mRNA vaccines

In 2020 a new kind of vaccine went from a line of genetic code to people's arms in less than a year. On 10 January scientists in China led by Zhang Yongzhen posted the genome of the new coronavirus online. Within days Moderna, a young company in Cambridge, Massachusetts, working with the US government's Vaccine Research Center, and BioNTech in Mainz, Germany, had designed vaccines from that code alone, without ever growing the virus. Moderna's first volunteer was injected in Seattle on 16 March, 66 days after the code appeared. In November trials with about 43,000 and 30,000 volunteers showed both vaccines, Pfizer and BioNTech's and Moderna's, about 95 percent effective against the disease. On 2 December Britain became the first country to approve one, and on 8 December, at 6:31 in the morning, Margaret Keenan, a 90-year-old grandmother, received the Pfizer–BioNTech vaccine at her local hospital in Coventry, the first person in the world to get it after its approval. The United States authorised it on 11 December and Moderna's on 18 December.

Messenger RNA, or mRNA, is the working copy that a cell makes of a gene: it carries the recipe for one protein to the cell's protein factories. The vaccines contain mRNA for the virus's spike, the protein it uses to enter our cells, slightly changed so that the spike keeps the shape it has before it attacks. The mRNA travels inside tiny bubbles of fat, called lipid nanoparticles. In the arm, cells read it and make spike proteins for a short time, and the immune system learns to recognise them without ever meeting the virus. The mRNA cannot reach the cell's DNA or change it. Because only the code is needed, a new vaccine can be designed in days, and made without the large cell cultures older vaccines need.

The idea was decades old. Messenger RNA was discovered in 1961 by Sydney Brenner, François Jacob and Matthew Meselson, and in the same issue of Nature by François Gros, Walter Gilbert and their colleagues. From 1984 scientists could make any mRNA in a test tube. In 1987–89 Robert Malone at the Salk Institute in San Diego, with Philip Felgner and Inder Verma, showed that mRNA wrapped in fatty droplets got into cells, which then made its protein, and in 1990 a team including Felgner and Malone made mouse muscle produce protein from injected mRNA. But mRNA made in the laboratory was fragile and caused inflammation, and most scientists lost interest. The Hungarian biochemist Katalin Karikó, who came to Philadelphia in 1985 and joined the University of Pennsylvania in 1989, did not: refused grants and demoted, she kept working. In 1997, at a photocopier at Penn, she met the immunologist Drew Weissman, who wanted to make an HIV vaccine. In 2005 they showed that swapping one of mRNA's four letters, uridine, for a natural variant, pseudouridine, hid the molecule from the immune system's alarms, and in 2008 that it also made far more protein. In Vancouver, Pieter Cullis's laboratory developed the fat particles that could carry mRNA safely into the body.

Companies took up the threads: CureVac in 2000; BioNTech, founded in Mainz in 2008 by Uğur Şahin, Özlem Türeci and Christoph Huber to make cancer vaccines; and Moderna, founded in 2010. Karikó joined BioNTech in 2013. At the Vaccine Research Center, Barney Graham's team, working on a vaccine against the MERS coronavirus, had learned to lock a coronavirus spike in its pre-attack shape. So when the pandemic came, the pieces were ready. Pfizer joined BioNTech on 17 March 2020. The US government's Operation Warp Speed paid for development and ordered 100 million doses from each company before the results were in, and the trials ran their phases side by side instead of one after another, while completing every necessary step. Both vaccines replaced every uridine with a modified letter, N1-methylpseudouridine, building on Karikó and Weissman's discovery.

No mRNA vaccine had ever been approved before. By 2023 more than 13 billion doses of COVID-19 vaccines of all kinds had been given, saving millions of lives, and serious side effects of the two mRNA vaccines proved exceptionally rare. The doses were unevenly shared: at the end of 2021, when in most countries of Europe and the Americas a majority had had at least one, in much of Africa fewer than one person in five had. The method can be updated for a new variant faster than any other, and mRNA vaccines and medicines are now being tested against other infections and cancer. On 2 October 2023 Karikó and Weissman were awarded the Nobel Prize in Physiology or Medicine for the discovery that made the vaccines work.