Finding What Doesn't Work

                When I pictured scientists designing experiments before coming to MIT, I always pictured several people using their vast wealth of knowledge on unfathomably complex systems to deduce that certain things must be true, and that only then would they proceed to run an experiment to verify that they were correct. Over the last two years, that misconception has gradually been lifted from my eyes, especially as of late through my experiences in my UROP at the Koch Institute and 20.109.

            I UROP for the Langer lab, which deals primarily in directed delivery of siRNA, with a few projects that I am aware of straying just slightly from this research focus. The experiment that the graduate student under whom I work entrusted me with involves attempting to deliver RNA oligonucleotides into cells by simply attaching cholesterol to them and hoping that the RNA will fuse with the cell membrane and enter the cell. The idea that a solution the ongoing problem in RNA delivery could be so simple sounded and continues to sound too good to be true to me, and this must have come across in my tone of voice to my supervisor as he said, “It’s probably not going to work, but no one else is doing this and we have to try it. Welcome to academia.” Exposure to this mindset of approaching experiments and research in general taught me that sometimes if you can figure out methods that don’t work, it can still contribute to your field and move the scientific community a step closer to solving the problem.

            I applied this way of thinking in the project proposal that Jessie Blumenfeld and I recently presented. Our project revolved around randomly mutating the NPC1 receptor, which is strongly implicated in Ebolavirus infection, to find a mutation which resisted Ebola binding to it but allowed the receptor to retain its normal function. If the project were successful, it would tell us that there are parts of NPC1 that are crucial for function and parts of it that are only there to help Ebola infect the host, and where these parts of the protein are. In having to consider what value the project would have if it were unsuccessful, I came to realize that even if we found that among all of our random mutations, none of them were able to produce functional, Ebola-resistance NPC1 receptors, we would learn that the key to curing or immunizing against Ebola does not lie in genetic alteration of the NPC1 receptor, which would save everyone else a lot of time.

            I consider this perspective a valuable new part of my tool belt as a biological engineer, and I am eager to continue to mature my intuition on creating valuable experiments.