Penn scientists win $3 million Breakthrough Prize for RNA research that enabled COVID-19 vaccines

Sixteen years after their research at the University of Pennsylvania paved the way for billions to be vaccinated against COVID-19, two scientists have been honored with a $3 million Breakthrough Prize.

The award for Katalin Karikó and Drew Weissman, one of five such honors announced Thursday for achievements in science and math, recognizes their success in modifying the genetic molecule called messenger RNA (mRNA) so it can instruct human cells to make customized proteins.

That concept could prove useful in treating all sorts of maladies — years ago, Karikó explored the idea as a therapy for heart disease — but its first widespread success came in teaching the human immune system to fight off the coronavirus. Two of the vaccines, the one made by Moderna and the joint effort from Pfizer and BioNTech, where Karikó now works, rely on mRNA.

In the nine months since the vaccines were authorized for use, preventing untold thousands of hospitalizations and deaths, Karikó and Weissman have won so many awards between them that they’ve lost count. But the Breakthrough Prize, an award sponsored by an international group of tech-industry titans, now in its 10th year, is by far the biggest payoff.

“I never sought any of this,” said Karikó, 66, a senior vice president at BioNTech in Mainz, Germany, who lives part time in Rydal, in Montgomery County, and maintains an adjunct position at Penn. “I went 40 years without any prize.”

“It’s been very wonderful,” said Weissman, 62, a professor at Penn’s Perelman School of Medicine. “I never thought it was possible.”

The scientists said they were grateful for the recognition, and stressed that many others have helped to develop RNA technology since their initial promising results were published in 2005 and 2008.

Yet before then, the field was seen by many as a dead end. In 1995, for example, Karikó failed to win federal funding for her research and, as a result, was turned down for a tenure-track position at Penn. Still, she stuck with it, working first with cardiologist Elliot Barnathan, then neurosurgeon David Langer, exploring the possibility of using RNA to treat the heart and brain.

But progress was slow. A key roadblock was that RNA, when administered to lab mice, sometimes provoked harmful inflammation.

By the early 2000s, Karikó was collaborating with Weissman, an immunologist, who shared her optimism that there just had to be some way to crack the puzzle. After all, messenger RNA occurs naturally in human cells, carrying vital instructions for the body to make proteins. That code is spelled out with the chemical “bases” taught in every high school biology class, abbreviated A, G, C, and U.

After years of trial and error, the pair found the key. Their laboratory version of mRNA needed just a slight tweak to the molecular structure attached to the “U,” and the inflammation disappeared.

The approach is now being explored as a treatment for all kinds of diseases.

In the vaccines, the mRNA carries the code for a harmless fragment of the coronavirus — its “spike” protein — enabling the recipient’s immune system to practice for a real infection. The platform has the advantage of being readily adaptable as new viral strains emerge, and it also seems to confer stronger protection than other types of vaccines.

Other diseases for which mRNA has shown promise include cystic fibrosis, sickle-cell anemia, and certain cancers. At Children’s Hospital of Philadelphia, researchers have even studied its potential for treating disease before birth.

Vindicated after her years of toil, Karikó is delighted to have so many others join the hunt.

Long before she tackled RNA, her scientific curiosity was evident when growing up in small-town Hungary. At age 5, she would observe intently as her father, a butcher, chopped up the carcasses of pigs and rabbits for sale. At area farms she watched, transfixed, as cows gave birth. She made a study of birds’ nests.

“I was climbing, always, the trees,” she said.

Her parents had limited schooling — her mother completed the equivalent of eighth grade, her father sixth — but there was no mistaking their brainpower. Karikó's mother was a skilled bookkeeper, and her father played the violin and could multiply two-digit numbers in his head, she said.

Karikó excelled in school, earning an undergraduate biology degree and a Ph.D. in biochemistry at Hungary’s University of Szeged. She came to Philadelphia in 1985 for a job at Temple University, hiding extra cash inside her daughter’s teddy bear because the Hungarian government allowed the family to emigrate with just $100.

She later worked next at the Uniformed Services University of the Health Sciences in Bethesda, Md., then came back to Philadelphia in 1989 to work at Penn, and still holds an adjunct position there.

Weissman, the son of an engineer and a dental hygienist, also displayed an early aptitude for science, taking apart everything from toasters to doorknobs to see how they worked.

“They were always getting me to put stuff back together,” he said.

As an undergraduate at Brandeis University, he was drawn to the laboratory and majored in biochemistry, then went to Boston University for a Ph.D. in immunology, in 1987. Among his postdoctoral positions was a fellowship at the National Institutes of Health, under infectious-disease chief Anthony Fauci. He came to Penn in 1997.

Among the other Breakthrough Prizes this year are two in the life sciences — one for Jeffery W. Kelly, who studies neurodegenerative disease at Scripps Research Institute, the other split among Shankar Balasubramanian and David Klenerman, both at the University of Cambridge, and Pascal Mayer, chief executive of the French company Alphanosos, for their work on DNA sequencing.

The two other prizes are in math, for Takuro Mochizuki at Kyoto University, and in physics, split between Hidetoshi Katori, of the University of Tokyo and RIKEN, and Jun Ye, of the National Institute of Standards and Technology and the University of Colorado.

The prizes’ founding sponsors are Google cofounder Sergey Brin; Facebook cofounder Mark Zuckerberg and his wife, physician-philanthropist Priscilla Chan; tech investor Yuri Milner and his wife, Julia; and 23andMe founder Anne Wojcicki.

Asked what they would do with their half of the $3 million, Karikó and Weissman both said they would spend some of it on their research. Karikó also pledged to support science education for students who, like her, come from families with limited means. Asked about the coincidence that the prize shared a name with the “breakthrough” infections occurring in some who have been vaccinated, both chuckled ruefully.

Other honors almost certainly are in store. Some in academia predict they will be considered for the biggest prize of all: a Nobel.

In the meantime, the pair remain focused on the science. Karikó is working on a variety of diseases in which patients’ proteins are deficient in some way. Weissman is at work on a vaccine that would protect against multiple coronaviruses, not just the one in this pandemic.

In both cases, they are relying on the approach that already has won them so much acclaim: messenger RNA.