They say the night gets darker just before dawn breaks. If so, we are indeed on the eve, however dark it is.
We are also in Italy on the eve of a third wave, as in the UK and Germany. Two more contagious variants of SARS-CoV-2 from the UK and South Africa will make matters worse before mass vaccination (mixed with MRNA and traditional vaccines) improves them.
But, if, as mentioned, the darkness anticipates dawn, let's try to imagine the full light of the day to come. Not just the first rays: even the intense midday sun.
The defeat of Covid could be just the beginning. It is conceivable that the same weapons used to defeat Covid-19, mRNA vaccines, can also defeat the cruelest killers. Even cancer, which kills nearly 10 million people a year.
MRNA vaccines: born yesterday, used today
The most promising Covid vaccines use nucleic acids called messenger RNA or mRNA. We currently have two: one from the German company BionTech SE and its US partner Pfizer Inc. The other is from the US company Modern. Among the other mRNA vaccines on the horizon is another German, CureVac NV.
Unlike mRNA vaccines, ordinary ones tend to be inactivated or weakened viruses which, when injected into the body, stimulate an immune response that can subsequently protect against the live pathogen.
But the production process of such vaccines requires various chemicals and cell cultures - this takes time and presents risks of contamination.
MRNA vaccines do not have these problems. They instruct the body to make the offending proteins, in this case the ones that envelop the SARS-CoV-2 viral RNA. The immune system then relies on these antigens, exercising for the day when the same proteins show up with the coronavirus "on their backs".
Here lies the greatest promise of mRNA: it can tell our cells to make whatever protein we want. Also antigens from many other diseases besides Covid-19.
How mRNA vaccines work
In its daily function, mRNA receives instructions from its molecular cousin, the DNA in the nuclei of our cells. Tracts of the genome are copied, which the mRNA carries to the cytoplasm, where small cell factories called ribosomes use the information to churn out proteins.
BioNTech and Moderna shortened this process, skipping the whole complicated thing in the nucleus with DNA. Instead, they first figure out which protein they want, then they examine the amino acid sequence that this protein produces. From this derive the precise instructions that mRNA must give.
A process that can be relatively fast, which is why it took less than a year to produce the vaccines, a rate previously unimaginable.
It is also genetically safe: mRNA cannot go back into the nucleus and accidentally insert genes into our DNA.
A weapon against all the "bad guys"?
Researchers have felt for nearly 50 years that it will be possible to use this technique to fight all kinds of diseases. As is usual in science, it takes enormous amounts of money, time and patience to solve all intermediate problems.
After a decade of initial enthusiasm, mRNA had become academically unfashionable in the 90s. Progress seemed to have stopped. The main obstacle was that mRNA vaccines tested on animals often caused fatal inflammation.
Katalin Kariko, the Hungarian scientist who emigrated to the USA in the 80s and is now in the process of competing for the Nobel Prize, has dedicated her entire career to mRNA, through ups and downs. In the 90s, it lost its funds, got demoted, suffered a pay cut and other setbacks.
But it remained standing. And then, after battling cancer herself, she made the turning point.
Cancer in the crosshairs
In the 2000s, Katalin Kariko and her research partner realized that replacing uridine, one of the "letters" of mRNA, avoided causing inflammation and did not compromise the genetic code. The mice remained alive.
The study of the female doctor was read by a Stanford University scientist, Derrick Rossi, who later co-founded Moderna. The same study was also the inspiration for Ugur Sahin e Ozlem Tureci, the two husband and wife oncologists and co-founders of BioNTech. The latter licensed Katalin Kariko's technology and even hired it. Not to fight the pandemic, which wasn't there at the time. They hired her to fight cancer.
One day the current weapons against cancer will seem like a primitive idea.
Bombarding a tumor with chemicals or radiation also damages other tissues. It will remind us of the dentists of the Far West, who extracted teeth without anesthesia, or at most by giving the patient a glass of whiskey.
The best way to fight cancer, Sahin and Tureci realized, is to treat each tumor as genetically unique and train individual patients' immune systems against that specific enemy. A perfect job for mRNA vaccines.
You find the antigen, get its fingerprint, decode the cellular instructions to target the culprit and let the body do the rest.
A look at Moderna and BioNTech's working agendas? They include drug trials for the treatment of cancers of the breast, prostate, skin, pancreas, brain, lungs, and other tissues, as well as mRNA vaccines against everything from influenza to Zika and rabies.
The outlook looks good.
Progress, it is true, has been slow. Part of the explanation Sahin and Tureci give is that investors in this sector have to put up large amounts of capital and then wait for more than a decade: first for research, then for regulatory approvals.
Covid could accelerate all these processes. The pandemic has led to the great debut of mRNA vaccines and their definitive proof of concept (which corresponds almost to the same in vivo experimentation). From now on, mRNA will have no problem getting money, attention or enthusiasm from investors, regulators, and policy makers.
This obviously doesn't mean the last mile of mRNA vaccines will be easy.
