Katalin Karikó’s neurosurgery department chair kept asking her about hitting his preferred metric of “dollars per net square footage,” in terms of funding her lab time with grants, or even prestigious publication. It’s amusingly anodyne and corporate when recounted by a now eminent scientist, who had just told her boss about beginning to collaborate with a cross-disciplinary immunologist Drew Weissman, with whom she would later share the Nobel Prize.
That’s from Breaking Through: My Life in Science, the October 2024 autobiography by biochemist Katalin Karikó, who shared the 2023 Nobel Prize in medicine for her work on mRNA which contributed to the rapid deployment of the covid-19 vaccine. I admire her greatly.
In an over-simplification, cell and gene therapies directly influence DNA, whereas her research focused on using mRNA to send a temporary message to cells. mRNA is considered more unstable and difficult to work on, so it had long been dismissed as not an effective means of treatment. She’s become a canonical example of a delayed payoff for hyper-fixation on a particular problem (almost 20 years with limited academic or industry recognition).
The autobiography is an enjoyable read, starting with her being raised in Soviet Hungary. She criticizes the surveillance system, but remembers fondly its elevation of science and spotting kids with promise from households with less education. She remembers that her school transcripts always had an “F”, for “fizkai” to clarify her parents had worked “physical” jobs and were low educated, which got her extra attention from educators in communist Hungary.
She says half of her elite biology college cohort came from this working class tradition: can any elite American institution claim this?
Below I share my notes for future reference.
My notes:
- She was born January 17 1955 in Szolnok, Hungary, then part of the USSR
- Her childhood memories include a “town griot” (oral historian) announcing on horseback that next Tuesday there will be a chicken vaccine — everyone spreads the message at the town water pump and then the vet students come, her first vaccine
- The first “biochemist” she met was the old woman who advised them on seasonally making soap with fat drippings from the smokehouse and sodium carbonate
- “History, of course, happens to children too”
- Her mother has 8th grade education; father a butcher who had gone to sixth grade, and was assigned to a collectivist butcher where her parents met
- 1956 Hungarian uprising
- In 1950s , Hungary used education and healthcare to prove socialism over capitalism
- Salk polio vaccine (developed in the 1950s at University of Pittsburgh) and then the Sabin spoonful (oral polio vaccine): 1969 Hungary cured polio before United States by 10 years (through willingness to adopt the vaccine)
- Author started off getting 4s in school (kinda like B’s in the American system), not naturally gifted but worked hard to 5s (A’s)
- Story of her father telling her some military veteran she was assigned to interview for a school essay was “a bullshit man” and that stuck with her: some bullshit men get praise
- She remembers the biology club teacher in high school who thought she could be a scientist before she did.
- That teacher Mr Toth (with accent over the o) also had her read The Stress of Life by Hans Syle (1956) which shaped her
- Syle: nature “rarely replies to questions unless they are put to her in the form of experiments”
- Her school transcripts had an F next to it for “fizkai” to clarify her parents had worked “physical” jobs and were low educated— which got her extra attention from educators in communist Hungary
- She says half of her elite biology college cohort came from blue collar: could American institutions have this?
- Later stage “goulash communism”was less repressive — “the happiest barrack in the communist camp”
- In her graduate lab they needed phospholipids to make Liposomes, then a new science, but couldn’t buy them commercially in communism so classmates went to a slaughterhouse to buy a cow’s brain and brought it to the lab to extract these naturally occurring lipids
- 1978: secret police arrive at her apartment and ask her to spy on her BRC colleagues, had already visited anonymously her father tending bar back home in the pub, though she says she never offered them anything
- “Looking back, I wonder if that is the most insidious part of a society that asks its people to turn against one another, to report one another to the state – not so much what does happen, but rather the way we are left wondering about whether and how much the events for our own life were influenced by forces just out of sight.”
- Her husband let her focus on work, they did not exchange last names
- Gave birth in November and back in lab by February. How to be a scientist and a mother? “The answer is simple, obvious: one needs high-quality and affordable childcare as I had in Hungary.”
- RNA is unstable and short lived by design, difficult to experiment on, so conventional wisdom was that it wasn’t worth working on
- RNases are very common enzymes that degrade RNA. They’re so ubiquitous that RNA researchers joked that if you want to decontaminate your lab of them, just demolish the building
- Of her father passing: “the long night that is grief”
- January 17, 1985: Kariko takes bus to work and is told her funding from the pharma company had ended. Just a few options in Europe, and they all declined to hire her without funding. She told her husband “I think we have to go to America”
- She sent her 2-5a paper to Robert Suhadolnik, a leading nucleoside analogues researcher and biochemistry lab at Temple University who offered her a $17,000 post doc role for a year (roughly $50,000 in 2025 dollars), with a j1 visa at Temple
- The famous teddy bear that she stitched their $1200 USD in 900 British pounds to sneak out of Hungary — her daughter Susan’s Bear and this got a lot of press attention
- Doctor rented her an apartment in Lynnewood Gardens (suburban Elkins Park): Her and husband stare at fireflies that night out after a long day of travel: Budapest to Brussels to NYC to weather delayed Philadelphia. In the darkness, insects they don’t have in Hungary looked magical
- She found her Temple lab in 1986 full of cockroaches, dirty, cluttered and messy compared to hers at BRC in Hungary
- “There were levels to Americas, destinations within destinations” (the swimming pool with a membership she couldn’t afford)
- Her Temple boss always yelling and slamming doors, including Regan era funding cuts: when she accepted an offer at John’s Hopkins, he told her to leave the lab but wouldn’t let her her use the phone to get a ride home
- Relocating to Bethesda, Maryland: spent off hours reading all the academic papers she could find and extra lab time, while husband and daughter stayed in suburban Phila until her Penn job
- Her “series of unfortunate events” that made her a cautionary tale over three distinct Penn episodes
- Penn’s Elliot Barnathan whom she liked gave her the job after seeing the Northern blot showing she isolated RNA in a sample in a way that was very hard to do then
- Da Vinci: experiments never err, only your expectations do
- Bill Kelley took over the role as Dean of Penn medical school, Jim Wilson as institute head and they were t interested in mRNA: they were all in on gene therapy (directly influencing DNA rather than using mRNA to send a message
- Then Penn hired Ed Holmes who hired his wife Judy Swain (signaling internal politics)
- At a talk she gave at Temple with her old angry boss in the audience, she chose to say how grateful she was that he helped bring her to United States— which was true and lightened the mood even if she could have shared less flattering details of his temper too. She did it for her so she wouldn’t stay stuck in the past
- After 5 years at Penn, she hadn’t brought in grants or funding so she was out so she asked to take a demotion to stay and focus on her work
- December 1996: we had successfully used mRNA to make a specific protein inside a cell
- Elliot accepts Centocor job with his patents, but helpfully young David has risen through ranks and gets her job in neurosurgery as molecular biologist
- She met Drew Weissman at the photocopier where she went in 1997 to get copies of journals. She had only been interested in mRNA therapies until Drew’s work in HIV made her consider vaccines; he and his team were coincidentally looking for a way to deploy mRNA at that time
- mRNA vaccine for HIV or otherwise , instead of delivering the antigen the mRNA vaccine provided instructions for making the antigen inside the cell
- Jesse Gelsinger’s unfortunate death (September 1999) at Penn slowing gene therapy research
- Her neurosurgery department chair Sean kept asking her about hitting his metric of “dollars per net square footage” in terms of funding her lab time, as she told him about her work with Drew Weissman
- Identified how to avoid inflammation and deliver the mRNA: Wrote their paper, got rejected by prestigious Nature, nearly got rejected by Immunity but even then when published got hardly any attention — not seen as a breakthrough. They started their own company to commercialize
- Moderna founded in Cambridge; the vc firm FHA backed it asked author about their patent but it was with Penn whose tech transfer office had licensed it to another firm (Cellscript)
- Told “not of faculty quality” when she tried to get reinstated after he mRNA breakthrough
- Her daughter won two gold medals in rowing
- May 2013, neurosurgery chair Sean Grady had her stuff removed from her lab — 17 years without meaningful funding
- She approached her former beloved supervisor to be CEO of their company and it didn’t take — but Moderna raised billions. She considered working at Moderna but chose BioNTech instead
- BioNTech moved all resources to the Covid vaccine — trying to beat the fastest-ever vaccine, for mumps in 4 years in 1960s — then verbal agreement with Pfizer
- STAT story: the story of mRNA how a once dismissed idea” (Nov. 2020) brought her to prominence, then Guardian story led with her
- BioNTech Pfizer and Moderna relied on their invention of modified uridines
- She recalls an academic hero of hers who gave a lecture that sadly showed he hadn’t stayed up to date on the literature after his success (she vowed to not do the same)
- “There is such a gap between what people know and what they would need to know to fully understand the vaccines and medicines that save lives. That gap right now is wide open for exploitation. We must somehow close it.”
- What if science journals went online sooner (so she didn’t have to use the photocopier) and she never met drew Weizmann at the photo copier
- “The mRNA molecule exists temporarily, to deliver a message”