Nobel Prize for Medicine: mRNA Covid vaccines

Chris Smith walks you through this year's Nobel Prize for medicine...

They've been administered to billions, and protected millions from severe Covid-19 infection. Now the mRNA vaccines that helped to conquer the SARS-CoV-2 pandemic have also secured a place in scientific history - with a Nobel Prize in Medicine - for the two scientists, Katalin Karako and Drew Weissman, who created them.

Ever since Edward Jenner carried out the first vaccination in 1796, vaccines have followed a fairly repetitive path: we inject weakened or related forms of infections or toxins; or we chemically brutalise infectious entities to render them harmless before administering the leftovers. Sometimes we modify harmless viruses to turn them into Trojan horses to carry inside the body key parts of infectious agents we want to protect against.

The net result is that the immune system makes antibody molecules - and to varying degrees white blood cells called T cells - that can neutralise and block the infectious threat should we meet it for real.

These methods work reliably and well, but they do have drawbacks. They can be slow and expensive to develop, live vaccines aren’t suitable for everyone, and when dealing with fast-evolving threats, it can be hard for the technology to keep pace with the infection.

But, from the moment that scientists cracked the genetic code and worked out how DNA stores our biochemical recipes, and transcribes the messages we needs into simpler, short lived copies called messenger RNA - or mRNA - strands, researchers realised that it might be possible to deliver our own messages into cells in a genetic form; including the instructions for substances normally used in vaccines, thus turning our cells into mini vaccine-manufacturing plants.

It sounded simple, but when scientists tried adding their own mRNA genetic codes to the body, the cells of the immune system somehow knew that the mRNA was foreign and destroyed it.

This was the challenge that confronted and frustrated Katalin Karako and Drew Weissman for many years. But their eureka moment came in 2005, when they showed that, compared with pristine mRNA made in a test tube or by microbes like bacteria, the mRNA strands found in our cells are chemically modified: extra molecules are added to some of the genetic letters in the sequence. It's a bit like the embellishments and decorations you see in old books around the opening letters of paragraphs. These enable the body to tell friend from foe.

So, they wondered, what would happen if they substituted more chemically colourful genetic letters into their mRNA genetic sequences? Would this avoid the immune trip wires that were being triggered?

Indeed it would. And the inflammatory response that had been thwarting their previous efforts was almost completely abolished, opening the door to the use of mRNA vaccines as a therapeutic vehicle.

There were still problems to overcome, of course, before the discovery could make its way into the clinic. Compared with it chemical relative DNA, mRNA - while easier to slip into our cells - is a much more fragile molecule, so scientists had to develop ways to package it in a stable form that would also ensure efficient delivery once it was injected.

The solution was to wrap up the mRNA molecules in tiny oily bubbles called lipid nanoparticles. Each shot of mRNA vaccine contains billions of them. Developing this technology was a breakthrough in its own right; and although Karako and Weissman developed the engine that powers the mRNA vaccine vehicle, some scientists have argued that the body of the car - in the form of the lipid nanoparticles - also deserved Nobel recognition. But, with so many researchers involved in this aspect of the work, it would have been arguably more unfair to single out just one for the award.

Before the pandemic struck, the technology had been quietly evolving in the background. mRNA-based vaccines for Zika, and a virus that is a close relative of the Covid virus, had both been developed and tested in animals.

But the Covid pandemic offered the opportunity to capitalise on the power and agility of this new approach in clinical medicine. The vaccines are easy to make, and update, at scale and very safe. And off the back of the impetus from Covid-19, the approach is unlocking new treatments for cancer, as well as other infectious and degenerative diseases.

COVID-19 gave mRNA vaccines the shot in the arm that the industry needed, but the technology’s impact is likely to reach far and wide, hence its recognition by the Nobel committee.  As Kariko herself says, "It is just limitless."