Think differently

Abstract

Asked to reflect on my own research and career after being selected for the great honor of the Women in Cell Biology Mid-Career Award for Excellence in Research, I found myself contemplating not only how I approach my own science but also how this approach contributes to the larger scientific enterprise. Here I discuss my motivations and their impact on how I conduct my research as one example of the myriad ways to be a scientist. I invite you to consciously consider how, as scientists, we view one another’s unique approaches and argue for the importance of diversity of perspective in scientific progress.

I recently participated in a community art pro­ject that asks participants to answer the question “Why do you do what you do?” in a single sentence, one short enough to fit on 8 × 10 card stock. The whole point was to go beyond superficial reasons and to identify your true driving passions. My answer was “Because asking questions makes our world purposeful.”

While that’s my motivation, no one else in the room had the same answer. And that’s actually a great outcome. A diversity of passions makes our society rich.

In much the same way, diversity of perspectives is the pillar of scientific progress: advances in understanding only emerge when one of us connects observations in a new way. Yet I fear that we, as scientists, don’t consciously appreciate, protect, and promote this diversity. By not doing so, we risk losing it.

For example, I’m one type of scientist. I came to my profession via my own unique path. In graduate school, I was drawn to the study of gene expression regulation in Epstein-Barr virus. During this early training, I developed a deep appreciation for interesting biology, fostered by my advisor’s repeated question: “Why would the virus do that?” For me, this appreciation sparked a passion for understanding the awe-inspiring complexity underlying the biology in the greatest mechanistic detail possible.

Tricia R. Serio

My current area of research has shifted to a phenomenon that first sparked my interest when I was an undergraduate student: how a unique group of proteins known as prions can act as elements of inheritance and infectivity. I approach this question from the same perspective that drove my thesis research: my fascination with the biology and its underlying mechanisms. This perspective, more than any other, has defined how I choose to conduct my research today:

1. I treat all hypotheses as working ones and continually try to disprove them, because my goal is to figure out how things really work rather than to be prescient. Even when our observations are consistent with our ideas, I ask my students and postdocs, “What about this?” or “If we’re right, then what would we predict?” I offer other interpretations or extensions of our work and collaborate with my students and postdocs to think about how we might use these questions to gain additional experimental support. Because we are thinking so deeply about a problem, I believe that we have the responsibility to be our own harshest critics.

2. I view research as a scholarly pursuit that occurs equally at and away from the bench. My PhD advisor frequently paraphrased Westheimer’s discovery to remind us that “six months at the bench can save you half an hour in the library.” Even now, I spend a significant amount of my time rereading published papers to view them from the new perspective of our advancing knowledge. And I try to pay this gift forward by including a journal club in our lab meeting rotation, extensively reading with new members of my group, and starting all writing projects by asking my trainees to develop detailed outlines of their papers, proposals, and theses that place their work within the context of the pertinent literature.

3. I believe that every question answered creates many new ones, moving us toward increasing mechanistic detail. As our work has progressed, it seems as though whole new levels of the unknown are revealed, providing an endless source of motivation and inspiration for me. But sorting through this complexity takes time and focus. For me, this progression works best when one person is responsible for one project, following lines of investigation where they lead, learning whatever approaches are needed to answer the next question, and holding all of the observations in his or her mind until they can be connected.

Of course, my way is just one way. And that’s a good thing, because there are downsides to my approach to science, as there are for all approaches to science. In my case, we study prions in Saccharomyces cerevisiae, because it is amenable to answering the type of questions that drive my passion for details without losing sight of the biology, but this choice raises questions about the validity of generalizing our findings to mammals. My self-critical approach to hypothesis testing and my insistence on individual projects by no means brings us even close to perfection and admittedly makes for slow progress. My view that papers are opportunities to tell stories about how some aspect of biology works limits my publication list. But I am proud of the new knowledge that we have created and of the successes of my trainees. And I am humbled that I have been selected to receive the incredible honor of the Women in Cell Biology (WICB) Mid-Career Award for Excellence in Research, despite these limitations.

When I consider the previous recipients of the WICB awards and other colleagues whom I admire in the community of science, I’m struck by the different ways that we all go about the business of advancing scientific understanding. I’m inspired by those who are different from me: they think at higher levels to propose conceptual advances and translate basic findings into practical uses. I would never see these things, but I use their insights as the foundation to make my own unique contributions. From my perspective, this network of thinking is what makes the scientific enterprise successful; if we all operated at the same level, we would never move forward.

A senior colleague, whom I admire greatly, once told me that she weighs the uniqueness of a candidate’s perspective heavily in her review letters for tenure decisions, arguing that this characteristic, more than any other, predicts long-term success. Yet I don’t think that this enlightened opinion is our default. Instead, scientists tend to view and evaluate our discipline as a series of never-ending either/or characteristics that don’t acknowledge the importance of our unique perspectives: significant versus incremental, innovative versus standard, translational versus basic, impact versus productivity, discovery versus hypothesis driven. I have bought into these dichotomies myself in reviews of other people’s work and have been on the receiving end of them as well. When I propose to push our understanding of some biological phenomenon to a greater depth of detail, I have to admit, if I’m honest with myself, that the critiques questioning whether or not this line of investigation will lead to new insights are fair. I often don’t know if they will myself, but I do know that staying grounded in the biology has never led me astray.

I’ve seen the relative importance of these dichotomies in the scientific community shift during the course of my own career—study sections were not supportive of genetic screens when I wrote my first grant, but the age of ‘omics has led us to embrace discovery-based research. In the face of such a drastic change in perspective by the time that I’ve reached the middle of my career, we should ask ourselves, “How useful are these dichotomies in evaluating good science?” The priorities we identify now shape the future of the scientific enterprise, and in setting those priorities, we must ask ourselves, “Are these choices purposeful?” In our restricted funding environment, our decisions act as a form of selection to limit diversity in perspective, and this changing landscape will be passed on to the next generation, who depend on existing laboratories for training.

When I look back at the aspects of my work of which I’m most excited and proud, they are almost exclusively the insights that I never predicted when we began the projects that led to their discovery. If I can’t always see the endpoints in my own work, then it’s ridiculous for me to try to do so in the work of others. Rather, I think the best that we can do is to evaluate our work by the soundness of the ways we ask and interpret questions. The rest is up to the biology, which is exactly the point of what we’re all trying to do.