Katalin Karikó and Drew Weissman, who together identified a chemical tweak to messenger RNA, were awarded the Nobel Prize in Physiology or Medicine on Monday. Their work allowed for the production of powerful Covid vaccinations in less that a year. It prevented the deaths of tens millions and helped the recovery of the world from the worst epidemic in a century.

The Covid shot, developed by the two researchers, has been administered millions of times worldwide. It has transformed the vaccine technology.

Covid was developed through slow and methodical scientific research. However, the anti-vaccine movements in America have been very strong. Skeptics have seized in part on the vaccines’ rapid development — among the most impressive feats of modern medical science — to undermine the public’s trust in them.

But the breakthroughs behind the shots unfolded little by little over decades, including at the University of Pennsylvania, where Dr. Karikó remains an adjunct professor and Dr. Weissman still runs a lab.

The unlikely scientists met in 1998 at a copying machine in the medical department.

Dr. Karikó, the daughter of a butcher who had come to the United States from Hungary two decades earlier when her research program there ran out of money, was preoccupied by mRNA, which provides instructions to cells to make proteins. Defiance of the long-held belief that mRNA is not clinically useful, she thought that it could spur medical innovation.

Dr. Weissman at the time was desperate to find new ways to develop a vaccine for H.I.V. that could be used to protect against this virus, which had been difficult to defend. A physician and virologist who had tried and failed for years to develop a treatment for AIDS, he wondered if he and Dr. Karikó could team up to make an H.I.V. vaccine.

When they started their research, it seemed that the idea was unlikely to work. The mRNA had a delicate nature, and when introduced into cells, it was destroyed instantly. The reviewers of grant applications were not impressed. Dr. Weissman’s lab instead relied on seed money that the university gives new faculty members to get started.

For years, Dr. Weissman and Dr. Karikó were flummoxed.

Mice treated with mRNA were lethargic. Numerous experiments failed. After one dead end, they went on to another. They were sickened by the immune system, which interpreted mRNA to be an invading pathogen.

Scientists eventually found that cells can protect their own mRNA through a chemical modification. The scientists then made the same modification to the mRNA they synthesized before injecting into the cells. It worked. The mRNA was absorbed by the cells without triggering an immune reaction.

The discovery “fundamentally changed our understanding of how mRNA interacts with our immune system,” The panel that awarded the award said that the work was also praised. “contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.”

At first, many scientists did not want to adopt this new approach. Their 2005 paper was rejected by Nature and Science journals, according to Dr. Weissman. The study was A niche publication named Immunity eventually accepted it.

But two biotech companies soon took notice: Moderna, in the United States, and BioNTech, in Germany, where Dr. Karikó eventually became a senior vice president. The companies studied mRNA vaccines to treat flu, cytomegalovirus, and other diseases. For years, none of the companies moved on from clinical trials.

The coronavirus appeared.

Drs. Karikó and Weissman’s work came together with several strands of disparate research to put vaccine makers ahead of the game in developing shots. The research in Canada allowed fragile mRNA molecule to be delivered to human cell safely, and the studies in the United States pointed to the way to stabilizing spike protein used by coronaviruses to infect cells.

By late 2020, a little more than a full year into the pandemic, which would kill at least 7 million people in total, regulators approved two vaccines that were remarkably effective, made by Moderna as well as BioNTech. Pfizer partnered up with BioNTech to produce this vaccine. Both used the modification Dr. Karikó and Dr. Weissman discovered.

In the United States, approximately 400 million doses each of the Pfizer BioNTech and Moderna vaccines have been administered. More than a hundred million doses have been administered around the globe. The use of the mRNA allowed both vaccines be updated against any new variants.

Dr. Karikó referred in an interview Published by the University of Pennsylvania Monday Her many years of hanging on the edges of academia. She had no grant and no permanent job when she met Dr. Weissman, in 1998. She knew she could only stay at Penn if someone else took her on.

In the interview, Dr. Karikó said that every October, her mother used to tell her, “I will listen to the radio that maybe you will get the Nobel Prize.” Dr. Karikó said she would answer: “Mum, you know, I never even get a grant.”

In the same interview Dr. Weissman stated that the prize was “obviously the most important award that a scientist can achieve.” He made it clear that “we couldn’t have come to the result without both of us being involved.”

Dr. Karikó is the 13th woman to be awarded the Nobel Prize in Physiology or Medicine since 1901, and the first since 2015. Women make up a tiny fraction of the 227 recipients of the Nobel Prize, reflecting the fact that women are underrepresented in science, and the scientific community, including Nobel Prizes.

In the past, mRNA was used to develop vaccines against many diseases. These include influenza, malaria, and H.I.V. which is still difficult to inoculate. Cancer vaccines that are personalized have also shown promise. They use mRNA tailored to an individual patient’s tumor to teach the person’s immune system to attack proteins on the tumor.

Drs. Karikó and Weissman’s discovery, scientists said, remained critical in allowing mRNA vaccines to escape destruction by patients’ immune systems and to trigger the efficient production of vaccine proteins.

“What is now recognized as a transformative technology required dedicated scientists to carry out fundamental research over many years to reach the position it was in 2020 when its rapid deployment as a vaccine technology was made possible by global collaboration,” Brian Ferguson, an Immunologist at the University of Cambridge stated. “The work of Katalin Karikó and Drew Weissman in the years prior to 2020 made this possible, and they richly deserve this recognition.”

The prize went to Svante Pääbo, a Swedish scientist who produced a complete Neanderthal genome and helped create the field of ancient DNA studies.

The first of six Nobel Prizes to be awarded in this year is for physiology and medicine. Each award is given to an individual or group that has made a significant contribution in a certain field.

  • The Royal Swedish Academy of Sciences will award the Nobel Prize in Physics on Tuesday in Stockholm. John Clauser, Alain Aspect, and Anton Zeilinger won the Nobel Prize in Physics last year for their independent work exploring quantum weirdness.

  • The Royal Swedish Academy of Sciences will award the Nobel Prize in Chemistry on Wednesday in Stockholm. Last year, Carolyn R. Bertozzi and Morten Meldal shared the prize for their work on click chemistry.

  • The Swedish Academy in Stockholm will award the Nobel Prize in Literature on Thursday. Annie Ernaux won the Nobel Prize in Literature last year for her work which dissected with clinical precision the most embarrassing, private, and scandalous moments of her past.

  • The Norwegian Nobel Institute will award the Nobel Peace Prize on Friday in Oslo. Last year the award was shared between Memorial, an organization from Russia, the Center for Civil Liberties, Ukraine and Ales Baliatski, who is a Belarusian activist in prison.

  • The Royal Swedish Academy of Sciences in Stockholm will award the Nobel Memorial Prize in Economic Sciences on Monday next week. The Royal Swedish Academy of Sciences in Stockholm will award the Nobel Memorial Prize for Economic Sciences on Monday next week.

All prize announcements are made in English. streamed live The Nobel Prize Organization

Emma Bubola Contributed Reporting