CRISPR Rampage

The news is constantly spinning with scientific discovery. New technologies, medical treatments — the list is endless. But less often does the discovery feel personal.

The recent introduction of CRISPR to the scientific community, in my mind, had that feel. Short for Clustered Regularly Interspaced Short Palindromic Repeats, this technology makes it possible to edit the genome. Suddenly, science has the ability to change the very substance that makes us human.

The power to edit genes is a monumental scientific advancement, introducing a whirlwind of research possibilities. Science fiction has not disappointed in depicting, rather dramatically, its own version of this scientific endeavor. The movie Rampage (2018), directed by Brad Peyton, considers the consequences of gene manipulation, as the rogue organization Energyne uses gene-editing technology to create enormous 50-foot-tall crazed animals. A wolf with wings, an oversized albino gorilla, and a crocodile with rhino-like features team up to lay the smackdown (if you’re counting, that’s Dwayne “The Rock” Johnson reference #1) on the city of Chicago. The movie provides an origin story for these creatures, who first came to light in the 1986 arcade classic and continued their rampage in a series of sequels across a multitude of video game consoles.

Naturally, the threat of gigantic beasts is one that only Dwayne Johnson can solve. His character, Davis Okoye, embarks on a rescue mission with a geneticist, Dr. Kate Caldwell (Naomie Harris), to discover what happened to these animals and how to save the day when the city of Chicago seems to have hit rock bottom (Rock reference #2). His quest is largely motivated by his close relationship with the newly enormous gorilla, George, whom he saved from poachers and befriended as part of his work as a primatologist.

Changing an animal’s size, features, and demeanor couldn’t be accomplished by modifying a single gene, so one might conclude that Rampage is a blatant misrepresentation of CRISPR technology. But for me this is a point of contention. If we’re concerned about misrepresenting science in movies, then we need to discuss the possibility that CRISPR is misrepresented by scientists a bit too, in their own efforts to communicate with the public.

There’s been a lot of hype from scientists about using this technology to cure diseases that affect humans, including Cystic Fibrosis and Huntington’s Disease. However, despite these claims, we have no idea if CRISPR can successfully be used to treat anything. While the theory is conceptually sound, it wasn’t until very recently that He Jankui, a scientist in China, reportedly used CRISPR to edit the genes of twins born in December of 2018, to make their cells resistant to HIV — the first known use of CRISPR in humans. Contrary to the positive hype about therapeutic applications, many scientists reacted to that news by arguing that the technology wasn’t yet ready for clinical use. This led to an outcry of harsh criticism of the Chinese scientist’s work from many in the scientific community.

In addition, scientific reports suggest that we have less control over gene editing than we thought. So while we may not edit the genome and accidentally make a hyper-violent mutant gorilla, it also may not be accurate to say that we can treat a super-specific problem, like a disease, without raising the possibility of incidental cognitive, physical, or other alterations.

Maybe, just maybe, these are exactly the kind of unforeseen consequences that Rampage was trying to bring to our attention. In the universe of the film, Dr. Caldwell is a key contributor to the development of CRISPR technology. She’s motivated by the hope of helping her brother, who has been diagnosed with cancer. But in trying to help him by advancing this technology, a totally valiant and feasible goal, she sets the stage for Energyne to design a biological weapon. The company fires her, takes her design, and alters it to create these massive creatures.

In Caldwell’s pursuit of a real-life scientific goal, ripped from the headlines, something negative and unforeseen happens. Today’s CRISPR scientists may not be facing fantastical beasts laying waste to their laboratories, but Rampage demonstrates that unexpected outcomes can occur irrespective of the worthiness of the goal. The nefarious actions of Energyne serve to show that once a pathbreaking technology is available, it’s difficult to say how and when it will be used. Thus, scientists must know their role (Rock reference #3) and understand that their work can quickly extend beyond the lab bench. And if they’re upset by how He Jankui used CRISPR in humans for a rational medical goal, they must anticipate that other potentially more objectionable efforts may also arise from their research endeavors.

Speaking as a neuroscientist, I think it’s okay to develop these new types of technologies without knowing the precise outcomes. But taking the time to consider the possibilities, and being willing to accept responsibility for them, will help guide the development process in ways that can make negative outcomes less likely. Whether this means that scientists take slower and smaller steps forward when designing and testing these new technologies in the lab, or that they dedicate more mental energy and funding to addressing the possible technological and ethical implications of their work, remain open questions. New external committees, like the one recently formed by the World Health Organization, can also establish guidelines for the editing of human DNA, helping to provide research oversight moving forward.

George, the gorilla, is ultimately saved and returned back to his gentle demeanor, but his titanic size proves irreversible. This exemplifies the potential long-term, permanent consequences of CRISPR on individuals, families, and communities. Similarly, this initial use of CRISPR in humans in China is likely the first opportunity to see the real downstream, long-term effects of using this technology on the human genome. It’s also probably our only opportunity, for a while, to evaluate whether this technology has the curative abilities that its advocates have promised. And perhaps will serve as a wake up call for scientists advocating for CRISPR who may be playing a little fast and loose with its potential real-world effects.

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