Load tolerance and disease

June 10, 2010 § Leave a comment

Continuing on the theme of ideas that were ahead of their time, John Higgins pointed out this article from 1962 (Frenster JH, 1962.  Load tolerance as a quantitative estimate of health.  Ann Intern Med. 57 788-94. PMID: 13959579)  Frenster was struggling with the fact that as new technology makes it easier to detect the symptoms of disease earlier and earlier, it becomes less easy to define the point at which disease starts. On the other hand, he was also aware that the same developments offered the tantalizing possibility of viewing disease as a quantitative phenomenon.

His proposal for how to think about this is to define a “unit of physiology” that he calls a body process (today we might say system), which transforms mass, energy or information.  He then asks us to look at a body process as taking an input load and converting it to an output; each process also has “resistances”, both internal and external.  A healthy process can manage its input load easily: in other words, it has additional capacity.  A partly diseased process might be able to keep up with a normal load, but any unusual demand would send it over the edge; and as the disease becomes more serious, you lose the ability even to cope with a normal load.

Frenster argues that a convenient way to determine just how healthy or diseased a process is would be to ask how much tolerance it has for additional load, an approach that was already being used to some extent for diabetes. He says:

“The decrease in process health and the gradual increase in process disease is thus a gradual movement along a continuum of values representing the changing balance between process capacity and applied loads and resistances; it is not a sudden discrete jump from one distinct value of health to another  of disease”

The use of the engineering analogy of “load tolerance” and the emphasis on quantitation in the definition of disease (Marc Kirschner likes to point out that hypertension is a disease that can only be defined quantitatively: qualitatively, you have a blood pressure.  Fine, but what is it?) does indeed give you a sense that this is someone who really wanted to be a systems biologist, or (maybe closer) a systems physiologist.  John comments that the tolerance-test approach is currently used in a handful of clinical situations, but even now the concept that such tests are probing the limits of a biological control system, which it would be helpful to study and understand, is poorly appreciated.

Frenster wrote a couple of other opinion pieces along similar lines, and then apparently gave up and started working on transcription and chromatin repression with Alfred Mirsky.  That was probably interesting enough — but if he had been born two or three decades later, he might have been a systems biologist.  Aren’t you glad you didn’t make the mistake of being born too early?

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