Filenews 11 January 2021
By Andreas Kluth
The deepest darkness is just before dawn, as it's called. Things are no doubt quite dark right now. The most contagious variants of SARS-CoV-2 spread from the UK to South Africa will exacerbate the pandemic before mass vaccination can improve the situation.
Take a look at some of the new vaccines, however. And then think of the dawn that will come - not only the first "rays" of the sun in the coming months, but also the bright light of future years and decades. It seems increasingly likely that the same weapons we will use to defeat the Covid-19 can also neutralize even the most grim "reapers" of human lives - including cancer, which kills nearly 10 million people a year.
The scientific revolution of mRNA
The most promising vaccines against Covid use nucleic acids called messenger RNA (mRNA). One of these comes from the German company BioNTech and its American partner, Pfizer. The other comes from the American company Moderna (the original spelling of its name was ModernA, while its abbreviation is MRNA). Another one is on its way from CureVac, which is also based in Germany.
Common vaccines tend to be inactivated or weakened, which, when injected into the body, stimulate an immune response that can later protect against the living pathogen. However, the process of receiving such vaccines requires various chemicals and cell cultures. This takes time and creates a risk of infection in the meantime.
MRNA vaccines do not have such problems. They teach the body itself to make the offensive proteins - in this case, those that "wrap" sars-coV-2's RNA virus. The immune system then nests inside these antigens, practicing for the day when the same proteins will appear with the corovirus attached to them.
That's where the biggest promise of mRNA lies: it can invite our cells to produce whatever protein we want. This includes antigens of many diseases other than Covid-19.
In its daily function, mRNA gets instructions from its molecular cousin, dna in the nuclei of our cells. Parts of the genome are thus copied, which mRNA transfers to the cytoplasm, where small cell factories called ribosomes use the information to produce proteins.
BioNTech and Moderna shortened this process, bypassing the entire complex business to the core with DNA. Instead, first they understand what protein they want - for example, a spike in the "coat" around a virus. They then examine the sequence of amino acids that produce this protein. From this they draw the exact instructions that mRNA should give.
This process can be relatively quick, so it took less than a year to produce the vaccines, which was previously unthinkable. It is also genetically safe - mRNA cannot return to the nucleus and introduce the wrong genes into our DNA.
Researchers from the 1970s had evidence that one can use this technique to fight all kinds of diseases. But as is usually the case in science, it takes huge sums of money, time and patience to solve all the intermediate problems.
After a decade of excitement, mRNA fell academically into disfacing in the 1990s. Progress seemed to stop. The main obstacle was that injecting mRNA into animals often caused fatal inflammation.
Katalin Kariko's path to the "desert"
It was there that Katalin Kariko - a Hungarian scientist who emigrated to the US in the 1980s and heroically devoted her entire career to mRNA, despite the relative "ups and downs". In the 1990s, she lost her funding, was demoted, saw a reduction in her salary and suffered other blows. However, she remained attached to it. Then, after a battle she fought with cancer herself, she made the crucial discovery.
In the 2000s, she and her research associate realized that removing uridine, one of the "letters" of mRNA, was enough to avoid inflammation without compromising the code. The mice stayed alive.
Her study was read by a scientist at Stanford University, Derrick Rossi, who was later co-founder of Moderna. It also came to the attention of Ugur Sahin and Ozlem Tureci, two oncologists who are spouses and co-founders of BioNTech. They licensed Kariko's technology and hired her. From the beginning, they were more interested in the treatment of cancer.
Today's cancer weapons will once look primitive, like silicon axes in an operating room. To kill a malignant tumor, it generally affects it with radiation or chemicals, while destroying many other tissues in the process.
Investors will no longer hesitate
The best way to fight cancer, as Sahin and Tureci realized, is to treat each tumor as genetically unique and to train each individual patient's immune system against that particular enemy. A perfect job for mRNA. You find the antigen, take its fingerprint, reverse the cellular instructions to target the "guilty" and let the body do the rest.
Take a look at Moderna and BioNTech's research. They include drug trials to treat cancers of the breast, prostate, skin, pancreas, brain, lung and other tissues, as well as vaccines against all types of disease, from influenza to that caused by the Zika virus and rabies. The prospects look good.
Progress, of course, has been slow. Part of the explanation given by Sahin and Tureci is that investors in this area must have a lot of capital and then wait more than a decade, first for clinical trials and then for regulatory approvals. In the past, very few were in a similar mood.
The Covid-19 could eject the speed of all these procedures. The pandemic led to a major debut of mRNA vaccines and definitive proof of the validity of their idea. Already, there are "whispers" about a Nobel Prize in Kariko. From now on, mRNA will have no problem receiving money, attention or excitement - from investors, regulators and policy makers.
This does not mean that this latest phase of development of this technology will be easy. However, in this dark hour, one is allowed to enjoy the light that faints at the end of the tunnel.
Source: BloombergOpinion
