The secret body, p.6
The Secret Body, page 6
The fourteen-day limit on how long a human embryo can be kept alive in a lab dish was first suggested in 1979 by a US ethics advisory board, and then endorsed in 1984 by a report for the UK government, known as the Warnock Report, named after the committee’s chair, the moral philosopher Mary Warnock.37 A few countries, including the UK, Spain and Australia, have since made it a criminal offence to grow a human embryo any longer.38 The Warnock committee had spent two years grappling with multiple conflicting interests over a technology that at the time was far from established.39 ‘Disputes were on the whole civilised,’ Warnock recalls in her memoir, but ‘I think that by the summer of 1984, tempers were a bit frayed.’40
The committee’s success was, at least in part, down to answering a question subtly different from the one that is usually asked. The central problem – as the press would always have it – lay in finding an answer to the question, ‘When does life begin?’ Warnock’s committee took the view that this was not a question of fact, as it seems at a glance, after all, but something which had to be decided. And since a live human embryo in the lab was something that had never existed before, they reasoned that really, the crucial new question was this: how should we regard this new entity, a living human embryo outside the uterus? In other words, their focus was on deciding when a human embryo in a lab dish reaches the point at which it needs protection.
Not everyone’s opinion could be reconciled, but the committee found consensus in setting a limit to the length of time any human embryo can be allowed to live in a lab.41 Their decision – the fourteen-day rule – was justified in several ways. In a fourteen-day-old human embryo, there’s no sign of a nervous system, which would be a prerequisite for feeling or thought. Also, many embryos are naturally lost during the first two weeks. On day 15, moreover, a groove appears in the discshaped embryo, called the primitive streak. This coincides with the embryo no longer being able to split and develop into twins. Arguably, before this moment, an embryo can’t be considered an individual, because if it was, how could it still be able to split and become two individuals? From this logic, the presence of the primitive streak, on day 15, can be taken as the moment at which a unique human being has come into existence.
One argument against a fourteen-day limit is that an embryo cannot possibly experience pain until much later in its existence. Neurons that transmit signals from the spinal cord to the part of the brain where pain can be perceived do not develop until a foetus is around twenty-three to twenty-four weeks old. And an argument against the idea that a human embryo becomes a distinct individual on day 15 is that embryos used for research are never destined to become a person anyway.
On the other hand, as decreed by Pope Pius IX in 1869, the Roman Catholic Church considers a person to have been created at the moment an egg is fertilised by a sperm. Interestingly, this position of the Catholic Church was directly influenced by scientific technology.42 In the early seventeenth century, microscopes could just about pick out the outline of sperm. Some scientists at the time theorised that tiny human beings must exist inside the sperm’s head. This view – wildly wrong of course – implied that men could take credit for creating the next generation, while women served merely to nourish and enlarge a person’s body.43 Catholic theologians took the theory of a preformed human body inside sperm to imply that personhood must begin at conception.
Roughly speaking, Hinduism also holds that life begins at conception, but allows for an embryo’s destruction in some situations. Judaism considers an embryo’s status to increase over time, and says a soul may enter on its fortieth day. Many Islamic scholars agree with this view, although the Muslim World League considers ensoulment to happen later, 120 days after fertilisation. From this – a very small snapshot of religious views – it is blatantly difficult to take on board the world’s diverse values in formulating global rules for embryo science. Anyone wishing to extend the current fourteen-day limit might hold back simply because widespread public discussion would ignite all sorts of strongly held feelings, which could lead to any possible outcome, including the limit being reduced rather than extended.44
At the time Warnock’s recommendation was adopted, no science was actually restricted by a fourteen-day limit, because it was technically impossible to preserve an embryo outside of the womb for this long. So the restraint primarily served to maintain the perception that science was being morally controlled. However, breakthroughs by Zernicka-Goetz and others, published in 2016, have reignited the debate.45
Zernicka-Goetz was driven by the fact that what happens to an embryo after its first week had been exceptionally hard to study: ‘I wanted to take a look inside this “black box”, [to] see what was going on.’46 Her team began with mouse embryos. Day after day, her team tested countless conditions of hormones, nutrients and growth factors that might keep the embryos alive longer than anybody had achieved before. The days became months. Not only did they change the broth the cells were kept in but they also tested, for example, whether the embryos might survive better if placed on a soft gel rather than the usual hard plastic dish – it turned out not to matter. Eventually, they saw a mouse embryo live in a lab dish longer than anybody had seen before, a couple of days longer than the time it normally took for embryos to be implanted. But this success was short-lived, because the method proved unreliable; it seemed to work one time and not the next. The iterative process of tweaking everything continued for many months more, until the procedure was robust.47 Finally, it worked. Then the next step was obvious – to test their method for mouse embryos on ones that were human.
One day in May 2013, they began to culture two human embryos donated from an IVF clinic.48 Amazingly, one of them started to develop. As this human embryo continued to live past eight days, it dawned on Zernicka-Goetz and her team that, because nobody had ever seen a living human embryo in a lab dish past this point, they had no way of knowing if what they were about to witness would be anything like what happens in the womb. By day 11, however, the embryo began to self-organise, and looked similar to what was shown in textbooks based on earlier studies of samples collected from operations.
On day 12 they terminated the project, and in every future experiment they never went beyond day 13, because of the international agreement born out of the Warnock recommendation, enforced by law in the UK. Around the same time, and in collaboration with Zernicka-Goetz, a team in New York, led by the Iranian-born scientist Ali Brivanlou, achieved a similar feat.49 Brivanlou had sent one of his team to Zernicka-Goetz’s lab to learn their method for keeping mouse embryos alive and then, back in his lab, tweaked the method for human embryos.50 Brivanlou vividly remembers the moment he met with his team to decide whether or not they should kill the embryos as the fourteen-day deadline approached. In the USA, the cut-off date is a guideline rather than a law, so continuing wouldn’t have been illegal, but Brivanlou decided to terminate the experiment. Without naming names, he told me there were tears in the team.51
These two lab team’s achievements were voted by readers of Science magazine as 2016’s breakthrough of the year, because their work opened up a new way of studying the earliest phase of human development, the beginning of human life. The feat itself was important – ‘mind-blowing’, Brivanlou says52 – because the discovery that an embryo can survive in lab conditions for so long, seemingly ‘implanting’ itself against the bottom of a lab culture dish, was unexpected. The implication is that an embryo is self-sufficient for some time after it implants, requiring little, if anything, from the mother’s tissue at first.
By thirteen days, however, there were signs, at least in Zernicka-Goetz’s lab, that the embryos needed something other than the culture they were in. Perhaps by including maternal tissue or complex human-made materials, they could be made to survive longer. It is highly unlikely that the fictional hatchery in Aldous Huxley’s Brave New World, used for growing cloned humans in incubators, will ever be possible, but as for how long a human embryo could possibly live outside a womb, nobody knows.
Brivanlou, for one, would like to try to grow human embryos for longer, up to twenty-one days.53 There’s so much that can be learnt from watching embryos develop, he says: from understanding the appearance and disappearance of countless structures as a new human begins, to figuring out what is happening when human development goes wrong. To circumvent restrictions, he and others are also studying so-called synthetic or artificial embryos. Essentially, these are clumps of stem cells treated so that they develop basic structures of actual embryos, without there ever being the slightest chance of their becoming a body. At least for the moment, artificial embryos do not pose any major ethical issues. But as for growing real human embryos, Brivanlou knows it wouldn’t be right to push ahead unilaterally. Human embryo research is morally, culturally and politically controversial, and society spans every conceivable opinion. There is a consensus in place, but it’s fragile.
Still, deciding how long a human embryo should be cultured for is not even the most pressing or challenging issue we now face. Recent advances in IVF have thrust to the fore other, even more complicated dilemmas.
Making a baby without sex is a vastly more sophisticated process today than it was when Louise Brown was born in 1978. Our understanding of the relevant science has advanced dramatically, and now there are a host of opportunities to make interventions and decisions, raising many difficult issues for parents and society.
The IVF process begins with daily injections. For about two weeks, a woman injects herself with hormones so that her eggs mature. The injections amount to a hormone dose higher than would naturally occur, causing several of her eggs to mature at once. Using a needle, passed through the vagina and guided by ultrasound, her eggs are retrieved. One by one, each is gently drawn out using light suction, until a dozen or so are collected over about twenty minutes, while the woman is sedated with anaesthetics. The eggs are usually surrounded by other small cells called cumulus cells. In a nearby lab, the collected eggs are examined under a microscope and graded – essentially for their looks – taking into account whether or not a good number of cumulus cells are present and whether or not the sample has a healthy-looking texture. Fresh semen is usually collected on the same day, at home or in the clinic.
Before being allowed anywhere near an egg, the sperm are often washed. This was first done in the mid-1990s when it was discovered that HIV could feasibly be passed on through the father’s semen to the mother or child. Nowadays, the process is used not only to remove infectious agents, but also because some components of seminal fluid can inhibit fertilisation when carried out in vitro. On the face of it, washing minuscule sperm might not sound easy, but there are several ways to do it. Commonly, semen is diluted in a solution containing antibiotics and protein supplements before being spun in a centrifuge – a device something like a washing machine but able to whizz around much faster – so that the sperm concentrate at the bottom of the tube. The liquid is siphoned off and the sperm are resuspended in a fresh solution – voilà, washed.
One IVF clinic in California offers a menu of sperm washes. They run from basic to premium. The process just described is basic. For a premium wash – more expensive, of course – sperm are centrifuged in a test tube containing layers of liquid that create a density gradient. This helps purify healthy sperm because dead sperm gather at the top of the tube and can be discarded. Another option – price on application – involves leaving semen in a tube full of culture broth. An hour or so later, the top part of the liquid, containing sperm capable of swimming up the tube of their own accord, is extracted, leaving dead or non-moving sperm at the bottom.
With the sperm washed, fertilisation is attempted in one of two ways. Thousands of sperm can be mixed with an egg cell in a lab dish and left in an incubator for a few hours, in the hope that, by chance, fertilisation will happen. Alternatively, a needle can be used under a microscope to insert a single sperm directly into an egg cell – a procedure called intracytoplasmic sperm injection – relieving the sperm of the task of finding and entering the egg of its own accord.
The next step is to give the fertilised egg time to grow. Again, there are countless options: the best way to culture a fertilised human egg for successful pregnancy is the topic of well over a thousand scientific papers.54 A small industry has grown up marketing culture broths as optimal for human embryo growth, each with varying amounts of glucose, amino acids, vitamins, antibiotics or growth factors.55 There are other variables too: levels of carbon dioxide and oxygen, temperature and humidity can all be adjusted in the incubator where the fertilised egg is kept. Movement might also be beneficial, so sometimes the developing embryo is kept on a gently rocking platform.56 All of this almost certainly affects an embryo’s growth and its potential for pregnancy, but nobody knows what’s really optimal, and each clinic has its own set-up.
To grade embryos for their likely chances of successfully leading to pregnancy, an embryologist looks at them under a microscope. They look for the cells to appear smooth and round, for example, and to see if all of the cells are dividing. A bulge, or ‘bleb’, as it’s called in scientific texts, can protrude from one or more of the embryo’s cells, for reasons that aren’t clear, and if this is happening a lot, the embryo gets a low grade. If the embryo grows to a couple of hundred cells or so, an embryologist can also assess whether or not it has gained the right structure of a hollow ball. These judgements are an art as much as a science. Embryologists make the best decisions they can, but it’s hard to pick out which are really most likely to lead to successful pregnancy just by looking at them.
In 2019, the ability of embryologists to assess embryo quality was compared with that of artificial intelligence (AI).57 The test was whether an individual embryologist’s assessment of the quality of an embryo matched that of the majority of embryologists more or less often than the AI. The software, based on an image-recognition system developed by Google, was fed 12,000 pictures of embryos already categorised as poor or good, to find patterns separating the two groups which it could look for in other embryos. By analysing the images in all sorts of ways, the software learnt to pick out subtle and complex differences in shapes and textures, which would be hard or impossible for an embryologist to know how to assess.
So the outcome of this mini Kasparov-versus-Deep Blue duel was that AI won, at least in the sense that AI was more consistent. Individual embryologists varied a lot in their scores, but the software was virtually always in agreement with the majority decision. Of course, this doesn’t prove that AI could help maximise a woman’s chances for pregnancy – not least because the majority human decision might not have always been right, and this wasn’t set up as an actual clinical trial. But it suggests AI could help. In a future upgrade, the software might be able to categorise embryos more precisely, picking out those with specific chromosomal abnormalities, for example.58
To more accurately assess the health of an embryo, a biopsy can be taken. Unlike taking a sample of bone, liver, kidney or other tissue from an adult body, a biopsy from an embryo doesn’t require a surgeon but an embryologist who can work with the most fragile of live samples, using pipettes and a minuscule needle under a microscope. From a biopsy of an embryo, its genes can be scrutinised – a process called pre-implantation genetic diagnosis or PGD.
To take a biopsy from an embryo, the first step is to pierce the thick, transparent membrane which surrounds it. This can be done in several ways, with a needle, with pulses of laser light or with a small squirt of concentrated acid, and each has its pros and cons. A laser is easy to use, for example, but also heats up the liquid around the embryo, which might be a concern even though there is data to say it’s safe.59 Whichever method is used, the embryo has to be pierced just right: too small a hole and a cell can’t easily be pulled out; too large and cells may come out of their own accord and be lost. A broth lacking calcium and magnesium ions is sometimes added to reduce how tightly the embryo cells are stuck to each other. Then, with the embryo held steady under a microscope, a pipette can gently suck out one or a few cells. Yet again, there’s an alternative: a pipette can be used to push against the embryo’s outer membrane, the pressure causing a cell to be expelled. Either way, there’s a chance that the cells being taken, or the embryo itself, is damaged in the process and has to be discarded. But being overly careful isn’t a good idea either, because the speed of obtaining the biopsy is crucial too; living embryos shouldn’t be out of their incubators for long. Then, while the biopsy is being analysed, the embryos are frozen, each potential life suspended, while science decides which of them might be born.
Apart from those who oppose any level of intervention in human reproduction, few would argue against allowing parents the opportunity to screen embryos following IVF in order to avoid a single genetic variation that would otherwise certainly lead to progressive motor and mental difficulties, as is the case with Huntington’s disease, for example. But for each prospective parent, none of the choices involved are easy. Decisions require taking a position on the moral status of an embryo and deciding what to do with embryos that aren’t going to be used – they can be destroyed, frozen or used in research. The cost of PGD is also a problem; most US health insurance companies will not pay for it.
Things become even more complicated when considering screening embryos for a genetic variation that won’t inevitably cause a problem. Today, there are over 400 conditions which can be tested for in the UK.60 Many of these are genetic variations which carry some level of risk, the precise level of which is often not clear.61 Certain genetic variations only cause problems late in life, by which time other treatments could feasibly be available. As well as this, the effects of most genetic variations are complex. A gene variant which correlates with an increased risk of a particular autoimmune disease, for example, also correlates with being better able to fight off HIV.62 Needless to say, there is no such thing as an ideal genetic inheritance; human diversity is fundamentally important. The problem of using PGD to select embryos for implantation is that it forces us to answer one of the most vital and fraught issues of our time: what really is a genetic disorder?
