The night is darkest just before dawn, they say. Dark is definitely right now. The more contagious variants of SARS-CoV-2 originating in the UK and South Africa will make the pandemic worse before mass vaccination can improve it.
But take another look at some of these new vaccines. And then gaze upon the coming dawn – not just its first rays in the months to come, but also the bright light of the years and decades to come. It seems increasingly plausible that the same weapons we’ll use to defeat Covid-19 could also defeat even darker Reapers – including cancer, which kills nearly 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 comes from the American company Moderna Inc. (its original spelling was ModeRNA, its symbol is MRNA). Another is on the way from CureVac NV, also based in Germany.
Regular vaccines tend to be inactivated or weakened viruses which, when injected into the body, stimulate an immune response that can later protect against the living pathogen. But the process of making such vaccines requires various chemicals and cell cultures. It takes time and offers possibilities for contamination.
MRNA vaccines do not have these problems. They ask the body itself to make the offending proteins – in this case, the ones that wrap around the SARS-CoV-2 viral RNA. The immune system then focuses on these antigens, practicing for the day the same proteins appear with the coronavirus attached.
This is where mRNA’s greatest promise lies: it can tell our cells to make whatever protein we want. This includes the antigens of many other diseases besides Covid-19.
In its daily function, mRNA takes instructions from its molecular cousin, DNA in our cell nuclei. Sections of the genome are copied, which the mRNA carries into the cytoplasm, where small cell factories called ribosomes use the information to make proteins.
BioNTech and Moderna shorten this process, skipping all the tedious business in the nucleus with DNA. Instead, they first determine what protein they want – for example, a spike on the coat around a virus. Then they look at the amino acid sequence that produces this protein. From there they derive the precise instructions that the mRNA must give.
This process can be relatively rapid, which is why it took less than a year to manufacture 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.
Researchers since the 1970s have felt that you can use this technique to fight all kinds of diseases. But as usual in science, you need huge amounts of money, time, and patience to sort out all the issues in between. After a decade of enthusiasm, mRNA became academically outdated in the 1990s. Progress seemed to be stalled. The main obstacle was that injecting mRNA into animals often caused fatal inflammation.
Enter Katalin Kariko – a Hungarian scientist who immigrated to the United States in the 1980s and heroically devoted her entire career to mRNA, through its ups and downs. In the 1990s, she lost her funding, was demoted, saw her salary cut and suffered other setbacks. But she stayed on it. And then, after battling cancer herself, she made a crucial breakthrough.
In the 2000s, she and her research partner realized that replacing uridine, one of the “letters” in mRNA, avoided causing inflammation without otherwise compromising the code. The mice remained alive.
His study was read by Stanford University scientist Derrick Rossi, who later co-founded Moderna. It also caught the attention of Ugur Sahin and Ozlem Tureci, two husband and wife oncologists and co-founders of BioNTech. They licensed Kariko’s technology and hired her. From the start, they were very interested in curing cancer.
Today’s weapons against cancer will one day seem as primitive an idea as flint axes in a surgical room. To kill a malignant tumor, you usually zap it with radiation or chemicals, damaging many other tissues.
The best way to fight cancer, Sahin and Tureci realized, is to treat each tumor as genetically unique and train each patient’s immune system against that specific enemy. Perfect job for mRNA. You find the antigen, get its fingerprint, reverse cellular instructions to target the culprit, and let the body do the rest.
Take a look at Moderna and BioNTech pipelines. They include trials of drugs to treat cancers of the breast, prostate, skin, pancreas, brain, lungs and other tissues, as well as vaccines against everything from influenza to Zika and rage. The outlook looks good.
Admittedly, progress has been slow. Part of the explanation given by Sahin and Tureci is that investors in this sector have to put in tons of capital and then wait over a decade, first for trials and then for regulatory approvals. In the past, too few were in the mood.
Covid-19, fingers crossed, can turbo-charge all of these processes. The pandemic has led to a major launch of mRNA vaccines and their definitive proof of concept. Already, there are whispers about a Nobel Prize for Kariko. Now mRNA will have no problem getting money, attention, or enthusiasm – from investors, regulators and policymakers.
That doesn’t mean the last stretch will be easy. But in this dark hour, it is allowed to bask in the rising light.
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