By Andreas Kluth
The night is darker just before dawn, they say. It is certainly dark now. The more contagious variants of SARS-CoV-2 from the UK and South Africa will make the pandemic worse before mass vaccination can make it better.
But take another look at some of these new vaccines. And then contemplate the dawn to come – not just your first rays in the coming months, but also the bright light of the coming years and decades. It seems increasingly plausible that the same weapons we will use to defeat Covid-19 could also defeat even more grim reapers – including cancer, which kills almost 10 million people a year.
The most promising Covid vaccines use nucleic acids called messenger RNA, or mRNA. One vaccine comes from the German company BioNTech SE and its American partner Pfizer Inc. The other is from the American company Moderna Inc. (its original spelling was ModeRNA, its ticker is MRNA). Another is coming from CureVac NV, also based in Germany.
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Common vaccines tend to be inactivated or weakened viruses that, when injected into the body, stimulate an immune response that can later protect against the live pathogen. But the process of making these vaccines requires several chemicals and cell cultures. This takes time and offers opportunities for contamination.
MRNA vaccines do not have these problems. They instruct the body itself to produce the aggressive proteins – in this case, those that involve SARS-CoV-2 viral RNA. The immune system then targets these antigens, practicing for the day when the same proteins appear with the coronavirus attached.
That’s where mRNA’s greatest promise lies: it can tell our cells to make any protein we want. This includes antigens from many other diseases besides Covid-19.
In its day-to-day function, mRNA receives instructions from its molecular cousin, the DNA in the nucleus of our cells. Excerpts from the genome are copied, which the mRNA carries into the cytoplasm, where small cell factories called ribosomes use the information to produce proteins.
BioNTech and Moderna abbreviate this process, skipping all the confusion in the nucleus with DNA. Instead, they first find out which protein they want – for example, a peak in the cap around a virus. Then, they examine the amino acid sequence that makes up this protein. From this they derive the precise instructions that the mRNA must give.
This process can be relatively quick, so it took less than a year to make the vaccines, a previously unimaginable pace. It is also genetically safe – mRNA cannot go back to the nucleus and accidentally insert genes into our DNA.
Researchers since the 1970s have a hunch that you can use this technique to fight all types of diseases. But, as usual in science, you need a lot of money, time and patience to solve all the intermediary problems. After a decade of enthusiasm, mRNA became academically out of fashion in the 1990s. Progress seemed to be faltering. The main obstacle was that the injection of mRNA in animals used to cause fatal inflammation.
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Enter Katalin Kariko – a Hungarian scientist who immigrated to the United States in the 1980s and heroically dedicated her entire career to mRNA, in its ups and downs. In the 1990s, she lost her financing, was demoted, had her salary reduced and suffered other setbacks. But she persisted. And then, after battling cancer, she made the crucial discovery.
In the 2000s, she and her research partner realized that changing uridine, one of the “letters” in mRNA, avoided causing inflammation without compromising the code otherwise. The rats remained alive.
His study was read by a Stanford University scientist, Derrick Rossi, who later co-founded Moderna. It also caught the attention of Ugur Sahin and Ozlem Tureci, two oncologists who are husband and wife and co-founders of BioNTech. They licensed Kariko’s technology and hired it. From the beginning, they were more interested in curing cancer.
Today’s weapons against cancer will one day seem as primitive as flint axes in an operating room. To kill a malignant tumor, you usually eliminate it with radiation or chemicals, damaging many other tissues in the process.
The best way to fight cancer, Sahin and Tureci realized, is to treat each tumor as genetically unique and to train the immune systems of individual patients against that specific enemy. A perfect job for mRNA. You find the antigen, get your fingerprint, reverse engineer cell instructions to target the culprit and let the body do the rest.
Take a look at the pipelines from Moderna and BioNTech. They include drug tests for the treatment of cancer of the breast, prostate, skin, pancreas, brain, lung and other tissues, as well as vaccines against everything from flu to zika and rabies. The prospects look good.
Read also: Experimental mRNA vaccines surface as Covid-19 pandemic increases
Progress, admittedly, has been slow. Part of the explanation that Sahin and Tureci give is that investors in this sector must invest a lot of capital and then wait more than a decade, first for tests and then for regulatory approvals. In the past, few were in the mood.
Covid-19, with his fingers crossed, can boost all these processes. The pandemic led to a major debut of mRNA vaccines and their definitive proof of concept. Already, there are murmurs about a Nobel Prize for Kariko. Henceforth, mRNA will have no problem getting money, attention or enthusiasm – from investors, regulators and legislators.
This does not mean that the last stretch will be easy. But in this dark hour, you are allowed to enjoy the light that is being born.