Few organisms in the history of science have been as important to our understanding of life as the humble fruit fly. The genus Drosophila melanogaster holds a particularly esteemed spot among the dozens of model organisms that provide insight into life’s inner workings. For more than 100 years, this tiny, but formidable creature has allowed scientists to unwind the infinitesimal mechanisms that make every living creature on the planet what it is.

And much of the work to understand the fruit fly has taken place and is taking place now, right here in California at the Cal Tech fly labs.

Over the decades, Drosophila have been key in studying brain, behavior, development, flight mechanics, genetics, and more in many labs across the globe. These tiny, round-bodied, (usually) red-eyed flies might appear irrelevant, but their simplicity makes them ideal models. They’re easy to breed—mix males and females in a test tube, and in 10 days, you have new flies. Their 14,000-gene DNA sequence is relatively short, but extremely well-studied and there are some 8,000 genes which have human analogs. (The fly’s entire genome was fully sequenced in 2000.) Crucially, a century of fruit fly research, much of it led by Caltech, has produced genetic tools for precise genome manipulation and shed light on the act of flight itself.

But how did Drosophila become the darling of genetics?

In the early 20th century, the field of genetics was still in its infancy. Thomas Hunt Morgan, a biologist at Columbia University with a background in embryology and a penchant for skepticism began with an effort to find a simple, cheap, easy-to-breed model organism. At Columbia, he established a laboratory in room 613 of Schermerhorn Hall. This cramped space became famous for groundbreaking research in genetics, with Morgan making innovative use of the common fruit fly.

Morgan, who joined Columbia University after teaching at Bryn Mawr College, chose the fruit fly for its ease of breeding and rapid reproduction cycle. Morgan observed a male fly with white eyes instead of the usual red. Curious about this trait’s inheritance, he conducted breeding experiments and discovered that eye color is linked to the X chromosome. He realized a male fly, with one X and one Y chromosome, inherits the white-eye trait from its mother, who provides the X chromosome. This led him to conclude that other traits might also be linked to chromosomes. His extensive experiments in this lab confirmed the chromosomal theory of inheritance, demonstrating that genes are located on chromosomes and that some genes are linked and inherited together.

After his groundbreaking research in genetics at Columbia University, Morgan moved to Pasadena and joined the faculty at CalTech in 1928, where he became the first chairman of its Biology Division and continued his influential work in the field of genetics establishing a strong genetics research program. Morgan’s work, supported by notable students like Alfred Sturtevant and Hermann Muller, laid the foundation for modern genetics and earned him the Nobel Prize in 1933.

CalTech then became a world center for genetics research using the fruit fly. Other notable names involved in fruit fly research at CalTech include Ed Lewis, a student of Morgan, who focused his research on the bithorax complex, a cluster of genes responsible for the development of body segments in Drosophila. His meticulous work over several decades revealed the existence of homeotic and Hox genes, which control the basic body plan of an organism (for which he won the 1995 Nobel Prize).

Seymour Benzer, another luminary at CalTech, shifted the focus from genes to behavior. Benzer’s innovative experiments in the 1960s and 1970s sought to understand how genes influence behavior. His work demonstrated that mutations in specific genes could affect circadian rhythms, courtship behaviors, and learning in fruit flies. Benzer’s approach was revolutionary, merging genetics with neurobiology and opening new avenues for exploring the genetic basis of behavior. His contributions are chronicled in Jonathan Weiner’s “Time, Love, Memory: A Great Biologist and His Quest for the Origins of Behavior,” a riveting account of Benzer’s quest to uncover the genetic roots of behavior. Lewis Wolpert in his review for the New York Times wrote, “Benzer has many gifts beyond cleverness. He has that special imagination and view of the world that makes a great scientist.”

Since Benzer’s retirement in 1991, new vanguard in genetics research has taken over at CalTech, which continues to be at the forefront of scientific discovery, driven by a new generation of researchers who are unraveling the complexities of the brain and behavior with unprecedented precision.

Elizabeth Hong is a rising star in biology, with her Hong lab investigating how the brain orders and encodes complex odors. Her research focuses on the olfactory system of Drosophila, which, despite its simplicity, shares many features with the olfactory systems of more complex organisms. Hong’s work involves mapping the synapses and neural circuits that process olfactory information, seeking to understand how different odors are represented in the brain and how these representations influence behavior. Her findings could have profound implications for understanding sensory processing and neural coding in general.

David Anderson, another prominent figure at Caltech, studies the neural mechanisms underlying emotions and behaviors. While much of Anderson’s work now focuses on mice as a model organism, the lab’s research explores how different neural circuits contribute to various emotional states, such as fear, aggression, and pleasure, essentially how emotions are encoded in the circuitry and chemistry of the brain, and how they control animal behavior. Using advanced techniques like optogenetics and calcium imaging, Anderson’s lab can manipulate specific neurons and observe the resulting changes in behavior. This work aims to bridge the gap between neural activity and complex emotional behaviors, providing insights into mental health disorders and potential therapeutic targets.

In 2018, the Anderson laboratory identified a cluster of just three neurons in the fly brain that controls a “threat display” — a specific set of behaviors male fruit flies exhibit when facing a male challenger. During a threat display, a fly will extend its wings, make quick, short lunges forward, and continually reorient itself to face the intruder.

Michael Dickinson is renowned for his studies on the biomechanics and neural control of flight in Drosophila. In the Dickenson Lab, researchers combine behavioral experiments with computational models and robotic simulations, seeking to understand how flies execute complex flight maneuvers with such precision. His work has broader applications in robotics and may inspire new designs for autonomous flying robots.

“He’s a highly original scientist,” Alexander Borst, a department director at the Max Planck Institute of Neurobiology in Germany, told the New York Times. 

Dickinson’s investigations also delve into how sensory information is integrated and processed to guide flight behavior, offering insights into the general principles of motor control and sensory integration.

As science advances, Caltech’s Fly Lab’s remind us of the power of curiosity, perseverance, and the endless quest to uncover the mysteries of life. The tiny fruit fly, with its simple elegance, remains a powerful model organism, driving discoveries that illuminate the complexities of biology and behavior. Just recently, scientists (though not at CalTech) unveiled the first fully image of the fruit fly brain. Smaller than a poppy seed, the brain is an astonishingly complex tangle of 140,000 neurons, joined together by more than 490 feet of wiring.

In essence, the fruit fly remains a key to unlocking the wonders and intricacies of life, and in the Fly Labs at Caltech, that spirit of discovery thrives, ensuring that the legacy of Morgan, Lewis, Benzer, and their successors will continue to inspire generations of scientists to come.