All Research Is Basic
by Alan Saltiel
This issue of LSI Explore focuses on an issue that is foremost in the minds of scientists and the public alike- the pursuit of new approaches to important and difficult diseases. At the Institute, new insights into human disease that can be applied directly in the clinical arena have come from studies of rare inherited disorders in specialized patients all the way to the genetics of worms. How are these major strides forward being made? What intellectual processes are being brought to bear? To many, our views of this subject are shaped by stereotypical anecdotes from the annals of scientific discovery. We are indoctrinated with the idea that there is a progression from pure, basic science, designed for and motivated by only the most abstract of intentions to uncover deep mysteries, to the applied, more practical work performed by savvy entrepreneurs, intended for prevention or treatment of disease. Of course, in the real world, such a progression is rare, and is neither logical nor even desirable. This myth has confused the public and even some scientists, created unrealistic expectations and impatience for faster outcomes.
Why is this a problem? The notion that research can be simply divided into the “basic” and “applied” implies that one is inherently more valuable than the other. As Pasteur said, “Nothing is more satisfying for the mind than to be able to follow a discovery from its very origin up to its latest development.” Some scientists view “pure” research as a higher form of intellectual pursuit, while at the same time we’ve seen a public call for more applied research that will yield faster solutions for vexing problems. Sadly, there remain academicians who are openly disdainful of those interested in putting their ideas into practice. Even more troublesome are new initiatives in Congress that are disease-specific, or the trend in disease-based foundations to focus solely on patient-oriented research. Both of these approaches often come at the expense of other approaches, essentially a zero sum game. There is little doubt that when it comes to decision making about the value or quality of research, there has been a shift to a small subset of scientists, or from scientists to non-scientists or ex-scientists. This will surely lead to short-sighted choices and ultimately mediocre work. But perhaps the biggest danger we face from this simplistic view is that we run the risk of separating the bench from the bedside, in the process losing the many synergies of cross-fertilization that occur among scientific colleagues from different backgrounds.
Frankly, we should know better. There are numerous examples of what happens when attempts are made to impose too much structure or overly specific goals on the process of discovery. Does anyone think it is working today in big pharma? Does the NIH or NSF have their priorities perfectly aligned? Is the intrusion of politics (or in some cases religion) into the debate about scientific resourcing helpful?
The success of the scientific enterprise requires us to embrace one crucial point: there is no single path to knowledge. This is true regarding the understanding of fundamental life processes, as well as the improvement of human health. For example, much of what we have learned about biological pathways arrived by the bedside-to-bench route. Positional cloning of genes responsible for clotting diseases in the Ginsburg Lab yielded the most basic insights into protein trafficking and secretion. At the same time, studies in model systems have taught much about human physiology and pathophysiology. Despite years of investigation, little progress was made into understanding how hormones control glucose production in humans or even mice. Scientists like Pat Hu finally turned to the roundworm C. elegans of all places, and because of studies in this model system, we now have a more thorough understanding of the metabolic and signaling pathways and how they are impaired in diseases like diabetes. By asking important questions and applying the appropriate tools, the “unpredictable” findings, along with all the potential implications and applications, can become the rule rather than the exception.
Scientific progress is not achieved by a single unique route, nor is that route usually a linear one. It is rather a complex network of processes, objectives, outcomes and often steps backward, all of which are usually incremental in nature. The state of scientific knowledge is naturally incomplete, which is what makes the quest to improve it challenging and fulfilling. If original, research is always “basic”, and is at the heart of any scientific endeavor, no matter what the setting.