Vol. 24, Issue 1: Fall 2016
Back to the Pet Shop: The Case for Bringing New Model Organisms into Research
Model organisms and animal trials usually bring to mind the ubiquity of the lab mouse or the fruit fly. Counting down five fingers: E. coli, Drosophila, C. elegans, mice, and zebrafish will already account for a large percent of all living things used in biological research. While there is still more that could be learned with each and every one of these creatures, the real question is if they truly provide the best window into science’s contemporary questions. In a recent special issue of Trends in Cell Biology, UNC’s Dr. Bob Goldstein and Cal’s own Dr. Nicole King discussed past examples of turning away from the standard arsenal of model organisms and reasons to consider making a habit of it in the future.
The organisms used in biological research tend to be chosen for convenience, ease of use, and cost-effectiveness. Gregor Mendel, the famous monk and “father of genetics”, used pea plants because they were the organisms available to him. A lot of modern biomedical research uses mice because of their relative closeness to humans and the diversity of genetically modified options that can be tailored to very specific research questions.
But some questions simply can't be answered using the tried-and-true traditional models. Telomeres, the ends of chromosomes of DNA, are present in every plant and animal. However, if DNA work was only done with a mouse or a fruit fly, these interesting features may never have been discovered. Instead they were discovered through a protozoan called Tetrahymena, which had a unique feature that made it perfect for discovery. Humans have 46 chromosomes and fruit flies have 8; Tetrahymena have tens of thousands. Tens of thousands of chromosomes means tens of thousands of telomeres, and researchers were able to find a specific genetic sequence that acted as a buffer zone for chromosomal tips. Like teaching a computer to recognize pictures, scientists needed a lot of initial data to later be able to easily identify telomeres in other organisms. Tetrahymena's myriad of chromosomes provided this.
While Mendel started the field, Thomas Hunt Morgan, the “father of Drosophila genetics”, used fruit flies to establish the groundwork supporting our understanding of the molecular basis of genetic processes today. However, despite being remembered for his work on a specific organism, Morgan used over 50 different organisms throughout his career, targeting his selections as needed to better answer his particular questions. For example, fruit flies were chosen because they provided a novel opportunity to study chromosomal genetics, but when he became interested in the development of left-right body asymmetry, Morgan turned to the fiddler crab because it could give a better answer to that question than a fruit fly.
Clearly, not all biological questions can be answered using traditional models. Dr. Goldstein and Dr. King envision a future where scientists jump from organism to organism to consistently use the best option for the question at hand. With more and more organisms being sequenced, technology can allow investigators to pick new models perfect for their questions with more ease than ever. Further, genome editing like CRISPR/Cas9 allows for relatively easy and cost-effective alterations to novel organisms, for example directly inserting fluorescent tags into native genes instead of relying on breeding transgenic animals or using ex vivo antibody staining.
One of the biggest challenges with using an untested model organism is figuring out how, and even if, it can be reared in a laboratory. Dr. Nicole King spent the beginning of her postdoctoral work growing every species of choanoflagellate she could find, an interesting sea creature thought to be important to the evolution of animals, eventually finding two that were well-suited to a lab setting and then optimizing the protocol for their use.
While finding new model organisms can be a time consuming process, with more professional scientists and interested undergraduates than ever, time is hardly a prohibitive issue. A few more groups developing protocols for more model organisms could be enough to trigger a paradigm shift that would open the funding floodgates for a strong emphasis on developing new organismal models. Advances in the field of model organism discovery are improving the biological and biomedical research fields and have the potential to accelerate advances into new areas of biological science. During future research design, it might be worth it for PIs to think twice before just sticking with mice.
About the Author
Malcolm Crawford is a junior transfer from Los Angeles majoring in Molecular and Cell Biology. His dream of becoming a MotoGP racer did not pan out, so he settled for striving to be a surgeon instead.