Why mRNA Vaccines Could Revolutionise Medicine

Almost 60 years ago, in February 1961, two teams of scientists stumbled on a discovery at the same time. Sydney Brenner in Cambridge and Jim Watson at Harvard independently spotted that genes send short-lived RNA copies of themselves to little machines called ribosomes where they are translated into proteins. ‘Sydney got most of the credit, but I don’t mind,’ Watson sighed last week when I asked him about it. They had solved a puzzle that had held up genetics for almost a decade. The short-lived copies came to be called messenger RNAs — mRNAs – and suddenly they now promise a spectacular revolution in medicine.

The first Covid-19 vaccine given to British people this month is not just a welcome breakthrough against a grim little enemy that has defied every other weapon we have tried, from handwashing to remdesivir and lockdowns. It is also the harbinger of a new approach to medicine altogether. Synthetic messengers that reprogram our cells to mount an immune response to almost any invader, including perhaps cancer, can now be rapidly and cheaply made.

Katalin Karikó — the Hungarian-born scientist who doggedly pursued the idea behind this kind of medication for decades at the University of Pennsylvania before joining BioNTech — and her collaborator Drew Weissman may be the Watson and Brenner of this story. They figured out 15 years ago how to send a message in a bubble into a cell and have it read. For years they had tried putting in normal RNA and found it did not work; the body spotted it was an alien and destroyed it.

But by subtly modifying one of the four letters in the message (replacing uridine with pseudouridine, a chemical found in some RNAs in the body anyway), they made a version that escaped the attention of the cell’s MI5 agents. Further refinements five years ago produced a recipe that worked reliably when delivered to cells inside a tiny oily bubble. The pandemic is the first time the technique has been tried in anger, and it worked: the first two Covid vaccines, BioNTech’s and Moderna’s, rely on these messengers.

The message tells the cell to make part of one of the virus’s proteins which then alerts the body’s immune system. Once invented, the thing is like a general-purpose vaccine. You simply rewrite the message between the same opening and closing sequences, put it in the same kind of bubble, and fire it off — almost as easy for genetic engineers these days as writing a text is for teenagers. It is faster, cheaper, safer and simpler than the old ways of making vaccines.

More conventional vaccine designs may still make a vital contribution to defeating the pandemic, Oxford’s included. And the messenger method has its drawbacks, such as the need for extreme cold storage. But in the long run, messengers probably represent the future of vaccines. Now the principle has been approved by regulators, there may be no need to go through the same laborious and expensive three-phase clinical trials every time. Faced with a truly lethal pandemic — with a 10 per cent mortality rate, say — the vanishingly small likelihood that a new messenger vaccine would be unsafe pales into insignificance. You could deploy it in weeks or days.

What is more, at the cost of a few billion dollars, the world may now be able to build a library of messenger vaccines for every plausible coronavirus and influenza virus with pandemic potential we can find, test them in animals and store the recipes on a hard disk, ready to go at a moment’s notice. Moderna’s vaccine was first synthesised in mid-January, before we even knew the coronavirus was coming out of China.

by Matt Ridley, The Spectator |  Read more:

Image: iStock

[ed. See also: Politics, Science and the Remarkable Race for a Coronavirus Vaccine (NYT).]