Managing views and expectations in science

Not surprisingly, the March 1^st issue of Nature Outlook titled "Lenses on Biology," has stuck a chord among scientists and aspiring scientists in the blogosphere. Many have offered their personal perspectives on what motivates them to pursue science and why science research actually matters (i.e. why society should invest so much in the process of scientific discovery).

While the answer to the first question varies from better appreciating the physical environment, to understanding how life works, to seeing the beauty in nature, to satisfying a burning curiosity, and to touching others' lives, the answer to the latter may seem unanimously obvious: Science matters because it reduces human suffering, improves daily life, and safeguards our future, no matter whether it's cancer biology, synthetic biology, climate change, ocean science, or stem cell biology.

It's not terribly hard to find historical evidence for the previous statement. Just think about penicillin, light bulbs, airplanes, vaccines, and in vitro fertilization and the concrete impact each has had on human life. However, if we're asked why it's important to study fungal growth, metal melting points, fluid dynamics, B-cell antigen recognition, and oocyte maturation, it takes a while for us to bridge the various degrees of separation between basic science and their ultimate practical applications.

This is even harder when the applications are uncertain or unknown, especially in biological research. For instance, why does it matter to understand the role of non-coding RNAs in regulating gene expression, to uncover genes upregulated in long-lived mammals, or to study the structure of the proteasome? Is it to develop a new cancer therapy, a longevity drug, or a treatment for neurodegenerative disease? In the process of working out the nuts-and-bolts of a scientific problem, it is certainly easy and inevitable to be drawn to research minutiae and lose sight of the ultimate goal.

Even if we do keep the "view of the forest" in mind, discouraging statistics suggest that such a forest may in fact be a mirage. Of 101 high-profile studies published between 1979 and 1983 heralding the promise of new therapeutics, only 5 resulted in licensed medical applications by 2002¹, giving a translational yield of about 5%. And this only looks at successful, published studies among what were surely many more failed attempts in the laboratory. Given the current regulatory requirements for clinical trials and approval, which are more stringent than those from three decades ago, this yield is likely to be even lower today, and the time to application even longer, with a higher financial barrier of entry into the clinic. So, it is important to ask again, why do we choose to invest so much time, energy, and heart on an endeavor whose failure rate far overshadows the success rate?

Again, on a personal level, answers may vary, but they are all in the spirit of emphasizing enjoyment of the process of scientific discovery in addition to (and even more than) the eventual discovery and its potential world-changing applications. For me, the solution to balancing the necessity of focusing on scientific details and the view of the big picture, of fulfilling my joy in working in a lab and my desire to make a social impact, was pursuing a joint MD-PhD degree. My hope is that practicing medicine, in addition to treating patients with current technologies, will help me identify critical areas in health care that need scientific innovation. At the same time, working in a laboratory will satisfy my intellectual curiosity and help me find ways of addressing pressing problems affecting patient health.

Given that my curiosity can be pulled in many different directions, one way of engaging in research with potentially higher clinical success rate is calibrating my scientific questions and interests against the needs and realities in the clinic and the complexity of the translational process. This way I can pursue questions that are personally interesting, clinically relevant, and clinically feasible. Of course, the latter is hard to predict, but will hopefully be more predictable with the knowledge I gain from my experience practicing medicine and doing research. Finally, like many other budding scientists, I'm attracted to the very uncertainty in the scientific process itself, because such uncertainty makes discoveries much more satisfying. Doing science is indeed a gamble, and the process involves a lot risk-taking. The likelihood discovering something astonishing is very low, but the possibility is what keeps us going.

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