Back to Prindle Institute

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.

CRISPR and the Ethics of Science Hype

image of pencil writing dna strand

CRISPR is in the news again! And, again, I don’t really know what’s going on.

Okay, so here’s what I think I know: CRISPR is a new-ish technology that allows scientists to edit DNA. I remember seeing in articles pictures of little scissors that are supposed to “cut out” the bad parts of strings of DNA, and perhaps even replace those bad parts with good parts. I don’t know how this is supposed to work. It was discovered sort of serendipitously when studying bacteria and how they fight off viruses, I think, and it all started with people in the yogurt industry. CRISPR is an acronym, but I don’t remember what it stands for. What I do know is that a lot of people are talking about it, and that people say it’s revolutionary.

I also know that while ethical worries abound – not only because of the general worries about the unknown side-effects of altering DNA, but because of concerns about people wanting to make things like designer babies – from what my news feed is telling me, there is reason to get really excited. As many, many, many news outlets have been reporting, there is a new study, published in Nature, that a new advance in CRISPR science means that we could correct or cure or generally get rid of 89% of genetic diseases. I’ve heard of Nature: that’s the journal that publishes only the best stuff.

I’ve also heard that people are so excited that Netflix is even making a miniseries about the discovery of CRISPR and the scientists working on it. The show, titled “Unnatural Selection” [sic], pops up on my Netflix page with the following description:

“From eradicating disease to selecting a child’s traits, gene editing gives humans the chance to hack biology. Meet the real people behind the science.”

In an interview about the miniseries, co-director Joe Egender described his motivation for making the show as follows:

“I come from the fiction side, and I was actually in the thick of developing a sci-fi story and was reading a lot of older sci-fi books and was doing some research and trying to update some of the science. And — I won’t ever forget — I was sitting on the subway reading an article when I first read that CRISPR existed and that we actually can edit the essence of life.”

89% of genetic diseases cured. Articles published in Nature and a new Netflix miniseries. Editing the essence of life. Are you excited yet???

So the point of this little vignette is not to draw attention to the potential ethical concerns surrounding gene-editing technology (if you’d like to read about that, you can do so here), but instead to highlight the kind of ignorance that myself and journalists are dealing with when it comes to reporting on new scientific discoveries. While I told you at the outset that I didn’t really know what was going on with CRISPR, I wasn’t exaggerating by much: I don’t have the kind of robust scientific background required to make sense of the content of the actual research. Here, for example, is the second sentence in the abstract of that new paper on CRISPR everyone is talking about:

“Here we describe prime editing, a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit.”

Huh? Maybe I could come to understand what the above paragraph is saying, given enough time and effort. But I don’t have that kind of time. And besides, not all of us need to be scientists: leave the science to them, and I’ll worry about other things.

But this means that if I’m going to learn about the newest scientific discoveries then I need to rely on others to tell me about them. And this is where things can get tricky: the kind of hype surrounding new technologies like CRISPR means that you’ll get a lot of sensational headlines, ones that might border on the irresponsible.

Consider again the statement from the co-director of that new Netflix documentary, that he became interested in CRISPR after he read about how it can be used to “edit the essence of life.” It is unlikely that any scientist has ever made so bald a claim, and for good reason: it is not clear what it means for life to have an “essence”, nor that such a thing, if it exists, could be edited. The claim that this new scientific development could potentially cure up to 89% of genetic diseases is also something that makes an incredibly flashy headline, but again is much more tempered when it comes from the mouths of the actual scientists involved. The authors of the paper, for instance, state that the 89% number comes from the maximum number of genetic diseases that could, conceptually, be cured if the claims described in the paper were perfected. But that’s of course not saying much: many wonderful things could happen in perfect conditions, the question is how likely they are to exist. And, of course, the 89% claim also does not take into account any potential adverse effects of the current gene editing techniques (a worry that has been raised in past studies).

This is not to say that the new technology won’t pan out, or that it will definitely have adverse side effects, or anything like that. But it does suggest some worries we might have with this kind of hyped-up reaction to new scientific developments.

For instance, as someone who doesn’t know much about science, I necessarily rely on people who do in order to tell me what’s going on. But those who tend to be the ones telling me what’s going on – journalists, mostly – don’t seem to be much better off in terms of their ability to critically analyze the information they’re reporting on. We might wonder what kinds of responsibilities these journalists have to make sure that people like me are, in fact, getting an accurate portrayal of the state of the relevant developments.

Things like the Netflix documentary are even further removed from reality. Even though the documentary makers themselves do not make any specific claims as to understand the science involved, they clearly have an exaggerated view of what CRISPR technology is capable of. Creating a documentary following the lives of people who are capable of editing the “essence of life” will certainly give viewers a distorted view.

None of this is to say that you can’t be excited. But with great hype comes great responsibility to present information critically. When it comes to new developments in science, though, it often seems that this responsibility is not taken terribly seriously.

On Gene Editing, Disease, and Disability

Photo of a piece of paper showing base pairs

On November 29, 2018, MIT Tech Review reported that at Harvard University’s Stem Cell Institute, “IVF doctor and scientist Werner Neuhausser says he plans to begin using CRISPR, the gene-editing tool, to change the DNA code inside sperm cells.” This is the first stage towards gene editing embryos, which is itself a controversial goal, given the debates that rose in response to scientists in China making edits at more advanced stages in fetal development.

Frequently the concern over editing human genes involves issues of justice, such as developing the unchecked power to produce humanity that would exist solely to service some population – for example, organ farming. The moral standing of clones and worries over the dignity of humanity when such power is developed get worked over whenever a new advancement in gene editing is announced.

The response, or the less controversial use of our growing control over genetic offspring, is the potential to cure diseases and improve the quality of life for a number of people. However, this use of genetic intervention may not be as morally unambiguous as it seems at first glance.

Since advanced testing was developed, the debate about the moral status of selective abortion has been fraught. Setting aside the ethics of abortion itself, would choosing to bring a child into the world that does not have a particular illness, syndrome, or condition rather than one that did be an ethical thing for a parent to do? Ethicists are divided.

Some are concerned with the expressive power of such a decision – does making this selection express prejudice against those with the condition or a judgment about the quality of the life that individuals living with the condition experience?

Others are concerned with the practical implications of many people making selections for children without some conditions. It is impractical to imagine that widespread use of such selection would completely eradicate the conditions, and therefore one worry could be that the individuals with conditions in the hypothetical society where widespread selection takes place will be further stigmatized, invisible, or have fewer resources. Also, the prejudice against conditions that involve disability might lead to selections that result in lack of diversity in the human population based on misunderstandings of quality of life.

Of course, on the other side of these discussions is the intuitive preference or obligation for parents or those in charge of raising people in society to promote health and well-being. Medicine is traditionally thought to aim at treating and preventing conditions that deviate from health and wellness; both are complex concepts, to be sure, but preventing disease or creating a society that suffers less from disease seems to fall within the domain of appropriate medical intervention.

How does this advancement in gene editing relate to the debate in selective birth? The Harvard example seeks to prevent Alzheimer’s disease, taking sperm and intervening to prevent disease. Lack of human diversity, pernicious ablest expressive power, and negative impact on those that suffer from the disease are the main concerns with intervening for the purported sake of health.

This article has a set of discussion questions tailored for classroom use. Click here to download them. To see a full list of our discussion questions, check out the Educational Resources page.

Lulu and Nana: The Surprise of Genetically-Modified Humans

Photograph of Dr. He in a lab

On November 25th, Chinese geneticist He Jiankui shocked the scientific community by revealing that he had (allegedly) used CRISPR technology to edit the DNA of now-born human twins. Against the advice of both global experts and personal confidants, He’s team aimed to remove a gene sequence from Lulu and Nana’s genetic code in an attempt to render them resistant to illnesses like HIV, smallpox, and cholera. Since the story first broke, a spiral of unsettling details has unraveled, from the project’s murky treatment of informed consent, to its use of potentially forged signatures on approval forms, misleading statements made by He to his institution, and the curious retainment of a foreign PR firm to produce videos advertising the otherwise-secretive experiment – to say nothing of the fact that it’s unclear how He planned to actually test the success of his genetic edits without simply exposing Lulu and Nana to various diseases. Altogether, this mess led The Atlantic’s Ed Yong to assert that “If you wanted to create the worst possible scenario for introducing the first gene-edited babies into the world, it is difficult to imagine how you could improve on this 15-part farce.”

Neither the potential for He’s experiment, nor the recognition of its moral problems are new (Rachel Robison-Greene wrote on this very topic for the Prindle Post less than a year ago) and though the results of He’s experiment have yet to be published, the story has already engendered its share of outcry. Although gene-editing therapy has been tested in limited cases, those instances have been heavily monitored and specifically curtailed to only affect the individual patient being treated; not only did He circumvent the general advice of the scientific community and surprise the world with this news, but he claims to have edited Lulu and Nana’s germline in a way that will inevitably be inherited by any children they may eventually have. If true, the ramifications of He’s experiment for Lulu and Nana’s future is exceptionally large.

More broadly, He’s surprise has brought a bevy of important questions about the ethics of germline editing, the equality of persons, the risk of eugenics, and the role that factors like bias and socioeconomic status will undoubtedly play in the use of this technology in the future. Although these sorts of questions have long been simmering on the back-burner of ethical debates, He’s announcement (and the suggestion that there are other possible patients still unborn) has rocketed them into the spotlight with unexpected urgency; whereas ethicists may have once thought we had years to quibble about the particulars of theoretical cases involving genetically-modified humans, the deadline for such conversations has, apparently, already passed.

He’s actions, though officially cautioned against, were not explicitly prohibited. Although the last meeting of the International Summit on Human Gene Editing warned in 2015 that such experimentation would be ill-advised in the absence of a consensus over norms within the discipline, the lack of such consensus gave He the confidence to forge ahead unfettered. Most disturbingly, there exists at least some evidence that He actively ignored the little advice he did seek on the ethical implications of his work.

Famously, in response to the greedy motivations of Michael Crichton’s fictional InGen company in the blockbuster novel-made-film Jurassic Park, mathematician Ian Malcolm decries the short-sightedness of the gene-editing scientists who cloned dinosaurs back to life with the phrase “Your scientists were so preoccupied with whether or not they could, that they didn’t stop to think if they should.” There are many elements in Jurassic Park that are unrealistic; human hubris, particularly in the realm of potential scientific progress, is not one of them.

As of this writing, He has reportedly been detained by the Chinese government; at present, his future appears to be as uncertain as Lulu and Nana’s. One thing that is not uncertain: as our collective technological capabilities increase exponentially, the need for informed ethical advisors on scientific projects (and scientific researchers informed about ethical principles) are needed now more than ever.

Iceland Has Almost Eliminated Down Syndrome through Selective Abortion. Is That a Good Thing?

Ultrasound image

A recent article from CBS News reported that almost 100 percent of pregnant women in Iceland choose to terminate their pregnancy, should a pre-natal screening test come back positive for Down Syndrome. Nearly 85 percent of all pregnant women in Iceland take this optional test. Only around one or two children are now born in Iceland with Down Syndrome per year. On the other side of the Atlantic, the Ohio state legislature is currently considering bills to criminalize selective abortion done for terminating a fetus with Down Syndrome. Obviously, opinions differ drastically on the moral permissibility of the termination of Down Syndrome pregnancies.

Continue reading “Iceland Has Almost Eliminated Down Syndrome through Selective Abortion. Is That a Good Thing?”