Selected Concepts and Theory

Here is a collection of essays that cover concepts related to the scientific method and to specific laboratory studies. Contents include:

How Not to do Science

I spent a few years during my postdoctoral training on an exciting project in cardiovascular science. My postdoctoral mentor at the time was convinced that the electron-dense coat seen in electron micrographs of portions of the cardiac sarcoplasmic reticulum (SR) were clathrin-coated vesicles. He suggested that the putative coated vesicles were involved in calcium transport. Given what we knew about the role of clathrin in receptor-mediated endocytosis, and the fact that calcium enters cardiac muscle cells during each contraction event, it wasn't a long stretch of the imagination to visualize these things shuttling excess calcium back out of the cell. In fact, everything fit together so well, we couldn't imagine any other explanation for what we saw.

Unfortunately, nature didn't see it that way. While I was chasing clathrin around in the heart (and Brown and Goldstein at UT-Southwestern were earning the Nobel Prize on the role of clathrin in coated pits), another cardiovascular research group correctly identified the nature of the 'coated vesicles' that I had so much difficulty isolating. It turns out that they weren't clathrin coated at all, and they really don't go anywhere. The structures are apparently involved in signal transduction, and our approach to understanding their function was a waste of time.

Oh, it wasn't a complete waste - I did learn a number of techniques and research strategies. I also learned an important lesson in how to conduct science. That is, if you are going to do an experiment you had better be prepared for any outcome, including the possibility that your hypothesis has no basis in reality. The fundamental difference between good science and what I was doing was that I had set out to demonstrate that the so-called 'coated vesicles' in cardiac SR were clathrin-coated and transported calcium. The experiments I conducted would demonstrate the presence of clathrin if it was there, but were designed to tell me nothing if it wasn't there. We didn't test the hypothesis - we set out to 'prove' it.

If it isn't so, it simply isn't, no matter how brilliant the theory - Nature is funny that way. Yet many scientists, past and present, brilliant and not so brilliant, have ignored facts and pursued avenues of investigation based on 'hunches,' or 'faith.' When those scientists are influential, they can delay progress for a very long time.

All scientific endeavors start out with a question or hypothesis (see Fact, Hypothesis, and Theory). How can you determine that you have asked a good question? Scientists must be excited about their work, or they wouldn't put up with the lack of material reward that has long been a trade-off for a scientific career. No doubt, you will be quite excited and happy if your hypothesis turns out to be correct. You will also have a very good idea of what to do next. Now ask yourself what you will do if your hypothesis turns out to be wrong. Will you be just as excited about the outcome? If the answer is no, and you have no idea where you would go from there, you have asked a bad question. The goal of science is to understand nature, not to predict it. Objectivity is an important key to progress, and lack of objectivity will ruin your progress.


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Created by David R. Caprette (caprette@rice.edu), Rice University8 Jan 96
Updated 20 Aug 07