In Praise of Imperfection

by Gili Zilberman-Schapira

As parents, we are often told not to call our children perfect. Psychologists advise against this for good reason: it can create pressure to live up to impossible standards, foster a fear of failure, and encourage children to hide their struggles rather than seek help [1]. In many ways, the same can be said for young biologists. In a typical group of biology students, few might be perfect, but many are likely perfectionists. Biology is a meticulous science; it demands precision, patience, and organization. It can be rewarding, but also tedious and full of setbacks. For these reasons, Biology attracts people who are detail-oriented, highly focused, and keep their “eyes on the ball”, qualities that are useful, but come at the risk of “tunnel vision”. Is perfectionism a double-edged sword?

We are trained to approach research with clarity: define a strong question, develop a structured, time-framed plan, and identify the best tools to pursue our hypothesis. These steps are essential, yet, even when well-executed, are not always sufficient to get research off the ground. Surprisingly, the very structure and discipline we rely on can become obstacles. Flexibility, sometimes mistaken for sloppiness or a lack of focus can be a researcher’s greatest asset. The ability to pivot, follow intuition, or explore a question that was not part of the original plan can make the difference between a dead-end study and desperate student, and a breakthrough.

One of my clearest memories from graduate school at Yale was sitting in an auditorium with other first-year students, trying to make sense of an unexpected result. Our dean at the time, Tom Pollard, would often say: “It is what it is — it’s biology”. That phrase stuck with me. Biology demands accuracy, but it is far from an exact science, or perhaps, we simply understand too little of its underlying principles to treat it as such. To truly make progress in biology, we must be willing to adjust, to stray from the path, and to move our gaze “away from the ball” and see where it takes us.

During my first year of PhD, which, for many students, including myself, is filled with confusion and challenges, I was exploring the microbiome. After several months of wondering and wandering, I finally settled on a project: studying the effect of probiotics on obesity by examining the gut microbiome of obese individuals. This topic was unexplored, intriguing, and seemingly feasible to tackle. I outlined a solid research framework and devised a step-by-step plan with my PI. Then, a few months into the project, while reviewing past literature, I realized that no one had ever clinically tested the actual effect of probiotics in healthy individuals. There were assumptions, correlations, and animal studies, but no controlled human trials. Yet, such investigation was not part of my well-defined, detailed thesis plan, which I had already started executing. Still, I decided to shift my research focus, initially only partially and hesitantly, and with time, after realizing this was the right path for me, in full. What began as a side question became the heart of my project. Fast forward 4 years, 50 human participants, 100 colonoscopies and endoscopies (procedures that allow direct sampling of the gastrointestinal tract), 800 samples, and over 4,000 sequenced samples later, we published the first clinically controlled study testing the real effect of probiotics in humans [2-3]. The result of an unplanned detour. The study revealed that probiotics are not only ineffective in promoting general health, but when taken after antibiotics, they may actually disrupt the natural recovery of the microbiome and push it further away from its healthy, balanced state.

We often celebrate science as a logical process: methodical, rational, planned. Flexibility, adaptability, and even a bit of messiness, are important components of the scientific process. Structure and precision matter, but so does imperfection. The willingness to go off course, change our plans, and entertain questions that may not have immediate answers are the heartbeat of discovery.

In the lab, as in life, the path to insight is rarely linear. And when we find ourselves unsure of where to go next, we might take comfort in the words of Lewis Carroll’s Cheshire Cat:

“Would you tell me, please, which way I ought to go from here?” “That depends a good deal on where you want to get to,” said the Cat. “I don’t much care where—” said Alice.

“Then it doesn’t matter which way you go,” said the Cat. “—so long as I get somewhere,” Alice added.

“Oh, you’re sure to do that,” said the Cat, “if you only walk long enough.”

The Cheshire Cat Appears in a Tree. Illustration by John Tenniel, from Lewis Carroll’s “Alice’s Adventures in Wonderland” (1865). Public domain. Source: https://www.bigiok.com/blog/Lists/Posts/Post.aspx?ID=74