New Tool to Fight Deadly Tsetse Fly
|
Version 0 of 1. After 10 years of effort, a team led by scientists at Yale has finally decoded the genes of the tsetse fly, a bloodsucking scourge of Africa. With that knowledge, they hope to find new ways to repel or kill the insects, whose bite transmits sleeping sickness, a parasitic disease that, like rabies, drives its victims mad before they lapse into a coma and die. The flies also carry nagana, which weakens or kills cattle and renders whole regions of Africa inhospitable to most livestock. There are now fewer than 10,000 confirmed cases per year of sleeping sickness — formally known as human African trypanosomiasis — but the disease occurs in epidemics. As recently as 1998, the number of estimated cases was 300,000. Treatment is long and difficult, and without it, the disease is always fatal. Sequencing the genome of Glossina morsitans, one of several tsetse species, took a decade, partly because tsetses have highly unusual biology — they are the only insects that nurse their young, among other traits — and partly because of global health politics. Since mosquito-borne diseases are the major threat to Americans, and some of the diseases had bioterrorism potential, early federal grants for gene sequencing all went to mosquitoes, said Serap Aksoy, who ran the tsetse sequencing project from her lab at the Yale School of Public Health. “Sleeping sickness is a neglected disease, an African disease,” she said, “so we didn’t get those funds.” The sequencing of G. morsitans, a species found in dry savanna, was done for only $10 million, mostly from the World Health Organization, the Wellcome Trust, the Ambrose Monell Foundation, and with time donated by scientists in the United States, England, France, Japan and various African countries. However, Dr. Aksoy added, now that the result is a genetic treasure trove and sequencing has become faster and cheaper, the National Institutes of Health will support sequencing of five more Glossina species. The other challenge for researchers was the fly itself. “Tsetse biology is just freaky,” said Leslie B. Vosshall, an insect neurobiologist at Rockefeller University. “This is an insect that breast-feeds its children.” Dr. Aksoy’s project, she added, was “long overdue because tsetses are one of the most neglected insects with public health importance.” While most flies lay hundreds of eggs in rotting fruit or carcasses, a tsetse mother gives birth to a single larva that weighs as much as she does. Inside her uterus, it nurses on a milk gland, drinking proteins that do what different but similar proteins in human breast milk do, including blending fats with water, passing on hormones and making iron digestible. “It’s an example of convergent evolution,” said Geoffrey Attardo, another Yale team leader and a co-author of the study, which was published Thursday by Science along with 11 companion papers in several PLOS journals. At birth, the larva, resembling a squirming sack of milk, wriggles beneath the soil and spends up to a month there before hatching as a hungry adult. “Other insects produce many progeny and hope a few survive,” Dr. Aksoy said. “With tsetse, the hatch rate is nearly 100 percent.” That parsimonious reproduction caused problems, because sequencers need the bug equivalent of identical twin girls to be sure that all the DNA they are working on is uniform; they use females because male Y chromosomes are full of so-called junk DNA, which lacks the codes for making proteins. With most insects this is easy; a female mosquito might hatch 500 identical females after each blood meal. But tsetses produce fewer than 10 descendants in a life span, half of them male. So all the sequencing — which involved 140 scientists — was done on 15 flies. Much of it, Dr. Aksoy said, relied on one mother and two daughters. The researchers found several spots on the genome they hope will eventually lead to better insecticides or repellents. For example, a gene called ladybird late, which also exists in fruit flies, controls milk production. When researchers disabled it in the lab, the larvae starved. If a chemical that did the same thing could be found, the flies would die out. As long as it was safe for mammals, it could be sprayed on cows for the flies to pick up, Dr. Attardo said. Another type of gene allows the flies to squeeze water droplets out of their immense blood meals, liquefy their milk and conserve water on hot days. Any disruption to that process could be fatal. Alternatively, tweaking gut or salivary gland genes could make the fly reject the parasites that cause sleeping sickness. “The mosquito immune system has been manipulated to give it a stronger response against malaria parasites,” said George Dimopoulos, a mosquito expert at the Johns Hopkins Bloomberg School of Public Health who praised the tsetse study. “I don’t see any reason that can’t happen in the tsetse fly.” Another possibility, said Dr. Vosshall, who studies insect olfactory genes, is that chemicals could be developed that block the fly’s ability to smell humans. Among the many papers published on Thursday were histories of how five European powers fought sleeping sickness in their colonies. An epidemic that began in 1901 killed a third of the inhabitants of some fly-infested regions. By World War II, it was largely under control. But the campaign against sleeping sickness may have had an unintended consequence: The widespread reuse of unsterilized syringes for vaccinations may have contributed to the spread of what in the 1980s became known as AIDS. |