Research Theory and the Art of Rat Exercising

So there was this researcher who studied the effects of exercise on rats, and of course he needed someone to exercise his rats. As a poor student in those days—and since I didn’t have to sacrifice the rats (the post-docs did that)—I became his rat exerciser for a semester.

He was studying the physiological basis for endurance (as in not tiring from a long run), and I was interested in that subject well enough. So I applied and got the job.

There were two competing theories about endurance, both having to do with the mitochondria, which were like little batteries floating around inside of cells. One theory was that exercise had the effect of inducing muscle cells to make more mitochondria, so that endurance entailed having an increased number of mitochondria. But the second theory was that the number stayed the same while each mitochondrion became, as a result of exercise, more proficient at doing its job of supplying energy to the cell. For instance, what increased might be the concentration of the enzymes inside of the mitochondria, and that could be demonstrated experimentally.

The researcher wanted a chemistry major for his rat exerciser because there were many chemical calculations in his research, and I would get to do a lot of that, as well.

But for me there was more to it than just that because I was also getting college credit for it, so I would have to write a term paper at the end explaining what I had learned from being a part of a research team. The paper was supposed to be about more than just the research topic itself but also about the practice and theory of being a researcher (as in showing if I might want to do that kind of work myself one day; my advisor whispered to me that I should show enthusiasm and depth of understanding in this paper). The job was full-time and in another city—a whole semester’s worth of credit—so this paper was supposed to be a humdinger.

And then there I was, off on my journey to be a rat exerciser. It was starting to feel a lot like an adventure, although I had to confess to having a little trepidation about finding material for this paper.

the null hypothesis

The first thing I’m glad to tell you is that it proved relatively easy—eventually—to find someone willing to answer questions so as to help me with this paper. (That took a big load off my mind). It wasn’t my own researcher who helped because he was mostly interested in getting me to go long-distance running with him, as in marathon distances. (There was that endurance thing again).

The building where I worked was an old dilapidated relic with a researcher on the other side of each door as I walked along the hallway. So over the weeks I would work my way along this hallway and explain about how I had to write a paper on the theory and practice of researching. The reception was generally fairly cordial (if I caught them when they weren’t too busy) but not especially helpful. And then I hit the jackpot. He was rather blunt, but power-packed.

“You mean stuff like a null hypothesis?” he asked me in a way that indicated that he firmly did not believe in a null hypothesis. (He had probably just been complaining to someone else about it and was still feeling hot and bothered by the subject when I’d walked in). So sensing that he was willing to tell me all about it, I answered, “Yes, stuff like that,” even though at the time I had never heard of a null hypothesis. (Here, I am of course only approximating this conversation, after all these decades, but it is pretty close).

A null hypothesis was the premise that there existed no relationship between the events being studied beyond what would ordinarily happen strictly by chance. And I supposed that there must be some utility in that, in some theoretical way. But what happened, unfortunately, was that it got paired with the notion of falsification. And so the combination turned into being the claim that if you could prove that the opposite of a premise was false, then the premise itself must be true.

But the problem with that was how, in the real physical world, there were more choices than just either/or. We could not say, “If it isn’t black, then it must be white,” because it might be green. Even in a formal system such as mathematics, I am recently learning, it is not always appropriate to prove a premise by disproving its opposite. That only works for certain scenarios.

Anyway, that was what this guy was complaining about. He had apparently read some paper where another researcher had been falsifying null hypotheses.

And I suppose that I should interject that even today one of my favorite biologists, a woman of remarkable insight, nonetheless proceeds irritatingly by falsifying mull hypotheses. She literally uses the words, “The null hypothesis is….”

Oh, well.

But back then, this researcher led me on a quick survey of the alternatives (just what I needed for my paper). So I will relate here this quick survey and then get to the subject of the rats.

alternatives

Back then, I of course asked this researcher what he did instead of null hypotheses. Was it just to make plain ol’ regular ordinary hypotheses?

“No, I’m a Newtonian,” he answered. “Hypotheses non fingo.” (That was Latin for “I don’t conjure up hypotheses”).

This researcher was a physiologist, not a physicist, so he wasn’t channeling Newton out of some kind of doing physics problems. He was referring to Newton’s philosophy of how to do science.

He explained that the phrase “hypothesis non fingo” was written by Newton in the introduction to the second edition of The Principia and that it was directed against Descartes who apparently did use hypotheses. Newton argued that science should stick to just describing what could be demonstrated empirically and so it should avoid using hypotheses (which Newton took to be guesses “either physical or occult” at greater a priori truths. An example of a hypothesis would be Descartes’ “vortices.” (I later looked it up. Descartes had speculated that vortices made the planets move—which was a naturalistic or “mechanical” explanation compared to Aristotle who had argued that it required an intelligence to make them move—whereas Newton had adopted neither view but had merely described their action mathematically). Newton’s view came to be called a form of “empiricism,” and later Descartes’ view was called “mechanical philosophy.”

I found that to be interesting because, prior to that, I had always assumed that Newton, as the author of Newtonian mechanics, was thereby also the author of what came to be called “the Newtonian world view” which was basically mechanical philosophy (it was a more elaborated version of a mechanistic “clockwork” Universe in a deep, hard, no-nonsense fashion). But what surprised me was that Newton himself had opposed what came to be called the Newtonian world view! Newton was saying, “Just calculate, don’t speculate” (with speculation being how he saw claims to knowing rock hard a priori truths and so hypotheses).

Popper’s view was that science did make such stabs at absolute truth but then tried to prove them false. The claims were considered tentatively true until proven false.

And I realized that this researcher was basically writing my paper for me. So to keep him going, I said, “If you don’t use hypotheses of any kind, then what do you do?”

He said, “I just stick it together and see if it works.”

And there it was. Whoa. There was the saying that would stay with me forever.

“I just stick it together and see if it works.”

Yeah, it wasn’t stated all fancy in perfect philosopher-ese lingo. But in its down-to-earth manner, it was telling us that there was an alternative to seeing the world in terms of truth and falsity (or in terms of a priori truths) as Descartes and later Popper did. And the alternative was to see things in terms of “Does it work?”

But more than that (and to introduce yet again a favorite theme of mine): Why does it work?

Well, it works (or not) because of the arrangement of things (how he had stuck it together). At the time, I imagined putting together a gismo to see if it would perform as expected.

Instead of making guesses at a priori truths and then trying to prove them false (Popper’s view), he compared one way of sticking things together with another way of sticking things together. Success was to find the arrangement that nature approved of.

And I knew that that wasn’t the usual way of looking at science, but it appealed to me.

It helped, I realized, to think of science in terms of models. And a model, almost by definition, was not about describing what was absolutely right. A model was an assembly of approximations and assumptions—every student had to memorize them—and further, a model was about how those approximations and assumptions went together (were organized) to generate answers that came close to the answers we got by measuring nature directly. The idea was to emulate nature in an operational sense, not to make a guess (a hypothesis) about how things “really are” in a static sense.

His example was formulating an anesthetic. “If you’re making a chemical to deaden a nerve, just stick it into your arm and see if you can feel your fingers.”

Somehow I suspected that in his early days (before it was illegal to experiment on oneself) he had indeed injected himself with an experimental anesthetic. He was what you called an “old-timer” in that regard.

He added, “First you have to figure out the place to put it—how close to the nerve—and things like absorption rates and solvents—the whole setup—and then you find out if it works. If it doesn’t work, then you adjust what you are putting together.”

I said, “What about when you decide what goes into the anesthetic formula itself? Is that about making hypotheses?”

“No, making the formula is about what to stick together, too, and about how it fits with the rest of the body.”

Like putting together a gismo to do a job, the body was put together in a certain way to make an operational pain mechanism. It was how the pain mechanism was organized that created how it could do its job. So an anesthetic worked by messing up that organization (which the anesthetic did by adding to, or canceling out, the available chemicals, thereby changing how the situation was put together). Thus to formulate an anesthetic required attention to how the formula should itself fit together so as to fit in the desired manner with how the rest of the body was fitting together to operate as it did.

And that made sense to me from my own experience in chemistry. If we added together two chemicals, we didn’t always get the same result but rather it depended on the setup of things such as temperature, air pressure, pH, catalysts, amount of stirring, and so on. Chemists studied how a reaction depended on the arrangement of the circumstances. And likewise, an anesthetic worked by changing the circumstances surrounding the travel of a nerve impulse, to get a different result.

Also, I had just finished taking a thermodynamics course where the emphasis in the textbook was on the role of arrangement in thermodynamics. (More on that in a later post). But suffice it to say that I was more than a little prepared to hear this researcher’s explanations (while also being glad to hear other views for this paper I was writing surveying research theories).

The researcher considered his own view to be very compatible with Newton’s view where it was all about the math. In both cases, it was all about keeping it to what could be demonstrated. When the math used terms derived from measurements of how structures fit together, then the math itself took on a physical grounding.

the rats

But what about the rats? So fa I still haven’t mentioned the rats. How did we get a rat to exercise, anyway? They weren’t exactly inclined to doing calisthenics.

The idea, of course, was to have the exercise be in a controlled measurable amount so as to make scientific comparisons. And that was (let’s face it) sort of a high bar to expect a rat to clear. But there were two main approaches to getting a rat to cooperate in a controlled measurable amount.

The first was to get a large barrel and fill it half full with water and then let the rat go swimming for a recorded length of time. Rats were very intuitive excellent swimmers. (That was why there was an old adage about if rats seem to be jumping from your ship then perhaps it was time for you to start looking for another ship). But they could not climb the walls of the barrel, so they just kept swimming in there until you took them out. And frankly, the rats didn’t seem to mind getting to have a little exercise, out of their cages.

But from a researcher’s point of view, the trouble with a swimming approach was that you could only do one rat at a time. Otherwise, they started climbing all over themselves (they being rats and all) which was not a measurable way of doing things.

So this researcher I worked for had built himself a treadmill that could handle 20 rats at a time. Overlying the moving rubber floor of the treadmill was a plastic setup of stalls, so that each rat had its own place to run.

But still, why should a rat choose to run? It wasn’t like being in a barrel of water where it had no choice but to do or die. So at the back end of the treadmill, where its motion would carry any rat that wasn’t running, the researcher had dangled some exposed electrodes, and it was my job to use a clicker to shock any poor rat who fell behind in his running chores. (Their tails would stick backwards into the electrodes).

And I know, it sounded like a job for a sadist. But the truth was that the rats caught on mighty quickly and did not have to be zapped too often. And they were probably better off than the control group who had to stay in their cages without any exercise. The runners would look up at me as they were running, as if to say, “Really? This is what I’m here for?” (They were albino rats, with pink eyes looking up at me like that).

But before you start booing your narrator for sadism, let me add that I figured out that I didn’t have to actually shock the rats in order to make them run because, if one of them was lagging, I could just put my face down close in front of this laggard and then the rat would be, like, “Okay. Okay, I’m going. I’m going.”

But I had to admit that that seemed to be a pretty existentialist way to go through life, for the rats. Imagine:

They would spend most of their lives in a cage, except occasionally there would be a big hand that reached in and disgorged upon them some rat chow (the exact same number of pellets every time). But on other occasions the big hand would pull one of them out of the cage and place it onto a small circular metal disk (where, unbeknownst to the rat, it was being weighed). And then other times still, it was the treadmill.

It was pretty easy for me to imagine them thinking those old existentialist lines, “What does it all mean?” and, “Why am I here?”

So I read them some existentialist poetry. Chief among them was Paul Simon’s song “Patterns.” (“Like a rat in a maze, the path before me lies. And the pattern never alters until the rat dies”). But I also introduced them to Thomas Hardy’s “Hap” and to Sartre’s “No Exit.”

Yet if truth be told, I never was a very good existentialist. I tended to think of Sartre as someone who too much liked to hear the sound of his own bellyaching. And I kept being distracted by other philosophies.

So soon I graduated into social commentary. “Should society be regimented?” I asked the rats on their treadmill. And that led easily into educational philosophy. (Yes, it was like gym class here). Or to some people’s minds, it was like how every school should be run.

 “Now, class,” I would tell them as they were lounging on the treadmill, waiting for me to flip on its switch to begin a run, “we’re all going to have a good day today, with everybody learning the same lesson at the same time.”

But the rats had this tendency to always come back to the existentialism, with those wondering looks in their beady little pink eyes, like, “What is it all for?” 

“Trust me, you don’t want to know,” I would tell them.

“Why am I here?”

“Oh, shut up and run.”

But I did learn that I didn’t want to be the kind of researcher who sacrificed animals.

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