I participate in several grant review panels each year that cover different areas of biological research. Despite the relatively broad subject areas that they address, such as signal transduction or genomics, I have noticed a strong similarity between many of the proposals I see. They tend to be focused on a few, relatively narrow topics that have been studied for years, and use just a handful of approaches. For example, in the field of signal transduction, it is common to see proposals to investigate the epidermal growth factor receptor (EGFR), but rare to see a study on other types of receptors. Yet the EGFR is the receptor type that we know the most about. A PubMed search on EGFR yields more than 10,000 papers. Repeating the same search for the insulin-like growth factor receptor, however, yields less than 150. There are many other examples.
In short, biological knowledge, like these proposals, is concentrated in a few areas separated by large swaths of ignorance.
There are many different reasons why. Some of this stems from a few schools churning out a disproportionate number of scientists in a particular field. Anyone know the story of Yale graduates and their influence on cell biology research? George Palade, a Nobel Prize winner, started a graduate program in cell biology at Yale in the early 1970s. This program generated more than 100 PhDs mostly focused on intracellular organelle biogenesis, which thus became a dominant theme in the field.
Technology is also a prominent reason for the heterogeneity of biological knowledge, because a new technology can tell us a lot about specific processes while leaving others obscure. For example, antiphosphotyrosine antibodies have allowed us to easily follow tyrosine kinase signaling pathways, but downstream signaling events mediated by other activated enzymes remain a mystery.
There are ways to bridge these gaps. Take new technologies, for example. MicroRNAs, which were discovered using genomics technologies, could fill many holes in our knowledge of mechanisms of posttranscriptional gene regulation and signal transduction. I do have a fear, however, that microRNAs will also become a specialized field, as has happened so many times before. Why? Because biologists are typically reductionists, who tend to pursue a general observation down to its most fundamental level.
Reductionism is driven by basic human nature and our difficulty in comprehending complex processes. Reductionism in biology is also strongly driven by journal reviewers. I can't count the number of times that I have submitted a paper only to have some reviewer ask for more details, extra experiments, and clarification of some arcane mechanism that was irrelevant. Eventually, reviewer expectations become our own when we have the opportunity to review our colleagues' papers. However, it is not realistic to expect that details will eventually add up to comprehensive knowledge. Biological systems are simply too complex, and we will end up knowing a lot about trees and being clueless about the forest.
Focusing on details might help get your papers published, but it is not the best approach to getting your grants funded. Reviewers, myself included, tend to be more impressed by the novelty or the broader impact of a proposal rather than its ability to exhaustively explore a problem. This does not mean that scientists should be superficial in their investigations, but that we should be more aggressive at filling in the gaps between our work and that of others.
There are a number of ways to do this. Make sure you are aware of the latest technology, because it can move your research in new directions. Take advantage of online citation resources. Who is citing the major labs in your field? If other fields are finding connections to your area, you are likely to find connections to theirs. But the most important thing is to simply try something new. Systems such as the EGFR are most important as models, rather than ends into themselves. Take the approaches that have proven successful in model systems and apply them to something different. It might be difficult at first, but you are more likely to discover something new. And isn't that why we became scientists in the first place?
Steven Wiley is a Pacific Northwest National Laboratory Fellow and director of PNNL's Biomolecular Systems Initiative.