How the Humble Fruit Fly Changed Science

Tracing the journey of the fruit fly from its entry into science to its current position as an important tool for genetic research

By National Centre for Biological Sciences, Tata Institute of Fundamental Research

curated by Nithila Madhu Kumar and Kailas Honasoge

Veronica Rodrigues observes the behaviour of Drosophila in the fly maze. (circa 1979)Original Source: Department of Biological Sciences, Tata Institute of Fundamental Research

This is a picture of Veronica Rodrigues, a biologist. The photograph was taken around 1979 when she was a PhD student at the Tata Institute of Fundamental Research (TIFR) in Bombay, India. Wondering what she’s looking at so intently?

Drosophila melanogaster with visible proboscis (2017-11-03) by Sanjay AcharyaOriginal Source: Wikimedia Commons

Well, fruit flies.

By Fritz GoroLIFE Photo Collection

Lab animals

Think about animals in a lab, and lab mice come to mind immediately. But there is another creature that has made its mark significantly in the labs of science: Drosophila melanogaster. Or, the common fruit fly.

Two red eyed Drosophila (2017)Original Source: Drosophila Facility, National Centre for Biological Sciences

Model organisms

Our interactions with Drosophila are limited to swatting them away when they're hovering around ripe bananas. In the world of science, however, the humble fruit fly is a model organism – a creature that is studied with the hope that learnings may be applied to other species as well.

Drosophila melanogaster (2009-07-05) by Thomas WydraOriginal Source: Wikimedia Commons

Drosophila has been used in research since the early 20th century. In this story, we look at fruit flies and their fascinating journey over the years, across countries, generations, and cultures.

Guinea Pigs (1961) by Paul SchutzerLIFE Photo Collection

Drosophila's debut into
science

Up until the late 19th century, guinea pigs and rats were scientists’ lab animals of choice. In the early 1900s, American geneticist William E Castle realised that fruit flies were easier to study since they bred at a much higher rate than guinea pigs or mice. Fruit flies also cost considerably less and were smaller.

Thomas Hunt Morgan (1891)Original Source: Wikimedia Commons

Castle’s decision greatly influenced Thomas Hunt Morgan, an evolutionary biologist and geneticist whose work on inheritance (around 1910) helped put the fruit fly on the map as a model organism.

LIFE Photo Collection

Putting Darwin and Mendel
to the test

The early 20th century was a time when radical ideas were spurring radical science. Charles Darwin’s theory of evolution and Gregor Mendel’s rules of heredity were widely accepted. But Morgan was not convinced by them because he thought they lacked experimental verification. His research with Drosophila, however, engineered a curious turn of events, and he went on to win the Darwin Medal in 1924 for his work on inheritance.

Columbia University Fly Room with a bunch of ripe bananas.Original Source: American Philosophical Society

The Fly Room

A bunch of overripe bananas was a permanent fixture in Morgan’s lab at Columbia University. While working in his famous ‘Fly Room’, Morgan observed something. 

A white eyed Drosophile next to a red eyed one (2017)Original Source: Drosophila Facility, National Centre for Biological Sciences

Most images of Drosophila will show you that it has bright red eyes. What Morgan noticed, however, was a male fruit fly with pale white-ish eyes. These eyes were the result of a random mutation of a gene, a fairly common occurrence.

DNA and gender (creative art) (2018) by Anmol VenkateshOriginal Source: Archives, National Centre for Biological Sciences

Morgan was able to identify that the gene with the random mutation was located in the flies’ sex chromosomes (think X and Y). This was a groundbreaking discovery because up until then, no one really knew where our genes were. Connecting these dots would prove to be the foundation of modern genetics.

By Herbert GehrLIFE Photo Collection

There was a small cascade of influences in the Drosophila world. Castle influenced Morgan. And Morgan, in turn, influenced his students to study the fruit fly further. One of them was Herman J Muller.

In the mid 1920s, Muller exposed fruit flies to a healthy dose of radiation. He discovered that ionizing radiation causes mutations in genes, and could be potentially harmful.

Interactions between physics and biology (creative art) (2018) by Anmol VenkateshOriginal Source: Archives, National Centre for Biological Sciences

Muller’s discovery sent shockwaves through the scientific community. His work connecting radiation and mutations connected physics and biology, two subjects that had not mingled much until this point. This acted as a trigger that eventually led to many physicists shifting over to biology.

Seymour Benzer (1974)Original Source: Archives, California Institute of Technology

Seymour Benzer and the fly

One of these converted biologists was Seymour Benzer, a man best described by this picture (note the fruit fly tie). Benzer made the shift to biology in the late 1940s, and initially worked on bacteriophage, a type of virus, but was later inspired to take up a new area of study: genetics and behaviour.

Genetic Family by Herbert GehrLIFE Photo Collection

Strange behaviour

Observing his daughters' acutely different personalities, Seymour Benzer grew interested in behaviour and the role of genetics and environment in determining it. In 1966, he joined Caltech under Robert Sperry, a neurobiologist, where he decided to study behaviour with Drosophila as his model organism.

White-eyed Drosophila (2006-11-16) by Paul ReynoldsOriginal Source: Wikimedia Commons

What Benzer really liked about fruit flies was their small size, short life span and statistically large populations. His lab studied the flies’ circadian rhythms and observed the effects of genetic mutations on behaviour. One particular mutation they studied was called, "drop-dead," because it caused perfectly healthy flies to suddenly, well, you know, drop dead.

The "I'm Not Dead Yet" or "INDY" mutation (2017)Original Source: Drosophila Facility, National Centre for Biological Sciences

Incidentally, there is also the "Kumbhakarna" gene that causes flies to take forever to snap out of induced-paralysis, as well as the “cheap date” gene that increases a fruit fly’s susceptibility to alcohol. But the topper must be the “I’m Not Dead Yet” gene that increases the longevity of flies. Who would’ve guessed that geneticists had a thing for Monty Python references?

Obaid Siddiqi and Seymour Benzer in PasadenaOriginal Source: Courtesy of Siddiqi Family

Fruit fly paralysis

For a few years in the early 1970s, a lanky Indian from Aligarh worked in Benzer's lab. Before joining the lab, Obaid Siddiqi, a microbiologist who worked on bacteria, spent a year at MIT learning neurobiology. In Benzer's lab, he worked on certain mutants of Drosophila that were temperature-sensitive—high temperatures would paralyse them. Siddiqi's interest in paralysed mutants had interesting origins. Listen to him in the next slide as he recalls a lecture from his MIT days...

Obaid SiddiqiOriginal Source: Archives, National Centre for Biological Sciences

Obaid Siddiqi on the lecture that cemented his interest in studying temperature-paralysed mutants
00:00

"When I was at MIT, there was a man, a Japanese scientist, David Suzuki. He came to MIT to give a lecture. David Suzuki had discovered the first temperature-paralyzed mutants of Drosophila. So I read David Suzuki's papers and David came to give a lecture at MIT and I remember that he had a test tube of Drosophila mutant paraTS, it is called paralyzed temperature sensitive, in his coat pocket. When he was lecturing, he took out the tube and held it in his hand and when he removed the hand, of course, all the flies were paralyzed and fell to the bottom. I was fascinated by this lecture, because anybody could see that this paralysis might involve the blocking of the nervous system. So I actually made up my mind right then that that was what I was going to work on-- to look at paralyzed mutants."

Obaid Siddiqi in the TIFR Molecular Biology Unit (1967)Original Source: Archives, Tata Institute of Fundamental Research

Olfactory creatures

Siddiqi returned to India where he was the head of the Molecular Biology Unit in the Tata Institute of Fundamental Research (TIFR), Bombay. He continued his work with Drosophila – their genetics and their neurophysiology. He began thinking about olfaction - or smell- in Drosophila – uncharted territory at the time. Fruit flies are extremely olfactory creatures and so it made sense to look at olfaction to understand their neurophysiology.

Obaid Siddiqi's notes on the designs for a fly maze (1991)Original Source: Archives, National Centre for Biological Sciences

Olfaction was a mainstay for Siddiqi and for TIFR's Molecular Biology Unit. This image shows Siddiqi's attempt (much later, in 1991) to improve upon a fly maze.

Veronica Rodrigues observes the behaviour of Drosophila in the fly maze. (circa 1979)Original Source: Department of Biological Sciences, Tata Institute of Fundamental Research

Which brings us back to that image of Veronica Rodrigues and her fruit fly maze.

Veronica Rodrigues' letter to Obaid Siddiqi about her interest in doing a PhD at TIFROriginal Source: Archives, National Centre for Biological Sciences

In the mid-1970s, the Kenya-born Rodrigues applied to TIFR to do a PhD under Obaid Siddiqi thinking he still worked on bacteria, as shown in this letter. She then decided to research olfaction in the fly, even building her own instrument – the Y-maze shown beside her in the previous photo.

By Herbert GehrLIFE Photo Collection

The difference between humans and flies

The fruit flies in Siddiqi’s lab helped steer understanding of olfaction. But around the same time, in the mid 1970s, larvae of fruit flies in a research lab in Germany unpeeled our knowledge of larvae cuticles, the outer protective covering of larvae. Biologists looked at mutant flies with strange looking cuticles (these mutants were also given fun names like “Hedgehog” and “Hairy-Barrel”) and studied the genes responsible for their appearance.

Drosophila and human chromosomes (creative art) (2018) by Anmol VenkateshOriginal Source: Archives, National Centre for Biological Sciences

What they found was that similar genes exist in more complex organisms. This was a stepping stone to eventually discovering that humans share versions of many genes with Drosophila. According to a 2001 study, it’s a 70% match.

Connecting the places of Drosophila research from the narrative (2018) by Nithila M.K.Original Source: Courtesy of Nithila M.K.

But no one knew this when Drosophila first entered research. For Castle, they were an easier alternative to guinea pigs and mice. Morgan picked Drosophila because it was an organism whose genes had already been studied to some extent. Benzer says he chose Drosophila because it was convenient. Siddiqi picked up from Benzer’s suggestion and, along with Rodrigues, pioneered a new field in Drosophila research.

An excerpt from Seymour Benzer's paper "From the Gene to Behaviour" (1972) by Seymour Benzer (Accessed through the Caltech Library)Original Source: Benzer S. From the Gene to Behavior. JAMA. 1971;218(7):1015–1022.

From the Gene to Behaviour

As research progressed from the 1970s, the potential to understand humans better through the fly was no longer incidental, but rather a motive to study Drosophila further. The fly helped establish connections between genes and the behaviour resulting from them. Benzer puts this succinctly in a 1971 paper titled “From the Gene to Behaviour”

Jacques Monod (1971-03-11) by FarabolaOriginal Source: Wikimedia Commons

Jacques Monod, a French biochemist, famously said that “anything found to be true of E. coli must also be true of elephants.” This implies that the simplest of model organisms can help us understand the most complex creatures. But is this always the case?

Model organisms and humans (2008)Original Source: Hunter, Philip. “The paradox of model organisms. The use of model organisms in research will continue despite their shortcomings” EMBO reports vol. 9,8 (2008): 717-20.

Sanjay Sane on the blinders one has on while working within a model system in biology.
00:00

As Sanjay Sane, a former student at TIFR, and now a scientist at NCBS, says here, using model organisms comes with a limitation. Despite the tools and knowledge at your disposal, there is always the possibility that the organism you are studying is not suited to the question you are pursuing.

Veronica Rodrigues observes the behaviour of Drosophila in the fly maze. (circa 1979)Original Source: Department of Biological Sciences, Tata Institute of Fundamental Research

Answering questions

There's a reason we keep coming back to the Rodrigues image. It gives us many perspectives to think about the history of Drosophila research. Today, we look back at a scientist who contributed significantly to our understanding of olfaction. But in the late 70s, this was a picture of a young biology student entering the fast-growing world of research with a question that she tackles with the help of a fruit fly.

Drosophila as being more than a tool (creative art) (2018) by Anmol VenkateshOriginal Source: Archives, National Centre for Biological Sciences

Drosophila is a model organism and a tool of understanding. But beyond the literal meaning in biology, it has also been a model in other ways. It connects stories. Stories of education, research, science and community. The fruit fly has propelled itself on an interlinking journey across many disciplines, countries, and people. It is the link between these stories that gives us new ways of seeing

Credits: Story

This exhibit was a project of second year undergraduate students who interned at the Archives at NCBS:

Nithila Madhu Kumar and Kailas Honasoge

With contributions from Kushal Choudhary and Shalom Gauri

Image Credits:

Veronica Rodrigues observes the behaviour of Drosophila in the fly maze
Courtesy of Department of Biological Sciences, Tata Institute of Fundamental Research

Obaid Siddiqi in the TIFR Molecular Biology Unit
Courtesy of Tata Institute of Fundamental Research Archives

Seymour Benzer
Courtesy of the Archives, California Institute of Technology

Obaid Siddiqi and Seymour Benzer in Pasadena
Courtesy of the Siddiqi Family

Columbia University Fly Room with a bunch of ripe bananas
Courtesy of the American Philosophical Society

Model organisms and humans
Courtesy of The European Molecular Biology Organization

Credits: All media
The story featured may in some cases have been created by an independent third party and may not always represent the views of the institutions, listed below, who have supplied the content.
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