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You Have Evolved From Worm to Man…

Whenever I begin to explain to somebody that I conduct research using worms, I am met with the same confused stare. I immediately follow up this statement with an explanation that the worms I work with differ greatly from the soil-dwelling annelids that most people envision when they hear the word “worm.” In fact, I work with the tiny nematode worm Caenorhabditis elegans. Once the distinction between “normal” worms and “lab” worms is made in the mind of my audience, I am usually met with a variation of the question: “Why on earth do you study worms?”

Measuring a minuscule one millimeter in length, these worms are nearly impossible to see without the aid of a microscope. C. elegans worms have a very primitive nervous system, their sperm crawl instead of swim, and they average only one crossover per chromosome pair per meiotic event (for reference, humans average two to three). At first glance C. elegans may seem an unlikely choice to use in studies impacting human health. However, much of the beauty of using C. elegans as a model organism lies in the very quirks mentioned above.

A worm expresses a GFP-tagged protein throughout its nervous system. Image Source: Bessereau Lab Website

Prior to my freshman year of college, when I began working in a neurobiology lab that relied exclusively on the use of C. elegans, I had never heard of the worms nor their use in academic research. When I found out that I would be working with a millimeter-long, simple animal, I was a bit underwhelmed. I was hoping to conduct research that would be applicable to human health, not the wellbeing of some nematode with which I was completely unfamiliar. On my first day in the lab, I was given an assortment of academic papers, reviews, and textbook chapters to help me acquaint myself with my new research subject. I begrudgingly began to flip through the seemingly endless pages that I had been given, honestly focusing more on the pictures than the knowledge contained in the text. However, when I turned to a page that contained a picture of a green fluorescent protein-tagged neuropeptide expressed in a live worm, it suddenly hit me. I realized that these worms, due to their transparent cuticle, offered researchers the rare opportunity to actually see inside a living creature without the aid of x-rays, MRIs, or any other technology. C. elegans was no ordinary little critter.

At this point, if the person with which I am speaking happens to have an uncanny knowledge of the peripheral branches of the tree of life, they might ask, “There are plenty of transparent animals, what makes C. elegans so special?” What makes C. elegans so special, my oddly expert colleague, is that these worms are hermaphroditic, meaning they contain both male and female sex organs and are capable of self-fertilization. That’s right, somewhere along the evolutionary timeline, these worms decided they were better off mating with themselves than going through the trouble of finding a mate. Okay, maybe it didn’t happen like that. In fact, I believe there was very little in the way of a decision on the part of these worms. Either way, this hermaphroditism greatly simplifies many of the tasks associated with studying any animal in a lab setting. It becomes far easier to maintain a line of animals with a specific genetic background when one animal can be placed by itself and it will give rise to a whole population of genetically identical animals. Additionally, male C. elegans worms still exist (by virtue of the worms’ gender determination mechanism), which makes genetic crosses both a possibility and a relatively trivial process. Working with C. elegans gives a researcher the best of both worlds from a genetic standpoint.

The C. elegans male and hermaphrodite differ by one copy of the X chromosome (hermaphrodite: XX, male: XO). Image Source: Wormatlas

If my audience hasn’t yet fallen asleep or moved on to a conversation not concerning the many advantages of nematodes in biological research, they’re probably curious to know whether these amazing little creatures have made any real contributions to science. Indeed they have. C. elegans worms have been the subject of research conducted by a total of six different Nobel Laureates. The research of these laureates has considerable range, covering topics from using GFP to identify expression patterns to using small RNA molecules to inhibit expression of specific genes. These miraculous little worms were also the first to have their whole genome sequenced. As a result, researchers have had a considerable amount of time to annotate the genome, an important step in recognizing how the genetic puzzle pieces fit together to determine the phenotype. Clearly, these seemingly insignificant animals have contributed a considerable amount to the field of modern biology.

Since I first started working in a worm lab over two years ago, I have developed a deep respect for the power the worms with which I work. These worms have played a role in many major events and discoveries in the past half-century. The short lifespan and easy manipulability of C. elegans make them well suited to model a wide range of biological processes, including many of those present in the human body. In fact, many researchers are now using the lowly worm to help understand human diseases and stress responses. As the German philosopher Friedrich Nietzsche states in his novel Thus Spoke Zarathustra, “You have evolved from worm to man, but much within you is still worm.” This sentence effectively sums up why I, and thousands of researchers like myself, have chosen the lowly worm as the subject of our studies.

HeadshotTyler Shimko is an undergraduate studying and conducting research in biology at the University of Utah. He has worked with C. elegans for the past two and a half years. You can follow him on Twitter @TylerShimko.

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