By Trina Wood
UC Davis vector biologist Greg Lanzaro is taking part in the newly-announced UC Irvine Malaria Initiative to genetically engineer new strains of mosquitoes to fight malaria in Africa. The project, led by UCI’s pioneering vector biologist Anthony James, will bring together experts in molecular biology, entomology, public health and community engagement from across the UC system.
They aim to develop a genetic approach to controlling malaria transmission by the mosquito Anopheles gambiae. The multimillion-dollar, multi-year effort is supported by a $2 million grant from the Bill & Melinda Gates Foundation, with additional support from the National Institutes of Health and other sources of funding.
Lanzaro has spent the past 35 years studying one of the deadliest creatures known to humankind—the mosquito. In particular, his research has focused on those species that transmit malaria and are responsible for nearly half a million deaths worldwide every year, 90 percent of them in Africa.
“Over the years, we’ve developed the technology to change the genetics of mosquitoes so that they can’t harbor or transmit the malaria parasite,” said Lanzaro, director of the UC Davis Vector Genetics Laboratory and professor in the Department of Pathology, Microbiology and Immunology in the School of Veterinary Medicine. “What we needed was a way to ensure that these genes would be expressed and spread through natural mosquito populations.”
Lanzaro said that when asked to comment on a November, 2015 paper appearing in Proceedings of the National Academy of Sciences that described “gene drive” technology, he thought, “wow, this is it!” This technique alters genes through the use of CRISPR, a gene editing tool, and ensures that all of the offspring from a parent carrying that copy will inherit that gene. It allows researchers to introduce genetic material into a wild population and have the frequency of that desired genetic trait carried through to successive generations at a nearly 100 percent success rate.
“I immediately emailed Tony James (author of the paper and a pioneer in creating genetically altered mosquitoes) to let him know if he was ever ready to take this to the field to let me know,” Lanzaro said.
Five minutes later, Lanzaro’s phone rang. It was James.
James and Lanzaro brainstormed ways of obtaining the funding that would be required for a project of this magnitude and what would be the first steps.
Identifying Field Sites for Trials
Before mosquitoes modified in the lab can be released in the wild, they need to be tested under controlled conditions. Lanzaro and James decided to identify field locations to test the efficacy of introducing new strains of mosquitoes that would not transmit malaria. They estimate it will take two years to identify a suitable site and another two to establish a field station and collect baseline data. Then another two to five seasons are needed to measure the impact of these new strains on mosquito populations in affected regions. The researchers will follow international and national regulations, and local people will have the final say in whether or not this strategy will be utilized.
“People have been talking about this strategy since the early 90s when I was a MacArthur fellow at the National Institutes of Health,” Lanzaro said. “But we have to go slow. We have to study this approach where it’s contained and we have a mitigation plan in place. I don’t think we could ever say with absolute certainty that something like this could be zero risk. On the other hand, a child dies every minute from malaria in Africa.”
As part of the project, UC Davis will receive $1.7 million for the first two-year phase aimed at identifying a field site. The best candidates so far look like oceanic islands where there is very little chance that the genetically modified mosquitoes could get to the mainland.
“Once you release these things into nature, that’s it,” Lanzaro said. “You can’t recall them. We want to do field trials in isolated areas, so if something does go wrong, you can go in and get rid of them using conventional mosquito control methods.”
The UC Davis research team will take a close look at the ecology of mosquitoes at different locations and narrow these down to four candidate sites. They will visit these sites, determine the density of mosquitoes there, but most importantly, look at the genetics of those mosquitoes to determine how isolated they are from mainland populations.
Lanzaro and his team have two years to identify the sites and another two to collect baseline data. If they can show the process works through this field trial, and all goes smoothly, they could release malaria-fighting mosquitoes to mainland populations in the future.
“This project is on the leading edge,” Lanzaro says. “It’s nice to be a part of something big like this that has the potential to save hundreds of thousands of lives.”
World Malaria Report 2016 (World Health Organization)
Malaria Strategy Overview (Bill & Melinda Gates Foundation)
Trina Wood is a communications officer for the UC Davis School of Veterinary Medicine. Twitter: @ucdavisvetmed