Katalin Karikó, a biochemist and researcher, is best recognised for her pivotal role in advancing mRNA technology, notably evident in the development of COVID-19 vaccines. In 2023, she was awarded the Nobel Prize in Medicine alongside Drew Weissman for their discoveries in enabling the modified mRNA technology used in Pfizer-BioNTech and Moderna’s vaccines to effectively prevent COVID-19 infection. While the world celebrates Karikó’s achievement, details of her arduous journey to success, spanning over 40 years, only began to surface following the global pandemic of 2020 to 2022.

We almost lost a world hero

Karikó, a Hungarian immigrant to the US, earned her PhD in biochemistry with a focus on RNA science in Hungary in 1978. In the 1980s, she relocated to the US with her family after losing her job in Hungary. Despite settling in the US, she lost her job twice before securing a position as a non-tenured research assistant professor at University of Pennsylvania, an Ivy League institution. During her stint at University of Pennsylvania, Karikó passionately pursued her research on messenger RNA as a potential vaccine. However, she encountered significant hurdles in acquiring funding and publishing in top scientific journals due to the then-limited interest in RNA vaccine therapy. Additionally, the instability of messenger RNA compared to DNA and its potential to elicit immune responses presented formidable challenges. However, a chance encounter with colleague Drew Weissman in 1998 at University of Pennsylvania led to a breakthrough. Together, they demonstrated how a specific modification in messenger RNA could reduce immune responses, thereby enabling the therapeutic use of modified synthetic messenger RNA without triggering an immune response. Karikó’s groundbreaking discovery laid the groundwork for mRNA-based gene therapy, which played a pivotal role in the rapid development of COVID-19 vaccines amidst the pandemic in 2020.

Prior to the emergence of COVID-19, Karikó’s career trajectory would be best described by many academicians as unremarkable, and some may even label her as an under-performer within the academic community due to her inability to secure research funding and publishing her findings in high-impact journals. It was only during the global pandemic that the world came to recognise the significance of Karikó’s contributions to science. Prior to this, she was passed over for a tenured professor position at the University of Pennsylvania and was even demoted, compelling her to part ways with the university in 2013. Despite these obstacles, the world emerged from the COVID-19 pandemic nightmare between 2020 and 2022, largely due to Karikó’s unwavering tenacity, laser-sharp focus on her research ideals, and determination in holding on relentlessly to her beliefs.

Karikó’s predicament

Karikó’s experience sheds light on the systemic issues within academia, where university researchers often face immense pressure to pursue trendy fields of science and technology in order to secure research grants and have their research published in high-impact scientific journals—criteria typically used to gauge academic success. Researchers like Karikó approach grant agencies, which can range from government ministries to private organisations, with proposals and these agencies assign reviewers to evaluate proposals and determine grant recipients. Unfortunately, research in “hot” areas, aligned with prevalent national policies or private foundations’ focus, are prioritised over exploratory research in areas that may not yet have immediate applications for the broader public. This trend stifles innovation and discourages researchers from exploring unconventional avenues that could hold significant promise for future breakthroughs.

Karikó’s journey underscores the lengthy and demanding nature of research, characterised by continual questioning, hypothesis refinement, and optimisation before achieving a fundamental understanding of the subject under study. This prolonged process places significant financial strain on university scientists, who must continuously seek research grants to cover manpower costs and procure necessary materials and equipment. Unfortunately, research endeavours lacking immediate, tangible outcomes often receive lower priority in the eyes of grant reviewers. Consequently, innovative “blue sky” ideas—creative concepts that may appear unconventional but hold the potential for groundbreaking solutions to future challenges—often languish due to researchers’ struggles in securing sufficient funding to sustain long-term research efforts required for their development.

This is the reason some people consider the development of the COVID-19 vaccine a “miracle”—not solely due to its life-saving impact, but also because many academics, confronted with the same immense challenges that Karikó faced, would likely have abandoned the pursuit of “blue sky” ideas to avoid career setbacks and financial instability. So, how can we foster the growth, development, and success of curiosity-driven, visionary concepts that hold potential to address future global challenges and, like Karikó’s mRNA discovery, potentially reshape the world?

Incentivising “Blue Sky” research

Universities can enhance their support for novel, “blue sky” research ideas across all disciplines by ensuring equitable funding and exposure opportunities alongside more mainstream research areas. This can include providing platforms for conference presentations, newsletter features, and media coverage. Establishing research grants specifically aimed at nurturing “blue sky” ideas can further incentivise academics to explore unconventional territories. For such grant systems to be effective, the review panel should comprise academics and non-academics such as those from the commercial or industry sectors. In the academic realm, professionals with a proven track record in unconventional research areas and representing diverse backgrounds should be included to evaluate ideas beyond disciplinary boundaries. These grants should prioritise the merit of novel and innovative ideas over the status of staff members, short-term returns in the form of publications, patents, industrial collaborations and more.

Universities can also cultivate a “blue sky” culture starting from individuals that are not bound or constrained by the existing research system, by offering small grants to students at the undergraduate level with promising “blue sky” proposals through a competitive selection process. These students would be provided with research laboratory space or equivalent in the case of non-laboratory research fields, and a mentor would be assigned to support them in exploring their unconventional ideas. Upon completion of their “blue sky” projects, students would earn academic credits towards their graduation requirements, thus fostering a culture of risk-taking and innovation among the student body.

However, for this “blue sky” culture to thrive, university management and staff must be committed to fostering it. The immediate rewards of pursuing research in “hot” areas often prove too tempting for researchers to resist, while the uncertain nature and lengthy development process of “blue sky” projects may deter rather than attract them. In this regard, the criteria for evaluating the research performance of staff members can be revised. In addition to traditional metrics such as the number of grants, publications, and citations, researchers can also be assessed for their willingness to embark on “blue sky” studies that may take a longer time to come to fruition.

Lesson for academia

So how do we evaluate the success of all these “blue sky” projects? Traditional metrics used for evaluating academic achievement remain relevant but could be accorded reduced weightage, and emphasis should instead be placed on appraising the evolution of ideas, their potential impact within the respective field, and the broader applicability across disciplines. While this evaluation approach may appear subjective and prone to bias compared to metrics like grants and publications, it is less likely to impede the maturation and exploration of “blue sky” ideas, which often require more time for acceptance and support within academia.

In recent years, the concept of “blue sky” research has been steadily gaining traction among Asian universities. In 2022, Hong Kong Baptist University introduced the “Blue Sky Research Fund”, committing HK$6 million (approximately S$1.02 million) to support curiosity-driven research projects. During the fund’s public forum to announce the recipients, Professor Kwok Ngai Ho, then Vice-President of the university, highlighted that “unexpected scientific breakthroughs may sometimes hold more value than research outcomes driven by specific agendas. However, the former may require several years or even decades to materialise.” Prof Kwok emphasised that the essence of scientists and intellectuals lies in their continual challenge of the status quo, underpinning the university’s commitment to foster “blue sky” research. He anticipates that through this innovative “Blue Sky Research Initiative,” the university will soon witness the emergence of numerous groundbreaking ideas and technologies.

It is probably true that the success rate of “blue sky” projects may be markedly lower compared to established “hot” area projects. Some may even argue that universities, especially those which are less financially well-endowed, should avoid such endeavours due to the lack of immediate returns in terms of industry funding and academic recognition. However, the case of Katalin Karikó challenges this notion. Her groundbreaking work contributed to preventing nearly 20 million COVID-19 deaths across 185 countries within the first year of vaccination rollout. Notably, companies like Moderna and Pfizer have collectively generated over US$100 billion in global revenues from vaccine sales. These achievements stem from the relentless pursuit of Karikó’s “blue sky” ambition, despite facing challenges as a non-tenured and unfunded researcher. The global pandemic underscores the importance of supporting such visionary initiatives for the betterment of future generations, serving as a compelling lesson for academia.

This piece was first written in Chinese and published in Lianhe Zaobao on 27 March 2024.