Research 101: Model organisms
I thought it worthwhile to create a series that offers a peek behind the curtain of scientific research. Most people outside of the field will never see what a real research lab is like, or understand what happens on a day-to-day basis. This can contribute to some of the distrust that surfaces on scientific topics, such as GMOs (which you can learn more about in my previous post). The public typically only sees the outcome of a select few research studies, and mostly studies that are high-profile.
So welcome to Research 101!
Let’s start by talking about model systems. This can be a tricky topic, since many people have conflicting opinions about using certain animals as model systems—mainly the cute, fluffy ones. Most of the information provide in this post has to do with the “cute” and “fluffy” animals (typically mice and rats; these are the animals used in laboratories that people often make the most fuss over). I think this is a result of not knowing exactly what these models are used for, or how they are used. It’s a little upsetting to see research laboratories portrayed as the “bad guys” in movies because they use animals in their studies. I want to be clear that scientific laboratories are not treating their animals poorly. Anyone who works with animals receives extensive training before even touching an animal. We also typically don’t work with what I’ll call “pet-type” animals (cats, dogs, bunnies, horses, etc.) or primates, unless there are specific circumstances. Primates, for example, are more often used in social experiments for psychology-based studies, rather than molecular research or medical testing.
With all that in mind, I’ll begin by answering a few simple questions.
What are model systems?
Model systems are often referred to as model organisms because, well, that’s what they are. The ‘model’ comes from the organisms being replacements for human research subjects, which I’ll explain a little more in the next section. They’re living creatures who are used in scientific studies for a wide variety of things (specific, right?). It’s a nice way to learn about biological processes in a real-world setting, instead of using cells grown in a flask.
These ‘living creatures’ can be complex organisms such as mice and rats, or simpler, single-celled organisms like bacteria. A sampling of models available to scientists includes yeast (the same or similar to the kind used to make bread), bacteria (E. coli is probably the most common), fish, worms (probably not the kind you’re imagining), fruit flies, mice, and rats.
Each organism has upsides and downsides. Fruit flies, for example, are often used because they are cheap and easy to maintain, produce copious amounts of offspring, and are easily manipulated on both the genetic and behavioral level. Fruit flies can also be a hassle because they have so many progeny (babies) and can escape and annoy neighboring labs with an infestation.
Why do we use model systems?
I think this is a question people outside research typically ask. To some, using animals in research seems like a waste of life (depending on the species, I’ve never heard anyone complain about researchers killing fruit flies). To me, model systems are a vital component of scientific research, and they aren’t taken lightly (again, depending on the species, as most people don’t care about the millions of bacteria that are killed in research on the daily).
Model organisms are used because human experimentation is generally frowned upon. Which sounds like a joke, but it’s true. One of the main goals of scientific research is understanding human complexity—biologically, chemically, etc. Another main goal is to increase the quality of human life and contribute to human health. These goals can only be achieved through model systems, because humans cannot be used in every day experiments, for two reasons.
One, humans are so biologically complex on a molecular scale that it would be impossible to figure out the function of anything without being able to isolate certain processes and genes. Since we can alter the function of model systems down to a single gene or protein, we can more easily determine the purpose of individual genes and proteins. In this way, we bypass the insane molecular complexity that humans have in order to generate an understanding of this complexity on a more basic level.
Two, not every experiment is safe for humans. I might argue most experiments are not safe (or plausible) for humans. As I stated above, we can’t alter the genetics of a human just to understand molecular processes. One, it’s difficult to alter genetics of a live system in the first place (it’s still not trivial to do so in some model organisms); two, the complexity makes it very challenging to elucidate effects of changing any genes.
Aside from altering genetics, drug development also needs to be taken into consideration when discussing model systems. If a potential new drug is identified, you can’t just willy-nilly give it out to people and assume it will work or assume it won’t just kill everyone you give it to (a bit dramatic, but I’m sure it gets the point across). A series of tests, called clinical trials (which I will be doing a post/posts on at some point), must be carried out, the first of which are done in the lab using mice or rats. These preliminary studies save time, money, and potentially lives by establishing dosage and determining unforeseen toxicities of any new drugs, before using them on humans. Again, testing drugs on animals is necessary, but is not taken lightly by the researchers involved.
I want to take a brief moment to stress that last point. Laboratory animal lives are not taken lightly. These animals are not used merely for enjoyment of the researchers, they are a valuable resource that is strictly accounted for. As I mentioned before, prior to even touching any animals we undergo specific training apply for extra ‘animal use’ approvals. The number of animals used in experiments is dictated in these approvals, with the bare minimum being used to prevent waste of life. Specific to using mice and rats, if a different model system can be used for the same purpose (such as worms or flies), it is highly recommended (and sometimes required) that the alternative system be used. These approvals also account for the types of experiments being done, the way the animals are housed and treated, and exactly step by step how the experiments will be carried out (as in, surgeries necessary, drugs administered, etc.). All of this has come from scientists wanting to be sure that any model system used is absolutely necessary.
What are some common model systems?
Worms: Caenorhabditis elegans
Research worms are not the kind you would use for fishing, at least not the type of fishing I’m used to. These worms are called C. elegans and are a type of roundworm commonly found in the soil. They are most often used to study developmental processes, aided by the fact that they are semi-transparent, and have a rapid, 3-day life cycle. Many labs also like to use C. elegans because it’s cheap and easy to maintain in a laboratory setting.
Fruit flies: Drosophila melanogaster
Fruit flies are also very, very common. They are incredibly easy to maintain, you can get thousands of progenies in a manner of days if you breed them correctly, and their genetics are simple to manipulate. Like the worms, fruit flies have a very short life cycle, which can help elucidate gene and protein functions in a short time frame while also having many biological replicates.
Zebrafish: Danio rerio
Like worms, zebrafish are clear, which makes tracking of proteins inside the animal easy. In my opinion, this makes zebrafish one of the coolest model systems out there, likely because of all the colorful experiments they can create. Also, like the worms, these fish are often used in developmental biology, because their translucent skin allows scientists to physically watch and track how organs grow and develop. Fish are a bit trickier to maintain, mostly because of all the fish tanks that require extra care.
Those are probably what I’d consider to be the “flashiest” model systems. Some of the other common organisms include yeast and bacteria, which aren’t as exciting to look at. What model system laboratories choose to use involves a variety of different factors, such as cost, time, and a bit of personal preference. In recent years, researchers have begun to introduce more what I’d call “non-standard” model organisms. These organisms are higher in complexity, much like mice and rats, but provide certain benefits that mice and rats don’t possess. I’ll give you an example.
The project that I’m working on now uses naked mole rats as a model system. Compared to the number of mice laboratories in the world, there are scant numbers of naked mole rat labs. Naked mole rats are being studied more and more because of their incredibly weird molecular biology, which is something we are just beginning to learn more about. They live very long for their size without exhibiting normal signs of aging. There are also very few reported cases of cancer in naked mole rats, so their apparent anti-cancer properties make them a good candidate for studying possible cancer resistance mechanisms that may be able to translate to humans. I think they are exciting systems that will provide insight into preventing cancer development and other pathologies associated with aging.
I hope this post provided some useful information on model systems. If you were on the fence or skeptical of using animals in a research setting, I also hope this at least gave you a good explanation of why they are necessary. They’re important tools in research, and as I said before (I really can’t say this enough), they aren’t taken lightly.
As always, I’ll provide some additional reading down below (all from sources I trust, though the first Wikipedia link is only a starting place!) for those who are interested and stay tuned for the next installment of Research 101!
Further reading:
