Malaria currently afflicts more than 200 million people across 87 countries. And the mosquito-borne disease kills about 435,000 of those people each year. Some of the mosquitoes that spread malaria no longer die when exposed to insecticides. That’s prompted scientists to try a new tactic: They’re infecting the insects with a modified fungus — one able to kill them with a spider poison.
The new tests show great promise. The fungus wiped out mosquito populations within two generations. If the result holds up, the modified fungus may one day become a tool for slowing the spread of malaria.
Some 92 in every 100 cases of malaria and 93 in every 100 deaths from the disease occur in Africa, according to the World Health Organization. So scientists decided to set up their new fungal trial in the West African nation of Burkina Faso.
The fungus — Metarhizium pingshaense (Meh-tah-RY-zee-um Ping-SHENZ) — infects and kills mosquitoes. Researchers made it even deadlier to the insects by adding a spider gene. That gene makes a spider-bite toxin called Hybrid. “We’re just bypassing the spider fangs and getting the fungus to do the same job,” says Raymond St. Leger. He’s an entomologist at the University of Maryland in College Park.
He was part of the team that engineered the fungus. It makes Hybrid, but only when it’s in the mosquito version of blood. This substance is called hemolymph.
In laboratory trials in 2011, researchers tested other engineered fungi, ones related to M. pingshaense. Those fungi infected and killed mosquitoes and the malaria-causing parasites that they carried. (These fungi don’t harm people, other insects or animals.) “That’s all well and good, but what happens in the lab doesn’t necessarily translate into field conditions,” notes Brian Lovett, also at Maryland. He’s an insect pathologist and bioengineer who worked on both studies.
The fungi don’t hold up well in heat or under ultraviolet light. So to learn more, researchers needed to test the fungi outdoors. Or, as close to outdoors as possible. But because the engineered M. pingshaense carries a foreign gene, researchers also needed to be cautious. “We can’t just waltz out into the open field and start applying it to people’s houses,” Lovett says.
No more mosquitoes
Lovett's team worked with scientists and villagers in a western region of Burkina Faso where malaria is common.
First, they built a giant frame. Then they enclosed it with two layers of netting. The team divided the frame into sections with huts on the inside. In each hut, a black cloth hung on one wall. This gave female mosquitoes a place to rest after feeding. The cloths were coated in sesame oil to help fungal spores stick. One hut had a cloth with no spores. Another had normal spores for fungi that don’t make the spider toxin. The third hut’s cloth held spores for Hybrid-making fungi.
Researchers then put 1,000 adult male mosquitoes and 500 females into each hut. The bugs were insecticide-resistant mosquitoes. Local people had collected them as larvae and eggs from puddles.
When the mosquitoes mate, females dive into a swarm of males. Afterward, females must feed on blood to nourish their eggs. For three nights each week, the researchers put calves into the huts. The mosquitoes drank blood from these baby cows. The researchers then counted how many adult mosquitoes survived in following generations.
In the hut without the fungus, 921 mosquitoes hatched in the first generation. About 25 days later, in the second generation, there were 1,396 hatchlings. In the hut with the normal fungus, just 436 mosquitoes in the first generation and 455 in the second. That hinted that the fungus alone could keep numbers down. But it didn’t wipe out the insects.
In the hut with the fungi that made the Hybrid toxin, 399 mosquitoes hatched in the first generation. In the second generation, only 13 adults survived. That’s not enough mosquitoes to form a mating swarm. So the population was essentially wiped out, Lovett explains.
His team repeated the experiment three times during the rainy season from June to October. Each time, they got similar results.
The researchers shared their findings May 31 in Science.
Survival of captured mosquitoes following exposure to a fungus engineered to make a spider toxin
In an outdoor study enclosed by nets, a genetically engineered fungus (orange line) killed mosquitoes more quickly than the unaltered fungus (yellow). The fungus was Metarhizium pingshaense. Both versions of the fungus killed roughly 75 percent of mosquitoes over two weeks. But the engineered fungus worked faster. “Control” mosquitoes were not exposed to either fungus.
Better than nature?
“The results are exciting, but there’s still a lot of work to be done,” says Adriana Costero-Saint Denis. She’s an entomologist (insect biologist) at the National Institute of Allergy and Infectious Diseases in Rockville, Md. That institute helped fund the research. The researchers still need to work out some details, Costero-Saint Denis says. For example, what’s the best place to hang the cloth? From the ceiling? On the walls? In bedrooms? Or perhaps near doors and windows?
Costero-Saint Denis does think the study’s setting was “better than the lab.” Although the setting was somewhat artificial, she notes, the temperature and humidity were natural.
Researchers will have to see if the engineered fungi work well in future real-world tests. If so, the fungi could be combined with insecticides or other tools to tackle malaria, says Nsa Dada. She’s a medical entomologist with the Centers for Disease Control and Prevention in Atlanta, Ga. A host of different mosquito species can transmit malaria. The new tests used just one. Dada wonders if the fungus would work as well against those other species.
As good as the new study was, it doesn’t prove that the engineered fungus is an improvement over nature, says Matthew Thomas. He’s an ecological entomologist at Pennsylvania State University in State College.
In two weeks, the genetically modified fungus cut the study’s mosquito populations by about three-quarters. But other species of unmodified fungi can kill 100 percent of mosquitoes in five or six days, says Thomas.
allergy The inappropriate reaction by the body’s immune system to a normally harmless substance. Untreated, a particularly severe reaction can lead to death.
bioengineer Someone who applies engineering to solve problems in biology or in systems that will use living organisms.
biology The study of living things. The scientists who study them are known as biologists.
bug The slang term for an insect. Sometimes it’s even used to refer to a germ. (in computing) Slang term for a glitch in computer code, the instructions that direct the operations of a computer.
Burkina Faso This low-income, land-locked country in West Africa is an agricultural region that gets most of its money from cotton-growing. Malnutrition (and stunted growth) is a big problem and life expectancy is only about 60 years. Two in every three adults here cannot read.
Centers for Disease Control and Prevention, or CDC An agency of the U.S. Department of Health and Human Services, CDC is charged with protecting public health and safety by working to control and prevent disease, injury and disabilities. It does this by investigating disease outbreaks, tracking exposures by Americans to infections and toxic chemicals, and regularly surveying diet and other habits among a representative cross-section of all Americans.
control A part of an experiment where there is no change from normal conditions. The control is essential to scientific experiments. It shows that any new effect is likely due only to the part of the test that a researcher has altered. For example, if scientists were testing different types of fertilizer in a garden, they would want one section of it to remain unfertilized, as the control. Its area would show how plants in this garden grow under normal conditions. And that gives scientists something against which they can compare their experimental data.
ecology A branch of biology that deals with the relations of organisms to one another and to their physical surroundings. A scientist who works in this field is called an ecologist.
egg The unfertilized reproductive cell made by females.
entomology The scientific study of insects. One who does this is an entomologist.
field An area of study, as in: Her field of research was biology. Also a term to describe a real-world environment in which some research is conducted, such as at sea, in a forest, on a mountaintop or on a city street. It is the opposite of an artificial setting, such as a research laboratory
fungus (plural: fungi) One of a group of single- or multiple-celled organisms that reproduce via spores and feed on living or decaying organic matter. Examples include mold, yeasts and mushrooms.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
generation A group of individuals (in any species) born at about the same time or that are regarded as a single group. Your parents belong to one generation of your family, for example, and your grandparents to another. Similarly, you and everyone within a few years of your age across the planet are referred to as belonging to a particular generation of humans.
hatchling A young animal that recently emerged from its egg.
hemolymph A fluid in invertebrate animals that’s similar to blood in vertebrates.
humidity A measure of the amount of water vapor in the atmosphere. (Air with a lot of water vapor in it is known as humid.)
hybrid An organism produced by interbreeding of two animals or plants of different species or of genetically distinct populations within a species. Such offspring often possess genes passed on by each parent, yielding a combination of traits not known in previous generations. The term is also used in reference to any object that is a mix of two or more things.
infect To spread a disease from one organism to another. This usually involves introducing some sort of disease-causing germ to an individual.
insect A type of arthropod that as an adult will have six segmented legs and three body parts: a head, thorax and abdomen. There are hundreds of thousands of insects, which include bees, beetles, flies and moths.
larvae (sing.: larva) Immature insects, which often have distinctly different forms from the adult. (Sometimes used to describe such a stage in the development of fish, frogs and other animals.)
malaria A disease caused by a parasite that invades the red blood cells. The parasite is transmitted by mosquitoes, largely in tropical and subtropical regions.
parasite An organism that gets benefits from another species, called a host, but doesn’t provide that host any benefits. Classic examples of parasites include ticks, fleas and tapeworms.
pathologist Someone who studies disease and how it affects people or other infected organisms.
population (in biology) A group of individuals from the same species that lives in the same area.
species A group of similar organisms capable of producing offspring that can survive and reproduce.
spider A type of arthropod with four pairs of legs that usually spin threads of silk that they can use to create webs or other structures.
spore A tiny, typically single-celled body that is formed by certain bacteria in response to bad conditions. Or it can be the single-celled reproductive stage of a fungus (functioning much like a seed) that is released and spread by wind or water. Most are protected against drying out or heat and can remain viable for long periods, until conditions are right for their growth.
swarm A large number of animals that have amassed and now move together. People sometimes use the term to refer to huge numbers of honeybees leaving a hive.
tactic An action or plan of action to accomplish a particular feat.
toxin A poison produced by living organisms, such as germs, bees, spiders, poison ivy and snakes.
transmit (n. transmission) To send or pass along.
ultraviolet light A type of electromagnetic radiation with a wavelength from 10 nanometers to 380 nanometers. The wavelengths are shorter than that of visible light but longer than X-rays.
World Health Organization An agency of the United Nations, established in 1948, to promote health and to control communicable diseases. It is based in Geneva, Switzerland. The United Nations relies on the WHO for providing international leadership on global health matters. This organization also helps shape the research agenda for health issues and sets standards for pollutants and other things that could pose a risk to health. WHO also regularly reviews data to set policies for maintaining health and a healthy environment.