Disease-Fighting Secrets of Genetically Modified Mosquitoes

Insects cover our planet. Filed into 750,000 different species, at any given time there are one million trillion bugs buzzing around the globe.

About 14,000 of those species are blood-feeders, meaning they drink their meals by puncturing the skin of vertebrates, including humans. Besides being a nuisance, blood-feeding insects, such as certain strains of mosquitoes, are infected with parasitic organisms that are no threat to the bugs themselves, but if transferred to humans, become toxic, or worse, lethal.

A new collection of studies from PLoS charts alternative strategies for curbing mosquito-borne diseases such as dengue and malaria using genetically modified insects. The idea is to create mosquitoes that are less infectious and pass their altered genetics to the next generation by breeding with their natural counterparts.

Even though GM insects offer potential relief from malaria and dengue, which remain untreatable, unpreventable diseases in much of the developing world, there is still a lot of skepticism, mistrust and even fear of genetically modified organisms of any sort. Careful regulation, program oversight, and public information campaigns are just as important as proving the efficacy of GM insect release.

These pictures show the different types of mosquitoes whose genetic profiles are changing in the name of science and public health.

Above:

Aedes aegypti

Aedes aegypti is a carrier mosquito for the virus that causes dengue fever in humans. Researchers discovered that by introducing Wolbachia bacterial strains into some insects, the dengue virus didn’t live as long as usual inside the mosquitoes. What’s more, because most Wolbachia strains are relatively harmless to the insects, the bacteria spread through mosquito generations, passing from mother to offspring.

A study in Zhiyong Xi’s lab at Michigan State University found that the Wolbachia bacterium stopped the dengue virus from replicating, and therefore kept it from spreading among mosquitoes. In fact, 14 days after the study started, 37.5 percent of the mosquitoes were unable to infect humans with dengue.

Another study, from Elizabeth McGraw’s lab at The University of Queensland, Australia, showed that by using a modified Wolbachia bacteria (wMelPop), the older mosquitoes -- the insects that typically pass dengue to humans -- had a shortened lifespan because they could no longer feed. From the age of 26 days onward, the mosquitoes with the wMelPop Wolbachia bacteria in their bodies started drinking significantly less blood than their uninfected counterparts.

Aedes albopictus

The Asian Tiger mosquito,Aedes albopictus, can carry diseases including dengue and chikungunya. Compared to its genetic relative A. aegypti, this mosquito is typically less likely to house a virus. Since A. albopictus carries less risk of infection, the latest advances in genetic engineering seemed to have been reserved for the more virulent A. aegypti.

But A. albopictus is hardier than its relatives, and travels longer distances from the equator. In the past 30 years, researchers have watched them move throughout Southeast Asia to Northern Asia to Europe to the United States. Combined with the fact that certain mutations of the chikungunya virus are now carried by these mosquitoes, more and more researchers believe finding a suitable eradication strategy is crucial.

A team of collaborators from the GM insect technology company Oxitec, Imperial College, and the University of Oxford took the first steps forward, showing they could stably deliver a transgene to A. albopictus embryos, the first genetic modification ever to be done on Asian Tiger mosquitoes.

Anopheles stephensi

Anopheles stephensi is a type of mosquito that can become infected by Plasmodium, parasitic protozoans that cause malaria in humans.

Two studies highlight different ways to get these mosquitoes to resist infection by Plasmodium strains. First, George Dimopoulos’s team at Johns Hopkins University created a genetically modified mosquito by triggering a certain protein (Rel2) to boost the bug’s immunity when it drank blood. The results showed that his genetic trigger worked: Rel2 increased after feeding, and there were fewer traces of Plasmodiumin the genetically modified insect’s saliva compared to the controls.

In a second study, led by Anthony James at UC Irvine, scientists showed that by introducing new genes that coded for immune system components from both mosquitoes and mice, they could create a transgenic insect that was resistant to the Plasmodium parasite.

Anopheles albimanus

George Dimopoulos, the researcher who showed that tweaking the Rel2 protein in A. stephensi turned on the insect’s immune system after a blood meal, has also done similar work in A. albimanus. In his proof-of-concept studies, he discovered that artificially increasing or decreasing Rel2 caused certain of the mosquitoe's immunity genes to turn on or off, respectively.

Anopheles gambiae

Anopheles gambiae is the most important Anopheles species for malaria in Africa.

A group led by Steven Sinkins at the University of Oxford found that simply introducing a modifiedWalbachia strain was enough to shorten the insect's lifespan, halt the development of the Plasmodiumpathogen, and activate the parts of the mosquito’s immune system that affect whether an infective parasite will live or die within the host.

Warmer Planet Could Be Dominated by Mosquitoes, Tics, Rodents and Jellyfish

Two mammal-eating "transient" killer whales photographed off the south side of Unimak Island, eastern Aleutian Islands, Alaska Image: Robert Pittman/Alaska Fisheries Science Center

Supplemental Material

• Overview The Future of Climate Change

Imagine a planet where jellyfishrule the seas, giant rodents roam the mountains and swarms of insects blur everything in sight. It may sound far-fetched, but enough global warming is likely to change the distribution of wildlife on Earth. While species that are under threat, such as the polar bear, seem to get all the attention, others are beginning to thrive like never before.

In the past three months, new studies have been published about killer whales, wandering albatross and trumpeter swans—all of which appear to be benefiting from climate change.

Melting ice is turning the Arctic Sea into a giant buffet for killer whales. They have been arriving in growing numbers to feed on belugas, seals and narwhals, according to a recent study by scientists from the University of Manitoba. Warmer temperatures make it easier for the whales to hunt because their prey is less likely to climb onto sea ice or hide below it to escape.

At the opposite end of the world, in Antarctica's Southern Ocean, changing winds have been helping the wandering albatross find food faster. Researchers say global warming has produced stronger air currents that allow the birds to spend less time away from their nests, increasing the odds that their chicks will survive.

"The duration of foraging trips has decreased, breeding success has improved and birds have increased in mass by more than 1 kilogram," wrote the study's authors, who called their findings "positive consequences of climate change."

In Arctic areas, global warming is happening at roughly twice the average speed, which has allowed Alaska's trumpeter swans to expand their breeding grounds northward into regions that were previously too cold, according to a study published in Wildlife Biology in December.

"We knew that the population was expanding, both in numbers and spatially on the landscape," said Joshua Schmidt, a biometrician for the National Park Service Inventory and Monitoring Program and a co-author of the study.

Ice age veterans swan around

After analyzing more than 40 years of data, researchers discovered the swans were benefiting in two ways from global warming: They had expanded their territory northward, and they were seeing about three more snow-free days than before 1940. These shorter winters mean the swans—which were hunted to the brink of extinction in the 1800s—now have more time to eat and grow strong before embarking on a long migration to the Pacific Northwest each fall, improving their chances for survival.

"Swans have been through an ice age or two, so climate change isn't something they haven't seen before," said James King, a biologist who used to work for the U.S. Fish and Wildlife Service in Alaska. After studying swans for about 50 years, King believes the birds "know how to deal with climate change." Historically, they have found ways to outsmart the cold by nesting near hot springs, which prolongs their breeding season, he said.

"There will definitely be some animals that will do better with longer summer and milder winter," said Paul Curtis, an extension wildlife specialist at Cornell University. "Fifty years from now, central New York may be as warm as North or South Carolina. It's a much faster change than we've seen any time historically, and it's just a question of how some of these species will respond."

---

White-tailed deer in the northern United States are already showing a population boom thanks to this year's lack of snowfall, which has made it easier for the animals to find food, said Curtis. He also believes a warmer spring could benefit snakes and salamanders, giving them more time to grow and add to their fat reserves.

A 2010 study in the journal Nature reported that yellow-bellied marmots in Colorado's Rocky Mountains are also flourishing thanks to climate change. The squirrel-like mammals can lose up to 40 percent of their body mass during hibernation, and longer summers are giving them more time to eat and store fat, helping them live through the winter and reproduce the following year. The adult marmots have gained half a pound on average and their numbers have more than doubled from 2000 to 2010, said researchers.

Acid-loving jellyfish?

Jellyfish populations are also suspected to be swelling because of climate change. In recent years, the creatures have been clogging the nets of fishermen, stinging record numbers of beachgoers and blocking the water intake lines of power plants in at least three countries. Some scientists are linking the phenomenon to warmer waters and ocean acidification caused by high levels of carbon dioxide in the atmosphere. Studies have found that today's oceans are 30 percent more acidic than in the 18th century, when the Industrial Revolution began.

However, a lack of historical data on jellyfish populations has caused some scientists to question whether the apparent boom is actually connected toglobal warming. A project called the Jellyfish Database Initiative was recently launched to determine whether the increases are happening on a global scale and if they could be part of a natural cycle.

Another creature that is likely to flourish in warmer waters is theSchistocephalus solidus tapeworm. The parasite spends most of its life growing inside the three-spined stickleback fish, which is about the size of a small sardine and lives in oceans and lakes throughout the Northern Hemisphere.

Scientists at the University of Leicester placed infected sticklebacks into a tank of water at 68 degrees Fahrenheit—about 9 degrees warmer than a typical summer's day in Britain—and found the tapeworms to grow four times faster than normal. The ordinary worms were able to produce about 12,000 eggs, while the larger worms laid almost 200,000, according to data published in the journal Global Change Biology in November.

Certain species of insects, like mosquitoes, ticks and invasive beetles, are also expected to benefit from warmer temperatures. In fact, a 2003 study published by the Ecological Society of America concluded that "all aspects of insect outbreak behavior will intensify as the climate warms."

Fewer ticks, fleas and beetles freeze

Extreme cold spells can kill a percentage of hibernating insects each winter, says Jody Gangloff-Kaufmann, a professor of entomology at Cornell University. Without these cold spells, more insects are likely to emerge in the spring.

"I anticipate the mosquito problems we normally see to be much more intense and begin earlier than usual if the weather continues to be mild," said Kaufmann, who believes ticks and fleas will also be able to feed more frequently thanks to warmer winter days.

Future levels of carbon dioxide may help beetles, as well, according to researchers from the University of Illinois, Urbana-Champaign, who found that Japanese beetles lived longer and laid more eggs after eating leaves that were grown in an environment with additional carbon dioxide.

---

"What we really don't know is what the long-term consequences of climate change are," explained Curtis. "There will definitely be winners and losers, and it's hard to predict what some of those will be." He said animals that can migrate—like whales and birds—are more likely to adapt, while species bound to a particular environment, or food source, will face greater challenges.

Even creatures that appear to be benefiting today may not be so lucky in the future.

Scientists predict the winds that are helping the wandering albatross will become increasingly violent by the end of the century, threatening the birds' survival. And Colorado's marmots don't easily adapt to heat, so rising temperatures may soon put them—and the plants they eat—at risk.

"It's hard to say if swans will even benefit long-term," said Schmidt, who explained that the ponds they live in may already be drying up. "If those sorts of things are occurring, it might be a zero-sum game. Or it might be negative."

Deadly Alcohol Needs Global Regulation, Health Expert Says

Image: Flickr/pamlane

When considering the world's worst killers, alcohol likely doesn't come to mind. Yet alcohol kills more than 2.5 million people annually, more than AIDS, malariaor tuberculosis.

For middle-income people, who constitute half the world's population, alcohol is the top health risk factor, greater than obesity, inactivity and even tobacco.

The World Health Organization has meticulously documented the extent ofalcohol abuse in recent years and has published solid recommendations on how to reduce alcohol-related deaths, but this doesn't go far enough, according to Devi Sridhar, a health-policy expert at the University of Cambridge.

In a commentary appearing today (Feb. 15) in the journal Nature, Sridhar argues that the WHO should regulate alcohol at the global level, enforcing such regulations as a minimum drinking age, zero-tolerance drunken driving, and bans on unlimited drink specials. (Scientific American is part of Nature Publishing Group.) Abiding by the regulations would be mandatory for the WHO's 194 member states.

Far from prohibition, the WHO regulations would force nations to strengthen weak drinking laws and better enforce laws already in place, Sridhar says.

Approaching a bottle a day

Alcohol consumption is measured in terms of pure ethyl alcohol to compensate for the varying strengths of beer, wine and spirits. A liter bottle of wine with 10 percent alcohol, for example, would be only 0.1 liter of pure alcohol. According to the WHO, Americans each drink 9.4 liters of ethyl alcohol per year on average. That's equivalent to 94 bottles of the aforementioned wine. [See list of top 20 booze-consuming countries]

As high as that might sound, Americans don't even crack the top 50 on the world charts. Europe, in particular Eastern Europe, dominates the drinking scene. Moldova has the top drinkers, downing 18.4 liters of alcohol per capita yearly. That's equivalent to 184 1-liter bottles of wine, or nearly four bottles a week per person. The legal drinking age in Moldova is 16, and there are few restrictions on when or where alcohol can be sold.

The price of such alcohol abuse is early death. One in five men in the Russian Federation and neighboring European countries dies as a result of alcohol, according to WHO data. Alcohol abuse is associated with cardiovascular diseases, cirrhosis of the liver, various cancers, violence and vehicle accidents. Alcoholic adults have difficulty working and supporting their families, too.

Sobering recommendations

Sridhar argues that the WHO is unique among health organizations in that it can create legally binding conventions. The WHO has done this only twice in its 64-year history: the International Health Regulations, which require countries to report certain disease outbreaks and public-health events; and the Framework Convention on Tobacco Control, which commits governments to making legislative moves to reduce the demand for, and the supply of, tobacco.

No other entity can attack the global problem of alcohol abuse, she said. When it comes to alcohol, though, the WHO has settled on merely recommendations, such as those outlined in the 2010 WHO Global Strategy to Reduce Harmful Use of Alcohol.

---

"Countries are aware of the problem, but several haven't made a real commitment to implementing the recommendations," Sridhar told LiveScience. "The problem is not with ministries of health but with ministries of finance, trade, etc. who prioritize other interests first."

In her Nature commentary, Sridhar said that the existing WHO recommendations could serve as the framework for a new international convention on alcohol regulation. Yet even the United States would struggle to meet several of the 10 recommended target areas, which include advertising restrictions, price hikes and tougher laws against drunken driving.

"Ministries of health would have a stronger domestic negotiating position in prioritizing alcohol regulation above economic concerns," with the WHO muscle behind them, she wrote.

Alas, football ads might never be the same.

Christopher Wanjek is the author of the books "Bad Medicine" and "Food At Work." His column, Bad Medicine, appears regularly on LiveScience.

Copyright 2012 LiveScience, a TechMediaNetwork company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

Mammals Made By Viruses

If not for a virus, none of us would ever be born.

In 2000, a team of Boston scientists discovered a peculiar gene in the human genome. It encoded a protein made only by cells in the placenta. They called it syncytin.

The cells that made syncytin were located only where the placenta made contact with the uterus. They fuse together to create a single cellular layer, called the syncytiotrophoblast, which is essential to a fetus for drawing nutrients from its mother. The scientists discovered that in order to fuse together, the cells must first make syncytin.

What made syncytin peculiar was that it was not a human gene. It bore all the hallmarks of a gene from a virus.

Viruses have insinuated themselves into the genome of our ancestors for hundreds of millions of years. They typically have gotten there by infecting eggs or sperm, inserting their own DNA into ours. There are 100,000 known fragments of viruses in the human genome,  making up over 8% of our DNA. Most of this virus DNA has been hit by so many mutations that it’s nothing but baggage our species carries along from one generation to the next. Yet there are some viral genes that still make proteins in our bodies. Syncytin appeared to be a hugely important one to our own biology. Originally, syncytin allowed viruses to fuse host cells together so they could spread from one cell to another. Now the protein allowed babies to fuse to their mothers.

It turned out that syncytin was not unique to humans. Chimpanzees had the same virus gene at the same spot in their genome. So did gorillas. So did monkeys. What’s more, the gene was strikingly similar from one species to the next. The best way to explain this pattern was that the virus that gave us syncytin infected a common ancestor of primates, and it carried out an important function that has been favored ever since by natural selection. Later, the French virologist Thierry Heidmann  and his colleagues discovered a second version of syncytin in humans and other primates, and dubbed them syncytin 1 and syncytin 2. Both virus proteins seemed to be important to our well-being. In pre-eclampsia, which gives pregnant women dangerously high blood pressure, levels of both syncytin 1 and syncytin 2 drop dramatically. Syncytin 2 also performs another viral trick to help its human master: it helps tamp down the mother’s immune system so she doesn’t attack her baby as a hunk of foreign tissue.

In 2005, Heidmann and his colleagues realized that syncytins were not just for primates. While surveying the mouse genome, they discovered two syncytin genes (these known as A and B), which were also produced in the same part of the placenta. This discovery allowed the scientists to test once and for all how important syncytin was to mammals. They shut down the syncytin A gene in mouse embryos and discovered they died after about 11 days because they couldn’t form their syncytiotrophoblast. So clearly this virus mattered enormously to its permanent host.

Despite their name, however, the primate and mouse syncytins didn’t have a common history. Syncytin 1 and 2 come from entirely different viruses than syncytin A and B. And the syncytin story got even more intricate in 2009, when Heidmann discovered yet another syncytin gene–from an entirely different virus–in rabbits. While they found this additional syncytin (known as syncytin-Ory1) in a couple different species of rabbits, they couldn’t find it in the close relative of rabbits, the pika. So their own placenta-helping virus must have infected the ancestors of rabbits less than 30 million years ago.

Now Heidmann has found yet another virus lurking in the ancient history of mammals. This one is in dogs and cats–along with pandas and hyenas and all the other mammals that belong to the so-called carnivoran branch of the mammal tree. In every carnivoran they’ve looked at, they find the same syncytin gene, which they named syncytin-Car1. In every species it is strikingly similar, suggesting that it’s experienced strong natural selection for an important function for millions of years. But it’s missing from the closest living relative of carnivorans, the pangolins. The diagram here, from the authors, shows how they see this evolution having unfolded. After the ancestors of carnivorans split from other mammals 85 million years ago, they got infected with a virus which eventually came to be essential for their placenta.

The big picture that’s now emerging is quite amazing. Viruses have rained down on mammals, and on at least six occasions, they’ve gotten snagged in their hosts and started carrying out the same function: building placentas. The complete story will have to wait until scientists have searched every placental mammal for syncytins from viruses. But in the meantime there is something interesting to consider. Some mammals that scientists have yet to investigate, such as pigs and horses, don’t have the open layer of cells in their placenta like we do. Scientists have come up with all sorts of explanations for why that may be, mainly by looking for differences in the biology of each kind of mammals. But the answer may be simpler: the ancestors of pigs and horses might never have gotten sick with the right virus.

(For more information on our inner viruses, see this 2010 story I wrote for theNew York Times and my book from last year, A Planet of Viruses.)

[Top image: Leonardo da Vinci's sketch of a human fetus. From Universal Leonardo]

Could Sleep Problems Predict Alzheimer's?

Frequent Night Awakenings Linked to Signs of Alzheimer’s, Researchers Find

Reviewed by Laura J. Martin, MD

The poorer your sleep, the more likely you may be to develop Alzheimer's disease, according to a new study.

"We found that if people had a lot of awakenings during the night, more than five awakenings in an hour, they are more likely to have preclinical Alzheimer's disease," says researcher Yo-El Ju, MD, assistant professor of neurology at Washington University School of Medicine in St. Louis.

Preclinical Alzheimer's disease is the term given to people who have normal mental skills but show brain changes associated with the degenerative disorder.

Ju is due to present her findings on sleep problems and Alzheimer's disease in April at the American Academy of Neurology's annual meeting in New Orleans.

The study is preliminary. It finds an association, but not a cause and effect.

"We don't know which is the cart and which is the horse," says Gary Small, MD, Parlow-Solomon professor on aging at the University of California Los Angeles and director of its Longevity Center. Are brain changes driving the sleep problems or vice-versa? More study is needed, says Small, who reviewed the findings for WebMD. Ju agrees.

Insomnia Slideshow: 20 Tips for Better Sleep

Sleep Problems and Alzheimer's Disease

Ju and her colleagues evaluated 100 men and women aged 45-80. All were free of dementia at the study start. Half of them have a family history of Alzheimer's disease.

Ju is in the process of enrolling or evaluating another 100 people. She expects to have those results by the meeting.

For 14 days, the men and women wore a device that measures sleep. They also completed sleep diaries and questionnaires.

The researchers analyzed spinal fluid. They looked at brain scans. They were looking for indicators of “amyloid plaques.” These are deposits found in the brains of people with Alzheimer's. Experts believe the deposits can begin forming 10 to 15 years before the symptoms appear, Ju says.

People slept an average of six-and-a-half hours, although they spent about eight hours a night in bed.

---

Sleep Problems and Alzheimer's: Study Results

About 25% of the 100 people had evidence of pre-clinical Alzheimer's disease due to abnormal indicators reflecting amyloid plaques. Those who woke up most frequently, more than five times an hour, were more likely than the others to have these abnormal biomarkers.

Ju can't say exactly how much more likely the diagnosis was in those who woke up often.

Those who spent less than 85% of their time in bed actually sleeping were also more likely to have preclinical Alzheimer's disease, they found.

About half of the group had more than five awakenings an hour, and about half spent less than 85% of their time in bed sleeping, Ju says.

While waking up five times an hour sounds like a lot, she says the sleep-measuring device may slightly overestimate the number of awakenings, but that ''people actually do wake briefly quite frequently during a regular night of sleep."

Ju cites animal studies finding that sleep changes drive the accumulation of amyloid. She suspects that is the case for people, too.

"But more study is needed," she says. "We don't have any information that tells us which direction the association is."

Meanwhile, getting a good night's sleep is advised. "Everyone should prioritize their sleep," Ju says. "We don't value sleep as much as we should. Sleep is a very important function that allows the brain to rest."

Sleep Problems and Alzheimer's Link? More Opinions

"This [study] is another indication there are early brain changes [in Alzheimer's disease]," says Maria Carrillo, PhD, senior director of medical and scientific relations for the Alzheimer's Association.

Which way the association develops is yet to be determined, she says.

"The trouble sleeping could reflect brain changes happening," Carrillo tells WebMD.

The study finding is not surprising, says UCLA's Small. "We know that getting a good night's sleep is important for the brain."

Of the new research, "the causal relationship is not clear," he says.

He suspects that inflammation may be playing a role. He and other experts believe brain inflammation and Alzheimer's may be linked. Perhaps the lack of sleep increases inflammation, he says. Small serves as speaker or advisor for Novartis, Forest, and Lilly.

The study was funded by the nonprofit Ellison Medical Foundation and the National Institutes of Health.

This study is due to be presented at a medical conference. The findings should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.

Bees Use Sign Language to Give Hornets the Finger

Tony Hisgett/CC BY 2.0

From waging war with rival colonies to cleaning house of dead bees and debris, honeybees do some amazing things. Perhaps most amazing is their ability to communicate with each other using a "waggle dance" as sign language, but it turns out that they don't just communicate with other bees.

The BBC reports on new research that suggests honeybees also send "sign language" signals to predators, warning would-be raiding hornets that they have been spotted and they'd better back off. Coolest of all is the fact that these signals actually work! More from the BBC:

Researchers already knew of this "characteristic shaking signal", in which all the guards bees simultaneously vibrate their abdomens from side-to-side for a few seconds when a hornet approaches the colony. In the wild, this produces a spectacular "Mexican wave" of vibrating bees.

This study, carried out on a small bee hive, revealed the hornets (Vespa velutina) responded directly to the bees' shaking signal. Warned wasps would retreat from the colony and try to catch bees in flight instead. To find this out, the researchers tethered live hornets to lengths of wire and held them at a variety of distances from the hive entrance. The closer the tethered hornet was held to the hive, the more intensely the bee guards shook their bodies. To confirm that the bees were specifically "talking to" the hornets with this signal, the team carried out the same tethering experiment with a harmless butterfly species (Papilio xuthus).

Head over to the BBC for more on how bees "talk" with hornets to warn them off. If only they could warn off farmers spraying neonicotinoids too...