by Ian Sample
An Anopheles stephensi mosquito feeding on a human host. A known carrier of malaria, the species can found from Egypt all the way to China. Photograph: Jim Gathany / CDC
Hundreds of genetically modified mosquitoes that are incapable of spreading the malaria parasite to humans have been created in a laboratory as part of a radical approach to combating the disease.
The move marks a major step towards the development of a powerful and controversial technology called a “gene drive” that aims to tackle the disease by forcing anti-malarial genes into swarms of wild mosquitoes.
The procedure can rapidly transform the genetic makeup of natural insect populations, making it a dramatic new tool in the fight against an infection that still claims over 400,000 lives a year. The same technology is being considered for other human diseases and infections that devastate crops.
“This is a significant first step,” said Prof Anthony James at the University of California, Irvine. “The mosquitoes we created are not the final brand, but we know this technology allows us to efficiently create large populations.”
But gene drive technology is so powerful that leading researchers have urged scientists in the field to be cautious. A warning published in August in the prestigious journal Science, by teams in the UK, US, Australia and Japan, said that while gene drives have the potential to save lives and bring other benefits, the accidental release of modified organisms “could have unpredictable ecological consequences.”
They call on scientists to ensure that experimental organisms cannot escape from their labs, be released on purpose, or even find their way out accidentally in the event of a natural disaster. Researchers should also be open about the precautions they take to prevent an unintended release, they said.
In the latest study, mosquitoes were engineered to carry genes for antibodies that target the human malaria parasite, Plasmodium falciparum. When released into the wild, researchers believe the modified insects will breed with normal mosquitoes and pass the anti-malarial genes on to their young, making an ever-increasing proportion of future generations resistant to the malaria parasite.
James and his team used a genome editing procedure called Crispr-Cas9 to write anti-malarial genes into the DNA of eggs belonging Anopheles stephensi mosquitoes. A major carrier of the malaria parasite in Asia, the strain is responsible for more than 10% of malaria cases in India.
In lab tests, the modified mosquitoes passed on their anti-malarial genes to 99.5% of their offspring, suggesting that the procedure was incredibly effective and efficient. To track which insects inherited the antibody genes, the scientists added a tracer gene that gave carriers red fluorescent eyes.
James, who signed the warning in Science, said more work was needed to perfect the gene drive before modified insects can be tested in field trials. But describing the experiments in Proceedings of the National Academy of Sciences, he wrote: “Strains based on this technology could have a major role in sustaining malaria control and elimination as part of the eradication agenda.”
Dr Simon Bullock, a geneticist at the MRC’s Laboratory of Molecular Biology in Cambridge, helped to perfect the use of Crispr genome editing in flies, and also signed the call for safeguards over gene drive research. “Gene drive technology has great potential to help tackle malaria and other global problems in public health. But the ability of genetic changes to spread rapidly in the wild population means that great caution should be taken when building gene drive systems in the laboratory.
“Accidental or malicious release of a gene drive system into the wild could have unpredictable ecological consequences and thus researchers must use multiple safeguards that are robust to human error and nefarious actions. Fortunately, several safeguarding strategies are already available,” he said.
But Bullock, who was not involved in the research, was surprised that the California group had not described the safeguards they put in place to ensure the mosquitoes did not escape. “Given the highly sensitive nature of this technology and their call for transparency in this area of research, I’m flabbergasted that the authors have not disclosed in the publication detailed information on the containment procedures used in this study and how they were evaluated,” he added.
Prof Anthony Shelton who studies pest management at Cornell University in New York said the California-based team was justified in its optimism over the procedure. “Before open field tests, they need to test their insects in small arenas and field cages to determine the potential for it to work on a larger scale,” he said. “In theory this technology should work in the field, but further tests are needed and only then will the full potential of this breakthrough be realized for the benefit of humanity.”
Prof Gregory Lanzaro at University of California, Davis added: “Concern that drug and insecticide resistance are eroding recent successes in managing malaria has drawn attention to alternative approaches, including the use of genetically modified mosquitoes. This new study marks a significant advance toward the development of this strategy.”