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Commentary: Nobel prize for mRNA vaccine shows power of perseverance

CHICAGO: Monday’s (Oct 2) Nobel Prize in medicine is a testament to the power of perseverance in science. Katalin Kariko and Drew Weissman won the award for their discoveries that helped enable mRNA to be used as a drug or vaccine.

It’s hard to imagine a more deserving Nobel Prize than one for an achievement credited with saving millions of lives. And we might never have gotten here if scientists like Kariko hadn’t persisted in the face of doubt.

The quick development of the COVID-19 vaccines might make mRNA seem like an overnight success. Certainly, the speed with which they were developed is among the reasons some sceptics have given for doubting their efficacy.

But turning these strands of genetic material into something that could be useful as a drug or vaccine required many breakthroughs over two decades. Scientists had to solve a host of problems: How to make the otherwise fragile genetic strands more stable; how to get it to the right cells in the body and control the amount of protein it prompts a cell to make; and how to prevent the immune system from seeing the mRNA as an invader and overreacting.  

Kariko and Weissman are credited with cracking the last item on that list. By swapping out a basic building block of mRNA called uridine for a related molecule called pseudouridine, strands of mRNA could get their message to cells without triggering an immune attack.

That discovery helped spawn the earliest biotech companies working on the technology, in turn, laying the groundwork for mRNA’s starring role in the pandemic. That chemical trick is included in Moderna’s and Pfizer-BioNTech’s COVID-19 vaccines, which are responsible for saving many millions of lives over the past two years.

DECADES OF CONVINCING THE WORLD

Some of the joy of Monday’s prize is that it rewards Kariko’s many decades of effort to convince the world mRNA held promise as a therapeutic. After coming to the US from Hungary in the mid-1980s, she struggled to get financial support for her research, moving from lab to lab to try to keep her work alive until a now-legendary encounter with Weissman over a Xerox machine while at the University of Pennsylvania.

They teamed up to work on mRNA, but even their successes met roadblocks. When she and Weissman discovered that critical chemical swap in 2005, the scientific community failed to recognise its importance. As she told PNAS in 2021, “We first sent to a Nature journal, and within 24 (hours), they rejected it as an incremental contribution. I started learning English only at university, so I had to look up the meaning of the word incremental!”

Kariko’s struggle to convince the world of mRNA’s value ultimately pushed her out of academia and to BioNTech, which she joined in 2013. By then, investors had started to come around to the idea that mRNA could be useful. But only a handful of companies were pursuing the idea.

All of that changed practically overnight when reports started popping up of cases of pneumonia due to a novel coronavirus. The pandemic was the ultimate test: While mRNA promised to accelerate the design and manufacture of a vaccine, it had never been proven in a late-stage clinical trial.

As we now know, it turned out to be a resounding success.

VACCINES ARE BUT THE LOW-HANGING FRUIT OF THE MRNA WORLD

Over the next two years, mRNA-based vaccines for RSV and the flu should arrive, as could a highly anticipated cancer vaccine from Moderna.

Yet for mRNA’s full potential to be realised – and Kariko’s dream of turning it into a therapeutic – the field will need another dose of her brand of intense determination. While undeniably world-changing, vaccines are also the low-hanging fruit of the mRNA world. To work, they only need to coax cells into making a fleeting amount of protein – enough to train the immune system so that it can eventually spot the real virus.

Turning mRNA into drug, one that not only gets to the right cells in the body but can offer some therapeutic benefit, is a much trickier proposition.

We’ll get there, eventually. While biotech companies are working on the problem, it also will require ongoing support of basic science like the work done by Kariko and Weissman. Congress shouldn’t forget that when considering painful cuts to the budget of the National Institutes of Health, the agency responsible for so much foundational research.

Monday’s prize is another reminder that the slog of basic science can have unexpected payoffs – and should be both celebrated and funded. And maybe it will help with another slog: Convincing those still distrustful of this “new” technology that decades of effort have gone into making it safe.

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