Last year, Prof. Anthony James announced that he and his colleagues had genetically altered Aedes aegypti mosquitoes in a fashion that could drastically reduce their populations. In a nutshell, the altered genes cause the female mosquitoes to be born without wings – this makes it rather difficult for them to go foraging for blood, and turns them into easy prey for almost any predator. The non-biting males are born with wings, and subsequently go off and mate with unmodified females, passing the modified genes along to their offspring. Now, James has done some more genetic engineering, to create mosquitoes that can’t spread malaria…
They started with mice that were infected with the Plasmodium falciparum parasite, which causes malaria. Those mice created antibodies in order to kill the parasites. The scientists identified the molecular components of this immune response, then altered the genes of the Anopheles stephensi mosquito in order to cause the same response to occur in their bodies – ordinarily, mosquitoes simply act as carriers of the parasites, exhibiting no immune response towards them.
In short, parasites picked up by the mosquitoes are killed by the insects’ altered immune systems, meaning that people subsequently bitten by those mosquitoes won’t develop malaria. Although the study was done using Anopheles stephensi, the technique could reportedly be used on dozens of different types of mosquitoes.
Unlike James’ previous efforts involving the flightless females, this approach would not actually reduce the numbers of mosquitoes present in an area. Much as many people might like the idea of the eradication of mosquitoes, this could be a good thing – it’s still unclear how the sudden elimination of a species as plentiful as the mosquito might affect ecosystems…
A significant benefit to that large portion of the world’s population that suffers from malaria. Small area controlled trials are next; but, there are lots of folks waiting for this to be a success.
Mosquito landing boxes in Tanzania
Researchers in Tanzania have chemically reproduced the stench of smelly feet in an innovative new approach to combat the spread of malaria in the country.
The scientific team at Tanzania’s Ifakara Health Institute has developed a potent serum — similar to that of human foot odor — to lure and kill mosquitoes, which can carry malaria and other diseases.
Four times more powerful in attracting mosquitoes than natural human odor, the synthetic smell is now being used in a pioneering research program aimed at killing mosquitoes outdoors using a “mosquito landing box…”
Mosquitoes are lured inside the boxes by the synthetic odor, which is dispersed by a solar-powered fan. Once inside, the insects are either trapped or poisoned and left to die.
“Substances we omit when we sweat, such as lactic acid, act as a signal to mosquitoes … The aim here was to produce a mixture that would mimic a human being.” The result, said Fredros Okumu, was a chemical blend that “smelt just like dirty socks…”
“This is a great example of an African innovator, with an African innovation, tackling an African problem,” said Dr Peter Singer, CEO of Grand Challenges Canada.
“Malaria kills about 800,000 people a year, mostly children, in Africa. At the moment existing technologies, such as bed nets and sprays, tend to repel mosquitoes inside the home.
“This technology attracts mosquitoes outside the home to kill them, and could be complimentary to what is there now,” Singer continued…
For Okumu, this is a personal as well as a scientific venture. Born in western Kenya, malaria has been apart of Okumu’s life for as long as he can remember.
“All the places I have lived have been malaria zones. When I was growing up I had malaria at least twice every year,” he said.
Most American and Europeans have little knowledge of this terrible disease. So many people die, so many children especially, it really is one of the grim reapers of African history.
Five years ago, Bill Gates made an extraordinary offer: he invited the world’s scientists to submit ideas for tackling the biggest problems in global health, including the lack of vaccines for AIDS and malaria, the fact that most vaccines must be kept refrigerated and be delivered by needles, the fact that many tropical crops like cassavas and bananas had little nutrition, and so on.
No idea was too radical, he said, and what he called the Grand Challenges in Global Health would pursue paths that the National Institutes of Health and other grant makers could not.
About 1,600 proposals came in, and the top 43 were so promising that the Bill & Melinda Gates Foundation made $450 million in five-year grants — more than double what he originally planned to give.
Now the five years are up, and the foundation recently brought all the scientists to Seattle to assess the results and decide who will get further funding.
In an interview, Mr. Gates sounded somewhat chastened, saying several times, “We were naïve when we began…”
He underestimated, he said, how long it takes to get a new product from the lab to clinical trials to low-cost manufacturing to acceptance in third-world countries…
That little won’t buy a breakthrough, but it lets scientists “moonlight” by adding new goals to their existing grants, which saves the foundation a lot of winnowing. “And,” he added, “a scientist in a developing country can do a lot with $100,000.”
Over all, he said: “On drawing attention to ways that lives might be saved through scientific advances, I’d give us an A.
“But I thought some would be saving lives by now, and it’ll be more like in 10 years from now.”
RTFA. A case study – series of studies – in developing philanthropy. Above all else, give the Gates’ credit for their commitment and dedication. It ain’t even easy to try to give money away to help people.
The first clinical trial for a vaccine against the most widespread strain of malaria, Plasmodium vivax, is now under way at the Walter Reed Army Institute for Research, near Washington DC. The BBC’s Jane O’Brien speaks with those heading the trial and individuals who are being bitten by infected mosquitoes to help further the research.
US army medic Joseph Civitello admits that becoming deliberately infected with malaria – one of the world’s deadliest diseases – is “definitely nuts”. But without such volunteers, it would be almost impossible to test a new vaccine aimed at protecting the military overseas and preventing some of the estimated 300 million cases of malaria that occur every year.
First Sgt Civitello is part of the world’s first clinical trial of a vaccine against Plasmodium vivax – the most widespread strain of malaria…
“It was weird because I did this knowing I was going to get sick,” says Sgt Civitello. “Fortunately I’m in a hotel room with doctors and nurses nearby and not out in the woods somewhere.”
Unlike most of the other volunteers in this unique trial, Sgt Civitello wasn’t given the test vaccine.
He’s part of a small control group – a human yardstick – needed by doctors to confirm that all the study participants have been infected. And as predicted, about 10 days after being bitten by mosquitoes in a laboratory, he displayed all the symptoms of malaria…
Twenty-seven other volunteers in the study had been given varying doses of the vaccine for several months prior to infection…
Then, at the beginning of November, they were bitten by mosquitoes imported from Thailand and infected with Plasmodium vivax malaria…
He adds: “What we do here plays a critical, pivotal role in the fight against malaria. Without this model of challenging the human body with malaria, we would be unable to effectively develop and figure out whether a vaccine works or not…”
RTFA for the details, the methodology, the human story of the volunteers for this first trial.
Regardless of assurances, knowledge of the history of precedent testing, you never feel quite confident of the outcome especially when – as in this study – you’re assured you are part of the control group. The last human trial I volunteered for was a double blind; so, none of us knew who was part of the control and who was getting the vaccine for the disease under test.
Test larvae have flourescent marker tied to gene
For years, researchers worldwide have attempted to create genetically altered mosquitoes that cannot infect humans with malaria. Those efforts fell short because the mosquitoes still were capable of transmitting the disease-causing pathogen, only in lower numbers.
Now for the first time, University of Arizona entomologists have succeeded in genetically altering mosquitoes in a way that renders them completely immune to the parasite, a single-celled organism called Plasmodium. Someday researchers hope to replace wild mosquitoes with lab-bred populations unable to act as vectors, i.e. transmit the malaria-causing parasite.
“If you want to effectively stop the spreading of the malaria parasite, you need mosquitoes that are no less than 100 percent resistant to it. If a single parasite slips through and infects a human, the whole approach will be doomed to fail,” said Michael Riehle, who led the research effort…
Riehle’s team used molecular biology techniques to design a piece of genetic information capable of inserting itself into a mosquito’s genome. This construct was then injected into the eggs of the mosquitoes. The emerging generation carries the altered genetic information and passes it on to future generations…
When Riehle and his co-workers studied the genetically modified mosquitoes after feeding them malaria-infested blood, they noticed that the Plasmodium parasites did not infect a single study animal.
“We were surprised how well this works,” said Riehle. “We were just hoping to see some effect on the mosquitoes’ growth rate, lifespan or their susceptibility to the parasite, but it was great to see that our construct blocked the infection process completely…”
“The eradication scenario requires three things: A gene that disrupts the development of the parasite inside the mosquito, a genetic technique to bring that gene into the mosquito genome and a mechanism that gives the modified mosquito an edge over the natural populations so they can displace them over time.”
“The third requirement is going to be the most difficult of the three to realize,” he added, which is why his team decided to tackle the other two first…
At this point, the modified mosquitoes exist in a highly secured lab environment with no chance of escape. Once researchers find a way to replace wild mosquito populations with lab-bred ones, breakthroughs like the one achieved by Riehle’s group could pave the way toward a world in which malaria is all but history.
Tons of detail in the article. Sooner or later the study will be published somewhere with free access.
A simple salad spinner will save lives this summer, if everything goes as planned by two Rice University undergraduates.
The spinner has been turned, so to speak, into a rudimentary centrifuge that medical clinics in developing countries can use to separate blood without electricity.
Rice sophomore Lila Kerr and freshman Lauren Theis will take their Sally Centrifuge abroad for nearly two months this summer as part of Beyond Traditional Borders (BTB), Rice’s global health initiative that brings new ideas and technologies to underdeveloped countries. Kerr will take a spinner to Ecuador in late May, Theis will take one to Swaziland in early June and a third BTB team will take one to Malawi, also in June. Such field testing is important to Rice students as they develop a range of tools to enhance global health.
Kerr and Theis are minoring in global health technologies and took the Introduction to Bioengineering and World Health class taught by Rebecca Richards-Kortum…director of Rice 360˚: Institute for Global Health Technologies…
“We were essentially told we need to find a way to diagnose anemia without power, without it being very costly and with a portable device,” added Theis, a political science major and native of San Antonio, Texas.
They found that a salad spinner met those criteria. When tiny capillary tubes that contain about 15 microliters of blood are spun in the device for 10 minutes, the blood separates into heavier red blood cells and lighter plasma. The hematocrit, or ratio of red blood cells to the total volume, measured with a gauge held up to the tube, can tell clinicians if a patient is anemic. That detail is critical for diagnosing malnutrition, tuberculosis, HIV/AIDS and malaria…
The centrifuge, assembled using plastic lids, cut-up combs, yogurt containers and a hot-glue gun, costs about $30 in parts, including the spinner.
Bravo! Another successful field expedient.
Daylife/Reuters Pictures used by permission
The chief executive of the world’s second biggest pharmaceutical company will today announce that he is putting into the public domain thousands of potential drugs that might cure malaria.
Andrew Witty, the British boss of Glaxo-SmithKline, will say in a major speech that multinational drug companies have to balance social responsibility alongside the need to make profits for their shareholders. There is, he will say, an “imperative to earn the trust of society, not just by meeting expectations but by exceeding them”.
GSK will publish details of 13,500 chemical compounds from its own library that have potential to act against the parasite that causes malaria in sub-Saharan Africa, killing at least one million children every year.
It took a team of five investigators a year to screen the two million compounds in GSK’s library – its entire collection of potential drugs and possibly the biggest such library in the world…
Speaking to the Guardian in advance of the announcement in New York, he said: “To my knowledge nobody’s ever put confirmed-hit structures into the public domain. Universities have done stuff like this but on a much smaller scale.
“I think it’s a significant contribution to give scientists around the world 13,500 new opportunities to start research.”
Witty will also announce an $8m fund to pay for scientists to explore these chemicals or others in an “open lab” within its research centre at Tres Cantos, Spain, which is dedicated to work on malaria and other diseases of the developing world.
It’s trying to create a permissiveness around scientific research in an area where we know the marketplace isn’t going to stimulate massive research,” he said.
“Given that there is only a handful of big companies who focus on malaria, this is a chance to get thousands of researchers involved – just like software companies encourage thousands of people to contribute their new ideas for software – and we’ll see what comes of it.”
RTFA. Imagine if this becomes a trend! It will seem like heresy to some for a corporate head to bow to conscience. Andrew Witty seems to mean it.
Microsoft founder turned philanthropist Bill Gates released a glass full of mosquitoes at an elite technology conference to make a point about the deadly disease malaria.
“Malaria is spread by mosquitoes,” Gates said while opening a jar onstage at the TED Conference — a gathering known to attract technology kings, politicians, and Hollywood stars.
“I brought some. Here I’ll let them roam around. There is no reason only poor people should be infected.”
While he asked the audience “How do you stop a deadly disease that is spread by mosquitoes?”, Mr Gates also noted that more money is spent finding a cure for baldness than eradicating malaria.
TED curator Chris Anderson quipped that when a video of the talk is posted on its website it would be headlined “Gates releases more bugs into the world.”
Always nice to see Bill Gates unleash his quiet sense of humor. And the TED conference appears to be as interesting and productive as ever.
Researchers at the University of Washington have developed a prototype malaria test printed on a disposable Mylar card that could easily slip into your wallet and still work when you took it out, even months later.
Paul Yager, UW bioengineering professor, and colleagues described the prototype cards in the December issue of the journal Lab on a Chip. These cards are a critical step in a long-term project funded by The Bill and Melinda Gates Foundation’s Grand Challenges in Global Health Initiative to develop affordable, easy-to-use diagnostic tools for the developing world.
“A pivotal issue in having this technology work is making these tests storable for long periods of time at ambient temperatures,” Yager said. “Normally people work with wet reagents. We’re saying we can dry the reagents down in order to store them without refrigeration. It’s the astronaut-food approach.”
The malaria cards contain reagents that would normally require refrigeration, but the researchers figured out a way to stabilize them in dry form by mixing them with sugar. Results showed that malaria antibodies dried in sugar matrices retained 80 percent to 96 percent of their activity after 60 days of storage at elevated temperatures.
While the prototype developed by the UW researchers only tests for malaria, Yager and his collaborators are working towards cards that also will test for five other diseases that, like malaria, cause high-fever symptoms: dengue, influenza, Rickettsial diseases, typhoid and measles. The “fever panel” of six diseases is merely a starting point, Yager said. The UW technology could be adapted to include other diseases in the future.
Third World, developing nations, anyplace with substandard access to medical diagnosis – all will benefit from research like this. RTFA. The Bil and Melinda Gates Foundation is picking up the tab.