Of mice and men (and petri dishes)

Science, Exercise, Physiology, Research

It takes eggs to make an omelet; it often takes lots of mice to do science. (And like the eggs, they don’t survive the process.)

How much do you understand about science?

In particular, when it comes to science in the news, how much of it do you really understand?

And when it comes to research about the effect of nutrition and exercise on health, can you really tell what is good science and what is not?

A recent piece of news about fake research, which you might have read about, should cause you to consider carefully your answer. (You can read a shorter perspective here.) Anti-science folks will take heart, no doubt, to once again see that it appears possible to make science say whatever we want it to. But that is not the point. (And it is not actually true, at least not of well-done science.)

Let’s face it, we can’t all be research scientists, or experts at evaluating which study is well designed and performed, and which is flawed. That’s why we rely on experts.

To be clear: I love science. Science is a wonderful thing. It is our best bet for making sense of the universe. It has been wildly successful at bringing about our technological world. Which is precisely why anyone who is trying to sell you something uses what appears to be science, but often is shaky, or not at all, in order to convince you to buy.

Therefore, there are peculiarities of scientific research about physiology, health, and biology in general, that we should all keep in mind when reading or hearing about new results. And that’s what I’d like to offer in this post.

Who am I to say those things?

For full disclosure, you need to know that I am “only” a physicist.

So, while I know a lot about particles and galaxies, I’m more fuzzy about things of sizes in between (like the human body). However, because I have training in science, I understand the general process of research, and the inherent limitations of the methodologies employed. And I tend to be very critical of what I read.

My purpose is therefore not to impart absolute truths (we don’t have such things in science, by the way, only very reliable understandings about how things work).

If the only thing you remember from this post is that you should be very doubtful of what journalists write, I’ll claim a big victory. So let’s get going.

Petri dishes

The most basic way of doing research in biology is to study cells and tiny living organisms in a special environment in which they normally should thrive. That’s what petri dishes are.

It used to be, and in many cases it still is the case, that in order to identify what ails someone, you would take a swab, and smear it onto various petri dishes. Depending on the characteristics of the medium in each dish, and where the bacteria would actually thrive, you could tell what bacteria were actually causing the infection. (That explains in part why it took so long to get the results.)

We’ve gone a little away from that nowadays, but what is still often being done is still using petri dishes.

For instance: Take cells of a certain type, like cancer cells, and cultivate them in a medium that is nourishing to them (i.e. a petri dish with the right medium for cancer cells to grow). Then you add some substance and see if the cells still thrive, or stagnate, or even die.

Research, Science, Physiology

A scientist “doing” the (petri) dishes…

If you find something that can kill cancer cells (or bacteria, or some fungus), you may have a candidate for a drug or medication.

That is how a lot of research on anti-oxidants is being done, for instance. Anti-oxidants of all sorts are found to be bad for cancer because in petri dishes they clearly impede the growth of the cells.

But there is a big, really big, problem with that approach. In fact, there are two huge problems:

  1. Petri dishes are not like a living organism. So what takes place there might not be the same as what will take place in the body, especially for cancer cells, because they interact with the entire organism.
  2. It is easy to deliver a specific molecule or drug to a cell (or bacteria or fungus) in a petri dish, but delivering it in a living organism is not the same. Our bodies have natural mechanisms for treating what comes into them; through eating, there’s digestion, through the blood, there is filtering by the liver and kidneys, our natural detoxifiers. So just because in works in a petri dish, it does not mean it will get to the right target in the right kind of shape in a real body.

This explains in large part why you should probably not give too much credence to anything about anti-oxidants and food supplements in general. They have been shown to not have much of an effect, if any, in humans in part because our bodies handle them in such a way that they are not the same once they reach cells. Moreover, once they reach cells living in real, complex organisms, often the interactions are not the same as those taking place in petri dishes.

Mouse model

A lot of research on the effect of drugs and nutrition regimen is done on what is called the “mouse model”. Basically, mice are being used, and researchers perform studies while maintaining a keen awareness that mice are an approximation, a stand-in, thus a “model,” for the human body.

That keen awareness is not always communicated by reporters of the results.

The good side to doing this is that mice are short-lived, compared to a human being, and scientists have developed breeds of mice that have very well known characteristics over the years. We even have mice that are bred to have cancer with a very high probability. Furthermore, we can manipulate mice genomes to the point of being able to induce certain conditions that can then be “cured” by drugs or specific food or exercise patterns.

Hence it is possible to do a lot of research in a fairly short amount of time. Generations of mice stand in for generations of human beings, but the research takes months instead of decades.

The downside, and you must keep this in mind, is that mice are not men. Especially mice that are bred for some very specific traits or diseases. Therefore, what takes place in mice is only a hint of what might be taking place in the human body.

I recently heard a top cancer scientist talking about how, according to her, we need to move away from the mouse model in medication research. Her argument was that many drugs that were found promising in specially bred mice were later on found to be totally ineffectual in humans. That’s a big downside, and a lot of research money wasted.

Despite opinions to the contrary by conspiracy theorists, scientists don’t like to waste money, and time, on fruitless research. Especially cancer researchers, who are human as well, and have loved ones who are affected by those diseases.

The bottom line is that just because some research says an effect was found in mice, it does not hold that the same is true for humans.

Science, Research, Physiology, Biology

From petri dish to humans, there is a really big step.

Cohort (and longitudinal) studies

Perhaps the least understood of the research methodologies is that of the cohort study. Sure, you probably think, one should be careful of petri dish and mouse model research, but when it comes to health and fitness being studied in real human beings, that’s another matter entirely.

Is it?

The advantages of petri dish and mouse model research come from the ability to observe in details what is taking place. The mechanisms might be observable through microscopes, and mice can be (and often are) dissected to verify what is going on.

Humans are not, as a general rule, dissected, as part of physiology research. At best, some biopsies are taken, but even that is limited. (This is a bit of humour. The part about dissection. Not the part about biopsies. That hurts for real.)

What researchers rely on instead is recruiting willing subjects (i.e. a cohort), asking them to follow a specific regimen (which could consist of a special diet, or exercise, or both), and then following-up on their progress through surveys over a period of time (long ones are called “longitudinal” for that reason).

Yup, basically, they are asking participants to fill a questionnaire about what they did, what they ate, how much of it, etc.

In the best designed research, there is close follow-through of the program by researchers. They might even sequester the subjects for the duration of the study, but that is very, very rare. In many cases, the questionnaires are asking about stuff that happened days, and even weeks, earlier, and there is no direct verification.

How well do you remember what you did, and how much you ate, on Wednesday of last week?

Therefore, often the researchers only ask about general habits and levels of activity, or take a sampling that they hope is representative by asking about the most recent day.

I think you understand where that is going: What you do on any given day may, or may not, be representative of your general diet and exercise habits…

Where does that leave us?

Again, I’m all for science. The more, the better. As a scientist, I am keenly aware that, at the very least, science is self-correcting; by which I mean that if somebody gets the answer wrong, for whatever reason, someone else will eventually point it out, and overall we’ll get it right.

But it might take a while. Because it is difficult to do science well when the subject is the human body and its complex, diverse, interactions with the environment.

There are things about physiology that we understand very well by now; I’ll get back to that topic next time. But keep in mind that biology, in comparison to physical sciences, is bloody complicated. Climate science, in comparison, as complex as it gets, is a breeze.

There is a lot of research that is well designed that can help us make sense of how our bodies work. The accumulation of individual pieces of evidence eventually lead to a more accurate bigger picture. That’s the process, and it works.

Just be careful of individual pieces of research being reported as having widespread, and very radical, implications for your health. The more fantastic the implications, the more cautious you should be.

Especially if somebody is using the findings to sell you something.

Images from Pixabay

More alike than not… except in the details

Sports, Exercise, Performance, Athletes

A diversity of shapes and speeds at the Rome marathon a few years ago. All athletes, in a way.

Time for a story. (Isn’t it always?)

Once upon a time, in pretty much all lands on this planet called Earth, the thinking of sports federations and elite coaches was that an Olympic athlete had to be of average height and build, with lean bone and muscle mass providing a streamlined body type.

For all Olympic sports.

Such athletes were selected and tested early, then subjected to years of grueling training. Only a very small portion of even such “ideal” athletes rose to the top of each sport and were deemed good enough to represent their respective countries against the rest of the world. (The story does not say what happened to those who did not rise to the top, but rumour has it that they started hating sports, and took up knitting instead.)

This had come about because there was a clear picture of the “ideal” human shape that had endured to some extent since the time of the original Olympic games in Greece. But with more clothing. No doubt the statues of antiquity, and later re-born in the Renaissance, had helped solidify such an image of the perfect athlete.

Allied to that image was the notion, very much born of religious thought, that only through a lot of hard work and pain could the most gains be made in training. Fierce competition, even among teammates, was seen as the way to build stronger individuals.

Thus many countries went about, and generations of kids, teenagers, and young adults went about their training. Only a very small portion of all those who started in such programs ever made it, and they won medals and set world records.

But this story is not about world records and Olympic medals. It is about how athletes were selected and prepared to compete.

It all changed, of course, when atypical athletes started winning medals and breaking world records. This came about because many countries simply did not have athletes with the expected, “ideal” body type. They were not expected to win, yet there they were, running faster, jumping higher, lifting heavier than the rest.

Suddenly, coaches caught on to what biologists must have realized much earlier: That there might be something about the specific genetic make-up of an individual that might make them better athletes at SOME sport in particular.

Nowadays, we fully understand that notion, and athletes are not expected to look the same across all sports. That explains why we see a lot of Kenyans and Ethiopians win marathons, and tiny little guys and gals ride race horses. Volleyball players are tall and somewhat lanky; ping-pong players somewhat short but extremely quick.

You get the picture. We each have specific genetic variations that make us more or less good at some activities or sports. Some are very visible, others not.

As the eminent (running coach) Jack Daniels pointed out in a seminar I attended a few years ago, you would not expect Shaquille O’neal and Mary Lou Retton to perform at an elite level at each-other’s respective sports. (The reference to those athletes provides an idea of the age of Jack Daniels, and of the attendees, not of the date of the seminar.)

Big differences are expected, for instance, between a basketball player and a gold medal winning gymnast. (Just to be clear, for those of a different age…) Mary Lou could not possibly dunk a ball, and Shaquille might very well break the asymmetric bars. Hence athletes are largely selected based on their body types nowadays.

Tragically, what hasn’t changed (yet) is the notion that training has to be uniformly hard and painful for everyone. That is why we see PE programs in schools that are still based on (unfriendly) competition and pitting everyone against each other to be the best, or to meet some specific standards of fitness arbitrarily defined by someone.

That’s in large part been identified as the prime culprit for turning the vast majority of people away from doing sports on a regular basis. If all that seems to matter is winning, and there can only be one winner, that means there are a lot of losers. And nobody likes being a loser.

So it starts by hating PE, then it becomes hating sports. Except for those you can watch while drinking beer, and even then, it is watching games, not playing.

Exercise, Movement, Daily

Watching is definitely not the same as doing.

At the same time, the understanding that we are all different has been taken much too far: Nowadays, a lot of folks think that they are simply not athletic, not meant to do sports. There are winners, who are jocks, who are meant to do sports, and then there’s the rest of us who should not do sports. Who cannot do sports.

Given the premises of differences between individuals and of personally hating sports, it is understandable that many reached the (erroneous) conclusion that they are not meant to move.

But the reasoning is incorrect, and one of the premises is false.

The facts, based on biology, are all pointing in the direction of our bodies being meant to move. Needing to move. Regularly.

Hating sports and exercise is a learned behaviour; it can be unlearned, replaced by something better.

We are all different, but even in our visible (and invisible differences), we are more alike than not.

The story time being over, I’ll conclude this post by pointing out the ways in which we are alike, and those in which we differ. And I’ll come back some other time to the fascinating topic of how to learn to like exercise.

Ways in which we are all alike: Basic morphology and physiology

Cells, Physiology

The marvelous machinery of life.

  1. We all have the same number of limbs, fingers, heads, internal organs (types and numbers), etc., and they all are built according to the same plan. (Yes, I know, there are accidents of biology, but the basic plan before those accidents is the same.)
  2. We all have muscles connected to bones in order to makes us move; those muscles all work according to the same principles, and allow sensibly the same movements to be performed by everyone.
  3. We use carbohydrates, lipids, and to a lesser extent proteins, to generate the energy that allows our cells to function. Including muscle cells, which are used to move our bodies. More specifically, there are fast and slow ways of generating that energy, and although they vary in relative terms, they are all present in all of us.
  4. We all obtain such nutrients from eating; our digestive system, comprised as it is of our own guts and the microbiome therein, functions fundamentally the same way in all of us. Besides nutrients, we need water and oxygen (not too much) for our metabolism to operate.
  5. We need to move; for our bodies to be healthy, we need to move. The stress imposed on our bones, muscles, and internal organs by intense activity is what keeps bones strong, muscles large(-ish), and organs performing their normal functions. Including digestion and waste disposal.
  6. All of our bodies respond to exercise (or to a lack thereof). If you exercise regularly, the body changes to adapt to the exercise, and the organs and energy systems hum along. If you don’t exercise, the body “relaxes” and things start to breakdown, fat reserves accumulate, digestion is slower and we get constipated, etc.

That’s just how our bodies work. We are all very much alike.

Ways in which we differ: The details of performance

Because of the details of how each of us is shaped (tall or short, thick-boned or thinner, etc.) and how cells function physiologically, there are aspects of performance in which we differ. Specifically:

Sports, Physical Activities, Training

So many sports, so many choices…

  1. How much endurance we have (mostly due to differences in energy systems at the cellular level, though that’s trainable to a great extent, perhaps the most of all aspects of performance)
  2. How fast we can be (also highly trainable, but limits imposed by physiology exist in each of us, also at the cellular level in muscles)
    How strong our muscles can be (small differences there)
  3. How big our muscles can become (bigger differences there)
  4. How flexible we can be (muscles, ligaments, but also joint movement; we can’t all be circus performers!)
  5. How coordinated we can be (agility, efficiency, also technically trainable to a great extent)
  6. How a wide range of our senses perform (eyesight, hearing, smell, etc.) and how efficiently our brains put all of that together

Taken together, and in the right combinations, the accumulation of small differences is what, along with adequate training, makes top performing athletes.

So, while it remains true that there can only be one winner in each discipline, and that at the top level (Olympics, for instance), only a small portion of the population is equipped to truly compete, we all have the potential to take enjoyment in some physical activity. And we may even do pretty well, locally or within the cohort of people our own age.

What matters most, however, is that we are all alike in fundamental ways. We all need to move, a lot, to keep our one and only body functioning optimally for a long time.

It’s up to us to figure-out what makes us enjoy it the most.

Exercise, Endurance, Physiology

The author, laughing at a well-deserved muscle cramp, after having completed an iron-distance triathlon.

For an interesting discussion of physiological differences in triathletes, see the recently published book Triathlon Science by Joe Friel and Jim Vance.

Pictures from Pixabay and the author.