It is Time to Move the Light

“It’s Time to Move the Light”

A man is crawling on his hands and knees, looking for his car keys underneath a lamppost. A woman comes along and starts to help him. After a while the woman asks the man: “Are you sure this is where you dropped them?”

The man replies: “No, I think I dropped them somewhere else.”

“Then why are we looking here?” she asks.

“Because this is where the light is.”

This analogy often comes to mind when I read grant proposals and manuscripts, in which experimental approaches, while quite feasible and technically sound, do not address the extended question or hypothesis.  Many times my criticism is deployed toward investigators who are so bound to a technique or experimental methodology that they force its application, even though it falls far short of their ultimate target.  So, I was actually surprised when I again thought of the ‘keys and lamppost’ while reading the recent Perspective postured by Todd Golde,  Anti-aβ therapeutics in Alzheimer’s disease: the need for a paradigm shift., (Golde et al., 2011) in Neuron. This time, however, my lamppost analogy was not directed to an individual investigator, but rather to a field of research and perhaps much of clinical and translational research.

In their manuscript, which all interested in clinical and translational research should read, Golde and colleagues present a simultaneously intriguing, frustrating, and somewhat depressing scenario.  Significant fundamental research has suggested that targeting amyloid beta-peptide (A beta) may be effective therapies for patients with early signs of Alzheimer’s disease (AD) pathology, yet currently A beta -directed therapies are being tested in fully symptomatic patients where they will most likely be shown ineffective. This dilemma is detailed in this well written and documented paper, which describes the unfortunate misalignment of preclinical and clinical investigations.  The authors call out for a preventative rather than treatment approach for AD.  Most importantly, they describe the need for improved early diagnosis and accurate staging of AD progression, which will require additional fundamental research in the areas of biomarker development and innovative imaging modalities.

I’m sure each of us will find traces of our own scientific challenges in Golde’s story, and I encourage us to broaden searches and approaches within our own research programs. Golde and colleagues have identified where the keys have been dropped, we now need to move the light.

Steve P. Sugrue, Ph.D.
Senior Associate Dean for Research Affairs
College of Medicine