Can Science Still Afford Serendipity?

A few years ago, Caetano Reis e Sousa, an immunologist at The Francis Crick Institute, and his team were investigating how the immune system detects tissue damage. They were specifically exploring the role of Gc globulin, a protein that scavenges actin filaments secreted by damaged and cancerous cells.

When they engineered Gc globulin knockout mice, the researchers observed that the animals showed tumor resistance. However, they soon noticed something intriguing: Wild type mice that expressed Gc globulin acquired tumor resistance when housed with Gc globulin-deficient animals.

Reis e Sousa and his team realized that they were treading in relatively unknown waters. “We said, ‘Okay, even if it's completely different [from the original hypothesis], maybe we should try and figure out what's happening,’” recalled Reis e Sousa.

Since mice tend to eat each other’s feces and transfer microbiota, Reis e Sousa and his team wondered whether the gut microbiome played a role in wild type mice showing tumor resistance like their Gc globulin-deficient cage mates. Through a series of fecal microbiota transplant experiments, the researchers found that the gut microbiome did indeed regulate tumor resistance.

“Then comes the bit that I never expected we would be working on, and we figured that this was quite different from everything we had done,” said Reis e Sousa. “The alternative name for Gc globulin, which is actually probably a better-known name for Gc globulin, is vitamin D binding protein.” To test whether vitamin D regulated cancer immunity, the researchers fed mice a diet rich in the vitamin. This led to increased tumor resistance, indicating that vitamin D acts through the gut microbiome to enhance anticancer immunity.¹

Through their work, the researchers serendipitously happened to demonstrate a link between vitamin D metabolism, the gut microbiome, and cancer immunity, which could potentially pave the way to better anticancer therapies.

The scientific record is peppered with such accidental discoveries that have shaped the field for centuries. From Alexander Fleming’s serendipitous observation that a mold killed bacteria—leading to the development of Penicillin—to Barnett Rosenberg’s chance discovery that platinum compounds blocked cell division—laying the groundwork for the chemotherapeutic cisplatin, science has many examples of accidental discoveries that changed the world.²

However, chance alone does not turn anomalies into such breakthroughs. Researchers note that serendipitous discoveries emerge from research environments that grant flexibility to pursue unexpected observations. As organizations slash funding and research timelines become rigid, threatening the conditions that allow scientists to follow detours, an important question looms: What happens when there is little to no room to follow the unexpected?

Atmospheres That Foster Serendipity in Scientific Research

Reis e Sousa believes that a crucial factor shaped his team’s serendipitous discovery of vitamin D influencing antitumor immunity. “We stumbled upon it because we were open to what the experiments were telling us, and we were willing to accept that we had to go where the science was pointing, as opposed to where we necessarily wanted to go in the first place,” he said.

However, he added that the willingness to stray from the original path is not the only thing that matters. “It's great to say you should follow the science but obviously you need to be well resourced in order to do that.” Backed by an institution and research grants that were not restrictive, Reis e Sousa believes he was fortunate to have the freedom to pursue unexpected observations. “It's a combination of being open to what the science is telling you but having the means of exploring it,” he said.

Russell Funk, a sociologist who studies the science of science at the University of Minnesota, agreed. “Chance favors the prepared mind,” he noted, adding that historians of science and psychologists have over time understood that a ‘"prepared mind” has two aspects: deep experience and knowledge of a subject to understand how important an unexpected observation is, and being open-minded. “Openness is something that's really valuable for serendipity.”

Wendy Ross, a cognitive psychologist who studies the role of serendipity in problem solving at London Metropolitan University, said that while openness seems to be an important factor in whether one would follow up on a serendipitous observation, there is not enough evidence to substantiate that. “What does seem to be important is having time and space and resources,” she noted.

Are Present-Day Conditions Eroding Serendipitous Observations?

Given the importance of a research environment that encourages scientists to pursue unexpected observations, Ross noted that the pressure on academics often leaves little room to stray away from their original line of enquiry. “What's actually happening in a lot of the academic research world is that the rest of the days [after teaching] are not being filled with thinking or contemplating or reading,” she said. “They’re being filled with administration tasks and things like that, which are taking the ability to pursue ideas on your own a little bit.”

Funk added, “The amount of planning and accountability and so forth that goes into current funding is really high and can make it difficult to deviate [from the original work].” This, in addition to the publish-or-perish attitude in academia, makes it challenging for scientists to pursue serendipitous discoveries. “[These] can create these blinders for us that lead us to not ask certain questions and not look in certain places,” said Funk.

Both Ross and Funk also noted that the shrinking number of in-person conferences means scientists interact with other experts less frequently, reducing the exchange of ideas that could lead to alternate lines of investigation.³

Reis e Sousa pointed out that a lack of appreciation of basic science could also impede scientific serendipity. “We are witnessing a gradual erosion of the understanding that fundamental science…is essential for progress,” he said. While biomedical scientists focus on applications towards human health, many such important discoveries have roots in basic science.

For instance, scientists discovered CRISPR-Cas9 while studying bacteria and adapted the technology to edit the DNA of animals, plants, and microbes with high precision.⁴ This discovery that arose from fundamental research has already had a revolutionary impact in the biomedical sciences, with contributions to improving cancer therapies and curing genetic diseases.

Reis e Sousa emphasized the importance of research funding and pursuing basic science even while chasing its applications. With the trend of chasing only application-based science without sparing thought for basic science, “we run the risk of strangling the goose that lays the golden eggs,” he said.

Encouraging Serendipity in Science

Given the constraints in today’s research environment, how can funding bodies, institutions, and other agencies inspire scientists to chase unexpected observations? “That’s the million-dollar question,” said Funk.

According to him, having provisions for smaller grants that would allow for open-ended questions could be one way forward. Scientists could approach such bodies, requesting small amounts to pursue an interesting and unexpected observation that may not be in the scope of their grant otherwise.

Aside from funding, Ross noted the importance of discussing negative results and failures. “Often, serendipity starts off as a failure, and when failures happen, we tend to just avoid them,” she said. Publishing and speaking about negative results could encourage conversations about alternate hypotheses, driving research forward in unexpected ways.

Reis e Sousa agreed to the need to rethink how scientists communicate their work. “[Publications and talks] imply that there was a very logical line of reasoning and experimentation that took you from here to the end point,” he said. This does not always represent the reality of the situation, wherein scientists may meander along various paths pursuing different observations that come out of their experiments.

He believes this process is comparable to wandering in a forest. “You start to go in one particular direction, but then you might actually retrace your steps and go in a slightly different direction. You might even go back and reexplore the first direction but now take a slightly different turn,” he said. “And if you are lucky, you might find the path that takes you…to the gold mine that is in the forest.”