The Life & Times of a Principled Scientist
By: Roshan Chikarmane
Tags: Medicine, Science, Biotechnology, Pharmaceutical

Originally published on November 29, 2018 in Johns Hopkins’ blog Biomedical Odyssey (link)

In a world that amounts to a maelstrom of stimuli and a cacophony of interacting processes, it is of great importance that one develops systems for recognizing specific types of scenarios and reacting appropriately to them. These systems, or principles, inform our future decision-making and spare us the tedium of having to deal with all situations as if we were encountering them for the first time. Hence, to be ‘principled’ is to consistently implement a set of principles. Like many other learned abilities, principles are gathered throughout one’s lifetime and can be acquired in a variety of ways. Oftentimes, they develop upon reflection of one’s own personal experiences. In some cases, they are learned from the experiences of those with whom you interact; in others, they are passed down through generations of scientists, all dedicated to the pursuit of a common goal.

On Nov. 3, 2018, the Johns Hopkins Brady Urological Institute held its 13th Annual Prostate Cancer Research Day, a full-day consortium where students and faculty share their latest findings. This year’s Prostate Cancer Research Day celebrated the life of Donald S. Coffey, professor emeritus at Johns Hopkins whose pioneering research has profoundly shaped our current understanding of genetics and epigenetics. Dr. Coffey earned his Ph.D. at the Johns Hopkins University School of Medicine in 1964 and, two years later, Paul Talalay hired him as an associate professor in the Department of Pharmacology and Molecular Sciences, where he was granted tenure in 1974. In the interim, Dr. Coffey was appointed to a faculty position in the Department of Oncology and helped found the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center along with its first director, Albert H. Owens. He later went on to accept two more faculty appointments, in the departments of urology and pathology, and served as president of the American Association for Cancer Research from 1997 to 1998.

Results from Dr. Coffey’s lab were the first to explain the role of the nuclear matrix — a meshwork of proteins and fibers that maintain DNA organization in cells — in DNA replication, chromatin architecture, gene expression, cell shape, tissue specificity and cancer. In addition to producing illuminating research, Dr. Coffey’s lab turned out a number of accomplished researchers, many of whom now hold faculty positions and have, in their own right, significantly expanded our understanding of cancer. A handful of those names include Drew Pardoll, who discovered gamma-delta T cells, NKT cells and interferon-producing killer dendritic cells, important components of the immune system; Bert Vogelstein, who developed the theory of somatic evolution in cancer; William Nelson, director of the Sidney Kimmel Cancer Center; Alan Partin, director of the Johns Hopkins Department of Urology; Ted DeWeese, director of the Johns Hopkins Department of Radiation Oncology and Molecular Radiation Sciences; Warren Heston, who first cloned PSMA, an important protein target for potential prostate cancer treatments; and Jonathan Simons, president and CEO of the Prostate Cancer Foundation.

On Prostate Cancer Research Day, a few of these individuals, along with other disciples of Dr. Coffey, shared various principles that they learned from him; principles that have since informed their approaches to scientific investigation.

If This Is True, What Does It Imply?

There is one piece of lab equipment that you cannot simply order from your favorite vendor: your mind. Alexander Fleming didn’t invent bacterial culture, nor did he intend for the plates on which he had grown Staphylococcus bacteria to be unintentionally contaminated by Penicillium mold. He did, however, take note of an unusual disappearance of bacterial colonies surrounding the mold and, after further investigation, discovered the penicillin class of antibiotics. This tale of discovery is illustrative of Dr. Coffey’s idea that, oftentimes, investigation of a specific phenomenon requires deeper thought rather than an immediate, impulsive next experiment. Practically all data illustrate a story, if only we would listen and think. What processes could have occurred to lead to such a result? What subsequent experiments could be used to answer the heart of the question? What does the data prove is and isn’t true? Do the implications of the data corroborate or contradict the current thinking? Even when experiments don’t go as anticipated, as with Alexander Fleming’s bacterial culture, there is knowledge to glean from the output. In fact, the only experiments that teach you something new are the ones that deviate from expectations.

Keep It Simple

Overcomplexity can stifle productivity and muddy thinking. There are often a handful of experiments that can be performed to answer the same question. It is wise to start with several independent experiments that most clearly answer specific subfacets of the research question, rather than immediately jumping into a bloated protocol, intended to provide a catch-all answer. More complexity leads to more phenomenology, which obscures insights. If your options are limited to a large, complex experiment, sequentially tackle specific subfacets of the research question when excavating the data. This principle also applies to scenarios that require clear communication of one’s research to others, such as the authorship of publications and the delivery of seminars. Precise communication is important, but only when tempered with the perspective of the audience is it truly informative. Make it easy for reviewers, readers and audience members to understand your work.

These priceless principles and others can be found in “The Real Final Exam,” an editorial authored by Dr. Coffey that was published in The Prostate, as well as his biography, The Donald Coffey Story. Like Dr. Coffey, I urge you to discover and share your own principles with people you most frequently interact with, particularly if you are working in a team with a common goal. In doing so, you just might find that your decision-making, as a team, is more streamlined as you come to understand each other’s approaches.