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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.

Is It Ethical to Extinguish a Species?

photograph of mosquito swarm, blurry from motion

Diseases like malaria, dengue fever, Zika fever, and chikungunya virus are responsible for hundreds of thousands of deaths each year. What is common to all of these illnesses? They are largely spread by mosquitoes who, while not being that harmful in themselves, are considered to be one of the deadliest creatures on the planet because of their ability to transmit disease. For example, one species of mosquito known as Aedes aegypti are mostly responsible for the transmission of dengue fever which kills 10-20,000 people every year. If this species of mosquito is deadly, why don’t we simply eradicate the species? A more important question, however, might be whether it is ethical to do so.

The idea of eradicating several species of mosquito has been proposed multiple times. Bringing about the extinction of Anopheles gambiae, which are prominent in the spread of malaria, could save millions of lives. Biologist Olivia Judson advocates for the use of genetic modification to cause “specicide.” She argues that “It is hard to argue that a targeted, genetic attempt to remove an insect that is clearly harmful to us is worse than the haphazard, expensive, destructive and largely unsuccessful approach we’re using now.” E.O. Wilson, a champion of biodiversity, has also advocated for the extinction of Anopheles gambiae noting, “Anopheles gambiae […] is specialized to live in human settlements and lives on human blood. As a result, it’s a principle conveyer of malaria. That’s one I wouldn’t mind seeing go.”

Many have wondered how the extinction of various species of mosquito might affect ecosystems. While Aedes aegypti is an important source of food for amphibians, bats, birds, fish, insects, and reptiles, it has been suggested that species could adjust to the loss of this food source while other mosquito species could fill the ecological niche. According to entomologist Joe Conlon, “if we eradicated them tomorrow, the ecosystems where they are active will hiccup and then get on with life. Something better or worse would take over.” Because of this, advocates of eliminating certain species of mosquitoes see little downside for the environment if they were driven to extinction. In the meantime, using genetic modification to eliminate the species may be preferred. The use of pesticides can be harmful to human health, and the elimination of mosquito breeding grounds pose greater risks of disrupting ecosystems.

One very prominent attempt to put this thinking into practice takes the form of Oxitec’s OX513A mosquito. Through genetic modification, the males of the species will not be able to produce viable offspring unless they are exposed to the antibiotic tetracycline. In other words, when released into the wild they will still be able to mate with female mosquitoes, but the resultant eggs will not be viable. Field trials of this genetically modified mosquito have been conducted in Brazil, the Cayman Islands, and Malaysia. As a result, the population of mosquitoes in the trial area have fallen by 80-95% and with a reduction of dengue fever cases by 91%. Since the modified mosquitoes are all male they must be replaced over time. However, since males do not bite humans, the immediate risk of a modified mosquito biting humans is minimal.

The prospect of eliminating an entire species carries some significant ethical considerations. One of these concerns is whether these edited genes are controllable. One of the reassurances of using a genetically modified mosquito is that the edited genes should disappear with their death; their offspring will not be viable, so there should be no chance of such organisms spreading. However, according to a study at Yale, mosquitoes captured up to two-and-a-half years after the release of OX513A carried genetic modifications signifying that some of their offspring did manage to survive. In other words, genes from the released OX513A mosquitoes did make it into the general population.

There are other important concerns. First, it is difficult to predict how changes to evolutionary pressures on viruses like dengue fever will affect their virulence. According to David B. Resnick at the National Institute of Health such modifications “might promote malaria resistance but increase yellow fever susceptibility.” In addition, there are concerns that Oxitec has not engaged as much public consultation as they should before releasing their mosquitoes in trial areas. There is also the more general concern about genetic modification. Various groups have opposed genetic modification as “they feel deeply that it is wrong to tamper with the DNA of wild things.”

But there is perhaps a more significant moral issue. Use of genetically modified organisms aside, there is still the question about eliminating a species. The most emphatic proponents of efforts to eradicate these mosquitoes seem to be those who focus on global health ethics. Eliminating certain species that cause great harm to humans will alleviate suffering and potentially save millions of lives, while at the same time their elimination is not likely to seriously harm ecosystems. From a global health perspective, the argument is clear.

Alternatively, from an environmental ethics standpoint there is concern about the unknown environmental effects. Even if the risk is minimal however, there is a more important question to consider: Does a species have inherent value such that it would be morally wrong to eliminate it even if their extinction served our interests? According to philosopher Paul W. Taylor a species is merely a class and only individual organisms within a class have inherent worth. Thus, there is nothing more immoral about eliminating a species like Anopheles gambiae than there is eliminating the individual insects.

Alternatively, JP Sterba emphasizes that species can evolve, become endangered, and go extinct. In effect, a species can be harmed or benefited, and therefore a species has a good of its own. If all species possess this kind of inherent value then eliminating Anopheles gambiae is immoral. This view asks us to look beyond whether we value Anopheles gambiae, or whether Anopheles gambiae is valuable for things we care about (like ecosystems), and consider the question of the value of the species from another vantage.

However, even if we accepted that a species has inherent value, that would not mean that it is more valuable than other considerations. So, perhaps, this very specific case is poignant because as the human species continues to practice ever more control over nature, we need to become better at understanding how and why things should be valued; these answers will be instructive in determining what we should (and should not) do with that control.

EEE and the Eradication of Mosquitoes

closeup photograph of mosquito

Mosquitoes have continuously posed a threat to humanity because of their ability to transmit dangerous diseases such as dengue, Zika, yellow fever, and others. Eastern equine encephalitis (EEE) is the newest viral epidemic that has hit the United States. EEE has actually been around for years, with an average of 5-10 people per year contracting the disease. However, this year there has been an increased amount of cases with 12 known deaths so far, the most recent being a resident of Elkhart County of Indiana.

EEE is spread through the mosquito species Culiseta melanura which feeds almost exclusively on birds and horses which is why it has been so rare. Transmission to humans requires a “bridge” species which will bite humans like the commonly known Aedes family, responsible for Zika virus transmission. Symptoms of EEE set in approximately 4-10 days after exposure and include headache, fever, chills, and body and joint aches. Typically, the immune system can fight off the infection on its own however 1-20 cases will develop the brain infection, encephalitis. This will result in tremors, seizures, paralysis, and possibly death. There are no current treatment options for this disease to date.

The virus has been predominantly affecting the Midwest and Eastern regions of the United States. Government official and environmental specialists are attempting to find a way to eliminate the risk of the disease for the community by taking preventative steps. For the public, they suggest wearing long sleeve clothing, not going out around sunset, and wearing bug spray. Unfortunately, these methods are only somewhat effective. Mosquitoes will continue to be out at a high density until the first frost. Further, the Connecticut Agricultural Experiment Center recently found data suggesting that the virus can survive over the winter, even if the mosquitoes won’t. This means that the outbreak will not just be limited to this year but next summer we could face another outbreak with more severe consequences. As the data suggests, it is more urgent than ever to find a way to protect people from contracting these terrible diseases spread through mosquitoes. Thus, the question forms, what is the best way to do this?

Scientists have been researching models that work with direct modification of the species to create a more effective form of protection. Recently published was a study done over 2016-2017 on the Islands of the city of Guangzhou, China. It was able to take out 94% of the Asian Tiger mosquito. This study was a combination of two methods: sterilization of the female mosquitoes and infecting the male mosquitoes with a bacterium that hinders the insect’s ability to reproduce and spread disease. Other methods of genetic modification have looked at ways to detect specific species of mosquitoes by wing beat and making them resistant to parasites that cause human diseases. These methods are a promising step towards protecting future generations from EEE and other outbreaks.

There are still limits to methods of genetic modification. None of the methods have yet to be 100% effective. Most of them require releasing millions of modified insects over an area, which makes it hard to set up for entire continents. Although this method was effective, translating it into a scaled-up technique for larger regions requires a lot more. If we genetically modify these species to be unable to reproduce and are able to put it in a wide scale method, the long-term consequences points towards full eradication.

When we look to the past, one of the most effective disease control methods was the eradication of the virus, Variola, which was responsible for smallpox. Is eradication of mosquitoes a justifiable method of disease prevention to protect people from epidemics, like that most recently of EEE?

Mosquitoes do have many negative qualities which would support eradication of a species as a whole. According to Vox, mosquitoes are responsible for killing 52 billion people that have lived on earth out of the total 102 billion. They carry yellow fever, malaria, Zika, dengue, West Nile, and now EEE, which have all taken many lives. Mosquitoes are universal, spread more disease than any other animal, and have been deemed “masters of evolution” because of their invincibility to pesticides and previous prevention methods. Not to mention, with climate change on the rise, there is a proliferation of mosquitoes increasing the risk of disease spread. By eliminating them, you would be protecting many, especially developing countries who are most commonly targets of the outbreaks.

On the other hand, not all mosquitoes are harmful. It is only the female mosquitoes that bite and spread disease. Females and males don’t excrete waste or aerate soil and are pollinators, feeding on plant nectar. They are also food sources for many birds, bats, fish, and frogs. Eliminating all mosquitoes could have effects on the food chain with a bottom up effect. Some say that this niche would be quickly replaced but Phil Lounibos, an entomologist from Florida University, says that this is an even greater risk. It is likely that mosquitoes would be replaced with an insect that is “equally, or more, undesirable from a public health viewpoint.”

While these are all valid considerations for why to protect the species, what really stands in opposition to full eradication is the moral argument that eradication is just wrong. Our justification for eradication is that this is a species that is dangerous to our species (humans), yet we are so dangerous to so many other species in the world. What kind of precedent does it set when we fully kill out a species? Who decides what species remain or die?

According to biologist Olivia Judson, eradication of disease causing mosquitoes, would save approximately 1 million lives and would only decrease genetic diversity of mosquito families by 1%. Although this outcome may sound ideal, there is the unknown of the long-term consequences of these actions. With diseases like EEE advancing, the pressure is on for scientists to find a way to contain disease transmission.

Modifying the Mosquito

Never in recent memory have the bounds of human impact on the world felt so wide. At a time when researchers are finding cans of soda at the bottom of the Marianas Trench, and scientists are grappling with the possibility of creating human-animal “chimera” tissues for study,  our ability to influence the world around us seems practically unparalleled. And when it comes to dealing with a public health crisis brought on by one of nature’s most annoying pests, it would seem that these limits may soon expand once again.

Continue reading “Modifying the Mosquito”