Lost in translation: can we afford to miss the trees for the forest?

Abstract

Is there a favorite Ivy League school to which you would like to apply? If so, the odds of an outstanding high school student getting accepted into one of these top-tier institutions averages out to approximately 9 %. Put another way, if you are one of the best and brightest in your high school, you have about a 1:10 chance of getting into the Ivy League school of your choice. These are pretty low odds. Then again, this is the Ivy League, considered by many to be the best of the best. Furthermore, regardless of whether you are accepted, is your future really “blown” if you are not accepted to your Ivy of choice? Of course not! There are dozens if not hundreds of amazing colleges in the USAwith very favorable acceptance rates. For example, UC Berkeley, The University of Chicago, Duke University, and Georgetown University each accept approximately 17 % of applicants. The University of Rochester, New York University, and The Universities of Minnesota, Virginia, Michigan, and Texas all have acceptance rates of over 30 %. Thus, any smart successful high school student will find a fantastic place to start their academic career. Furthermore, if a student continues to be successful at any one of these colleges, then graduate or medical school is easily reachable. Let us now compare these numbers to those of an established successful scientist trying to stay afloat. Currently, the success rate for an NIH R01 grant is the same as the chances of a top high school student getting into his/her Ivy League School of choice—about 10%. Again, these are pretty low odds. Unfortunately, unlike the top high school student, who has a myriad of other viable options, if this successful scientist cannot maintain R01 funding, there are few alternatives—a lifetime of work will be tossed aside, with jobs and careers damaged if not lost. These are sobering times. As reviewers try to pick and choose between outstanding proposals, successful careers hang in the balance. Which research proposals should be selected for potential funding and which should be left in the pile? A major criterion for making these critical decisions revolves around judgment of the work as “innovative” and “impactful” with high “translational” potential. Yet is anybody really capable of making this judgment? Should we even be trying to do so? Examples from history would argue that the answer is emphatically “NO!” The decade was the 1950s. Microbiologist Salvador Luria, when looking at his petri dishes, discovered that some bacterial hosts were able to suppress bacteriophage growth, while others were not. For lack of a better term, Dr. Luria called these suppressing bacteria “restricting” hosts [1]. This observation sounds interesting but pretty tame. Not clearly innovative and definitely not at all translational. Nearly 10 years later, another microbiologist, Werner Arber, discovered that these restricting bacteria actually produced an enzyme that cleaves phage DNA and destroys it [1]. To be consistent with Luria’s terminology, this enzyme was deemed a “restriction enzyme.” Finally, after about 10more years, microbiologist HamiltonO. Smith discovered a second enzyme in another restricting bacteria (Hemophilus influenza) that cleaved DNA at a very specific DNA sequence [2]. This enzyme was called “Hind.” Now, the story is becoming a little more interesting, but still is significant only in the world of bacterial biology—not overly innovative and still with very limited translational potential. In fact, this series of observations, which spanned nearly 20 years, would very likely have failed to meet current NIH definitions of translational because nobody could really predict the true potential of their findings until Daniel Nathans put all of these findings together and demonstrated how restriction enzymes could be used to map and manipulate DNA S. R. Hammes University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA