The Nobel-awarded science that hides in the latest Spider-Man movie

In the latest film of Spider-Man, an absolute hit this summer, we are presented with a downcast superhero, Peter Parker (the alter ego of Spiderman), with unbearable physical pain and unexpected changes in his body. As often happens in stories of dystopian worlds and superpowered heroes, we can wonder if the plot has sparks of reality, that is, if it is based on scientific evidence even if exaggerated, or if it is totally implausible. As a researcher myself, I often lament that screenwriters do not consult scientists to make their plots more plausible and prefer to invent them. Precisely the difference between fantasy and science fiction is this: whether there is any scientific evidence to support the plot. In the case of Spider-Man: brand new day, the script has a bit of everything.

First of all, we are told that the protagonist's physical changes are due to the fact that the spider DNA incorporated into his genome evolves very rapidly and affects his entire body. This cannot be the case for two important reasons: the first is that it is impossible for a one-off process, such as a spider bite, to transmit foreign DNA to all the cells in the body, from muscles to neurons, from silk-producing glands to the eye. We do not have any technology nor do we know of any virus or mechanism to effectively infect billions of cells. But, of course, we will have to accept this because otherwise, Spiderman would not exist. Agreed. Now comes the second question, which is crucial for this film: the much faster evolution of the arachnid DNA. This is also not true, since once a fragment of DNA is incorporated into a chromosome, the cell makes no distinctions and treats it as its own. That is to say: it duplicates, mutates, and repairs like the rest of human DNA, because there is no difference between the two. This makes us raise an eyebrow. However, it turns out that the next part of the plot, which is the attempt to silence –or at least, control and diminish the effect– of those arachnid genes that Spiderman does not want, does have solid scientific evidence behind it. In fact, it is based on a Nobel Prize, the one for Physiology or Medicine in 2006!

The real science of Spider-Man

Let's take it step by step. In the movie, Peter Parker talks to Dr. Bruce Banner, who is also a superhero (Hulk). Dr. Banner is a scientist and is looking for a way to control when and how he transforms, deciding that the best thing is to "silence" the genes, the genetic instructions that are activated when he turns into a superhero. The way he does this is by means of small interfering RNA (in science, the acronym is siRNA). Peter Parker sees the light, and asks if these siRNAs are very specific, so that he can "silence" only the genes he is interested in—the spider ones—at will. Well, siRNAs are a very efficient way to silence genes. We have been using them in the laboratory for years precisely to decrease the function of a specific gene. In addition, there are various precision therapies to treat rare diseases, approved by the United States FDA, based on siRNA. The first approval was about seven years ago, to treat a rare transthyretin amyloidosis disease of the liver that affects about 50,000 people worldwide. The success of this therapy has allowed other similar ones to be approved as well.

But what is the function of siRNAs? Why are they effective? Genes are DNA sequences. To perform their function, "photocopies" are generated in RNA format, called messenger RNA, which is dynamic and can be transported and read. In fact, messenger RNA must be read and translated into proteins, which are what actually perform the function within cells. Messenger RNA has a short life; it is used and degraded, and thus the cell can control how much protein it needs of each type.

Among the control mechanisms for the amount of RNA needed, there is a selective degradation mechanism using very short RNAs. We have several short ones that bind very specifically to messenger RNAs; when they do, it is as if we marked them with a post-it that says “degrade me” and the cell takes care of doing so so that they cannot be translated into proteins. siRNAs are the artificial way we have to “simulate” these natural short RNAs, they are substitutes for what works naturally in the cell, and they cause the degradation of these unwanted messenger RNAs. In precision gene therapies with siRNA, the messenger RNAs that cause the disease are degraded and we do not let them make protein. siRNAs would be gene switches: if siRNA is present, the target genes are silenced; if they are not there, the genes are expressed. In Peter Parker's case, these siRNAs would block the production of spider proteins and allow him to preserve his humanity, the expression of human genes over spider ones.

Although the basis of the argument is scientifically solid, as you can imagine, the action of siRNAs is not as simple as it seems. In the first place, we do not know how to reach all the cells in the body. And, secondly, the effect of siRNAs does not allow for an immediate response; there is a time lag both when they act, silencing genes, and when they stop having their effect. However, and in perspective, science has provided a brilliant “plot device” that has reached many viewers. Therefore, long live science in the movies!