A Century of Fruit Fly Research Sheds Light on Human Health and Disease

FOR IMMEDIATE RELEASE:
10/26/2001
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NIGMS Communications Office
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In March 2000, a team of scientists announced that it had unscrambled the genetic code of a tiny fruit fly called Drosophila melanogaster. Within a week, dozens of stories about this scientific tour de force appeared in newspapers and magazines around the world. Why did the media pay so much attention? The Drosophila genome was the largest genetic code unscrambled thus far, and the completion of this project in record time validated amethod later used to sequence the human genome.

Another reason for the media interest is the similarities between human and fly genes. Of the 289 human genes that, when "misspelled," are known to cause diseases in people, 177 have direct counterparts in the fruit fly. A complete catalog of fly genes is an extraordinary tool that will help researchers understand how genes work--not only in flies, but also in humans and other organisms. The achievement is a boon to the thousands of scientists who study human health using the fruit fly, which is one of a number of valuable model systems that aid researchers in making breakthroughs in the fight against disease.

Drosophila became a model system for studying how genes work nearly 100 years ago, when Dr. Thomas Hunt Morgan, then at Columbia University, found an unusual fruit fly on his laboratory wall. This fly's eyes were white instead of the usual red. Years later, researchers discovered that this strain of fruit fly had white eyes because one of the fly's genes hadn't worked properly. These observations touched off an enormously productive field of study.  For decades, NIGMS- and other NIH-supported basic scientists have used the fruit fly model system to make connections between specific genes, normal and abnormal development, and disease in animals, including humans.  Some of their achievements are described below.

became a model system for studying how genes work nearly 100 years ago, when Dr. Thomas Hunt Morgan, then at Columbia University, found an unusual fruit fly on his laboratory wall. This fly's eyes were white instead of the usual red. Years later, researchers discovered that this strain of fruit fly had white eyes because one of the fly's genes hadn't worked properly. These observations touched off an enormously productive field of study.  For decades, NIGMS- and other NIH-supported basic scientists have used the fruit fly model system to make connections between specific genes, normal and abnormal development, and disease in animals, including humans.  Some of their achievements are described below.

In the 1970s, Dr. Edward Lewis and his coworkers at the California Institute of Technology pinpointed the genes that control the development of body segments, features that make a fruit fly recognizable as an insect. This finding set the stage for other scientists to discover that the same genes control developmental patterning processes in humans, who do not have recognizable segments. Around that time, researchers studying development in fruit flies began to devote their attention to organs, particularly the eyes, the ovaries, and the testes. Dr. Seymour Benzer, also at the California Institute of Technology, found fly eyes to be convenient targets. He and his colleagues could easily identify important eye genes because the loss of these genes impairs flies' ability to run toward light. Ovaries and testes intrigued scientists for a different reason. Dr. Thomas Cline of the University of California, Berkeley and Dr. Bruce Baker of Stanford University reasoned that since only females have ovaries and only males have testes, they could study the genes that affect these organs to figure out why the organs develop differently in the two sexes and apply that knowledge to understanding human development.

Dr. Charles Zuker of the University of California, San Diego identified certain genes that, when they malfunction, make a fly's eyes degenerate, causing blindness. Scientists now know that the genes that cause eye degeneration in flies are also present in humans. Mutations in these human genes are responsible for many cases of macular degeneration, the most common cause of blindness in adults. Detailed studies of the fly genes that cause eye degeneration should provide clues about how to correct--or even prevent--macular degeneration in people. Throughout the 1980s and 1990s, fly researchers studied the development of other organs, particularly the heart, the brain, and the respiratory system. Dr. Mark Krasnow and his coworkers at Stanford University School of Medicine discovered that a growth-promoting molecule called "branchless" directs the proper development of fly respiratory tubules--a network of large and small pipe-like structures that carry oxygen into a fly's body. Recently, the scientists found that this protein's ability to regulate the development of small respiratory tubules is controlled by oxygen. Something very similar happens in human embryos, where oxygen-regulated growth factors initially control the development of the major blood vessels and later control the development of the smaller capillaries. The striking parallel between the development of the fly respiratory system and the human circulatory system promises to help researchers better understand how blood vessel overgrowth sustains cancer cells, and possibly how enhancing the growth of oxygen-carrying vessels may help treat heart disease.

Fruit flies have been important tools for studies of the brain and diseases that impair the function of the central nervous system. One way scientists use flies in this research is to create flies with human disease genes and then observe what happens to the flies. For example, in March 2000, Dr. Welcome Bender of Harvard University and Dr. Mel Feany of Brigham and Women's Hospital engineered flies with Parkinson's disease, the second most common neurodegenerative disorder in humans. The scientists gave the flies a human gene that provides brain cells with instructions for making a protein called alpha-synuclein. When this gene malfunctions in humans, the protein piles up in brain cells. The scientists discovered that--just like people with Parkinson's disease--flies with the human gene have trouble controlling their movements. The flies also have lots of extra alpha-synuclein in their brain cells. By studying these flies, researchers hope to be able to determine the link between the alphasynuclein gene and brain degeneration. Scientists should also be able to use fruit flies to identify potential new drugs to treat Parkinson's disease.

For decades, scientists have also studied fly brains to figure out why flies--like humans--have daily cycles of activity and night-time rest, known as circadian rhythms. In the 1970s, Dr. Jeffrey Hall of Brandeis University and Dr. Michael Young of The Rockefeller University discovered that a gene called period is the internal alarm clock controlling flies' activity and rest cycles. Since then, scientists have identified many other fly genes that affect circadian rhythms, including a gene recently discovered by Dr. Michael Rosbash of Brandeis University, called take-out, that may determine when during the day a fly gets hungry. Humans have period genes and many--perhaps all--of the other genes that affect flies' daily cycles. By continuing to study circadian rhythm genes in flies, researchers are likely to gain a better understanding of human maladies such as insomnia, jet lag, and perhaps even eating disorders.

Although scientists studying fruit flies have made impressive strides in understanding development, disease, and behavior, much more work lies ahead. Fortunately, future researchers can look forward to an easier time of figuring out what the thousands of newly identified fruit fly genes do. After nearly two decades of groundwork laid by fruit fly researchers, Dr. Kent Golic of the University of Utah finally succeeded in June 2000 in "knocking out" genes in flies, a technique in which researchers get rid of a working gene to see what happens when it is gone. This technical breakthrough is expected to fuel a dramatic increase in knowledge about fly and human genes.

Writer: Alison Davis, Science Writing Contractor