Nearly 40 years since the first ‘ test-tube baby’, how close are we to editing out our genetic imperfections – and should we even try to do this?



A design for life: advances in IVF and genetic research are giving prospective parents a lot more control in the type of child they have.
Photograph: Aliaksei Lasevich / Alamy Stock/Alamy Stock Photo

C omfortably seated in the fertility clinic with Vivaldi playing gently in the background, you and your partner are brought coffee along with a folder. Inside the folder is an embryo menu. Each embryo has a description, something like this:

Embryo 78 – male
No serious early onset illnesses, but a carrier for phenylketonuria (a metabolic malfunction that may cause behavioural and mental disorders. Carriers just have 1 copy of the gene, so don’ t get the situation themselves).
Higher than average risk of type 2 diabetes plus colon cancer.
Lower than average risk of asthma and autism.
Darkish eyes, light brown hair, male pattern baldness.
40% chance of being released in the top half in SAT tests.

You can find 200 of these embryos to choose from, all made by in vitro fertilisation (IVF) from you and your partner’ s eggs plus sperm. So , over to you. Which will you choose?

If there’ s any kind of future for “ developer babies”, it might look something like this. It’ s a considerable ways from the image conjured up when artificial conception, and perhaps also artificial gestation, were first mooted as a serious technological 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 the satirical novel about it.

That book had been, of course , Brave New World , published within 1932. Set in the year 2540, it describes a modern society whose population is grown in vats in an impersonal central hatchery, graded into five tiers of different cleverness by chemical treatment of the embryos. There are no mom and dad as such – families are considered obscene. Instead, the gestating fetuses and babies are tended by workers within white overalls, “ their hands gloved with a soft corpse‑ coloured rubber”, under white, dead lights.

Brave New World has become the unavoidable reference point for all media discussion of new advances within reproductive technology. Whether it’ s Newsweek reporting in 1978 on the birth of Louise Brown, the first “ test-tube baby” (the inaccurate term speaks volumes) as a “ cry round the brave brand 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 in the direction of Huxley’ s hatchery with its racks of tailor-made infants in their “ numbered test tubes”.

The particular spectre of a harsh, impersonal and authoritarian dystopia normally looms in these discussions of reproductive control and choice. Novelist Kazuo Ishiguro, whose 2005 novel, Never Let Me Go , described children produced plus reared as organ donors, last month warned that will thanks to advances in gene editing, “ we’ lso are coming close to the point where we can, objectively in some feeling, create people who are superior to others”.

But the potential customer of genetic portraits of IVF embryos paints an extremely different picture. If it happens at all, the aim will be to not engineer societies but to attract consumers. Should all of us allow that? Even if we do, would a list of many or even hundreds of embryos with diverse yet sketchy hereditary endowments be of any use to anyone?

The particular shadow of Frankenstein ’ t monster haunted the fraught discussion of IVF within the 1970s and 80s, and the misleading term “ three-parent baby” to refer to embryos made by the technique of mitochondrial move – moving healthy versions of the energy-generating cell spaces called mitochondria from a donor cell to an egg along with faulty, potentially fatal versions – insinuates that there should be something “ unnatural” about the procedure.

Each new advance puts a fresh spark of life straight into Huxley’ s monstrous vision. Ishiguro’ s dire prediction was spurred by the gene-editing method called Crispr-Cas9, created in 2012, which uses natural enzymes to target and snip genes with pinpoint accuracy. Thanks to Crispr-Cas9, it seems most likely that gene therapies – eliminating mutant genes that will cause some severe, mostly very rare diseases – may finally bear fruit, if they can be shown to be safe for individual use. Clinical trials are now under way.

But modified babies? Crispr-Cas9 has already been used to genetically improve (nonviable) human embryos in China, to see if it is achievable in principle – the results were mixed. And Kathy Niakan of the Francis Crick Institute in the UK has been given a licence by the Human Fertilisation and Embryology Expert (HFEA) to use Crispr-Cas9 on embryos a few days old to learn more about problems in these early stages of development that can result in miscarriage and other reproductive problems.

Most nations have not yet legislated on genetic modification in individual reproduction, but of those that have, all have banned this. The idea of using Crispr-Cas9 for human reproduction is largely declined in principle by the medical research community. A group of scientists warned in Nature less than two years ago that genetic manipulation from the germ line (sperm and egg cells) by strategies like Crispr-Cas9, even if focused initially on improving wellness, “ could start us down a path toward non-therapeutic genetic enhancement”.

Besides, there seems to end up being little need for gene editing in reproduction. It would be a hard, expensive and uncertain way to achieve what can mostly be performed already in other ways, particularly by just selecting an embryo that has or lacks the gene in question. “ Almost anything you can accomplish by gene editing, you can accomplish simply by embryo selection, ” says bioethicist Henry Greely associated with Stanford University in California.

Because of not known health risks and widespread public distrust of gene modifying, bioethicist Ronald Green of Dartmouth College in Brand new Hampshire says he does not foresee widespread use of Crispr-Cas9 in the next two decades, even for the prevention of genetic condition, let alone for designer babies. However , Green does notice gene editing appearing on the menu eventually, and perhaps not only for medical therapies. “ It is unavoidably in our long term, ” he says, “ and I believe that it will become among the central foci of our social debates later in this hundred years and in the century beyond. ” He warns this might be accompanied by “ serious errors and health problems since unknown genetic side effects in ‘ edited’ children plus populations begin to manifest themselves”.

For now, although, if there’ s going to be anything even vaguely resembling the popular designer-baby fantasy, Greely says it will originate from embryo selection, not genetic manipulation. Embryos produced by IVF will be genetically screened – parts or all of their GENETICS will be read to deduce which gene variants they will carry – and the prospective parents will be able to choose which usually embryos to implant in the hope of achieving the pregnancy. Greely foresees that new methods of harvesting or even producing human eggs, along with advances in preimplantation hereditary diagnosis (PGD) of IVF embryos, will make selection a lot more viable and appealing, and thus more common, in 20 years’ time.

PGD is already used by couples who seem to know that they carry genes for specific inherited illnesses so that they can identify embryos that do not have those genes. Therapy, generally on three- to five-day-old embryos, is executed in around 5% of IVF cycles in the US. In the united kingdom it is performed under licence from the HFEA, which allows screening for around 250 diseases including thalassemia, early-onset Alzheimer’ s and cystic fibrosis.

As a way associated with “ designing” your baby, PGD is currently unattractive. “ Ovum harvesting is unpleasant and risky and doesn’ to give you that many eggs, ” says Greely, and the effectiveness for implanted embryos is still typically about one within three. But that will change, he says, thanks to developments that can help human eggs much more abundant and conveniently available, combined to the possibility of screening their genomes quickly and inexpensively.


Carey Mulligan, Keira Knightley and Andrew Garfield in the 2010 film adaptation of Kazuo Ishiguro’ s i9000 Never Let Me Go, in which clones are produced to supply spare organs for their originals. Photograph: 20th Century Fox/Everett/Rex

Advances in methods for reading the particular genetic code recorded in our chromosomes are going to make it a schedule possibility for every one of us – certainly, every newborn baby child – to have our genes sequenced. “ Within the next 10 years or so, the chances are that many people in wealthy countries will have large chunks of their genetic information within their electronic medical records, ” says Greely.

But using genetic data to predict what kind of individual an embryo would become is far more complicated compared to is often implied. Seeking to justify unquestionably important research around the genetic basis of human health, researchers haven’ to done much to dispel simplistic ideas about how genetics make us. Talk of “ IQ genes”, “ homosexual genes” and “ musical genes” has led to the widespread perception that there is a straightforward one-to-one relationship between the genes and our traits. In general, it’ s not.

There are thousands of mostly rare and unpleasant genetic diseases that can be pinpointed to a specific gene veränderung. Most more common diseases or medical predispositions – for instance , diabetes, heart disease or certain types of cancer – are usually linked to several or even many genes, can’ t become predicted with any certainty, and depend also upon environmental factors such as diet.

When it comes to more complicated things like personality and intelligence, we know very little. Even if they may be strongly inheritable – it’ s estimated that as much as 80% of intelligence, as measured by IQ, is definitely inherited – we don’ t know much in any way about which genes are involved, and not for want associated with looking.

At best, Greely says, PGD may tell a prospective parent things like “ there’ h a 60% chance of this child getting in the top fifty percent at school, or a 13% chance of being in the top 10%”. That’ s not much use.

We might learn better for “ cosmetic” traits such as hair or eyesight colour. Even these “ turn out to be more complicated than a lots of people thought, ” Greely says, but as the number of individuals whose genomes have been sequenced increases, the predictive capability will improve substantially.

Ewan Birney, director from the European Bioinformatics Institute near Cambridge, points out that, even though other countries don’ t choose to constrain and manage PGD in the way the HFEA does in the UK, it will be extremely far from a crystal ball.

Nearly whatever you can measure for humans, he says, can be studied by means of genetics, and analysing the statistics for huge numbers of people frequently reveals some genetic component. But that information “ is not very predictive on an individual basis, ” states 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 future. ”

If the genetic basis of qualities like intelligence and musicality is too thinly spread plus unclear to make selection practical, then tweaking by hereditary manipulation certainly seems off the menu too. “ We don’ t think we are going to see superman or a divided in the species any time soon, ” says Greely, “ mainly because we just don’ t know enough and are improbable to for a long time – or maybe for ever. ”

If this is all “ designer babies” could mean during principle – freedom from some specific but uncommon diseases, knowledge of rather trivial aspects of appearance, but just vague, probabilistic information about more general traits like wellness, attractiveness and intelligence – will people go for it within large enough numbers to sustain an  industry?

Greely suspects, even if it is used at first simply to avoid serious genetic diseases, we need to start thinking tough about the options we might be faced with. “ Choices is going to be made, ” he says, “ and if informed people never participate in making those choices, ignorant people will make all of them. ”

The Crispr/Cas9 system utilizes a molecular structure to edit genomes.

The Crispr/Cas9 system uses a molecular structure in order to edit genomes. Photograph: Alamy

Eco-friendly thinks that technological advances could make “ design” significantly versatile. In the next 40-50 years, he says, “ we’ lmost all start seeing the use of gene editing and reproductive technologies to get enhancement: blond hair and blue eyes, improved sports abilities, enhanced reading skills or numeracy, and so on. ”

He’ s less optimistic about the outcomes, saying that we will then see social tensions “ since the well-to-do exploit technologies that make them even better off”, raising the relatively worsened health status of the world’ t poor. As Greely points out, a perfectly feasible 10-20% improvement in health via PGD, added to the similar advantage that wealth already brings, could lead to an extending of the health gap between rich and poor, each within a society and between nations.

Other people doubt that there will be any great demand for embryo selection, especially if genetic forecasts remain sketchy about the many desirable traits. “ Where there is a serious problem, like a deadly condition, or an existing obstacle, such as infertility, I might not be surprised to see people take advantage of technologies such as embryo selection, ” says law professor and bioethicist Ur Alta Charo of the University of Wisconsin. “ Yet we already have evidence that people do not flock to technology when they can conceive without assistance. ”

The poor take-up of sperm banks offering “ superior” sperm, she says, already shows that. For most women, “ the emotional significance of reproduction outweighs any idea of ‘ optimisation’ ”. Charo feels that “ our ability to love one another with all our imperfections plus foibles outweighs any notion of ‘ improving’ our kids through genetics”.

All the same, societies are going to encounter tough choices about how to regulate an industry that offers PGD by having an ever-widening scope. “ Technologies are very amoral, ” states Birney. “ Societies have to decide how to use them” – and different societies will make different choices.

One of the simplest things to screen for is sex. Gender-specific abortion is officially forbidden in most countries, although it still happens in areas such as China and India where there has been a strong social preference for boys. But prohibiting selection by sex is another matter. How could it even be applied and policed? By creating some kind of quota system?

And what would selection against genetic disabilities perform to those people who have them? “ They have a lot to be concerned about here, ” says Greely. “ In terms of whether modern society thinks I should have been born, but also in terms of how much healthcare research there is into diseases, how well understood it really is for practitioners and how much social support there is. ”

Once selection beyond avoidance of genetic condition becomes an option – and it does seem likely – the ethical and legal aspects are a minefield. Whenever is it proper for governments to coerce people in to, or prohibit them from, particular choices, such as not really selecting for a disability? How can one balance individual freedoms plus social  consequences?

“ The most important consideration for me personally, ” says Charo, “ is to be clear about the specific roles of personal morality, by which individuals decide whether to search out technological assistance, versus the role of government, which can stop, regulate or promote  technology. ”

The girl adds: “ Too often we discuss these technologies as though personal morality or particular religious views are an enough basis for governmental action. But one must surface government action in a stronger set of concerns about advertising the wellbeing of all individuals while permitting the largest range of personal liberty of conscience and  choice. ”

“ For better or worse, humans will not forgo the opportunity to take their evolution into their personal hands, ” says Green. “ Will that make existence happier and better? I’ m far from sure. ”


A scientist at your workplace during an IVF process. Photograph: Ben Birchall/PA

Easy pickings: the future of designer babies

The simplest and surest way to “ design” an infant is not to construct its genome by pick’ n’ blend gene editing but to produce a huge number of embryos plus read their genomes to find the one that most closely fits your desires.

Two technological advances are expected for this to happen, says bioethicist Henry Greely of Stanford University in California. The production of embryos for IVF must become easier, more abundant and less uncomfortable. And gene sequencing must be fast and cheap sufficient to reveal the traits an embryo will have. Force them together and you have “ Easy PGD” (preimplantation genetic diagnosis): a cheap and painless way of generating large numbers of human embryos and then screening their entire genomes for desired features.

“ To get much broader use of PGD, you need a better way to get eggs, ” Greely states. “ The more eggs you can get, the more attractive PGD turns into. ” One possibility is an one-off medical intervention that will extracts a slice of a woman’ s ovary plus freezes it for future ripening and harvesting associated with eggs. It sounds drastic, but would not be much even worse than current egg-extraction and embryo-implantation methods. And it can give access to thousands of eggs for future use.

An even more dramatic approach would be to grow eggs through stem cells – the cells from which all other tissue sorts can be derived. Some stem cells are present in umbilical blood, which could be harvested at a person’ s delivery and frozen for later use to grow organs – or ovum.

Even mature cells that have advanced above the stem-cell stage and become specific tissue types could be returned to a stem-cell-like state by treating them with natural molecules called growth factors. Last October, a group in Japan reported that they had made mouse ovum this way from skin cells, and fertilised them to generate apparently healthy and fertile mouse pups.

Thanks to technological advances, the cost of human whole-genome sequencing provides plummeted. In 2009 it cost around $50, 000; nowadays it is most like $1, 500, which is why several private businesses can now offer this service. In a few decades it could price just a few dollars per genome. Then it becomes feasible to think about PGD for hundreds of embryos at a time.

“ The science for safe and effective Easy PGD is likely to can be found some time in the next 20 to 40 years, ” says Greely. He thinks it will then become common for kids to be conceived through IVF using selected genomes. He or she forecasts that this will lead to “ the coming obsolescence of sex” for procreation.