by Nessa Carey
Other options for people at high risk of passing on a genetic disease (apart from not becoming parents) are to adopt or to use eggs or sperm from donors who don’t carry the mutation. But here we come up against a very striking phenomenon. In general, a lot of people seem to want a child who is ‘theirs’ – a child who contains the parents’ genetic material. Maybe there is some biological imperative, buried deep within brain development, that drives this. It could certainly make sense in evolutionary terms. But we really don’t know why this drive seems to be so strong, and in many cases the people who feel like this can’t explain it themselves.
If an individual can’t explain at either an emotional or intellectual level why something matters so strongly to them, is there really any imperative for the scientific and medical communities to support these desires? A recent ethical review suggested that there is, concluding: ‘We may nevertheless have good reasons to respect them, and those reasons may not be that they are good desires but that they are the desires of people for whom we should, a priori, have respect.’7
Consenting adults and imaginary babies
One of the most important concepts in medical ethics is that of ‘informed consent’. There are various related definitions of this, a pretty good one being: ‘The process by which a patient learns about and understands the purpose, benefits, and potential risks of a medical or surgical intervention, including clinical trials, and then agrees to receive the treatment or participate in the trial.’8
Germline gene editing of an embryo creates an extraordinarily complex consent scenario. Our automatic reflex is to assume that the consent will come from the woman who is hoping to become pregnant. She is the one who will undergo hormone treatment to induce ovulation; her eggs will be harvested and edited; one or more embryos will be implanted into her uterus; she will be pregnant for nine months and then give birth. Throughout all of this she is the one carrying the clinical risk, so it seems natural that she will need to give consent. In most cases where her male partner is involved, we would anticipate that he would also need to consent to the use of his sperm.
But here’s where it gets weird. The actual germline editing won’t be happening to the mother or father. It’s the child whose DNA will be changed for ever and for future generations, and they can’t be asked for, or give, consent. At the time when the procedure takes place, they are just a cell or a small bundle of cells. How do you obtain informed consent from someone who doesn’t exist? Even more challengingly, how do we assume consent on behalf of someone who may never exist? The embryo may not develop properly in the laboratory; it may develop but never be implanted into the mother; the pregnancy may not proceed to term.
How do we balance the rights of a possible but currently non-existent person against the rights of the living humans who want to become parents of a child who is genetically theirs but with one potentially devastating characteristic negated?
Cui bono?
Who benefits? This is sometimes an approach that is used to help navigate through some of the ethical and scientific mazes that new medical technologies throw at us all the time. Can we use this thought process to approach the dilemmas and paradoxes created by the potential of germline gene editing?
For many of us, our immediate reaction may be that it’s of course a good thing to decrease disability because this decreases human suffering. The seemingly obvious conclusion from this is that germline gene editing for serious conditions is therefore undoubtedly a good thing. But some of the pushback from this has come from certain disabled people themselves. They have argued that this conclusion implies that disabled people are perceived as inferior to people without disabilities.
It’s another of those situations which is complicated because of the difficulties that arise when we start extrapolating to people who don’t, and won’t, exist. It’s tempting to argue that we are not denigrating the individual with a disability, we are simply saying that their quality of life might have been better without that condition. But we don’t know that, because that person doesn’t exist. So we are at risk of trying to weigh up the rights of and benefits to a hypothetical individual in an alternative non-existent universe.
The World Health Organization has estimated that there are over 16 million people worldwide who are able to walk simply because of immunisation campaigns that have hugely cut the rates of polio. Yet it’s very rare for anyone to suggest that polio immunisation should be scaled back because it’s wrong to drive down the numbers of people who develop paralysis. This perhaps implies that we view certain disabilities differently, depending on how and why they happen. But why does the cause of a disability matter? Does that imply that genetically-determined disability is ‘natural’ whereas one that is the result of an infection is not? If it’s appropriate to use vaccine technology to decrease disability, why is it not appropriate to use gene editing to obtain the same effect? Is this another situation where we view our own genomes as somehow intensely personal to us, our genetic possessiveness coming to the fore?
The question of benefit – and specifically societal benefit – is a major focus of health economics. In societies where medical interventions are predominantly governed by publicly funded state healthcare, the equation seems quite straightforward. If the lifetime costs of supporting someone with a disability are higher than the costs of gene editing an embryo and offering all the necessary IVF support to a prospective parent, there is a clear financial imperative for the state system to support gene editing. A similar logic may apply in private health systems which operate through insurance models, although the economics of this tend to be more challenging for the companies involved. But there must be a degree of discomfort around skewing ethical decisions based on a monetary appraisal of the costs of existence of different people. As one of the reports on the ethics of gene editing has pointed out, this approach is ‘the paradigmatic outlook of the eugenics† movements’.9
In the public system that prevails in the UK, access to healthcare is not affected by your genetic status. This is very different from the insurance-driven model in the United States. Germline gene editing could free the edited individual and all their descendants from an overwhelming financial burden. The concern with this is that it may further entrench economic advantage and social inequality. It is likely that only families with significant amounts of money would be able to gain access to germline gene editing for their offspring. In adulthood these edited individuals are likely to have a major advantage in terms of health, access to jobs and availability of health insurance over those whose parents could not afford gene editing.
Who defines disability?
There is a tendency to talk about disability as if there is just one definition and only one way of looking at a situation and an individual. The UK’s Equality Act 2010 states that you are disabled ‘if you have a physical or mental impairment that has a “substantial” and “long-term” negative effect on your ability to do normal daily activities’.10 One obvious limitation of this is that it doesn’t capture the impact of technology. Do you wear glasses? Without them, would you be able to drive a car, cross the road safely, use a computer all day? No? Yet you probably don’t count yourself as disabled, because a technological aid allows you to go about your normal daily life, and even make a fashion statement while you do so.
But if you are a bitterly poor person in the Democratic Republic of Congo or rural Mississippi, averagely poor eyesight could significantly hamper your life chances, because it may be remarkably difficult for you to obtain corrective glasses.
Considerations such as this move us away from a strictly medical model of disability and into the social model. In this model, individuals are disadvantaged not by their disability as such but by the societally-imposed barriers that they face. This can be quite easy to observe in practice. Less than a quarter of the stations on the London Underground network have step-free access. On the equivalent network in Stockholm every station has step-free access. Travel on the Stoc
kholm system and you will see wheelchair users quite frequently, but it’s very rare to see someone using a wheelchair on the London Tube. Access to transport and the opportunities it opens up is controlled not by the disability but by the metropolitan infrastructure.
If at least some disability can be viewed as a social issue rather than a medical one, what are the implications of this for germline gene editing? About 75% of cases of profound congenital deafness are caused by single gene mutations.11 Many of these occur unexpectedly in a family, where both parents are unaffected carriers. But there are situations where many members of a community are born deaf, because over time more and more deaf people have become parents together, and have found that life is easier for them and their children when part of a similar society.
This situation is possibly more common in the world of deafness than in most other types of disability and this is partly driven by a very strong influence – sign language. Just like spoken languages, sign languages have developed repeatedly in different groups. There’s no definitive number of sign languages but it possibly runs into a few hundred.12 These languages are rich and varied, and act as a signifier and characteristic of a distinct cultural group.
It is perfectly feasible that gene editing could be used to prevent cases of congenital deafness, by ‘correcting’ the causative mutation. But if deafness is intimately connected with sign language, and language is a cultural signifier, would we be using gene editing to attack a cultural group rather than to solve a medical problem? Is this acceptable?
What are the ethics of using gene editing in the opposite way? In 2002, a lesbian couple in the US decided to have a child. Sharon Duchesneau and Candy McCullough asked a friend to be the sperm donor and he agreed. The birth of their son sparked a huge ethical debate, and for once this wasn’t about the reproductive rights of same-sex couples.
Sharon Duchesneau and Candy McCullough were both deaf. The friend who was the sperm donor was a deaf man from a family where the condition had been present for five generations. By choosing a deaf sperm donor from this background, the women had increased the chances that their child would share the same condition as his mothers. It wasn’t guaranteed, but it was a much higher chance than if they had used the sperm from a hearing man. And their son was indeed born deaf.
The mothers justified their decision: ‘In an interview with the Washington Post, the women claimed they would make better parents to a deaf child. They believed they would be able to understand the child’s development more thoroughly and offer better guidance, and said the choice was no different from opting for a certain gender. They also said they were part of a generation that viewed deafness not as a disability but as a cultural identity.’13
Support and condemnation were instant. Deaf commentators were for and against and the same was true for hearing people. Was this a slippery slope towards designer babies or a pragmatic decision to make communication with your child easier? A denial of full potential or a welcome into a cultural community? An abuse of power or a non-argument about a hypothetical hearing child who doesn’t and won’t exist?
Of course, these women were free to procreate with whomever they wished and there was no medical intervention anyway so it wasn’t a case that any ethics committee or regulator needed to grapple with (probably to their intense relief). But just as it will be possible to ‘correct’ a mutation that causes deafness by using gene editing, it will be just as easy to introduce the mutation into an embryo that doesn’t possess it. Which will bring us straight back to the difficult issues already raised – who has rights here? Is it the child who will be born, the hypothetical child who won’t exist, or the parents?
We may not have to deal with this specific problem immediately in the world of interventional gene editing. But we will almost certainly have to deal with it one day.
Notes
1. https://www.nhs.uk/conditions/pregnancy-and-baby/newborn-blood-spot-test/
2. https://www.25doctors.com/learn/how-much-sperm-does-a-man-produce-in-a-day
3. One of the most recent is the July 2018 report from the Nuffield Council on Bioethics, ‘Genome editing and human reproduction’, which has been invaluable for this chapter.
4. https://ghr.nlm.nih.gov/condition/leigh-syndrome#inheritance
5. https://www.newscientist.com/article/2107219-exclusive-worlds-first-baby-born-with-new-3-parent-technique/
6. https://www.newscientist.com/article/2160120-first-uk-three-parent-babies-could-be-born-this-year/
7. ‘Genome editing and human reproduction’. Nuffield Council on Bioethics (July 2018).
8. https://www.medicinenet.com/script/main/art.asp?articlekey=22414
9. ‘Genome editing and human reproduction’. Nuffield Council on Bioethics (July 2018).
10. https://www.gov.uk/definition-of-disability-under-equality-act-2010
11. https://www.american-hearing.org/understanding-hearing-balance/
12. https://www.k-international.com/blog/different-types-of-sign-language-around-the-world/
13. https://www.theguardian.com/world/2002/apr/08/davidteather
* When I was an academic at a medical school in the UK, one of the real-life tutorial cases we used was that of a woman whose offspring were at risk of Huntington’s disease. She terminated ten pregnancies before finally carrying a foetus who was not at risk. It’s hard to imagine how much anguish that family went through.
† Eugenics refers to movements that promulgated doctrines of selective reproduction of humans to promote the accumulation of positive traits and decrease the presence of negative ones. It originated in the UK in the mid-19th century and has re-emerged several times, most notoriously in Nazi Germany.
8
SHALL MAN STILL HAVE DOMINION?
What’s the deadliest animal on the planet, in terms of the numbers of human deaths? It’s a favourite question for pub quizzes and school tests alike. Sharks, lions and snakes tend to be high on most people’s guess lists. The last is a good guess, as snakebites account for hundreds of thousands of deaths each year.2 Sharks and lions on the other hand only account for a few tens of deaths each year.
But the clear winner in the human mortality stakes is actually the mosquito. About three quarters of a million people die every year because of the ‘little fly’.3 Of course, unlike snakes, lions and sharks the mosquito itself doesn’t kill us. No one has ever had a limb ripped off by the irritating little buzzers. The reason why mosquitoes are so deadly is because of the diseases they transmit.
The mosquito itself is uninterested in the diseases. It’s simply carrying out its life-cycle, and the diseases come along for the ride. It’s only the female mosquito that spreads diseases. When eggs are developing in her body, the female needs certain nutrients to nourish them. The best source of these nutrients is blood, and sadly for us, we humans are the preferred blood source of some particularly troublesome mosquito species.
When a mosquito sucks blood from a person infected with certain disease-causing microorganisms, she ingests these creatures as part of her meal. These multiply and develop inside her, finding a very pleasant environment in her salivary glands. When she feeds again, this time on a different human, the pathogens are passed on in her spit.
The human health burden created by this process is very heavy. Mosquitoes transmit four related organisms, all of which can cause various forms of malaria. There were 216 million cases of malaria in 2016, and 445,000 deaths. 90% of these deaths occurred in sub-Saharan Africa.4 Malaria isn’t the only illness that uses the mosquitoes as its postal system. The same is true of dengue fever, which infects 100 million people globally, hundreds of thousands of whom progress to the haemorrhagic form, characterised by excessive bruising and bleeding. The mortality rate for this extreme version is 5%, equating to thousands of deaths. Yellow fever and Zika virus are also spread by mosquitoes, although Zika can additionally be spread sexually.5
In a very rapid response to a relatively new health crisis, clinical tria
ls are already underway for vaccines to combat Zika virus. While everyone is hopeful these will work, there’s not the same level of optimism about immunising against malaria. Despite decades of research it’s proven incredibly difficult to develop vaccines to protect against this disease. The one-celled organisms that cause this illness have very complex life-cycles that make them difficult opponents. As a consequence of this, most efforts to control the spread of malaria have focused on prevention. These techniques include relatively simple measures such as nets impregnated with insecticides which cover beds and protect the sleepers, as mosquitoes are most active at night.
These insects thrive in warm, wet environments because they lay their eggs in standing water. Community approaches to preventing the spread of mosquito-borne illnesses often include removing these breeding sites, which can be as innocuous as an upside-down bin lid that has filled with rainwater.
These prevention strategies seem to have plateaued in their effectiveness, because malaria rates are no longer dropping. There’s a variety of reasons for this, many of which are due to the complexity of building long-lasting and effective health campaigns that can be sustained in some of the poorest communities in the world. Major conflicts and civil wars impede progress dramatically. The shifts in the planet’s weather systems as a consequence of climate change will almost certainly result in mosquitoes and their disease payloads increasing their range. A new approach is needed, and it’s needed soon.
The Very Friendly Mosquito
Although the ‘Friendly Mosquito’ may sound like a follow-on piece to The Very Hungry Caterpillar, it’s actually a trademark owned by a company called Oxitec. It the name of a genetically modified form of a specific mosquito species, the one that spreads the pathogens that cause dengue, Zika and yellow fever.6
