Abuzz over Hopkins mosquitoes

Dennis O'Brien | 26 Mar 2007
Baltimore Sun
Jason Rasgon wants to assure the world of one thing: His genetically modified mosquitoes do not have eyes that glow in the dark.

Yes, under fluorescent bulbs, some of the mosquitoes at the Johns Hopkins Malaria Research Institute will glow a bright red or green. When magnified, they look like space aliens.

But Rasgon and colleagues say it's what you can't see that makes these bugs important: They're prototypes for a generation of genetically modified mosquitoes that could be released into the wild to help eradicate malaria.

Rasgon and a team of Hopkins researchers have become international celebrities since they published a report highlighting the survival skills of their designer strain of Anopheles stephensi -- an otherwise common mosquito genetically engineered to resist mouse malaria.

Over several months, their enhanced mosquitoes had a higher survival rate than nonresistant strains that fed on the same diet of malaria-infected mouse blood.

The findings, published in Proceedings of the National Academy of Sciences, show that it might be possible to genetically design a mosquito that cannot only survive outdoors but also outcompete and replace the breeds that spread malaria and kill up to 2.7 million people a year worldwide.

"It's one more tool in the arsenal," said Rasgon, who describes himself as a "mosquito geneticist."

The release of an anti-malarial designer mosquito is many years away. But experts say the findings validate the concept of attacking malaria by genetically modifying the insect that spreads it.

"It's definitely important work," said Ken Olson, a virologist at Colorado State University who has created a genetically modified mosquito that he hopes will replace breeds that spread dengue fever.

Researchers first showed in 2002 that inserting a peptide into the genome of the same family of Anopheles stephensi made it resistant to mouse malaria.

The gene, known as SM1, prevents the malaria parasite from penetrating the mosquito's midgut and reaching the salivary glands -- a necessary step for transmitting malaria in a mosquito bite.

What surprised the Hopkins scientists was the response to the latest work in the international press. "It's been kind of nuts," Rasgon said.

Since preliminary reports of his study surfaced more than a week ago, Rasgon has been interviewed 60 times.

Most of the questions came from an international press corps fascinated by the development of a genetically modified insect. While genetically altered animals and plants might pass as curiosities in the United States, the European public takes them more seriously -- and often regards them as threats.

The lead author of the study, Marcelo Jacobs-Lorena, a veteran Hopkins mosquito expert, was in Sweden when the story broke and unavailable for interviews. That left Rasgon, a 32-year-old co-author who came to Hopkins 2 1/2 years ago, to explain things to the world.

"There have been calls from everywhere -- British, African, Asian and French," Rasgon said.

Many international news accounts describe the mosquitoes as having eyes that glow, and Web images show them with their eyes glowing bright green from fluorescent lights.

The fluorescent eyes are a minor detail to the researchers -- the result of a routine genetic tag inserted into the mosquito's eggs so researchers can tell the transgenic mosquitoes from the wild types.

The researchers also were surprised by the press attention because the work itself isn't new.

"It's not a new concept," said Adriana Costero, a program officer for the National Institute of Allergy and Infectious Diseases that partially funded the Hopkins study. The government has funded transgenic mosquito research for 15 years, she said.

The work is one of several continuing malaria research efforts. In another approach, researchers at the Center for Vaccine Development at the University of Maryland School of Medicine published a study this month identifying proteins on the surface of a malaria parasite that could be instrumental in creating a vaccine.

Improved housing, sanitation and mosquito-control efforts effectively eradicated malaria in the United States by the late 1940s, according to the federal Centers for Disease Control and Prevention.

The CDC reported 1,324 cases in the United States in 2004 and 1,278 cases in 2003. The vast majority were infected overseas, the agency says.

But in Africa and Asia the disease remains a major killer, prompting scientists to focus on the genetics of both mosquitoes and their parasites.

Mosquitoes pass the parasites along in their saliva, collecting it from one infected human and passing it to another when they bite. There are four types of malaria parasites known to infect humans, but the most dangerous, Plasmodium falciparum, accounts for 97 percent of malaria infections. Dozens of other malaria parasites infect birds, mice and other vertebrates

"The adult human immune system adapts, so infected adults don't die as readily, but young children under 5 and pregnant women are the most vulnerable," said Sarah Volkman, a molecular biologist who studies malaria at the Harvard School of Public Health.

So far, the parasites have proved to be elusive targets.

"The malaria parasite has lots of strategies to battle the immune response, along with any pressure put on it by a drug," Volkman said.

For the study, the researchers put an equal number of their transgenic mosquitoes in glass cages with wild-type mosquitoes and let them feed on malaria-infected mice for several weeks.

After nine generations -- a period of several months -- the researchers found that their genetically modified insects laid more eggs and had a higher survival rate and made up 70 percent of the population.

As promising as that sounds, Rasgon says releasing a genetically designed mosquito to fight malaria on a large scale is up to 20 years away.

"We have a lot of work still ahead of us," he said.

For starters, the researchers used a malaria parasite that infects mice, not humans. And even if researchers find a mosquito gene that prevents transmission of the human malaria parasites, there's still no mechanism to ensure that the desired gene will pass on to enough members of subsequent generations to make it a deterrent.

Rasgon also knows that releasing a genetically modified insect into the wild will raise environmental concerns in areas of the world that are highly suspicious of such research.

"We always have to be worried about unintended consequences," he said. "But we also have to weigh the unknown risks versus the fact that 300 million people are infected every year, that 1 [million] to 3 million people die from it -- and most of those are children. I'd say with those numbers, we have to at least consider using everything available."