Gene drives wrongfully hailed as biological panacea

Some have called it a magic wand. Others have referred to it as the beginning of a new scientific revolution. Regardless of how you may see it, it’s a subject matter that shouldn’t be discussed by only scientists.

CRISPR-Cas9 is the latest state-of-the-art gene editing tool that has taken over the scientific community in recent years (Vox, “A Simple Guide to CRISPR, One of the Biggest Science Stories of the Decade,” 10.25.2017). While the concept of modifying DNA is certainly not a new invention, CRISPR’s main strength lies its transformation of the complicated process of gene editing into something quick, efficient, precise and ridiculously cheap. In other words, it has the potential to cut out undesirable segments of DNA, eradicate hereditary diseases and even guide humanity to a future where people can shape their body into whatever they want. It’s what discouraged many people from thinking that something like designer babies is “unlikely” (Harvard Gazette, “Designer Genetics Not in Near Future,” 12.02.2004), but rather as something “inevitable” (MIT Technology News, “Engineering the Perfect Baby,” 03.05.2015).

One area of CRISPR research that has gained a lot of attention recently is the development of gene drive technology, which may give humans the power to modify or even exterminate entire species in the wild. According to evolutionary biologist and gene drive pioneer Kevin Esvelt, the purpose of a gene drive is to use CRISPR to override the traditional rules of Mendelian inheritance and introduce a genetic change in organisms that will be passed down to nearly all of its descendants (The New Yorker, “Rewriting the Code of Life,” 01.02.2017).

In a typical situation, a parent organism can only pass down its genome to half of its offspring as per the rules of inheritance discovered by Gregor Mendel, the father of modern genetics. As a result, even if scientists were able to genetically modify organisms in the past, they would still encounter immense difficulty in forcing specific genetic changes across an entire population. With gene drive, however, that 50-50 chance of inheritance can skyrocket to as high as 99 percent (Bulletin of the Atomic Scientists, “Gene Drives: The Good, the Bad, and the Hype,” 10.14.2016). This, of course, has groundbreaking implications.

“The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species… [G]ene drives will be capable of influencing entire ecosystems for good or for ill,” stated Esvelt when he first introduced the possibility of using CRISPR to develop gene drives (eLife, “Emerging Technology: Concerning RNA-guided Gene Drives for the Alteration of Wild Populations,” 07.17.2014).

We possess the technology to change the world’s ecosystems, but does that mean we should use it? Many people certainly seem to think so, and the proposed benefits seem irrefutable. For instance, one innovative project currently underway is the use of gene drives to eliminate malaria from mosquitoes. Scientists are working on genetically modifying the Anopheles gambiae mosquito, a species known for spreading the malaria parasite, so that the female mosquitoes become sterile (NPR, “To Fight Malaria, Scientists Try Genetic Engineering to Wipe Out Mosquitoes,” 12.14.2016). That way, once these modified mosquitoes are released into the wild, they can breed with other members of their species and effectively die off. Other scientists are looking towards using gene drive to wipe out invasive species and save endangered native animals.

Esvelt himself has become heavily involved in gene drive technology (The New Yorker). His current project aims to reduce the rate of Lyme disease on Nantucket Island in Massachusetts by genetically modifying the island’s white-footed mice to become immune to the disease. Then, ticks will be unable to transfer the bacteria that cause the disease, and the entire transmission cycle will collapse.

However, as promising as all this may sound, it’s doubtful that gene drives will provide a lasting, viable solution. In fact, it’s possible that this technology allows scientists to deal with these serious issues in the wrong way. We may have become too infatuated with how sleek and shiny CRISPR appears to consider better, less risky solutions.

For one thing, ecosystems aren’t so simple that we can just inject new variants of a species into the wild and expect everything to go exactly as we planned. There are too many nebulous factors involved for scientists to be able to correctly predict the outcome of every ecological experiment. One of the test subjects may escape into a different environment or a completely unrelated species may become caught in the crossfire. Most of the time, as Esvelt notes, the gene drive may have little to no effect on the ecosystem at all. Ultimately, it’s arrogant to treat the ecosystem like a math problem with a simple, clean answer.

Even Esvelt seems aware of these limitations, stating, “Let me be the first to say that we do not understand how ecosystems work. They are fantastically complex” (YouTube, “Kevin Esvelt: Open until Dangerous: Gene Drive and the Case for Reforming Research to Reduce,” 06.17.2017).

As if affirming this admittance of ignorance, nature itself seems to have knocked gene drive down several pegs. According to a recent report by population geneticist Philipp Messer, the genetically modified mosquitoes that the team designed to pass down an infertility mutation to all their off- spring started developing a resistance to the gene drive (Nature, “Gene Drives Thwarted by Emergence of Resistant Organisms,” 01.31.2017). In other words, gene drives may not be the permanent solution that many people claimed it to be. “In the long run, even with a gene drive, evolution wins in the end,” Esvelt commented in response to the news (The Atlantic, “When Evolution Fights Back Against Genetic Engineering,” 09.12.2016).

But that’s not even the worst part. Upon creating a detailed mathematical model that describes what happens when genetically modified organisms are released, Esvelt discovered that the chances of altered genes spreading to unintended parts of the ecosystem were much higher than he originally predicted (The New York Times, “‘Gene Drives’ are Too Risky for Field Trials, Scientists Say,” 11.16.2017).

“I [feel] like I’ve blown it … [Championing this idea was] an embarrassing mistake,” Esvelt admitted.

To be honest, the entire idea of gene drives seemed faulty to begin with, mainly because the desired population modifications were not introduced naturally. Instead of working hand-in-hand with evolution, gene drives attempt to solve ecological problems by simply creating more unsustainable arms races akin to the one we have between antibiotics and bacterial diseases. For instance, even if gene drives eradicated a species of mosquitoes that spread malaria, it wouldn’t be long before a different species of mosquitoes eventually emerged that can spread the bacteria to human hosts.

Instead of making sudden, irreversible changes to the ecosystem, a much more reasonable solution is the one offered by evolutionary biologist Dr. Sharon Moalem in his book “The Survival of the Sickest.” In it, Dr. Moalem describes how the best way to combat diseases like malaria is to change the conditions of the environment so that the nature of the disease evolves in a way that works in our favor. For example, consider how the widespread use of mosquito nets would not only stop mosquitoes from infecting humans but essentially invalidate mosquitoes in general as vectors for the disease. As a result, evolution may provide an alternative way for malaria to spread, perhaps one that wouldn’t cause the parasite to completely incapacitate the body and instead only slightly weaken it so that the disease can spread similarly to the common cold.

Rather than risk a high-stakes gamble on gene-editing technology, it may be wiser in the long run to contemplate less invasive methods to solve our ecological problems. Humans don’t have a great track record to begin with, after all.

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