Mutant flies' lessons on human diseases

The common fruit fly and human beings may look nothing alike but appearances can be deceiving. The two species not only share around 70% of the same disease-causing genes but they also have many of the same major organs. This similarity, combined with the flies' brief life-spans and ability to reproduce quickly, make them invaluable for scientists studying genetics and diseases. But when you consider that small mammals like mice share even more genetic similarities with humans, why are fruit flies still so commonplace in research labs? Genetically engineered Fruit flies can be genetically manipulated to show diseases that are found in humans - some have been given kidney stones, others diabetes and even others have been sent into space. Engineered flies also have the ability to breed for many generations. Recently, the global fruit fly community met up at the Genetics Society of America's 53rd annual Drosophila research conference to share their findings into how flies can help human beings. One study was able to produce kidney stones in fruit flies, which the researchers presented through a time-lapse video. Most human kidney stones are formed of a compound called calcium oxalate. Although a fruit fly's kidney is much simpler than a human's, it performs a similar role. When flies are fed food high in oxalate, they get stones just like humans. "This was the first time in history that people were able to see kidney stones form. We know from humans how painful they are so it is not something you can ethically test for in animals, but the flies do not appear affected by the stones," said Prof Julian Dow from the University of Glasgow who produced the time-lapse. "We can now use these flies to screen for new drugs for humans that block the formation of stones." One of the first fly mutants ever discovered - named Rosy after its eye colour - was found to closely reproduce the rare human kidney stone disease, xanthinuria. Dr Michael F Romero, from the Mayo Clinic, collaborated with the research and found a way to slow down kidney stone formation by blocking the gene responsible for transporting oxalate. He believed that with further testing this could be used to treat humans. "I would call this translational science. This is physiology. We can fast forward through time by using an organism which does the same functions as a human, but does it faster," he said. Another study identified key genes that can tell when a fly is close to death. Prof John Tower from the University of Southern Carolina led the research, which aims to discover the human genes behind longevity. He said that the genes and pathways that regulate the flies' lifespan appear closely parallel to those in humans. "We expect that the underlying genetic reason why aging exists is the same between fruit flies and humans as the damage and deterioration of tissues that occurs is similar." But he added that there were still many steps between finding a chemical that works in flies to developing a drug for humans. The relative ease of the genetic tools that allow scientists to manipulate the flies is very important, said Oxford University's Dr Timothy Weil. "We are able to control and manipulate their genes in an easy and creative way. By doing this we can discover what happens if we make a mutation in a gene that's relevant for the disease being researched." Space flies Prof Carl Thummel from the University of Utah School of Medicine uses fruit flies to model human metabolic disorders. He said the flies can faithfully replicate the human system, and that exposing flies to a high sugar diet results in the symptoms of type 2 diabetes. Similarly, putting fruit flies on a high fat diet results in increased body fat. "We can use the fly to study the molecular basis of both normal and abnormal human metabolism. These studies allow us to achieve a level of detailed understanding that is not possible with human research," he said. But he added that fruit flies and humans "clearly have different challenges to meet for their survival" so aspects of research would not always apply to humans. Scientists at Nasa have even sent fruit flies into space. Dr Sharmila Bhattacharya from Nasa's Ames research centre found flies that had been exposed to space flight showed a reduction in their innate immune functions, which are vital for defence against invading germs. Past experiments on blood taken from astronauts has suggested that some of these same changes also occur in humans. "The advantage from the flies is that we have a model system that can give evidence of similar changes in humans." But anything that is learned from a simpler system such as a fly must then be validated in more complex systems. Such carefully controlled studies were not possible with humans, said Dr Bhattacharya, but researchers are able to pinpoint some of the genes most affected by space travel and therefore help prepare astronauts for going on long planetary explorations in space. A fruit fly breeds quickly and develops from egg to adult in less than two weeks. Females can lay up to 100 eggs in one day, making it possible to breed many generations cheaper and much faster than mammals such as mice - which can cost on average about £16 ($26). And the fruit fly genome could be changed more than in other multicellular animals, such as mice, said Prof Thummel. "This has allowed us to understand detailed mechanisms of biology at a level of resolution that is not possible with other animal models." Dr Weil believes that research on fruit flies was "helping to build the foundation of understanding that will directly lead to the treatment of human diseases in the future. "Regardless of the choice of model organism, the goal of the whole scientific community is to advance human health," he said.