Katalin Karikó

#1In 1995, Katalin Karikó had a decision to make.

#2Her academic career at the University of Pennsylvania was going nowhere.

#3Grant applications kept getting rejected. Instead of moving up the faculty ladder, she was being demoted to a lower research position.

#4And academia was only one of her problems.

#5Doctors had found suspicious lumps in her breast.

#6Her husband, Béla Francia, had gone to Hungary and become stuck there for months because of an immigration problem.

#7The family had recently bought a house.

#8There were plenty of reasons to change research topics, change universities, or simply decide that mRNA had taken enough from her.

#9Karikó accepted the demotion.

#10Then she went back to working on mRNA.

#11Not because she had foreseen a pandemic.

#12COVID-19 did not exist.

#13She was looking at something much smaller.

#14The results of the next experiment.

#15Karikó had arrived in the United States in 1985 with her husband and their two-year-old daughter, Susan.

#16Hungary restricted how much money people could take out of the country, so the family sold their car and hid some of the cash inside Susan's teddy bear.

#17Philadelphia was supposed to offer Karikó something she had struggled to find at home: room to keep doing science.

#18The molecule she kept chasing was messenger RNA.

#19mRNA is a temporary set of instructions. Give a cell the right mRNA, and in principle you can tell that cell to make a particular protein without permanently changing its DNA.

#20Then the message disappears.

#21It sounded almost ideal for medicine.

#22In practice, mRNA was fragile, difficult to deliver, and notoriously hard to turn into a useful drug.

#23But Karikó kept seeing small signs that it could work.

#24While collaborating with cardiologist Elliot Barnathan at Penn, she experimented with using mRNA to make cells produce functional proteins.

#25Karikó remembered an old dot-matrix printer spitting out one set of results.

#26The machine beeped as it printed.

#27The experiment was working.

#28It wasn't a drug.

#29It wasn't a breakthrough that transformed her career.

#30But it was enough to justify another experiment.

#31That distinction would become important.

#32The science could move forward even while her career moved backward.

#33Barnathan helped keep Karikó's work alive after her demotion.

#34Then he left Penn.

#35Once again, Karikó needed somewhere to work.

#36This time, David Langer stepped in.

#37Years earlier, Langer had been a young medical trainee around Karikó's lab. He once told her that he intended to learn everything she knew.

#38Karikó had a characteristically competitive answer.

#39By the time he learned everything she knew now, she told him, she would know much more.

#40Years later, their positions had changed.

#41Langer was working in neurosurgery. He convinced the department chair that they needed a molecular biologist.

#42Karikó got another place to do her experiments.

#43Her survival in science wasn't the story of a lone genius smashing through every locked door.

#44Sometimes somebody else opened the next one.

#45And because Karikó was still at Penn, she happened to be standing near a copier in 1997 when another scientist wanted to use it.

#46His name was Drew Weissman.

#47Scientists still copied journal articles on paper in those days, and Karikó and Weissman developed what Weissman later called a friendly fight over who got to use the copier first.

#48Waiting around gave them time to talk.

#49Weissman was an immunologist. He had trained at the National Institutes of Health, including work in Anthony Fauci's lab, and came to Penn interested in developing vaccines.

#50He had worked with DNA.

#51Proteins.

#52Peptides.

#53Viruses.

#54What he didn't have was RNA.

#55Karikó did.

#56They started working together.

#57Their personalities were different. Karikó was fast and talkative; Weissman was quieter.

#58But they had something more useful in common.

#59When an experiment produced the wrong result, neither of them was especially interested in pretending it hadn't happened.

#60They wanted to know why.

#61Soon they got a result that would force them to ask that question for years.

#62Karikó and Weissman put laboratory-made mRNA into human dendritic cells.

#63These are immune cells that help detect threats and teach other parts of the immune system what to attack.

#64The mRNA worked.

#65The cells made plenty of the protein encoded by the message.

#66But they also did something else.

#67They produced a powerful inflammatory response.

#68For Weissman, that wasn't necessarily terrible news at first.

#69He wanted vaccines. Activating the immune system can be useful when you're trying to train it against a pathogen.

#70For Karikó, it was a serious problem.

#71She wanted mRNA to become a medicine that could be given repeatedly.

#72If the body treated the molecule itself like a dangerous intruder every time it arrived, that dream looked much less practical.

#73For years, grant reviewers and academic committees had been rejecting mRNA.

#74Now the human immune system seemed to be rejecting it too.

#75Maybe the molecule really was unsuitable for medicine.

#76Karikó and Weissman chose a different question.

#77Why was this happening?

#78They spent years investigating how RNA triggered immune cells.

#79Then they noticed something peculiar.

#80Another form of RNA, called tRNA, did not provoke the same reaction.

#81Why not?

#82Naturally occurring tRNA contained many chemically modified nucleosides.

#83The laboratory-made mRNA they were using did not.

#84So what if they changed the building blocks of their mRNA?

#85They tested modified nucleosides, including pseudouridine.

#86The immune response changed dramatically.

#87The modifications could greatly reduce the excessive innate immune alarm triggered by the synthetic RNA.

#88They had removed a major obstacle.

#89Not every obstacle.

#90This did not mean that swapping one letter for pseudouridine instantly produced a COVID vaccine.

#91Researchers still had to improve RNA purification, stability and protein production. They needed effective ways to deliver mRNA into cells. The COVID-19 vaccines would eventually use N1-methylpseudouridine, alongside lipid nanoparticles and other technologies developed by many different researchers.

#92But in 2005, Karikó and Weissman had found a way around one of the barriers that had made therapeutic mRNA so difficult.

#93Surely people would pay attention now.

#94They didn't.

#95Karikó and Weissman submitted the work to a prominent journal.

#96It was quickly rejected.

#97One word in the response stuck with Karikó:

#98incremental.

#99English wasn't her first language, and she had to look up what it meant.

#100The paper eventually appeared in *Immunity* in 2005.

#101Weissman thought the phone might start ringing.

#102Perhaps companies would want the technology.

#103Perhaps other scientists would want to collaborate.

#104The next day passed.

#105No call.

#106Then the next month.

#107Then the next year.

#108Karikó later remembered the years from 2005 to 2010 as a period when almost nobody seemed to care.

#109Even after the discovery, winning grants remained difficult.

#110One of her 2007 proposals didn't even make it into the group of applications discussed in detail by the study section.

#111She had helped make what would eventually become a Nobel Prize-winning discovery.

#112Her career still hadn't received the message.

#113Then somebody from a completely different field found the paper.

#114Derrick Rossi wasn't trying to make a vaccine.

#115He studied stem cells.

#116One challenge in his field was getting ordinary adult cells to temporarily produce a set of proteins that could reprogram them into a more stem-cell-like state.

#117DNA could do that.

#118But permanently inserting DNA into a cell's genome created risks.

#119mRNA offered an appealing alternative.

#120It could deliver the instructions, produce the proteins, and then disappear.

#121The inflammatory response was a problem.

#122Then Rossi encountered Karikó and Weissman's modified-mRNA work.

#123His experiments using modified mRNA to reprogram cells drew attention.

#124And the idea began to look much bigger than stem cells.

#125If mRNA could temporarily instruct cells to manufacture proteins, perhaps it could become an entire class of medicines.

#126That thinking helped lead to the creation of a company in 2010.

#127Moderna.

#128Modified RNA.

#129Money and industry were finally beginning to take mRNA seriously.

#130Karikó's academic career must have taken off too.

#131It didn't.

#132By 2013, serious money was moving into mRNA biotechnology.

#133Karikó believed the technology was finally approaching what she called "prime time."

#134But her next step wasn't a bigger laboratory at Penn.

#135She started looking at companies.

#136That summer, her daughter Susan Francia was competing in rowing in Europe.

#137Susan had been the toddler whose teddy bear carried the family's hidden money into America. She had since become an elite American rower and won two Olympic gold medals.

#138Karikó traveled to Europe to watch her compete.

#139During the family's trip, she stopped in Mainz, Germany.

#140There she visited a still-small biotechnology company called BioNTech.

#141Karikó had one important condition.

#142She wanted to keep working with nucleoside-modified mRNA.

#143Another company she had approached wasn't interested in pursuing that direction.

#144BioNTech co-founder Uğur Şahin didn't necessarily agree at the time that the modification was as important as Karikó believed.

#145But he was willing to let her work on it.

#146Karikó joined BioNTech.

#147She wasn't hired to prepare for a future coronavirus pandemic.

#148Much of the company's ambition centered on cancer.

#149Karikó spent most of each year in Germany, away from her family in the United States, working on ways to turn mRNA into real medicines.

#150Seven years later, the molecule suddenly faced a test nobody had planned for.

#151In January 2020, reports of a new coronavirus were emerging from China.

#152Şahin studied the early information and became alarmed by how quickly the virus might already be spreading.

#153BioNTech launched an urgent vaccine program.

#154The world did not invent mRNA vaccines from scratch that year.

#155Different researchers had been building the pieces for decades.

#156Karikó and Weissman had helped solve a major problem involving excessive innate immune recognition of synthetic mRNA.

#157Other scientists improved mRNA design, purification and protein production.

#158Researchers working on lipids developed nanoparticles capable of protecting fragile RNA and delivering it into cells.

#159Coronavirus researchers had spent years learning how to present the spike protein to the immune system effectively.

#160Companies had developed the manufacturing and clinical infrastructure needed to turn mRNA into an actual product.

#161In 2020, all of those separate lines of work suddenly became useful at the same time.

#162That November, Pfizer and BioNTech reported that their vaccine showed roughly 95 percent efficacy against COVID-19 in the pivotal trial analysis.

#163Moderna's vaccine also produced strikingly strong results.

#164For decades, the question had been:

#165Can mRNA really become a medicine?

#166Now the question was becoming:

#167How quickly can we make it?

#168On December 18, 2020, Karikó and Weissman sat down at Penn and received the Pfizer-BioNTech vaccine.

#169More than two decades earlier, they had met while competing for time at a copier in the same university.

#170Then they had watched human immune cells react aggressively to laboratory-made mRNA.

#171They had spent years asking why.

#172They had found a way to reduce that reaction.

#173They had published it.

#174And for years, almost nobody had called.

#175Now people around the world were receiving vaccines built partly on the scientific path that followed from those experiments.

#176Karikó and Weissman rolled up their own sleeves.

#177And the mRNA went into them.

#178On October 2, 2023, Karikó called Weissman.

#179This time it wasn't an early-morning research idea.

#180They had won the Nobel Prize in Physiology or Medicine.

#181The Nobel committee wasn't saying that Karikó and Weissman had single-handedly invented the COVID-19 vaccines.

#182Its citation was more precise.

#183They were honored for discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19.

#184It was the problem they had been working on in the experiments that led to their 2005 paper.

#185The two scientists who had once argued over a copier were sharing a Nobel Prize 26 years later.

#186But even that isn't a clean ending to the mRNA story.

#187After COVID-19, the platform expanded into other vaccines and kept moving toward one of its much older ambitions: cancer treatment.

#188In 2026, one personalized mRNA treatment program for melanoma reported successful Phase 3 results.

#189Around the same time, another mRNA program in colorectal cancer was stopped.

#190One worked.

#191Another didn't.

#192In that sense, the situation isn't completely different from the world Karikó knew decades earlier.

#193She didn't keep going because she possessed a prophecy that mRNA would inevitably succeed.

#194When she was demoted, she found another place to work.

#195When mRNA caused inflammation, she asked why.

#196When a paper was rejected, she submitted elsewhere.

#197When nobody called, she kept experimenting.

#198Karikó hadn't seen 2020 coming.

#199She just kept looking closely enough at the result in front of her to see the next question.

#200In August 2026, personalized mRNA cancer therapy produced two very different outcomes just days apart.

#201One melanoma program cleared a major Phase 3 hurdle. Another colorectal cancer program was stopped.

#202If the platform was built on the same basic idea, why did one trial move forward while the other hit a wall?