Katalin Karikó, pictured, and Drew Weissman won the Nobel Prize for advances in mRNA research that led to the first Covid vaccines.
When Drew Weissman received a call from Katalin Karikó in the early morning hours this past Monday, he assumed his longtime research partner was calling to share a nascent, nagging idea. Weissman, a professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, and Karikó, a professor at Szeged University and an adjunct professor at UPenn, both struggle with sleep disturbances. Thus, middle-of-the-night discourses between the two, often over email, has been a staple of their friendship. But this time, Karikó had something more pressing and exciting to share: They had won the 2023 Nobel Prize in Physiology or Medicine.
The work for which they garnered the illustrious award and its accompanying $1,000,000 cash windfall was completed about two decades ago, wrought through long hours in the lab over many arduous years. But humanity collectively benefited from its life-saving outcome three years ago, when both Moderna and Pfizer/BioNTech’s mRNA vaccines against COVID were found to be safe and highly effective at preventing severe disease. Billions of doses have since been given out to protect humans from the upstart viral scourge.
“I thought of going somewhere else, or doing something else,” said Katalin Karikó. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
Unlocking the power of mRNA
Weissman and Karikó unlocked mRNA vaccines for the world back in the early 2000s when they made a key breakthrough. Messenger RNA molecules are essentially instructions for cells’ ribosomes to make specific proteins, so in the 1980s and 1990s, researchers started wondering if sneaking mRNA into the body could trigger cells to manufacture antibodies, enzymes, or growth agents for protecting against infection, treating disease, or repairing tissues. But there was a big problem: injecting this synthetic mRNA triggered a dangerous, inflammatory immune response resulting in the mRNA’s destruction.
While most other researchers chose not to tackle this perplexing problem to instead pursue more lucrative and publishable exploits, Karikó stuck with it. The choice sent her academic career into depressing doldrums. Nobody would fund her work, publications dried up, and after six years as an assistant professor at the University of Pennsylvania, Karikó got demoted. She was going backward.
“I thought of going somewhere else, or doing something else,” Karikó told Stat in 2020. “I also thought maybe I’m not good enough, not smart enough. I tried to imagine: Everything is here, and I just have to do better experiments.”
A tale of tenacity
Collaborating with Drew Weissman, a new professor at the University of Pennsylvania, in the late 1990s helped provide Karikó with the tenacity to continue. Weissman nurtured a goal of developing a vaccine against HIV-1, and saw mRNA as a potential way to do it.
“For the 20 years that we’ve worked together before anybody knew what RNA is, or cared, it was the two of us literally side by side at a bench working together,” Weissman said in an interview with Adam Smith of the Nobel Foundation.
In 2005, the duo made their 2023 Nobel Prize-winning breakthrough, detailing it in a relatively small journal, Immunity. (Their paper was rejected by larger journals, including Science and Nature.) They figured out that chemically modifying the nucleoside bases that make up mRNA allowed the molecule to slip past the body’s immune defenses. Karikó and Weissman followed up that finding by creating mRNA that’s more efficiently translated within cells, greatly boosting protein production. In 2020, scientists at Moderna and BioNTech (where Karikó worked from 2013 to 2022) rushed to craft vaccines against COVID, putting their methods to life-saving use.
The future of vaccines
Buoyed by the resounding success of mRNA vaccines, scientists are now hurriedly researching ways to use mRNA medicine against other infectious diseases, cancer, and genetic disorders. The now ubiquitous efforts stand in stark contrast to Karikó and Weissman’s previously unheralded struggles years ago as they doggedly worked to realize a shared dream that so many others shied away from. Katalin Karikó and Drew Weissman were brave enough to walk a scientific path that very well could have ended in a dead end, and for that, they absolutely deserve their 2023 Nobel Prize.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.
Donna Shirley pictured at her home in Tulsa, with a model of the Sojourner rover she was in charge of that explored Mars.
"Periodically, I'll hear somebody say they got into the space program because of me, and that makes me feel really good," Shirley told Leaps.org. "I look at the mission control area, and there are a lot of women in there. I'm quite pleased I was able to break the glass ceiling."
Her $25-million, 25-pound microrover – powered by solar energy and designed to get rock samples and test soil chemistry for evidence of life – was named after Sojourner Truth, a 19th-century Black abolitionist and women's rights activist. Unlike Mars Pathfinder, Shirley didn't have to travel more than 131 million miles to reach her goal, but her path to scientific fame as a woman sometimes resembled an asteroid field.
The Sojourner Rover in 1997 on Mars.NASA/JPLAs a high-IQ tomboy growing up in Wynnewood, Oklahoma (pop. 2,300), Shirley yearned to escape. She decided to become an engineer at age 10 and took flying lessons at 15. Her extraterrestrial aspirations were fueled by Ray Bradbury's The Martian Chronicles and Arthur C. Clarke's The Sands of Mars. Yet when she entered the University of Oklahoma (OU) in 1958, her freshman academic advisor initially told her: "Girls can't be engineers." She ignored him.
Years later, Shirley would combat such archaic thinking, succeeding at JPL with her creative, collaborative management style. "If you look at the literature, you'll find that teams that are either led by or heavily involved with women do better than strictly male teams," she noted.
However, her career trajectory stalled at OU. Burned out by her course load and distracted by a broken engagement to marry a fellow student, she switched her major to professional writing. After graduation, she applied her aeronautical background as a McDonnell Aircraft technical writer, but her boss, she says, harassed her and she faced gender-based hostility from male co-workers.
Returning to OU, Shirley finished off her engineering degree and became a JPL aerodynamist in 1966 after answering an ad in the St. Louis Post-Dispatch. At first, she was the only female engineer among the research center's 2,000-odd engineers. She wore many hats, from designing planetary atmospheric entry vehicles to picking the launch date of November 4, 1973 for Mariner 10's mission to Venus and Mercury.
By the mid-1980's, she was managing teams that focused on robotics and Mars, delivering creative solutions when NASA budget cuts loomed. In 1989, the same year the Sojourner microrover concept was born, President George H.W. Bush announced his Space Exploration Initiative, including plans for a human mission to Mars by 2019.
That target, of course, wasn't attained, despite huge advances in technology and our understanding of the Martian environment. Today, Shirley believes humans could land on Mars by 2030. She became the founding director of the Science Fiction Museum and Hall of Fame in Seattle in 2004 after leaving NASA, and to this day, she enjoys checking out pop culture portrayals of Mars landings – even if they're not always accurate.
After the novel The Martian was published in 2011, which later was adapted into the hit film starring Matt Damon, Shirley phoned author Andy Weir: "You've got a major mistake in here. It says there's a storm that tries to blow the rocket over. But actually, the Mars atmosphere is so thin, it would never blow a rocket over!"
Fearlessly speaking her mind and seeking the stars helped Donna Shirley make history. However, a 2019 Washington Post story noted: "Women make up only about a third of NASA's workforce. They comprise just 28 percent of senior executive leadership positions and are only 16 percent of senior scientific employees." Whether it's traveling to Mars or trending toward gender equality, we've still got a long way to go.