Lessons learned

Senior scientists share what they gleaned from their mistakes

It’s a scene in the lab that many of us are all too familiar with: You’ve reached the end of an experiment that has taken hours or days only to find out it has failed. As you’re looking through your lab notebook wondering where you went wrong, it hits you. You added the wrong buffer at step 13. Or perhaps your calculations were wrong and you added 10 microliters when you should have added 100. Whatever the mistake, big or small, most of us can relate.

Part of being a successful scientist is learning from your mistakes and moving on. Scientists are only human, after all. Even the most successful and respected scientists can recall instances when they learned lessons the hard way. We asked a handful of senior scientists to share such stories and the knowledge they gained from the experiences. 
 

Banerjee Banerjee

Ruma Banerjee

University of Michigan Medical School
Associate editor, Journal of Biological Chemistry 

In my first foray into research as a summer intern in (Obaid) Siddiqi's laboratory at the Tata Institute of Fundamental Research in Bombay (now Mumbai), I found myself working on the sugar-digesting enzyme found in Drosophila legs. Being averse to wasting especially precious reagents, I did not see the point of repeating controls — i.e., assays lacking enzyme — only to get the expected answer. So I dispensed with running (what I thought were) wasteful controls after the first set of experiments and charged ahead with generating data. As I proudly displayed my results at the group meeting, I was dismayed to be told that my data were not usable and was made to understand why. I smile when I think back on that experience, especially as I regularly pound away about inadequate or insufficient controls in my own lab meetings.

Dohlman Dohlman

Henrik Dohlman

University of North Carolina School of Medicine
Associate editor, Journal of Biological Chemistry 

The first story is about a colleague whose undergraduate adviser had encouraged him to apply to graduate school and that he should consider attending Washington University (in St. Louis). He did apply, did great things, met his wife, earned his Ph.D. and is now an accomplished scientist at the National Institutes of Health. The only thing is that he misunderstood the advice and attended the University of Washington, not realizing they were different schools in different states. Happy ending.

The other anecdote is about how my thesis adviser wanted to help another graduate student isolate receptor preparations from whole cell lysates. He picked up a centrifuge tube from his student’s ice bucket and demonstrated how to decant the soluble material carefully without disturbing the pellet. Only after the liquid went down the drain did the student have the courage to say that he had meant to discard the pellet and analyze the supernatant. Despite the setback, the student, Lewis “Rusty” Williams, went on to a brilliant career at the University of California, San Francisco,  and in industry and was later elected to the National Academy of Sciences. The adviser, Robert Lefkowitz, did even better and won the Nobel prize in 2012.

Guengerich Guengerich

F. Peter Guengerich

Vanderbilt University School of Medicine
Interim editor-in-chief, Journal of Biological Chemistry 

When I was a graduate student, I needed to prepare 15N-labeled lysine for my thesis research. I ordered 15NH4NO3 to do the appropriate reaction. I proceeded through the synthesis and did the labeling experiment with my molds. However, no 15N label was in the expected product of lysine. After backtracking, more detective work and finally calling the company, they admitted that they had sent me NH415NO3 — the 15N label in the wrong nitrogen. Although the company did replace this with the correct material, I lost a month of my time. So I have warned my students and postdocs not to trust blindly things they buy. Most are what we order, but over the years we have received wrong chemicals, bad oligos and so forth. If things aren’t going smoothly in your experiments, check your commercial reagents to be sure they are what you think they are.

Toker Toker

Alex Toker

Beth Israel Deaconess Medical Center, Harvard Medical School
Associate editor, Journal of Biological Chemistry

I recall, as a freshly minted Ph.D. from the U.K., arriving in the U.S. for a postdoc in the lab of (Lewis) Cantley, who had just discovered (phosphoinositide 3-kinase). A major recurring lab requirement was purification of PI3K enzyme from rat liver. Everyone in the lab took turns in this ordeal, which included many steps of column chromatography in the cold room followed by assaying fractions with 32P-ATP. PI3K is a notoriously unstable enzyme, and,  given the many steps involved, the purification sometimes failed, meaning no one in the lab would have active enzyme for their experiments and projects. As I took my first few stabs at this purification as the new postdoc, I ended up with dead inactive enzyme each time. Even though this was a tough purification procedure, the experience was pretty disheartening. Obviously, I made mistakes at different steps, but it taught me one important lesson that I have carried with me since and try to instill in all my students and postdocs — persevere. Always persevere in science, and if you love what you do you will succeed.

Jen McGlaughon Jen McGlaughon is a graduate student in the molecular biology and genetics department at Cornell University.