A Friday Rant on Mechanisms

Mar 25 2011 Published by under [Education&Careers]

Grant reviewers love studies that elucidate the "mechanism" of a phenomenon, using definition #2 above. They want the experiments to point to the means by which the effect of interest is produced. By understanding the mechanisms, new therapeutic targets may appear.

Consider the following:

A proposal aims to determine which of several receptors for a substance are involved in a known effect, and which part of the organ system of interest is involved. Experiments will determine which receptor on which cells produce the known phenomenon.

Mechanistic? According to review, NO!

The reviewers encourage additional experiments in cell signaling to make the studies "mechanistic."

 

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"Mechanisms" exist at many levels. For example, type 1 diabetes mellitus occurs because the beta cells of the pancreas undergo autoimmune destruction and can no longer produce insulin for blood glucose regulation. That is the mechanism of the illness. Various organs may be damaged by long-term diabetes. Because patients with lower blood sugars have less risk of these complications, we presume that hyperglycemia mediates end-organ damage. Further study reveals that glucose can alter a number of processes within the cells of various organs damaged by diabetes. High blood glucose comprises one mechanism of organ damage in diabetes. All of the cellular systems modulated by hyperglycemia are also mechanisms at a different level. Successful therapies may target mechanisms of disease at any level, not just the cellular level.

I understand how appealing studies of intracellular processes can be in our world of reductionist science. Experiments with cultured cells avoid the inconvenience and ethical issues of experiments on whole animals or human subjects. However, at some point we have to take all of these detailed observations (yes, even mechanistic studies of intracellular processes are measured through observation, measurement, and description of effects) back to the whole organ/whole being level to make sure they turn out to be true! We can cure a lot of cancer in petri dishes but not in people. These is also value to understanding stuff at a higher level before drilling down into the cells. Otherwise, we may study the wrong cells and end up with nonsense.

I feel a bit better now. Anything else I can drop off in the comments at FYF.

3 responses so far

  • However, at some point we have to take all of these detailed observations (yes, even mechanistic studies of intracellular processes are measured through observation, measurement, and description of effects) back to the whole organ/whole being level to make sure they turn out to be true!

    Physiomotherfuckenology, FTMFW!!!!!!!!!!!!!!!!!!

  • gerty-z says:

    I wish the word "mechanism" could be removed from scientific vernacular. I'm sure that it had a real meaning at some time, but now I feel that it is just used to piss on other people's work. No matter what you have done, someone will ALWAYS claim that you are "lacking mechanism" if they want to sink you. At least, that is how it sometimes seems to me.

    But what do I know.

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