The Use of Model Organisms in Biomedical Research
“So you study worms?” “Interesting, but……..is it really that important?”. The person I just met looked as if he was a bit confused after I told him about my research. In fact, this is often the response of our audience when my colleagues and I talk about our research to those not in the field. I work in a Washington University School of Medicine laboratory that is primarily funded by the National Institutes of Health. We do most of our research using a tiny nematode (or roundworm) – Caenorhabditis elegans (C.elegans) – that naturally lives in the soil. So how are studies on these free-living soil nematodes related to today’s biomedical issues? This is an important question, given that C. elegans is one of the most commonly used model organisms in biomedical research.
Because of ethical and feasibility issues, non-human organisms have long been used in biomedical research. In fact, much of our current understanding of our own body came from studies of other organisms. This accomplishment is made possible by the fact that all organisms on earth originate from a common ancestor. Therefore, the underlying biological processes are remarkably similar, especially those that are essential to life. Historically, biologists used a wide variety of organisms for their research. However, most modern biologists focus on a smaller list of organisms, so- called model organisms.
Model organisms are non-human organisms that are extensively studied not out of interest in the organisms themselves, but to understand some biological mechanisms shared between species. Model organisms were selected based on a variety of properties such as short life-cycles, low maintenance costs and ease of genetic manipulation. The large amount of both biological and technical data makes experimental design efficient and results valuable.
Model organisms have contributed greatly to the biomedical field. For example, most of our understanding of the basic principles of molecular biology, such as how DNA is replicated was developed and studied in Escherichia coli. E. coli, a species of bacteria that normally lives in our gut. It has been widely used to study biological phenomena that are shared in all living organisms.
Baker’s yeast – Saccharomyces cerevisiae – is often the organism of choice for understanding mechanisms that only exist in eukaryotes (bacteria such as E. coli are prokaryotes, but humans and most of the organisms we are familiar with are eukaryotes), and have contributed heavily to the understanding of how eukaryotes cells grow and divide. The next level of complexity is represented by the “simple” multicellular organisms – the nematode (C. elegans) and the fruit fly (Drosophila melanogaster). These organisms contributed greatly to the understanding of modern genetic and developmental biology. Finally, mammalian specific traits are most often studied with the house mouse (Mus musculus). Given the similarity of M. musculus to humans, it is one of the most heavily used research animals in the world and has helped to define the molecular basis of many human illnesses.
Despite the huge success of model organisms, some question the future of using these organisms. There are several parts to this argument. First, it was said that model organisms’ future has been hindered by its own success. Because of the huge advances in understanding basic biological principles, some suggest that model organisms have completed their task. On the other hand, new genome sequencing techniques and improvements in cell line studies make the direct studies of human disease much more feasible than before.
In my opinion, however, model organisms have much more to give. We may now have a better understanding of the basic biological principles but our overall understanding of cell biology is still primitive, a point that applies all the more to the complex biology of the entire organism. Mass sequencing data may help to identify genes and mutations responsible for some diseases, but these are usually insufficient to reveal their mechanisms. Cell line studies also have major limitations. Finally, a great deal of our understanding of a given biological process actually came from research initially seemed to be unrelated. For example, a major discovery – microRNA was identified through studying the larval development in C. elegans. MicroRNA was later found to be well preserved in both animals and plants and was associated with numerous biological processes and diseases (including cancer, heart disease, depression, and many others).
In my view, due to the extremely complex nature of biology, the relatively “simple” model organisms will continue to provide insight for the understanding of our own biology. It is probably easier to understand the biology of one cell (E. coli and yeast) or 959 cells (C.elegans) compared to trillions (1012) of cells, however scientists today are still struggling with the biology of a single cell. In addition, recent advances in biology allow for the integration of research on different organisms in a much more efficient manner than in the past, making the contributions of model organisms stronger than ever. There is little doubt, therefore, that model organisms will—and should play a crucial role in biomedical research in the foreseeable future.