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

At the last movie of Spider-Man, absolute success this summer, we are presented with a downcast superhero, Peter Parker (thealter ego of Spiderman), with unbearable physical pain and unexpected changes in the body. As often happens in stories of dystopian worlds and superpowered heroes, we can ask ourselves if the plot has sparks of reality, that is to say, if it is based on scientific evidence even if exaggerated, or if it is totally implausible. As a researcher, I often regret 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 that supports the plot. In the case of Spider-Man: brand new day, in the script there is a little 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-time process, such as a spider bite, to transmit foreign DNA to every cell in the body, from muscles to neurons, from silk-producing glands to the eye. We have no technology nor do we know of any virus or mechanism to effectively infect trillions of cells. But, of course, we will have to accept this because otherwise, there would be no Spiderman. Agreed. Now comes the second issue, which is crucial for this film: the much faster evolution of 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 if it were 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 DNAs. This makes us turn up our noses. Now, 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 these arachnid genes that Spiderman does not want, it does have solid scientific evidence behind it. In fact, it is based on a Nobel Prize, the one for Physiology and Medicine in the year 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 looks 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 becomes a superhero. The way he does it 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. Furthermore, there are several 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 in the liver that affects about 50,000 people worldwide. The success of this therapy has allowed others similar to it to also be approved.

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 the ones that actually perform the function within the 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.

Within the control mechanisms of how much RNA quantity is needed, there is a selective degradation mechanism through the use of 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 messenger RNAs that we do not want. 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 those of the spider.

Although the basis of the argument is scientifically sound, as you can imagine, the action of siRNAs is not as simple as it seems. Firstly, 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 lag time 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 a lot of viewers. Therefore, long live science in the movies!