The Do-Over

Project swap

Russell D'Souza
By Russell D'Souza
August 01, 2017

Science always has intrigued me. In a high school chemistry class, I was taught that an atom was the smallest constituent of matter. I remember getting home from school and spreading some common salt on the kitchen table to observe the particles using a pair of binoculars. I was fascinated by biology and chemistry combined, and I became interested in the functioning and mechanisms of biological molecules. I completed a bachelor’s degree in chemistry and a master’s degree in biotechnology from reputable institutions in India. I hoped I was ready to take on the role of a successful biochemist.

I landed my first job at a pharmaceutical company in Mumbai. I joined the drug metabolism and pharmacokinetics department and was responsible for performing cell-based assays to determine the efficacy of small molecules. I was happy and settled well in my new laboratory.

After a year or so, I decided I needed to expand my knowledge, and I applied for a graduate program in the U.S. After rejections from several universities, I was admitted to the biochemistry and molecular biology program at Wayne State University School of Medicine. I was ecstatic!

The first year entailed rigorous coursework and qualifying examinations, which I cleared comfortably. I had made up my mind about joining a laboratory, so I did not perform the mandatory laboratory rotations. I was given a project early in my second year to study polymorphisms in a human assembly factor that aids in the assembly of the mitochondrial ATP synthase in yeast. It was a subject without much literature. I thought I'd be a pioneer in the field. This notion brought about the project's downfall.

We initially identified 10 polymorphisms we were to study in our yeast system. However, we never got past the first two missense mutations. Every time we expressed the human gene in yeast, we observed different results. We performed the experiments again and again but failed to get consistent results. We devoted almost a year to working on two of the 10 polymorphisms with no real data in hand. I was almost finishing my third year of graduate studies, and I had nothing but a few enzyme assays and western blotting results. I began to realize that these polymorphisms that I was eager to characterize might be of no value, since there was no human pathological phenotype reported.

I began to doubt myself. I wondered if I had the potential to be what I had hoped. At the low point in my graduate career, emotionally and scientifically, I was almost ready to quit.

The saving grace was my graduate mentor and my departmental graduate committee. Being too far into the program, I was told to hang in there. I sat down with the graduate committee, and we decided on a smaller project that would help me graduate. This involved studying mutations in alpha and beta subunits of the mitochondrial ATP synthase, again in yeast. Again, I didn’t know what to expect. I started by doing a literature survey of this area. It was my good fortune that plenty of studies on the bacterial ATP synthase were similar to my new project. They gave me a general idea of the results to be expected.

Suddenly, I had renewed hope. I began performing a battery of biochemical tests on these yeast mutants, and we came across phenotypical characteristics that had not been observed or reported before. Somehow, we began to fix the pieces of the puzzle in the new project, a process that had seemed so arduous during my previous one. I began reading a lot more and started to design some of the experiments. I was an entirely different person after completing my new project. I finally graduated in the summer of 2016.

I think about what I could have done differently. I’ve learned that reading the scientific literature is an important part of graduate life. We get so blinded by a new project that we do not make an effort to find out if similar work is out there and what questions it addresses. Unexplored areas of research may provide breakthroughs, but you have to ask the right questions. I also learned not to fear communicating my thoughts about my projects with my peers. My advice is to talk to your committee or senior graduate students and ask for their suggestions. Identify setbacks early, and back off when things go awry. There's no point in going ahead with something that’s a dead end.

At times I still wonder about the possible outcomes of my second project if I had begun with it. It had so many avenues to explore, but I couldn’t do them all, as it was time for me to graduate. Could an earlier project change have saved me a year in graduate school? Maybe. In retrospect, I have absolutely no regrets about my choices. I mean, this is science. Things don't necessarily work out the way you want them to.

Russell D'Souza
Russell D'Souza

Russell D'Souza is a postdoctoral fellow at the National Institutes of Health.

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