Since the american pharmaceutical companies Pfizer and Moderna developed their own vaccines against Covid-19 using mRna technology, the criticisms and doubts didn’t wait to come. Among the many, one of the most relevant concerns is about the speed of development. How is it possible that these vaccines are safe and reliable if the technology behind them has never been tested before? The answer is simple: mRna vaccines are not a last-minute discovery, but the result of the combination of numerous studies, three in particular, which began as early as 1960’. In these 60 years, the path that has led to today's triumph has been anything but roses and flowers.
But let's go in order. First of all, what is mRna? Messenger RNA is the molecule, discovered in 1960, which acts as an intermediary between DNA, the string of instructions for producing proteins in the heart of the cell, and the factories of the actual proteins, cellular structures called ribosomes. The messenger molecule, mRNA, carries copies of transcribed DNA segments to the ribosomes, where these instructions are translated.
All very interesting. But why and how can mRna be crucial in the production of vaccines? Up to now, commercial vaccines have used modified viruses or fragments of them to train the immune system to attack invading pathogens. An mRna vaccine, on the other hand, would carry instructions to teach the body to produce its own viral proteins, an approach that mimics the infection more precisely and therefore should generate a better immune response.
On paper, the idea is simple and amazing. However, the reasons that over the years have led to a lack of interest in messenger RNA lie in the practical difficulties. Indeed, isolating mRNA from cells is impossible without it completely degrading. A first breakthrough came in 1984, when Harvard biologist Doug Melton discovered how to reproduce mRNA in the laboratory, but the problem was anyway its delicacy.
Furthermore, the attempt to produce synthetic mRna useful in the fight against certain diseases collides with the strong and efficient machine that our body is. Perceived as foreign, synthetic mRna stimulates inflammatory reactions and is rejected, unable to reach the cells. We have to wait until 2005 for the solution to this thorny problem. The Hungarian biologist Katlin Karikò and the colleague of the University of Pennsylvania Drew Weissmann discover that modifying a "letter" of the mRNA inhibits the problematic immune reaction. The mRNA manages to escape the control mechanisms and reach the cells. We are at a turning point.
Even though mRNA is now protected from cell rejection, it needs to be able to deliver it intact to the cells themselves. In the 1990s, a team of biochemists from Inex, a Vancouver company founded by Pieter Cullis, pursued this goal by working with lipid membranes the size of one-hundredth of a cell. It's not easy: human cells have a defense system that prevents anything other than their food from gaining access. Furthermore, some lipids have electrical charges that destroy the cell membrane immediately after contact. However, Cullis and colleagues discover how to manipulate the electrical charge of these lipid envelopes so that their toxicity vanishes once they enter the blood.
At this point the recipe is almost ready. The last missing ingredient is the precise code to be provided to the cells to start producing the protein capable of triggering the necessary immune response. In the case of Covid-19, as for other coronaviruses, the one you want to produce is the spike protein, which is the hook-shaped atomic structure that the virus uses to invade cells. Thanks to the studies by researchers McLellan and Graham on other coronaviruses, such as MERS, it is now possible to trace exactly the section of code inherent to the spike protein, inserting the appropriate modifications in order to stabilize the mutations.
When at dawn on December 31, 2019, a mysterious pneumonia from Wuhan knocks on the door, every piece is in its place, ready to be exploited. In less than one year, Pfizer and Moderna deliver two extremely effective vaccines against Covid-19, both using the mRna technology. The mRna vaccines are born from the combination of studies and efforts that have lasted for 60 years. It is too early to predict the effects that this technology has brought with it, but what is certain is that we are facing a new era of medicine.