Katalin Karikó: learning from failure

Posted 03 November 2023
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By Henry Oliver
Contributing Author
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Of all her admirable qualities—persistence, dedication, disinterested pursuit of science—what stands out the most is Karikó’s ability to learn from failure.

‘Things could have gone so differently, for the scientists and for the world.’ That was what David Langer said about his colleague Katalin Karikó, the recent Nobel Prize winner, who invented the technology behind the COVID-19 vaccine with her research partner Drew Weissman. Karikó spent her career researching mRNA, despite innumerable failures. She is a lesson in the ways that failure can lead to success.

Karikó received her PhD in Hungary in the late 1970s, after learning about mRNA as an undergraduate. In 1985, the University of Szeged, where Karikó worked, ran out money for its research programme. Karikó moved to the USA and got a job at Temple University. Four years later she was forced to leave Temple: after a dispute with her boss, he threatened to have her deported. In 1990, she went to the University of Pennsylvania to work under Dr. Elliot Barnathan. Their collaboration showed initial promise with a groundbreaking experiment, but when Barnathan left for a biotech role Kariko found herself once again without funding or a lab. She was adrift.  ‘They expected I would quit,she told Gina Kolata.

David Langer brought her into his lab. But their experiments together  failed. And then he too left the university, as did the department chair. She was alone. And the failures were huge. When they injected animals with mRNA, the animals died. The university told Karikó she could only continue by taking a demotion. There was no funding and no belief in her work. 

Karikó took the demotion and stayed at Penn. She was constantly working to try and secure funding. ‘Every night I was working: grant, grant, grant,’ she told Danian Garde, ‘And it came back always no, no, no.’

Because she stayed at UPenn, she met a new faculty member, Drew Weissman. Despite the failures, she confidently told him she could make an mRNA vaccine for AIDS. They started working on the problem of why the mRNA was killing animals, but almost all of their grant applications were rejected. Karikó is not a good grant application writer, which is one of the reasons she was demoted. (When she worked with Weissman, she was earning less than her lab technician.) One of her former colleagues recalled about her career setbacks, ‘Karikó’s history was still only discussed in hushed tones as a cautionary tale for young scientists.’ As he said, ‘Usually, stories like Karikó’s end in obscurity and disappointment.’

Weissman secured funding. By 2005, when Karikó was fifty, they published a paper, after several leading journals turned them down. Weissman told the journalist Ting Yu, ‘I told Kati our phones are going to ring off the hook, but nothing happened. We didn’t get a single call.’ They spoke to venture capitalists and pharmaceutical companies, to no avail. In 2013, Karikó left the University of Pennsylvania to work at BioNTech. She told David Cox that the university (which had decided she ‘wasn’t faculty quality’) laughed about BioNTech because it didn’t have a website. BioNTech later developed the covid vaccine. Karikó and Weissman’s paper had also been read by the founder of Moderna, another firm that developed a covid vaccine.

Of all her admirable qualities—persistence, dedication, disinterested pursuit of science—what stands out the most is Karikó’s ability to learn from failure.

A 2019 study of failure which looked at large data sets of science funding applications, startup exits, and terrorist attempts, found that failure tends to happen as much to the people who later succeed as to those that don’t. What matters is not how much failure you experience—everyone experiences plenty; what matters, is how you react to failure.  Success is based on incremental improvement after each attempt, and quickly coming back to try again after each failure. That is the dynamic that distinguishes the ultimate successes from the ultimate failures. 

Not every failure is valuable. Some people keep failing, without learning from their mistakes. That’s what happened with Karikó’s grant applications. But she did learn from her failures in the lab. Without her collaboration with Weissman, who was able to write  grant applications, Karikó may not have succeeded. But she was able to learn from the failures of her experiments and to keep failing, iterating towards the answer. As the MIT Technology Review put it, “a team’s learning process is a good indicator of whether or not it will succeed at some point.”

Failure gives you experience and feedback which you can put to good use. But simple repetition isn’t rough. Failing faster is a key indicator of success. And with each attempt you need to find “a balance between reusing what you did well, versus creating and recreating and improving on those you didn’t do quite well.” As well as incremental improvements, to succeed, you must be learning from failure at a high enough rate. 

In this, Karikó embodies Edison’s advice: many of those who give up don’t realise how close they were to success. She kept failing, at a high enough rate, that once she found her partner—a sadly delayed process—she was able to turn her experience into success. She demonstrates the truth of what Marc Andreessen said: failing forwards and failing fast is a good idea for tactics, but not for strategy. Andreessen warns against letting short-term metrics district startup founders from their ultimate goal. Karikó was never diverted from mRNA—even when the whole field seemed so unpromising many other researchers left it to work on other problems. She knew where to take the feedback: the university thought her results meant she should quit; she knew they meant she should try another way.

What distinguished Karikó was her risk appetite. Matt Clifford and Alice Bentick have talked about the way successful founders can thrive without lots of resources and clarity. Working with uncertainty, with limited means—going from zero to one—is the hallmark of founding a company. Karikó is a lesson in the alchemy of turning failure into success under those conditions. She had a personal competitive advantage, what Clifford and Bentick call “Edge”, but she worked in institutions where that mattered much less than her ability to write a grant application.

The bureaucracy of academic funding and talent assessment was unable to see Karikó’s potential because they measured conformity with a process. But Karikó had strong internal motivation. She told Joe Walker in a recent interview that she had learned when she was young,  from a book about stress by Hungarian endocrinologist Hans Selye, that if you worry about what other people think of you, hold grudges, or, compare yourself to people getting promoted ahead of you, it distracts you from your work, and from succeeding. From Selye, she learned: “You have to always end every conversation in your mind with ‘What can I do?’” 

Even in response to biassed teachers, when confronted with hostile management, dealing with lack of funding, or faced with the loss of colleagues, Karikó asked herself this question. That was how she could learn from her failures, by always saying “What can I do?”

Henry is a writer, with a book about late blooming talent coming out next year. His Substack, The Common Reader, focusses on biography, literature, philosophy, and talent. In 2022 he was awarded an Emergent Ventures grant.