The Science of SciFi: Rampage!

What happens when you use modern gene editing technology to revamp an 80s arcade game? A questionable film carried by Dwayne “The Rock” Johnson’s biceps and the CGI charisma of an albino gorilla.

The recent Warner Brothers film “Rampage” first caught my attention when The Rock tweeted this response to an article from the health news website Stat:

Now, I’m not usually one to rush to see movies about giant animals smashing things, but as a biochemist I was intrigued about the representation of CRISPR, a prevalent gene editing technique, in popular media. Not to mention, I was excited to watch Dr. Kate Caldwell (Naomie Harris) explain genetic engineering to a pistol-slinging secret government “cowboy” played by Jeffrey Dean Morgan.

Let’s take a minute to look at the science behind the three enormous beasts that terrorize Chicago in this film. The movie opens with a giant rat destroying the space station and an astronaut barely escaping with three “experiments” in heavy-duty containers. The astronaut dies in the crash, but the canisters somehow survive. They contain a pathogen specifically designed to infect its host with DNA that will accelerate growth, increase aggression, and insert other weaponizing traits. The pathogen works by using CRISPR, which the movie states many, many times.

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats, so it’s no wonder the movie never bothers to define the acronym or explain how it works. The name comes from a region of repeating bacterial DNA that researchers found to act as the bacteria’s defense against attacking viruses. The regions of DNA between each repeat contain virus DNA that work with a protein to identify invading viruses and cut their DNA so that they cannot harm the host bacteria.

Scientists are excited about CRISPR because it allows them to target ANY gene using just a short RNA sequence that can be made quickly and easily in the lab. Scientists can use CRISPR to cut a gene to make it inactive, but they can also get the DNA to repair itself in a way that inserts new DNA into the cut site. This is currently being explored to fix harmful genetic mutations or insert new genes where patients have damaged copies.

Helpful diagram of how CRISPR acts as a defense system from invading viruses. Figure from Ekaterina Pak’s article in Harvard blog Science in the News

As Dr. Caldwell explains in the movie, one of the challenges of using CRISPR technology to treat patients is that the gene editing machinery needs to get inside the cell to fix damaged DNA. Also, unless it is used in an embryo or tissue that is rapidly dividing and making new cells, there is no way for the new gene change to be passed on to more cells. This makes it virtually impossible to “fix” an entire organ or organism because you would need to edit all of the cells individually. In “Rampage”, however, Dr. Caldwell has been working with new technology that helps CRISPR machinery spread between cells, , although no details are provided.

How close are we to having “infectious” gene editing machines? The most interesting (and scary!) use of genetic engineering today is called gene drive. In gene drive, a gene of interest is inserted along with the CRISPR machinery. This machinery recognizes the target gene sequence, and during sexual reproduction the machinery will cut the matching chromosome from a non-modified parent and insert the new gene along with more CRISPR machinery. This creates offspring that will all have the mutation and pass it on for many generations until it is present in the whole population.

Adapted from DiCarlo et al. (2015) Nature Biotechnology

Scientists have proposed using CRISPR gene drive to spread malaria resistance genes at an accelerated rate through mosquito populations, essentially performing rapid forced evolution in nature. However, those same scientists have recently raised concerns about using gene drive to accelerate evolution due to the risk of spreading the trait outside its intended geographical population and out-of-control gene editing.

In a more scientifically accurate version of “Rampage”. The gene drive “pathogens” crash to earth, infecting many cells of many animals nearby. The infectivity is too low to cause serious physical changes in the exposed animals, but some of their gametes (eggs or sperm) become infected with the CRISPR gene drive machinery. These animals then have offspring that have one of the traits mentioned in the movie such as accelerated growth, aggression, porcupine spikes, sonar hearing – it is unlikely that the gene editing machinery could handle multiple mutated genes at once. These traits then spread through the population rapidly, leading to lots of giant gorillas or wolves with aggression problems, but unfortunately for viewers, these animals would probably not have the skills to level the city of Chicago.

The film gives us a good opportunity to think about important ethical questions surrounding CRISPR: Should we be able to make changes like this in nature or in the case of human disease? What are unintended consequences of manipulating evolution?

“Rampage” doesn’t discuss the benefits of CRISPR beyond Dr. Caldwell’s brief mention of gene therapy perhaps being able to help treat her ill brother, which makes me wonder what impression the movie makes on the public’s perception of science and ethics. I would like to think that “Rampage” simply brings awareness to an amazing recent scientific discovery. While I, like most scientists, always intend to do good with my research, I need to remember that what I do in the lab could potentially be dangerous or used for harm. That’s why it’s incredibly important for the media and for non-scientists to engage with scientific ethics, but these discussions are only useful when the public is accurately informed about the science at hand. While “Rampage” does a good job explaining difficult scientific concepts, I worry that its portrayal of scientists as maniacal anti-heroes interested in destruction and control undermines the goals of the real-life scientific community to use these tools for good.

By Kelsie Anson