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

This blog is open to discussions. Feel free to comment.

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