TODAY'S PAPER

Seeding tomorrow's medical discoveries

F. William "Bill" Studier, a Brookhaven National Laboratory scientist, was part of the team whose discoveries are used in several COVID vaccines. Credit: Stony Brook University

Eddie Cantor said it takes 20 years to make an overnight success, and this is certainly true of science, where a discovery can lead to revolutionary applications many years, sometimes decades or even centuries later. When Isaac Newton discovered his laws of motion, he certainly did not imagine that those very laws would be used to launch satellites 300 years later. When Michael Faraday discovered the laws of electromagnetism that make the generation of electricity possible, a British politician asked him what good it was, to which he is said to have replied, "Someday, sir, you can tax it." Even Faraday could not have imagined that 150 years later electricity would pervade almost every aspect of our lives. Even an everyday device like a smartphone is based on several Nobel Prize-winning discoveries.

If we want a society that remains at the forefront of technologies tomorrow, we have to continue to produce the scientists of tomorrow by inculcating in young people a love of science and how it works. This requires a serious commitment to science education from the earliest years. Science is not a rote collection of facts. It is a way of discovering truths about the natural world through observation and experiments, along with theories that help us interpret and understand the results. We also have to support the basic science of today, which is the seed corn for the completely unpredictable technologies of tomorrow. Trying to pick winners or focusing just on short-term applications is a guarantee of small, incremental gains rather than real, technological revolutions.

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Eddie Cantor said it takes 20 years to make an overnight success, and this is certainly true of science, where a discovery can lead to revolutionary applications many years, sometimes decades or even centuries later. When Isaac Newton discovered his laws of motion, he certainly did not imagine that those very laws would be used to launch satellites 300 years later. When Michael Faraday discovered the laws of electromagnetism that make the generation of electricity possible, a British politician asked him what good it was, to which he is said to have replied, "Someday, sir, you can tax it." Even Faraday could not have imagined that 150 years later electricity would pervade almost every aspect of our lives. Even an everyday device like a smartphone is based on several Nobel Prize-winning discoveries.

If we want a society that remains at the forefront of technologies tomorrow, we have to continue to produce the scientists of tomorrow by inculcating in young people a love of science and how it works. This requires a serious commitment to science education from the earliest years. Science is not a rote collection of facts. It is a way of discovering truths about the natural world through observation and experiments, along with theories that help us interpret and understand the results. We also have to support the basic science of today, which is the seed corn for the completely unpredictable technologies of tomorrow. Trying to pick winners or focusing just on short-term applications is a guarantee of small, incremental gains rather than real, technological revolutions.

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I was reminded of this by the COVID-19 vaccines, which are widely said to have been developed at unprecedented speed, available less than a year after the pandemic broke out. In fact, these vaccines were built on decades of fundamental science, including discoveries made by F. William Studier and his colleague John Dunn at Brookhaven National Laboratory. While studying how T7, a virus, attacks the bacterium E. coli, they and their colleagues figured out how to make large quantities of any RNA or protein of choice. Moderna and Pfizer, makers of today’s mRNA COVID-19 vaccines, rely on Studier’s approach, which uses genetic elements derived from T7 to produce the mRNA instructions for making coronavirus spike proteins. When those mRNAs are delivered to our cells, our cells make the corresponding spike proteins. Those spikes train our immune system to be ready to fight the real COVID-19 virus if we are exposed.

Venki Ramakrishnan

Meanwhile, Katalin Kariko at the University of Pennsylvania discovered that injected mRNA would normally be quickly destroyed because the cell senses it as coming from a virus. But unexpectedly, she discovered that it could evade the cell’s response if one of the building blocks of the mRNA was synthetically modified.

Both Studier’s T7 system to produce large amounts of mRNA and Kariko’s discovery of the need to modify it were essential to produce the lifesaving mRNA vaccines we have today. Today, both Pfizer and Moderna make their mRNA using Studier’s T7 system while feeding it the modified building blocks based on the one that Kariko first identified. The synthetically modified mRNA is stable in the cell and allows large amounts of the COVID-19 spike protein to be made.

In both cases, the research was begun in pursuit of pure knowledge — and the practical applications were quite unanticipated and came decades after the original findings.

Venki Ramakrishnan is a Nobel Prize-winning biologist at the MRC Laboratory of Molecular Biology in Cambridge, England.

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