Big science verses smart questions

I feel that I have spent my career doing ‘small science.’ The research that made up my PhD and post-doctoral studies involved annual requests for funds simply to cover my research costs. Winning one of the big grants that brought bounteous funding, allowed you to plan ahead and gave career security was always out of my academic reach. We were also involved in research during the early days at Niche but we were little more than small cogs in large scale endeavours. That said, I believe that the Niche team made its own tiny contribution to human progress. In 2012 an opportunity arose for us to join a consortium undertaking what can only be called ‘big science,’ and since we have been involved in three such programmes.

A close observer of scientific enterprise might notice that it is often divided into these two paradigms: ‘big science’ and ‘small science.’ Big science refers to large-scale, collaborative projects funded by high-value grants, often involving expensive infrastructure, such as particle accelerators, space telescopes, or genome-sequencing initiatives. Small science, on the other hand, focuses on addressing specific, often narrowly defined questions, typically with modest funding and smaller research teams. While both approaches have their merits, few scientists get to work on the big-ticket items. And that raises the question, do big budgets outperform the efficiency, adaptability, and serendipitous discoveries associated with the more modest approach? My own experience suggests that small science not only provides answers to difficult questions more rapidly but also fosters unexpected secondary understanding and advancements.

Going big

Big science has been instrumental in addressing some of mankind’s most profound questions but it has required extensive financial and infrastructural support. Though they have not had the same impact as the Human Genome Project, the Large Hadron Collider (LHC), or the Hubble Space Telescope, our multimillion pound projects like our RASP-UK (www.rasp.org.uk), MID-Frail (www.midfrail-study.org) or Frailomic (www.frailomic.org) projects have yielded transformative insights. These societal investments are often justified by their ability to tackle grand challenges. Large-scale projects enable the collection and analysis of vast datasets that would be impossible for smaller teams to handle. Many technological breakthroughs, such as the development of CRISPR gene-editing technology, have emerged from large-scale initiatives [1]. Big science is not without its limitations. These projects involve high levels of bureaucracy and are resistant to changes in focus, limiting their ability to adapt to new scientific questions.

For example, big science projects often take years or even decades to plan, fund, and execute [2]. The LHC took nearly 30 years from conception to the discovery of the Higgs boson in 2012 [3]. During this time, smaller-scale experiments in particle physics continued to make incremental progress, refining theories and exploring alternative models. In our own projects, the incremental advances in understanding during the course of our projects have always outpaced the project outcomes. For example, in the few short years between us conceiving and reporting of our Frailomic and RASP-UK projects there had been a step change in biomarker understanding that we could not have predicted.

It is well-recognised that high-value grants are often awarded to established researchers or institutions, potentially sidelining younger or less conventional scientists who may have innovative ideas [4, 5]. This bias serves to stifle creativity and limit the diversity of approach. Large projects are often rigid in their objectives, making it difficult to pivot or explore unexpected opportunities. For instance, the James Webb Space Telescope, while groundbreaking, has faced numerous delays and cost overruns, limiting its ability to adapt to new scientific priorities [6, 7].

Pocket-sized pondering

So is bigger better? Small science, characterised by targeted, incremental investigations, offers several advantages over big science. By breaking down complex problems into smaller, more manageable problems, researchers can achieve rapid, incremental progress and adapt to new findings. Limited resources drives researchers to explore alternate means to gaining answers using a fraction of the resources – it makes you ask smarter questions [8].

Small science projects often yield results more quickly than large-scale initiatives. For example, the discovery of CRISPR-Cas9 as a gene-editing tool emerged from basic research on bacterial immune systems, funded by modest grants [1]. This discovery revolutionized molecular biology long before larger genomic projects could achieve similar outcomes. Similarly, the discovery of helicobacter pylori as a causative agent of ulcers was made by a small research team working with limited funding [9].

Small science is particularly conducive to serendipity. Because researchers are often exploring uncharted territory, unexpected findings are common. For instance, the discovery of penicillin by Alexander Fleming arose from a small-scale investigation into bacterial cultures [10]. Similarly, the development of the polymerase chain reaction (PCR) technique, which transformed molecular biology, was the result of a small, curiosity-driven project [11]. The invention of the microwave oven resulted from Percy Spencer’s curiosity when he noticed a candy bar melting in his pocket while working with radar technology. Investigating this unexpected phenomenon, Spencer developed the microwave oven, revolutionizing cooking methods and creating a multibillion-dollar industry.

Small science allows researchers to pivot quickly in response to new data or emerging opportunities whereas big science projects are constrained by their scale and funding structures. Small science allows early-career scientists and unconventional thinkers to explore radical hypotheses without the constraints of bureaucratic funding structures [12].

?Conclusion

A key advantage of small science is its alignment with the incremental nature of scientific progress. By focusing on smart questions—specific, well-defined problems that can be addressed with available resources—researchers can make steady progress without the need for large-scale funding. This approach is particularly important in an era of limited research budgets and increasing competition for grants. From my own observations I can say that you often find that advances emerging from small science often keeps apace with readouts from large-scale studies. This democratisation of science can lead to a greater diversity of ideas and approaches. Small science allows for rapid iteration and refinement of hypotheses. This iterative process is essential for scientific progress, as it enables researchers to build on previous findings and explore new directions.

While big science has its place in addressing grand challenges, small science offers a more efficient, adaptable, and serendipitous approach to scientific discovery. By focusing on smart questions and incremental progress, small science can provide answers to difficult questions more rapidly and foster unexpected secondary learnings. To maximize scientific innovation, funding agencies should prioritize a balanced ecosystem that supports both big and small science, with an emphasis on flexibility, diversity, and curiosity-driven research. For me, small science wins every time.

?References

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6. National Academies of Sciences, Engineering, and Medicine. (2021).?Assessment of the James Webb Space Telescope. National Academies Press.
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8. Ioannidis JPA. (2011). More time for research: fund people not projects.?Nature, 477(7366), 529-531.
9. Marshall BJ, Warren JR. (1984). Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.?The Lancet, 323(8390), 1311-1315.
10. Fleming A. (1929). On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenzae.?Br J Exp Pathol 10(3), 226-236.
11. Mullis KB. (1990). The unusual origin of the polymerase chain reaction.?Scientific American, 262(4), 56-65.
12. Fortunato S, et al. (2018). Science of science.?Science, 359(6379).

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