The whole world is in the midst of COVID-19 chaos! I think that "social distancing" should not be a very painful pill for us to swallow. Most of the time, doing research is a "solitaire." One of the unexpected benefits of "social distancing" is that it leaves a surprisingly cleaner daily calendar. Without many out-of-control social obligations, "distancing" actually leaves more precious time for each of us to spend meaningful time with the students, friends, and family we care about the most.
The whole world is slowing down—ironically for most of us—in the midst of chaos. Is "slowing down" a good thing? Slowing down allows us to think through things more carefully and design better experiments. It is a different way of working—a delayed but "correct" way to work more efficiently, which will benefit us in the long run. So, it is time to embrace the slow pace (or you can call it having fewer distractions). It is a journey forcing us to go back to the forgotten joy of uninterrupted deep thinking.
One of the biggest challenges for novice biomedical researchers, or even senior investigators alike, is how to navigate through the jungles of literature and design meaningful and smart experiments in their daily research lives. It is hard indeed! Designing and redesigning an experiment requires a painful and seemingly never-ending literature search, comparing notes, and deep thinking—the process will mostly deliver frustration rather than instant gratification. Even more, being a better researcher requires one to be skeptical and keep defying our ingenious ideas through the lens of "controls" and "alternative hypotheses"—it is a painful process. Understandably, in the cycle of a researcher's daily life, most of us tend to opt for more tangible "tasks" when we step into the lab. Surely, the gratification of finishing the task of sub-culturing cells generates far more instant relief during an intense research day than staring at a computer screen, trying to sift through PubMed search results without generating an immediate checklist. As important as it is, the "thinking" part of the day is often overtaken by the desire to finish trivial tasks.
Is there a framework that could potentially help us design smarter experiments?
Asking the right question through a testable hypothesis
Aristotle's theory of experimental science is hypothesis-driven. Despite the booming big data science advocating for a process of so-called data generation or hypothesis generation, an experiment starting from a clear goal (hypothesis) in mind often leads to better experimental design. Restrain yourself from tackling too many ambiguous goals, and choose a more defined question. Regardless of how appealing or fancy the approach is, if your current best approach is not coupled with a very defined hypothesis, you will very likely be running a "garbage-in, garbage-out" experiment. Yes, I mean garbage data.
Clarifying the purpose of a given experiment
To prevent running a "garbage" experiment, it is paramount to know the purpose of your experiment and what you will achieve in the best-case scenarios. Every experiment should have a purpose. The purpose can vary—from developing new methods to exploring provocative hypotheses. However, the purpose should be clearly perceived. Do this exercise: can you describe the goal of your new experiment in one sentence, NOW? If you hesitate for a second, think again!
Rethinking the true purpose and advantages of a complicated approach
The same exercise of "clarifying the purpose" is also applicable to the approach you are going to take, especially the fancy and most likely expensive ones. One of the most exciting parts of discovery is being able to apply new technologies. Fast-evolving sequencing, imaging, and gene-editing approaches are dazzling. However, craving "cool" technology is a common sin when designing smart experiments. Adapting new protocols often takes time. Troubleshooting might lead to unexpected pitfalls which were not disclosed in "hot technology" papers. When attempting to take on a new technology, be sure to wait until the technique is fully mature and the protocols have been reproduced by other labs. Ensure the new technology is absolutely essential to exploring your hypothesis and, importantly, that it really can answer your hypothesis. If an easily interpretable western blot could answer your hypothesis, do it! Forget the phospho-proteomics. The golden rule is to seek reduction, simplification, and the use of existing alternatives. Keep in mind, less is more.
Don't fall in love with your hypothesis
The specific goal of different experiments might differ, but one thing is in common—the fundamental goal of designing an experiment is to test a null hypothesis. In other words, to prove your favorite hypothesis wrong. When designing experiments, we have to keep adding controls because we must prove that whatever we are seeing is not due to technical or system noise/bias. Results are only as good as their controls. By default, we should spend most of our time thinking about controls. If the experimental group's pattern is indeed different from the control, we are one small step closer to the truth. When interpreting data, we have to keep pulling ourselves away from our beloved hypothesis. There is a reason why blind tests are so desirable. Let the data speak! Yes, we love our hypothesis. Yet, being intoxicated by such love leads to a loss of sobriety. Craving "as expected" positive results is a recipe for the unintended wrong interpretation of data. If everything is simply as you expected, is it really a new discovery?
Respecting others' ideas
Recent sociological research studied the key factors that lead to divorce. Guess what the number one factor is? Contempt! Although it seemingly sounds irrelevant to research design, contempt oftentimes becomes an unconscious attitude when we "smart" scientists think about others' ideas. Constructive brainstorming requires some level of humility when discussing with peers; it requires all of us to be critical of the goal and the design of the idea, but without contempt for the idea itself. Balancing mixed emotions while remaining confident is a skill to be polished every day.
