New guidelines for preclinical research….

NINDS director Story Landis leads a very long author list on this Perspective piece in Nature, here.  The article is open-access, so there should be no difficulty in taking a look, even for our readers without subscription. Note particularly the guidelines proposed in Box 1.

The piece comes about as a result of a meeting held at NIH in June of 2012, the aim of which, was to improve the reproducibility of findings from animal studies, particularly those used in preclinical research. The conclusions, while pretty predictable, are entirely appropriate–as a journal editor, I face the continuous challenge of getting our authors to avoid some of the obvious traps (like pseudo-replicates).

Note that these guidelines are not intended for the exploratory research that often precedes the design and execution of hypothesis-testing experiments that could be published.

Experiment planning

I was having one of my regular meetings with one of our junior faculty members in Molecular Neuroscience this morning and we started talking about how to prove causality in some intriguing hippocampal physiology data.

And that’s when we both launched into a very common technique that neuroscientists often use when designing a crucial experiment. I like to call it the “god-like gedanken experiment”. Basically it involves creating a thought experiment in which all of the methodological constraints are removed–as are the need to think about controls.
So for example, if we we thinking about the phenomenon of lightening preceding thunder, and we wanted to get at the question of causality–i.e. does lightening actually cause thunder–we would create a thought experiment in which we would artificially induce a lightening bolt and attempt to cause thunder.
Obviously there are practical problems in creating wild-type lightening bolts (at least as far as I know, not being particularly up to date in the weather engineering business).
And clearly in this case, the thought experiment doesn’t really advance science very far–the phenomenon of lightening having been well studied since at least the time of Dr. Franklin.
But this type of thought experiment can be of great utility for bench-top bioscientists, because it facilitates the mental process of stripping the phenomenon being studied down to its mechanistic parts.
When we don’t have to worry about how a drug might cross the blood-brain barrier or how to engineer a reporter gene into a particular type of neuron in mice of a particular age, then we can focus on concentrating instead solely upon the biological process. This process is, from the standpoint of experimental design, a series of mechanistic steps, which the scientist is attempting to reveal through experimental measurements.
So first, the god-like gedanken experiment, then worry about the practicalities and the controls.