Reinventing the Wheel

CRISPR /Cas9 gene-editing: staying on top of technology is a full-time job for researchers

New Year’s Eve has always been more of a time for reflection for me, rather than a time for partying. Perhaps this stems from growing up in a Canadian climate where late December and early January (or more accurately, October through April) and the accompanying bone-chilling cold and darkness were more likely to entice me to curl up in a fetal position than chug champagne.

Just as chess champion Garry Kasparov maintained that “Life Imitates Chess,” I would venture to modify that and say that “Life Imitates Science!” Wait! Does that even make sense?! Of course not—life is science, while, pardon the treachery fellow chess players, but it is—sorry—after all, only a game. However, there is something to be said about the parallels between life and the career of a scientist. And it all begins with New Year’s Eve reflections. 

Speaking both from experience of years gone-by and based on much anecdotal inference, it seems that young people have a tendency to feel immortal. After all, for a healthy young person, age 70, 80, 90 is eons away, and the end of life is practically inconceivable. And of course, statistics bear out these ideas, clearly demonstrating that in general, young people are more reckless drivers and greater risk takers than those who are older.

In parallel, younger scientists also feel as though the scientific world is in the palm of their gloves. I don’t mean that younger scientists are reckless, but that those embarking on careers as independent researchers are very focused on the here-and-now, as they should be. And growing up scientifically in an age where technology is rapidly advancing on so many fronts, I suspect that today’s young scientists have neither the time nor inclination to think about their careers in 20 years’ time. After all, many of us fight those early years to survive in academia—the struggle for tenure. But just as in life, aging brings on thoughts of mortality, tenure and initial successin sciencealso bring about renewed reflections on one’s future career in science.

If most young researchers think the way I did, then they may take it for granted that once one derives a measure of success in running a lab, they are confident that can be readily continued in perpetuity. But is this really the case?

Far be it from wishing to dissuade young people from a career in academic science, I do however wish to convey the need for long-term, treadmill-like persistence for success and satisfaction in this field. I have harped on how, in the past, PhD students were required to master several techniques in the course of their studies, whereas today’s students have become “jacks of all trades,” who (although they may not need to completely master the techniques) must be fluent with dozens of new technologies, many of which crop up at a startling pace. Today’s students must be highly skilled at the use of technology, particularly sucking out the benefits of computer searches that include finding technical solutions to a range of problems. But what is expected of those directing the research and running their own labs?

I find that to stay competitive in this field, I have not only had to adapt technologically to an ever-changing landscape of techniques and methods, but also conceptually to continually find new niches. First, from a technological standpoint, there is no such thing as staying current—to stay current, one needs to constantly move forward an adopt new and emerging technologies. And it can be a significant challenge to introduce new technologies in a small-to-medium sized lab comprised primarily of graduate students, when the principal investigator (PI) does not actively work in the lab. 

Just to highlight a few examples of how the research technologies in biomedicine have evolved since I have been a PI, when I first started up my own lab, the technology of knocking down a specific gene in cultured cells (to study the role of the protein encoded by that gene) was only starting to become established. Today, however, the use of the newly discovered CRISPR systems to knock down, and even more significantly, to edit or tag genes in the cell, is re-revolutionizing the science that can be done. While understanding the concept of CRISPR techniques is not especially difficult, being able to sort out the design of such editing at the molecular level and successfully direct the lab to incorporate these technologies has been a considerable task. Despite the many fine papers, excellent blogs, websites and troubleshooting readily available online, these systems are so individualized to each laboratories’ needs that it required weeks of reading, schematic scribbling and planning until we were able to set up these complex systems. And while I am very satisfied that we have met the challenges of incorporating these technologies, I suspect that the next ones will be even harder to overcome. It is important to note that I used CRISPR as a representative example, but our lab has launched into a variety of new technologies, from structural biology to super-resolution microscopy and beyond, each with its own significant learning curve. 

At the same time, my lab has been laser-focused (pun intended) on understanding endocytic membrane trafficking and mechanisms of endocytic recycling; in short, how receptor are internalized from the plasma membrane and eventually returned to the plasma membrane. While I think there have been significant advances in our field by many outstanding researchers over the past couple decades, it seems that this brick-on-brick, sure-and-solid level of advance is not sufficiently attractive for low-hanging fruit funding in recent years. To me, it seems as though we researchers are being asked to reinvent the wheel—to continually find new groundbreaking discoveries, rather than ‘incrementally’ advancing knowledge in the field. Good or bad? That’s a debate for another new year…

As a result, I have spent an enormous amount of energy to try to connect my area of expertise with tangential fields. We have connected endocytic trafficking to mitochondrial biology, and more recently, to centrosome biology. The ability to divert my lab’s research focus from its almost exclusive focus on endocytic pathways to these new realms over the past several years has been almost overwhelming for me. Even mastering the literature of a tiny area of research has become a near-impossible task—so the immersion in several new and unfamiliar fields to the level that we are able to study relevant questions and publish responsible data has taken a toll on me. 

I no longer have the cocky confidence of a newly-minted PhD. I hope that I will be up to the challenge for the next 20 years or so.

And as a Nobel Laureate for literature once wrote:  The times they are a-changing” 

About Steve Caplan

I am a Professor of Biochemistry and Molecular Biology at the University of Nebraska Medical Center in Omaha, Nebraska where I mentor a group of students, postdoctoral fellows and researchers working on endocytic protein trafficking. My first lablit novel, "Matter Over Mind," is about a biomedical researcher seeking tenure and struggling to overcome the consequences of growing up with a parent suffering from bipolar disorder. Lablit novel #2, "Welcome Home, Sir," published by Anaphora Literary Press, deals with a hypochondriac principal investigator whose service in the army and post-traumatic stress disorder actually prepare him well for academic, but not personal success. Novel #3, "A Degree of Betrayal," is an academic murder mystery. "Saving One" is my most recent novel set at the National Institutes of Health. Now IN PRESS: Today's Curiosity is Tomorrow's Cure: The Case for Basic Biomedical Research (CRC PRESS, 2021). All views expressed are my own, of course--after all, I hate advertising.
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