In the late 1970s, a pair of biologists chatted over a microscope, working together to examine some mutant fruit fly embryos. The mutants in view were stumpier and spikier than usual; the scientists agreed these defects were worth further study. As they focused on their tiny subjects, they could not have known that this moment would eventually lead to a landmark treatment for the most common type of skin cancer. The scientists hadn’t set out to cure a disease — they were simply trying to understand how life works.
Basic Research is the Knowledge Base for Applied Science
Research with clear, immediate applications is often much easier to justify to the public than discovery for the sake of knowledge, and it’s understandable that politicians have sometimes ridiculed this kind of research as an impractical waste of public funds. When the aim of a study is to fill gaps in our understanding of the natural world, it is known as “basic” or “foundational” science. Because basic science does not aim at a specific application, like a particular disease cure or a drought-resistant crop, no one can predict the final, real-world impact of any individual line of discovery. But understanding the world we live in and the creatures we share it with has proven an essential fuel for technological, agricultural, health, and medical advances, as well as for managing and conserving our environment and natural resources.
Knowledge Can Come From Surprising Places
A surprising number of the practical outcomes of biological research have origins in the study of a few seemingly insignificant species — creepy crawlies, vermin, microscopic blobs, and spindly weeds. They might not be glamorous, but they are some of our closest allies in scientific endeavors to make the world a better place. These species are called model organisms — creatures chosen for intensive research because they have traits that make them particularly suited to laboratory studies. Many model organisms grow quickly, are easily examined under a microscope, or can be readily manipulated genetically.
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Art by Alex Cagan, @ATJCagan. For more information on these Nobel prize-winning studies see: (1) Aplysia sea slugs, (2) Caenorhabditis elegans worms, (3) Tetrahymena ciliates, (4) Drosophila melanogaster fruit flies, (5) Saccharomyces cerevisiae yeast[/caption]
The common ancestry of life on Earth means we can learn a lot about humans even from distant cousins like the bugs that infest rotten fruit in your kitchen. Have you ever seen those small flies that seem to pop up out of nowhere around your old bananas? Those fruit flies are actually one of the most famous and important model organisms, and research on them has sparked some of modern biology’s major insights, including the rules that govern inheritance and evolutionary change.
Flies Can Tell Us About Cancer
Those spiky larvae seen under the microscope in the 1970s were among many unusual flies with genetic mutations unearthed in an epic hunt for genes with crucial roles in the development of a complex animal from a single egg. Eric Wieschaus and Christiane Nüsslein-Volhard, who later won a Nobel prize for their work, named this particular gene Hedgehog — for the spiky embryos that result when it is mutated (1). Related genes were identified in mammals, and decades of work eventually revealed the genes’ connections to cancer and other diseases. Since 2012, two drugs that specifically inhibit tumor growth by targeting the Hedgehog pathway have been approved by the FDA to treat basal cell carcinoma, giving patients with advanced cases of this type of skin cancer a better chance of survival (2,3).
Just as flies are suited to genetic studies, each model organism fills a scientific niche. For example, mice and rats are mammals, like humans, meaning that they share many important biological characteristics. The stripey zebrafish has a backbone like humans do and boasts an exquisitely transparent embryo, which allows scientists to watch development happen in real time. The nematode worm Caenorhabditis elegans can be rapidly grown in dishes, and because its cell divisions can be individually tracked through a precisely defined ballet, it’s perfect for studying development. The mustard cress Arabidopsis thaliana is a fast-growing weed with a tiny genome that is much easier to study than the massive genomes of key crops like wheat and corn. Arabidopsis has played a critical role in helping us understand plant biology, which is vital for agriculture and global food security. This knowledge will be crucial to feeding the world’s growing population — especially as climate change makes our weather patterns less predictable, alters landscapes, and encourages the spread of crop diseases.
Dung Gnats Taught Us About the Basis of Rare Human Diseases
Without knowing why scientists choose particular species, research on model organisms can appear frivolous. Some model organisms have been labeled anything from useless to downright disgusting. Take, for example, the dung gnat Sciara coprophila. Studies on this poop-loving insect revealed the phenomenon of genomic imprinting (4), in which genes are turned on or off depending on whether they were inherited from the father or the mother.
In order to advance, we cannot choose what organisms to study based on aesthetics or cleanliness. As it turns out, imprinting exists in humans — and has important consequences. For example, there is a stretch of chromosome 15 that is turned off in the copy inherited from your mother but turned on in the paternal copy. If, however, the paternal chromosome 15 is missing or has a mutation in the imprinted region, the result is Prader-Willi syndrome, a serious disease characterized by cognitive disabilities and constant hunger, often leading to obesity and type 2 diabetes.
Another nearby region of the chromosome shows the opposite pattern: the maternal genes are normally activated while the paternal ones are turned off. Individuals missing the maternal copy of these genes have Angelman syndrome, which causes developmental delays, seizures, and frequent smiling and laughing. Thanks to this discovery in the dung gnat, we are able to better understand these human diseases and others related to imprinted genes, which is crucial if we hope to develop better treatments.
Yeast Can Model a Myriad of Cellular Processes
Some model organisms differ even more from us than insects do. For example, humans and the microscopic yeast that we use to make bread and beer shared a common ancestor a billion years ago. Yet brewer’s yeast, Saccharomyces cerevisiae, is one of the most thoroughly studied organisms on the planet, and is especially useful for understanding genetics. These single-celled organisms share many characteristics with human cells, but can be rapidly grown in great numbers in a flask or petri dish.
Brewer’s yeast isn’t a pathogen, but it also serves as a model for more difficult-to-study fungal species that do cause disease in humans, like Candida albicans, the pathogen behind yeast infections, including throat “thrush”. Biologists continue to study brewer’s yeast because of powerful existing research resources, such as collections of thousands of strains that each have a single gene deleted from the genome, which allow researchers to more precisely examine the role of each gene.
The 2016 Nobel Prize for Medicine or Physiology was awarded to a yeast researcher, Yoshimori Ohsumi, for his work on autophagy, a kind of cellular housekeeping that helps clear the cell of damaged proteins and other potentially toxic debris. The role of this recycling and disposal system in human disease was not appreciated until Ohsumi and his colleagues’ work in the 1990s revealed the yeast genes that orchestrate the process (5). Thanks to the knowledge and tools made possible by this basic research, studies of autophagy in animals have exploded since the 2000s, revealing its complex roles in embryonic development, cell starvation, infection defense, neurodegenerative disease, and cancer.
The Basic Research of Today is the Scientific Breakthrough of Tomorrow
The road from a discovery to its impact on society is rarely straight. Few of the scientists in these stories could have predicted how their work might one day be applied. Every day in labs across the country, scientists start down new paths that could eventually lead to the next cancer drug or technique for eliminating disease-carrying pests. But it will only be possible to follow these new paths if we, as a society, continue to support the pursuit of knowledge — with or without clear applications.
Today’s investment in some seemingly obscure, weird quirk of a model organism may tomorrow surprise us with a wealth of new possibilities.
About the Author
Nicole Haloupek (@haloupek) is a freelance science writer and a PhD candidate in Molecular and Cell Biology at the University of California, Berkeley. Cristy Gelling (@cristygelling) is a lapsed yeast geneticist and currently the Communications Director for the Genetics Society of America (@geneticsGSA), an international scientific society representing researchers and educators in the field of genetics. Among the Society’s members are many who study model organism biology, population genetics, and other foundational topics.
- Nüsslein-Volhard, C. and Wieschaus, E. (1980). Mutations affecting segment number and polarity in Drosophila. Nature 287, 795–801.
- Ingram, I. (2012). Vismodegib granted FDA approval for treatment of basal cell carcinoma. Oncology (Williston Park). 26, 174, 213.
- Rimkus, T., Carpenter, R., Qasem, S., Chan, M. and Lo, H.-W. (2016). Targeting the Sonic Hedgehog Signaling Pathway: Review of Smoothened and GLI Inhibitors. Cancers (Basel). 8, 22.
- Crouse, H. V. (1960). The controlling element in sex chromosome behavior in Sciara. Genetics, 45 (10), 1429.
- Tsukada, M., & Ohsumi, Y. (1993). Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS letters, 333(1–2), 169–174.