu eventually, and perhaps not just for medical therapies. “It is unavoidably in our future,” he says, “and I believe that it will become one of the central foci of our social debates later in this century and in the century beyond.” He warns that this might be accompanied by “serious errors and health problems as unknown genetic side effects in ‘edited’ children and populations begin to manifest themselves”.
For now, though, if there’s going to be anything even vaguely resembling the popular designer-baby fantasy, Greely says it will come from embryo selection, not genetic manipulation. Embryos produced by IVF will be genetically screened – parts or all of their DNA will be read to deduce which gene variants they carry – and the prospective parents will be able to choose which embryos to implant in the hope of achieving a pregnancy. Greely foresees that new methods of harvesting or producing human eggs, along with advances in preimplantation genetic diagnosis (PGD) of IVF embryos, will make selection much more viable and appealing, and thus more common, in 20 years’ time.
PGD is already used by couples who know that they carry genes for specific inherited diseases so that they can identify embryos that do not have those genes. The testing, generally on three- to five-day-old embryos, is conducted in around 5% of IVF cycles in the US. In the UK it is performed under licence from the HFEA, which permits screening for around 250 diseases including thalassemia, early-onset Alzheimer’s and cystic fibrosis.
As a way of “designing” your baby, PGD is currently unattractive. “Egg harvesting is unpleasant and risky and doesn’t give you that many eggs,” says Greely, and the success rate for implanted embryos is still typically about one in three. But that will change, he says, thanks to developments that will make human eggs much more abundant and conveniently available, coupled to the possibility of screening their genomes quickly and cheaply.
Advances in methods for reading the genetic code recorded in our chromosomes are going to make it a routine possibility for every one of us – certainly, every newborn child – to have our genes sequenced. “In the next 10 years or so, the chances are that many people in rich countries will have large chunks of their genetic information in their electronic medical records,” says Greely.
But using genetic data to predict what kind of person an embryo would become is far more complicated than is often implied. Seeking to justify unquestionably important research on the genetic basis of human health, researchers haven’t done much to dispel simplistic ideas about how genes make us. Talk of “IQ genes”, “gay genes” and “musical genes” has led to a widespread perception that there is a straightforward one-to-one relationship between our genes and our traits. In general, it’s anything but.
There are thousands of mostly rare and nasty genetic diseases that can be pinpointed to a specific gene mutation. Most more common diseases or medical predispositions – for example, diabetes, heart disease or certain types of cancer – are linked to several or even many genes, can’t be predicted with any certainty, and depend also on environmental factors such as diet.
When it comes to more complex things like personality and intelligence, we know very little. Even if they are strongly inheritable – it’s estimated that up to 80% of intelligence, as measured by IQ, is inherited – we don’t know much at all about which genes are involved, and not for want of looking.
At best, Greely says, PGD might tell a prospective parent things like “there’s a 60% chance of this child getting in the top half at school, or a 13% chance of being in the top 10%”. That’s not much use.
We might do better for “cosmetic” traits such as hair or eye colour. Even these “turn out to be more complicated than a lot of people thought,” Greely says, but as the number of people whose genomes have been sequenced increases, the predictive ability will improve substantially.
Ewan Birney, director of the European Bioinformatics Institute near Cambridge, points out that, even if other countries don’t choose to constrain and regulate PGD in the way the HFEA does in the UK, it will be very far from a crystal ball.
Nearly anything you can measure for humans, he says, can be studied through genetics, and analysing the statistics for huge numbers of people often reveals some genetic component. But that information “is not very predictive on an individual basis,” says Birney. “I’ve had my genome sequenced on the cheap, and it doesn’t tell me very much. We’ve got to get away from the idea that your DNA is your destiny.”
If the genetic basis of attributes like intelligence and musicality is too thinly spread and unclear to make selection practical, then tweaking by genetic manipulation certainly seems off the menu too. “I don’t think we are going to see superman or a split in the species any time soon,” says Greely, “because we just don’t know enough and are unlikely to for a long time – or maybe for ever.”
If this is all “designer babies” could mean even in principle – freedom from some specific but rare diseases, knowledge of rather trivial aspects of appearance, but only vague, probabilistic information about more general traits like health, attractiveness and intelligence – will people go for it in large enough numbers to sustain an industry?
Greely suspects, even if it is used at first only to avoid serious genetic diseases, we need to start thinking hard about the options we might be faced with. “Choices will be made,” he says, “and if…. read more>>
- Brave New World, by Aldous Huxley