Molecular Biologist
She persevered with her awesome ideas, careful experiments, unnoticed successes, and the repeated sting of grant requests rejected, to provide research which aided development of the covid vaccine.
FAMILY BACKGROUND
KK grew up in a two-room adobe house with a reed roof in the small village of Kisujsallas in Hungary. Her father was a butcher, her mother a bookkeeper. There was no running water. No television or refrigerator.
They had a garden. They had pigs. KK watched a neighbor’s cow give birth. She went on excursions to a nearby forest and remembers being curious about birds, plants, nature.
EDUCATION
KK was not just a good student – she was fiercely competitive at science. By 8th grade, she ranked third best in the country in biology.
As an undergraduate at a university in Hungary, KK worked at the Biological Research Center in a laboratory focused on liposomes: bubbles that could be used to encapsulate genetic material. Hungary was then behind the ‘Iron Curtain” (under Russian influence and domination), where it wasn’t easy to order laboratory ingredients. So, the scientists looked up how to purify the phospholipids needed for their experiment. The investigator who ran the lab rode his bike to the slaughterhouse to pick up a cow brain so they could make their own phospholipids.
“This is the way I learned science, always, that there is no problem. You cannot buy something? You make it,” KK said.
In graduate school, KK started working with RNA.
Editor’s note – RNA stands for ribonucleic acid, a molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. RNA and DNA (deoxyribonucleic acid) are nucleic acids. Along with lipids, proteins and carbohydrates, nucleic acids constitute one of the four major macromolecules essential for all known forms of life.
KK wrote and defended her PhD thesis while pregnant with her first child after marrying several years earlier.
THE LONG, OFTEN DIFFICULT PATH, OF A SCIENCE RESEARCHER – YOU MUST LOVE YOUR WORK TO PERSEVERE!
Eventually, the lab where KK was working, lost its funding. She looked for an opportunity in the United States, settling on a postdoctoral position at Temple University in Philadelphia.
The family bought one-way tickets and sold their car, smuggling the money inside a big brown teddy bear with red-rimmed eyes. A seam runs down its back, where KK performed the ‘surgery’ on the bear. She keeps it in her daughter’s childhood room to this day.
KK worked at Temple for three years. Then, she got a job in Bethesda, Maryland (several driving hours from Philadelphia), living there most of the week. She would read science papers until the library closed at 11 p.m., then stay at a friend’s apartment or simply spread a sleeping bag out on the office floor. At 6 a.m., she would start her experiments and go for a run.
Eventually, KK got a job at Penn’s medical school, a junior position that had the word “Professor” in the title but was off the prestigious and secure ‘tenure track’. She would need financial grants or friendly colleagues with extra funding to support her work.
KK worked first with a cardiologist. Together, they showed that messenger RNA could trigger human cells to pump out a complicated protein on demand. It was a ‘proof of concept’ that opened the door to an array of medical applications.
After new blood vessels are stitched into patients for heart bypass surgery, about 10 percent of the blood vessels will close during the first year, mostly because of blood clots. KK and the cardiologist wanted to pretreat blood vessels, by flushing through them messenger RNA that encoded therapeutic proteins. They hoped it would reduce the risk of a dangerous clot after surgery.
A gene therapy scientist (“GT”) joined Penn a few years after KK and occupied a neighboring lab bench. GT had enough money in her science budget to hire a lab technician but not enough to buy equipment. KK recognized GT’s plight, giving GT an old refrigerator, which had been KK’s “first precious piece of lab equipment”.
There weren’t many tenured female faculty then and the ones GT knew did not have children. When GT asked another faculty member if she would take a vacation that year, the scientist said during the last week of August, she planned to leave at 5 p.m. and play golf every evening for that week – in other words, that was the scientist’s idea of a vacation.
HOOKED ON SCIENCE
GT realized: “This is tough. I don’t know if I can do that. But we (GT and KK) both decided to ‘put on the jets.’ We ran a hand-to-mouth campaign (for university and outside grants support), but we were both so hooked on the science.”
As a PhD in a clinical department run by physicians with medical degrees who saw patients, KK was viewed by others there as a “second-class citizen”. At some point, KK sensed there was apparently not an interest in having her get promoted – and in fact, “KK talks about it as being demoted,” said a biologist colleague. “It released her from the idea that she had to do this stuff (always be deferential to senior management) to climb the promotion scale. She could focus on her science. But in reality, I felt bad, because it was clear she was so bright and had such good ideas.”
BALANCING FAMILY AND CAREER
KK is low-key about the difficulties of balancing family life with professional struggles. She often says her daughter learned to get up, get dressed and take care of herself. She tears up a little remembering how little money she and her husband had.
KK’s daughter remembers her childhood differently. It’s true, she never saw her parents relax. Spring break meant a week hanging out in her mom’s lab because there was no money for a vacation. But there was close-knit joy in their family – and deep pride in one another’s work.
KK’s husband remodeled their house after his workday ended and built much of their furniture. KK was busy with work but found time to cook Hungarian food and bake chocolate cakes from scratch. The daughter would do her homework, then hear the distinctive rattle of her mother pouring peanut M&Ms into a dish. The daughter would run downstairs, and they would take a family break together.
MAINTAINING THE PERSPECTIVE OF A SCIENTIST
KK was obsessed with messenger RNA, but colleagues say she also knew not to fall too deeply in love with any specific outcome and to learn from the data – even when it was disappointing. “Experiments never err, your expectations do,” DD likes to say, paraphrasing Leonardo da Vinci.
DL began working with KK in a lab while he was a medical student. He was impressed with KK’s compulsive energy. She would spend a long day at work and then show up the next morning with a stack of new scientific papers, already highlighted, for him to catch up on.
Later, when DL was in his neurosurgery residency, he learned that KK was about to have her lab defunded at Penn. He pleaded with Penn’s neurosurgery department chair to take her on because he wanted to keep learning from her.
Together, DL and KK worked on the idea of delivering messenger RNA to the blood vessels of the brain. It was a potential therapy for people suffering cerebrovascular spasm, a complication after certain types of strokes, when blood vessels spasm and trigger secondary strokes. The messenger RNA would deliver the code for an enzyme that synthesized nitric oxide, helping to dilate blood vessels and reduce the risk of death.
CHALLENGE – KNOWING ‘THE GAME’ AND WHETHER TO PLAY IT
DL respected KK but also saw how her inability – or unwillingness – to navigate the scientific research system worked against her. The fact she was an immigrant who spoke with an accent, that she was a woman in science may have made it easier for her to be overlooked. But more than that – she didn’t play the game. He recalled KK standing up at a lab meeting and making a pointed, but accurate, critique of data being presented by a well-funded professor.
She was not asked to come back.
Her science faculty friend recalled. “She knows she’s brilliant and she doesn’t suffer fools. And the reality of American scientific research, which continues today, is that pursuit of money is high on the list of priorities. KK is kind of the opposite. She does nothing for money. The reality is, she is doing the best science she can do, and she has zero political savvy about how to navigate this world.”
TEAMWORK
In the late 1990s, KK met a shy immunologist, DW, who wanted to create an HIV vaccine and was considering different technologies. She told him about messenger RNA, touting its vast potential. She offered to make messenger RNA for one of DW’s experiments.
“I make the RNA, that is what I’m doing. I’m good at it,” said KK (in her Hungarian accent) to DW. When DW tested it in specialized immune cells he was interested in, he found the messenger RNA triggered an inflammatory response – definitely not what DW was looking for – a blow for KK.
“I was so sad,” said KK. “How did I miss that?”
Solving that problem would be the beginning of what would become a world changing scientific collaboration.
One of KK’s gifts as a scientist, her colleagues say, is her ability to design and execute thoughtful experiments, including thinking hard about the controls. A control can seem like an afterthought – a comparison run in parallel to ensure the results are really linked to whatever the scientist was testing. In a vaccine trial, the control is the group of people who receive e a placebo shot.
In KK’s experiments with her lab-generated RNA, she used as a control a naturally occurring kind of RNA, called ‘transfer RNA’. It did not trigger an inflammatory response. This was a clue.
KK and DW tried modifying their messenger RNA chemically to mimic the transfer RNA. They discovered that replacing a single letter of its four-letter alphabet could stop the messenger RNA from activating the immune system and increase tremendously the amount of protein cells produced.
They published their findings and patented the work. A year later, KK and DW founded a company RNARx, to commercialize this modified RNA, winning a small-business grant from the NIH (National Institutes of Health) with the idea that messenger RNA could be used to treat anemia.
The idea was ahead of its time.
Two biotechnology companies – BioNTech in Germany and Moderna in Massachusetts – would recognize the potential even as RNARx struggled to find investors.
As biotech interest began to heat up outside their lab, the pair kept working on the science. Another scientist (NP) who coincidentally had grown up in Hungary, had been meeting with KK every summer since he was in college. He came to Penn to work with KK and the immunologist after he earned his PhD.
They had solved one problem – the immune reaction caused by messenger RNA – but still faced a different one: How would they get this incredibly fragile material into the body? NP worked on that.
KK taught him everything she knew about RNA. Typically, as scientists move through their career, their labs get larger, and they spend less time running their own experiments. But KK didn’t have that success, and she also loved, and was unusually talented at, the benchwork.
“KK taught me a lot, everything, about RNA,” said NP.
By 2013, KK had retired from Penn as a senior research investigator. Her academic career looked nothing like a traditional success. But KK wasn’t done. She wanted her work to reach patients. She joined BioNTech, then a little-known start-up company that had never created an approved medical product. She would live in Germany for 10 months out of the year.
“I could sit here in Pennsylvania and see the grass growing,” KK said, looking out on her wooded backyard in the Philadelphia suburbs. “And then I decided to go to Germany, to a biotech company that didn’t have a website, leaving my husband and my family behind. What the hell am I doing? For one week, every night, I cried myself to sleep.”
CAREER SATISFACTION
When the coronavirus pandemic hit in early 2020, the questions KK had chipped away at on the margins of molecular biology became the red-hot center of science and medicine. KK’s fierce dedication, once seen as quixotic, was recognized as visionary. Her work undergirds coronavirus vaccines from Pfizer and German partner BioNTech and Moderna.
The vaccine effort is far bigger than any one scientist’s dream. When the credits roll, a constellation of researchers, crisscrossing scientific disciplines and stretching back more than half a century, will get mentioned. But KK and her immunologist partner who she met at a photocopier nearly 25 years ago, will be two of the stars.
“I think she should be given credit for saving the world,” said a gene-therapy scientist at Penn, who occupied the lab bench next to KK when they were starting their careers. Her ideas were “so ahead of her time, she had a hard time convincing people that they would actually work. They seemed too ‘science fiction-y’ to people and too challenging.”
KK had failed, repeatedly, to win the grants that would help give her scientific independence. It might have been easier to temper her impatient enthusiasm and direct her efforts toward mainstream topics. But with tenacious, almost fanatical energy, she simply worked harder – arriving at the lab at 6 a.m. on weekdays and working nearly every weekend.
By mid-2021, as if making up for lost time, KK and her original science partner, have scooped up nearly every major award in science and medicine and both are considered contenders for a Nobel Prize.
KK looks at the setbacks differently. The years without money, fame or prestige and the times she brought broken-down lab equipment home for her husband to fix or saved Hungarian pickle jars to store the ingredients for her experiments – these were essential. She wasn’t working for anyone else’s idea of success. She was working for herself.
KK remembers when, years ago, she overheard a colleague telling another scientist, “KK works for me.”
KK immediately spun around to face him. “I don’t work for you. Do you think that Saturday, Sunday, I am here for you?” she asked. “I am here for me. I am here to learn more and understand.”
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This career story is based on several sources: primarily an article written by Carolyn Y. Johnson, published 10/1/21 (probably by The Philadelphia Inquirer or possibly The New York Times -oops, this Editor cannot tell which, from the printed copy he retained) and by online research, including Wikipedia.
