By Andreas Kluth
They say the night is darker just before dawn. It was certainly right now. The most contagious variants of SARS-CoV-2 coming out of the UK and South Africa will make the pandemic worse before mass vaccination can improve it.
But look again at some of these new vaccines. And then he contemplates the dawn that will come, not only the first rays of the coming months, but also the bright light of the coming years and decades. It seems increasingly likely that the same weapons we will use to defeat Covid-19 can also defeat even the heaviest reapers, including cancer, which kills nearly 10 million people a year.
The most promising Covid vaccines use nucleic acids called messenger RNA or mRNA. A vaccine comes from the German company BioNTech SE and its American partner Pfizer Inc. The other comes from the American company Moderna Inc. (its original spelling was ModeRNA, its ticker is MRNA). Another is on its way to CureVac NV, also based in Germany.
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Ordinary vaccines are usually inactivated or weakened viruses that, when injected into the body, stimulate an immune response that can subsequently protect against the living pathogen. But the process of making these vaccines requires various chemicals and cell cultures. This takes time and provides opportunities for pollution.
MRNA vaccines do not have these problems. They instruct the body itself to make the offensive proteins, in this case, those that surround the SARS-CoV-2 viral RNA. The immune system then hosts these antigens, practicing the day the same proteins appear with the coronavirus attached.
Herein lies the greatest promise of mRNA: it can tell our cells to make the protein we want. This includes antigens from many other diseases in addition to Covid-19.
In its daily function, mRNA takes instructions from its molecular cousin, the DNA of our cell nuclei. The sections of the genome, which the mRNA transports to the cytoplasm, are copied, where small cell factories called ribosomes use the information to produce proteins.
BioNTech and Moderna shorten this process by skipping the whole complicated core business with DNA. Instead, they first find out what protein they want, for example, a tip in the shelter around a virus. They then observe the amino acid sequence that this protein makes. From this derive the precise instructions that the mRNA must give.
This process can be relatively quick, which is why it took less than a year to make the vaccines, a pace that until now was unimaginable. It is also genetically safe: mRNA cannot return to the nucleus and insert anything accidentally into our DNA.
Since the 1970s, researchers have had the intuition that you can use this technique to fight all kinds of diseases. But, as is usual in science, large sums of money, time and patience are needed to solve all the intermediate problems. After a decade of enthusiasm, mRNA went out of fashion academically in the 1990s. Progress seemed to stop. The main obstacle was that injecting mRNA into animals often caused fatal inflammation.
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Enter Katalin Kariko, a Hungarian scientist who emigrated to the United States in the 1980s and who has heroically dedicated her entire career to mRNA, through its ups and downs. In the 1990s, she lost her funding, was degraded, had her salary cut, and suffered other setbacks. But he stayed with her. And then, after fighting herself, she made the crucial breakthrough.
In the 2000s, she and her research partner realized that the exchange of uridine, one of the “letters” of the mRNA, avoided causing inflammation without compromising the code. The mice were kept alive.
His study was read by a Stanford University scientist, Derrick Rossi, who later co-founded Modern. It also came to the attention of Ugur Sahin and Ozlem Tureci, two oncologists who are husband and wife and co-founder of BioNTech. They licensed Kariko’s technology and hired her. From the beginning, they were more interested in curing cancer.
Today’s anti-cancer weapons will one day seem like such a primitive idea as flint axes in an operating room. To kill a malignant tumor, usually remove it with radiation or chemicals, damaging many other tissues in the process.
Sahin and Tureci understood that the best way to fight cancer is to treat each tumor as genetically unique and train each patient’s immune system against that specific enemy. A perfect job for mRNA. You’ll find the antigen, get your fingerprint, reverse the cellular instructions to target the culprit and let the body do the rest.
Check out the Modern and BioNTech pipes. They include drug trials to treat cancers of the breast, prostate, skin, pancreas, brain, lung and other tissues, as well as vaccines against everything from the flu to zika and rabies. The outlook looks good.
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It is true that progress has been slow. Part of the explanation given by Sahin and Tureci is that investors in this sector must place masses of capital and then wait more than a decade, first for trials and then to obtain regulatory approvals. In the past, too few were in the mood.
The Covid-19, with its fingers crossed, can turbo-charge all these processes. The pandemic has led to a major debut of mRNA vaccines and their definitive proof of concept. There are already rumors about a Nobel Prize for Kariko. From now on, mRNA will have no problem getting money, attention or enthusiasm, from investors, regulators and policymakers.
This is not to say that the last stretch is easy. But in this dark hour, it is allowed to enjoy the light that is glimpsed.