It might seem fitting that the world’s largest collection of fruit flies is largely hidden, spread across backrooms at Indiana University. But despite that, this three-millimeter insect’s giant impact can be detected across the past century’s greatest discoveries in genetics, cell biology and medicine.
Co-directors of the Bloomington Drosophila Stock Center Kevin Cook and Cale Whitworth wound through multiple levels, sharing freight elevators with carts loaded down by vials of flies on their way to the stockrooms.
Each strain of the fly (drosophila melanogaster, or just drosophila to scientists) is labeled in the order it was acquired — now past 600,000. But Cook was searching for the small numbers, the old ones. He reached up to the first shelf and produced a small vial with a fiberglass plug, Strain 145. Inside were around 100 white-eyed flies. He held it carefully.
“This is the beginning of Genetics with a capital ‘G’,” Whitworth said. “Not fly genetics.”
The ancestors of these flies were instrumental in Thomas Hunt Morgan’s 1911 Nobel-winning discovery of the role chromosomes play in inheritance. Fed and cared for by scientists every week for more than a century, their lineage persists in these four glass vials. To the right person, it’s like holding the Holy Grail.
“We're kind of a living library,” Whitworth said. “We're always adding stocks to the collection.”
Fruit fly hub for science
Because of their short life cycles, genetic simplicity and prolific reproduction, fruit-flies make for ideal test subjects in genetic research. Experiments that could take months in species like mice can be done in weeks, and they’re far easier to care for.
That’s why fruit-fly research is behind many of the most revolutionary discoveries in the past century of genetics and cell biology.
As the world’s largest supplier, it’s difficult to overstate the Bloomington Drosophila Stock Center’s stature.
The center maintains over 93,000 strains of flies used for genetic and cellular research across the world and in outer space – NASA credits the stock center for its drosophila lab on the International Space Station. Last year, the stock center sent shipments to 885 institutions in 46 countries and was cited in around 2,000 publications.
Bloomington inherited its first stock of 1,675 from Caltech forty years ago. Since then, it’s absorbed collections from other stock centers around the world and developed many strains of its own. Some of these lineages have passed through the labs of Nobel Prize winners, including IU professor Hermann Joseph Muller and Caltech’s Edward Lewis.
Since Cook started here in the 1990s, the secrets yielded by Indiana flies have bloomed as geneticists developed more advanced methods and understanding.
“When I started working for the stock center, most of the research was focused on fundamental processes: How do cells work? How do tissues work? How do genes work?” Cook said. “Over the time that I've been here, fly research has become more important to understanding human diseases.”
Geneticists cracked the fruit fly genome in 2000, and the human genome followed a year later. A comparison of the two led to a surprising discovery.
“We've been able to see that fly genes and human genes look an awful lot alike,” Cook said. “And we've been able to tell that processes that occur in human cells happen in fly cells.”
Technologies such as CRISPR gene editing enable scientists to create new strains of flies with precision, modeling forms of human illness, including cancer, Alzheimer’s and Parkinsons. Because these conditions manifest the same way in a fly’s cellular pathways, gene editing allows scientists to conveniently observe them in a living creature.
“In principle, you can do it in other organisms,” Cook said. “But in practice, you can only do those sorts of things easily in the fly.”
Caring for the stock
The scope of the whole operation is enormous and running it is a feat of organizational planning.
Each of the 93,000 drosophila strains has four vials stored in separate locations. A single vial contains around 100 individuals.
“That’s a lot of flies,” Cook said.
Flies are tracked, fed, bred and transferred with clockwork regularity across their two-week life cycle. Eighty-seven stock wokers keep the center running 18 hours per day, with responsibilities ranging from quality control to fruit-fly healthcare and fly sorting.
The work requires attention to detail and manual precision that can’t be replicated by robots, according to Whitworth. Some staff even refer to the flies as their pets.
“That care is what differentiates us from other approaches to taking care of flies, which are done by robotics,” he said. “Things can get missed and stock can become contaminated.”
These tiny creatures collectively eat 90 pounds of food three times per week, a polenta-like porridge of cornmeal, soy flour and agar that staff produce in house. A small team with industrial dishwashers clean and sterilize tens of thousands of vials.
At the helm are six PhD level staff scientists, a computer developer, a research coordinator, a business manager and a personnel supervisor, among others. Many others in the biology department are involved in running the facilities that support it.
Altogether, running the stock center costs around $3.5 million per year, but virtually none of that comes from the university or the state. The bulk of operating funds, around 80 percent, are covered by selling flies to other labs. Most of the rest is supported by a grant from the National Institute of Health.
Besides that, Lawrence Washington, whose late wife Kathleen Matthews devoted most of her career to building the stock center, gifted $500,000 in June to help ensure her legacy could continue.
Impactful discoveries
In thirty years, the stock center staff has multiplied by over 20 and the number of stocks by over 30. Understanding of genetics and the ability to manipulate DNA have advanced considerably, due in no small part to the work of researchers around the world on Bloomington’s flies.
And the uses for drosophila continue to expand.
“Now when I go to conferences, almost every talk, almost every presentation is related to using flies to understand some human disease or some condition,” Cook said. “That's been a big change.”
New techniques allow researchers to design individualized treatments for cancer patients using their DNA to create “avatar” flies and experimenting with drug combinations before prescribing them to a human. They can also activate specific genes in intestinal cells to identify the genetic basis of certain cancers.
“We can take that knowledge and try to develop therapeutic approaches that help human patients that also have these exact same mutations in their pathways,” Whitworth said.
This June, researchers at Harvard published for the first time a complete wiring diagram for every neuron in a fruit-fly central nervous system, which could change the way scientists understand the brain and its functions. Now faculty at IU can pinpoint specific neurons to learn about the role they play in behavior, memory and circadian rhythm.
These research techniques are still young and still reaching their potential. Whitworth said the most rewarding part of working at the stock center is seeing the impact Bloomington’s flies can make.
“I often make the argument,” he said, “that it might be shorter for me to tell you what flies can't do than what they can do.”
