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Gene Drives and the Desire for Control

photograph of French Alps weir created by the Barrage de Roselend

Whether discovering a child’s sex before it’s born, amassing wealth to protect against economic uncertainties, or even checking the morning’s weather report before leaving the house, we seemingly have a distaste for life’s uncertainties and, wherever possible, look to exercise influence over the world around us.

However, as Epictetus notes in The Enchiridion, we control surprisingly little. We can’t control what happens to us, nor the actions or thoughts of other people. Moreover, we can’t even exercise complete control over our bodies, with them demanding food and water, needing to expel waste, invariably getting damaged, becoming sick, and eventually failing us altogether.

This lack of control becomes even starker when seen in the context of the natural world, where we’re practically powerless. Flora and fauna, weather and ecosystems, and the interactions between our little blue planet, the solar system and the universe all sit outside our sphere of influence. While we can check the weather before leaving the house, we can’t change it. We can domesticate some animals, but whether we use them or they use us is debatable. We can cut down trees and slaughter wildlife, but destruction and control aren’t necessarily synonymous.

Ultimately, in existence’s totality, we’re subject to, rather than the wielders of, power.

So, unsurprisingly, opportunities for (the illusion of) control are intrinsically appealing. When an innovation promises to relocate phenomena from the realm of happenstance, we more often than not jump at the chance, looking to replace uncertainty with reliability. For example, the invention of mechanized timepieces, like watches and clocks, revolutionized public and personal life, allowing people to monitor how they spent their lives more accurately than ever before – exercising precise control over something which, for the longest time, was more of an organic experience; the passing of time. This increased control led to changes in broader social structures and was a fundamental component of the industrial revolution; time shifted from something we inhabit to a valuable commodity.

Today, advances in genetic technologies promise a similar expansion of our sphere of influence, allowing us to shape the very building blocks of life as we see fit.

It has led to countless philosophical debates about designer babies, personalized medicine, cloning, and synthetic biology, amongst others. This genetic revolution has numerous intersections with our desire to shape the natural world, but of particular note is the use of gene drives.

Gene drives are a self-perpetuating method of species alteration. In short, it works by hijacking inherence in sexually reproductive organisms so that engineered genetic traits are likely (or inevitably) passed on from one generation to the next at an increasing rate.

For example, say we wanted to eliminate mosquitoes. We could genetically engineer several thousand of them within a lab so that they’re only capable of producing male offspring. Additionally, this alteration would be made to the germline – the genetic material passed from one generation to the next – so that the descendants of these genetically modified mosquitoes would also only produce males. These mosquitoes would reproduce with their wild counterparts upon release, producing male offspring carrying this altered gene, who would then go on to reproduce, and so on. Over time, and with each generation, more and more mosquitoes would have the male-offspring-only gene, and the population of wild mosquitoes would increasingly skew away from females and towards males. Eventually, in its most extreme form, we’d reach a point where only male mosquitoes are left, and without any females, mosquito reproduction would cease, and the species would die off.

Now, deliberately causing a species to go extinct might sound ridiculous given the current extinction rate occurring globally. But eliminating certain species could have substantial benefits, according to gene drive proponents.

Eliminating Anopheles Stephensi, a type of mosquito and one of the vectors for malaria in the Indian subcontinent and South Asia, could drastically alleviate the burden caused by malaria, a disease that killed 627,000 people in 2020. Gene drives could also be applied in conservation efforts. Like with mosquitoes, conservationists could use the technology to crash the population of an invasive species, like the U.K.’s Grey Squirrel populace. Doing so would afford the native Red Squirrel a chance to repopulate, free from competition from the larger and more aggressive, originally North American, counterpart.

Now, these outcomes would invariably be desirable. No one’s arguing that keeping malaria in the world, leading to the deaths of countless people, mostly children, is a good thing (or at least, if they’re making that argument, they’re wrong). Also, preserving the Red Squirrel would have ecological and social value. However, there’s a principal question here, just because we could, in theory, use gene drives to shape nature as we see it, does that mean we should? Do we lose something important when we aim for maximum control?

According to philosopher Michael Sandel, the random nature of reality has moral desirability. In The Case Against Perfect, Sandel writes:

The problem is not the drift to mechanism but the drive to mastery. And what the drive to mastery misses, and may even destroy, is an appreciation of the gifted character of human powers and achievements. To acknowledge the giftedness of life is to recognize that our talents and powers are not wholly our own doing, nor even fully ours, despite the efforts we expend to develop and to exercise them. It is also to recognize that not everything in the world is open to any use we may desire or devise. An appreciation of the giftedness of life constrains the Promethean project and conduces to a certain humility.

Sandel’s focus here is human augmentation. However, I think his work still has something to tell us about our relationship with nature: we forever run the risk of hyperagency – the desire to shape the world to serve our goals. For Sandel, to try and exercise our will without limitation is to reject the giftedness of life. It is to abandon any sense of humility and consider existence nothing more than a vehicle through which our desires can be satiated. A prerequisite of accepting nature as a gift, given to us by the randomness of existence, is that we take it as it is. Like receiving a gift from a loved one, to complain that it doesn’t meet requirements is to dismiss something crucially important; to eliminate within ourselves the virtue of acceptance and openness.

Now, not everyone buys this argument. It seems difficult to argue that the randomness of nature is somehow a gift when one has malaria, zika, ebola, or countless other horrific diseases. Nor do I think Sandel would make this argument. But I think his work illuminates a risk we run as beings with the desire to improve the conditions of our existence. Viewing the universe as something we have the inherent right to manipulate risks distorting the relationship between person and nature, depriving the former of the humility that an openness to the unintended provides. Gene drives may offer us the unparalleled power to shape the natural world how we see fit, but we must be on guard to the dangers of what we may lose when we subjugate biology and genetic inheritance itself to our control.

The Pugly Truth

photograph of bulldog skull evolutionin profile

Last month, the Oslo District Court issued a ruling effectively banning the breeding of British Bulldogs and Cavalier King Charles Spaniels in Norway. The verdict was the result of a case brought by the Animal Protection Norway (APN), who argued that such practices are in violation of the Norwegian Animal Welfare Act. But why might this be the case? And what does this mean for the morality of owning purebred dogs?

A long history of human-guided breeding has given rise to numerous critical health issues for purebred dogs, and it was these very issues that formed the foundation of the APN’s court case. British Bulldogs, for example, have been bred to develop wide skulls and short snouts – allegedly in order to provide them with a more expressive face, emulating that of a child. As a result, bulldogs have developed severe breathing problems. Bulldogs are therefore unable to properly regulate their temperature through panting and are highly susceptible to heatstroke. In fact, the heads of bulldogs have become so deformed that the breed is mostly incapable of reproducing without human intervention. This is because their enlarged skulls are no longer able to pass through the pelvic canal of the mother, and – for this reason – 95% of bulldogs have to be delivered via Caesarean section. Bulldogs also suffer from an array of other problems with their heart, eyes, skin, and hips – with bulldogs suffering from the highest rate of hip dysplasia of any breed. These health issues are so severe that most airlines now refuse to transport bulldogs and other brachycephalic (shortened head) breeds, for fear that these dogs will not survive a flight.

The overbreeding of Cavalier King Charles Spaniels, on the other hand, has resulted in these dogs carrying more harmful genetic variants than any other breed. As a result, these dogs are at serious risk of developing allergies, dislocated knees, hip dysplasia, cataracts, and heart defects – including myxomatous mitral valve disease, a condition that leads to the degeneration of their heart valves.

Our obsession with breeds such as the British Bulldog and the Cavalier King Charles Spaniel is understandable. Years of intensive overbreeding has resulted in two varieties of dog that are, well, absolutely adorable. And the same goes for many other purebreds. When Men in Black was first released, the character of Frank filled me with a deep and abiding love for pugs. That love endured for many years, and developed into a resolute desire to own a pug of my own – at least, until I began to learn about the genetic tragedy of the breed. Like bulldogs, pugs suffer from a wealth of breathing and thermoregulation issues related to their shortened snouts. Their shallow eye sockets also make them highly susceptible to proptosis – a condition in which the dog’s eyeball is literally left dangling from its socket. Research now suggests that their deformed skulls may also be the cause of the many neurological issues that plague pugs: one third of the breed can’t even walk normally.

Given the horrendous health consequences of pure-breeding, the ruling by the Oslo District Court seems justified. It’s also the reason why – in 2009 – the British Kennel Club (whose aesthetic standards are largely responsible for breeders’ selection of certain traits) issued new regulations for British Bulldogs in an effort to encourage the breeding of healthier dogs. The American Kennel Club, on the other hand, has refused to make any such modifications to their standards.

While modified kennel standards and legal bans are important steps in breeding healthier, happier dogs, they’re not the only ways of effecting meaningful change. What, then, does morality require of us as individuals? Should those who own purebred dogs immediately give up their beloved pets? Clearly not. There’s also no reason to pass over that purebred pup you bonded with at your local shelter. Those animals that have already been bred – though potentially plagued by genetic issues – are deserving of dignity, kindness, and (most importantly) love. Instead, it would seem that our most important moral responsibility is to do all we can to minimize the number of dogs suffering from easily avoidable ailments by stemming the supply of new purebreds. And this is a surprisingly simple task to achieve. In a capitalist system such as ours, supply changes to meet demand. Thus, if we refuse to purchase purebred dogs, breeders will have little reason to continue to produce such varieties.

The only real benefit to be gained from breeds like the British Bulldog, Cavalier King Charles Spaniel, or pug is aesthetic enjoyment. But given the enormous harm suffered by dogs belonging to these breeds – and the ready availability of much healthier alternatives for prospective dog owners – this isn’t enough to justify us in continuing to patronize breeders. Morality requires us to focus less on aesthetics, and more on the health – and, ultimately, happiness – of our most loyal companions.

DNA Dating

photograph of person looking at phone display of tinder profile

Recently Geneticist George Church attracted controversy for his involvement in Digid8, a startup company which proposes to use DNA comparisons in dating apps to help limit the probability of two people who share a genetic mutation exposing their potential offspring to serious genetic disease. The idea has been met with charges of racism and trans-phobia, yet Church maintains that this is an important step towards the elimination of all genetic diseases. While charges of Nazi-like eugenics projects are premature at this stage, there are genuine moral dilemmas involved with projects like this.

The central idea behind the project is to let users know about their and a potential partner’s genetic background. For instance, it will inform them if they carry recessive genes connected to genetic illnesses like sickle cell anemia, Huntington’s disease, or Tay-Sachs. It is possible for a person to carry such genes but not have the disease if they also carry a healthy dominant gene. However, if two potential parents both have the recessive gene, then their offspring has a twenty-five percent chance of suffering from the disease. Through a dating app, potential matches would be made aware of this and could be given the opportunity to plan accordingly.

As genetic testing gets cheaper, projects like this become more possible. Ethical concerns are abundant, ranging from the issues involved with sharing genetic information with a corporation to the potential to share additional genetic markers that go beyond disease. We also need to distinguish between this specific proposal and Digid8’s implementation of it, and the more general idea which could be implemented in different ways. It is possible for specific proposals to be implemented poorly or unethically apart from the ethics of whether such DNA comparisons should be used at all. Since the specific proposals are still in planning and because other companies may follow suit, I will focus on the general moral concerns.

DNA comparison to help make informed pregnancy considerations is not new. Existing prenatal genetic screening already offers us the opportunity to make these types of decisions. So there is a good deal of overlap concerning the ethical dimensions at play. In addressing the issue of eugenics in prenatal screening, Tom Shakespeare distinguishes between strong eugenics where there is an effort at population-level control of reproduction at the state-level, and weak eugenics which promotes technologies of reproductive selection via non-coercive individual choices. Such a distinction allows us to “avoid rhetorical excesses” and “disingenuous dissociations with unfortunate historical precedents.”

But we might also be concerned about the kinds of conditions being screened for. As Shakespeare notes, not every form of genetic variation constitutes a disease. While social barriers can make life harder, people born with Down’s syndrome or congenital deafness may be healthy individuals presenting no medical problems. On the other hand, there are genetic conditions where, regardless of social context, one will experience suffering, pain, and premature death. Thus, one of the most important questions is about which conditions and genetic markers are appropriate to identify and screen for.

An important factor that also needs to be considered when addressing genetic illness is the fact that several thousand illnesses are triggered by environmental factors. For instance, while there is a genetic component to diabetes, developing the condition is heavily dependent on individual diet. With different conditions being a result of genetic/environmental interaction, determining the ethics of screening for certain conditions becomes a tricky matter.

There are also additional concerns regarding public information. Currently, prenatal screening practices done in hospitals and clinics afford the possibility of consultations and counseling with obstetricians, geneticists, or pediatricians, while DNA comparison through a social media app does not afford such consultation unless it is specifically sought. This means that there is a greater chance of potential couples making uninformed or badly informed decisions. If a dating app presents information about possible genetic conditions, the person needs to have the reliable resources necessary to make informed choices about who they choose to date.

Despite these concerns, there are good reasons to pursue services that allow for DNA comparison. Certain diseases are responsible for much suffering, and so there are ethical reasons to try to prevent a child from being born with them. As Shakespeare argues,

“conditions like Tay-Sachs disease or anencephaly causes major suffering, leading to a very premature death. It is important to argue that living as a disabled person is a viable and valuable form of existence, but that existing without any possibility of a real life is not living at all.”

Services like that proposed by Digid8 may help prevent significant suffering.

There is also value in knowing what one may be in for in a potential pregnancy, even if this information may not affect the decision to have a child. In prenatal testing, women sometimes seek prescreening even while knowing that the results will not affect their choices. The information can still be valuable to a candidate parent about what they may expect. Similarly, as Church notes, the Digid8 service is not intended to block dates for people carrying dominant disease genes. Instead, this kind of information can be helpful for potential couples in their plans for creating a family.

On the other hand, there are obvious ethical concerns with DNA comparison. While it may only constitute weak eugenics in the democratic world where there is more choice and freedom and where laws and regulations will try to protect human rights, other areas of the world may not use the technology in the same way. For example, while democratic nations may limit the uses of the technology to inform users about serious and debilitating genetic conditions, authoritarian nations may seek to expand the DNA comparisons to support pseudo-scientific aims or may use the information to restrict and isolate groups of people and create greater social barriers. Thus, such technology could also be used for strong eugenics purposes. Without careful ethical oversight the technology could be used and tailored for more niche purposes like designer babies, to prevent the birth of gay and transgendered people, or to help groups of people engage in self-segregation practices.

There is much potential for good or bad in the DNA comparison services like that Church proposes, and discovering and solving the ethical problems that occur will likely take time. Trying to sort out the ethical issues involved in situations like this will be aided with input from those who have genetic conditions. Their experiences and testimonials may vary, but we need to listen to people directly affected. Those who suffer from Huntington’s are far more likely to favor prenatal diagnosis over those who are at-risk. Thus, sorting out what kinds of laws, policies, and codes of conduct may be required for DNA comparison must factor these experiences into account.

By Means of Human Selection: The Birth of Three-Parent Babies

In the late 1990’s, doctors at the St. Barnabus Institute in New Jersey developed a groundbreaking new technique—they successfully produced a child using the genetic material of three different donor parents.  The motivation for the innovation was to help certain at-risk couples have healthy biological children of their own.  The procedure, if successful, blocks the spread of disease that is sometimes passed through mitochondrial DNA—a genetic contribution passed to children by their biological mothers.  Some women pass on mitochondrial DNA that causes muscular dystrophy or respiratory problems.  Leigh Syndrome, a fatal disease, is also passed through mitochondrial DNA.  

Continue reading “By Means of Human Selection: The Birth of Three-Parent Babies”