In my previous post, I described how Drosophila melanogaster serves as an important and relevant model organism for biological research. But how is fruit fly research actually helping us to better understand ourselves? In my future “Translational Findings” posts, I will talk about how fruit flies are furthering our understanding of a specific human-related issue. These will include diseases such as Parkinson’s or Alzheimer’s disease, developmental and genetic disorders such as autism or Down syndrome, and other human concerns like addiction, sleep, or aging.
In this first Translational Findings post, however, I would like to give an overview of the history of fruit fly research and how it has already contributed to human health. Fruit flies have been used as a model organism for over a century, so the list is long. To narrow it down, I will focus on describing the important findings that led to Nobel Prizes: four of them since Thomas Hunt Morgan published the first scientific paper using Drosophila melanogaster in 19101!
The first Nobel Prize was awarded to Thomas Hunt Morgan himself in 1933. He studied heredity and was interested in understanding how physical traits were passed down through generations. Morgan began by searching for visible variations among fruit flies so he could determine how those traits were inherited. Finally, he found white-eyed flies among a stock of normal red-eyed flies (Figure 1). He and his students began studying the pattern of inheritance for the white-eyed trait, and they later found other mutations to study as well. Their findings led to a radical new theory of heredity which suggested that genes (the pieces of DNA that contain the information for the traits) are carried in a linear arrangement on chromosomes, and these chromosomes are passed down through generations. Their findings showed the physical mechanism for genetic inheritance and are now considered the foundation of modern genetics.
The second Nobel Prize was awarded to Hermann Müller, one of Morgan’s students. After leaving Morgan’s lab, Müller began researching methods for inducing mutations in fruit flies instead of waiting for them to occur spontaneously. In the 1920s, he made a breakthrough when he noticed a connection between radiation and lethal mutations and, in 1927, published a paper demonstrating that X-rays damaged chromosomes and caused genetic mutations2. Although the public was beginning to realize that radiation was dangerous (Marie Curie died in 1934 as a result of her own research), this was the first evidence of specific harmful effects. Müller began publicizing the dangers of radiation soon after, and earned a Nobel Prize in 1946 for his work.
In 1995, the third Nobel Prize for fruit fly research was shared by Christiane Nüsslein-Volhard, Eric Wieschaus, and Ed Lewis. Using recently developed techniques that allowed DNA to be more easily manipulated (such as X-ray induced mutations), these scientists screened thousands of mutant flies and identified several genes responsible for development in Drosophila melanogaster3. Their research paved the way for understanding how multicellular organisms develop from single cells, and showed that development is genetically controlled. Shortly after their discoveries, studies in other species found closely related developmental genes in vertebrates, confirming an evolutionary link between fruit fly and human biology.
The final Nobel Prize was award to Jules Hoffmann, Bruce Beutler, and Ralph Steinman in 2011 for their research in immunity. Humans have two methods for defending against infections: innate immunity, which is inherited, and adaptive immunity, which responds to invaders and “learns”. Hoffman’s research in fruit flies showed that a gene called Toll was important for the fly’s innate immune system. He found that the Toll gene contained instructions for a receptor responsible for recognizing certain bacterial and fungal infections and triggering an immune response4. Beutler later found related “Toll-like” receptors with the same function in mammals, demonstrating that this innate immunity control mechanism is shared across species through evolution. A few years later, Steinman showed that Toll-like receptors activate the adaptive immune system in mammals as well.
Fruit fly research has already made huge contributions to understanding human biology, and it shows no signs of stopping. In today’s research environment, research in flies has gone beyond the genetic research it founded and has moved into more complex issues such as disease and behavior. Which new major contribution will earn this little insect its fifth Nobel Prize?
- Morgan TH (1910). SEX LIMITED INHERITANCE IN DROSOPHILA. Science (New York, N.Y.), 32 (812), 120-2 PMID: 17759620
- Muller HJ (1927). ARTIFICIAL TRANSMUTATION OF THE GENE. Science (New York, N.Y.), 66 (1699), 84-7 PMID: 17802387
- Nüsslein-Volhard C, & Wieschaus E (1980). Mutations affecting segment number and polarity in Drosophila. Nature, 287 (5785), 795-801 PMID: 6776413
- Lemaitre B, Nicolas E, Michaut L, Reichhart JM, & Hoffmann JA (1996). The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell, 86 (6), 973-83 PMID: 8808632