Researchers have rendered a population of mosquitoes in a lab sterile using the gene-editing tool CRISPR-Cas9 by homing in on a specific target in insect DNA — the doublesex gene — raising the possibility of eradicating disease-carrying species of the insect entirely, according to a new study published Monday in Nature Biotechnology.
In the study, scientists at Imperial College London used the technology to wipe out a population of caged mosquitoes that are able to transmit malaria, targeting a genetic sequence that leads to male and female traits. After a number of generations, they found that 100% of these mosquitoes were affected.
‘The difference in the gene content between male and female is very, very minimal’ in mosquitoes and humans alike, said study author Andrea Crisanti, professor of molecular parasitology and microbiology at Imperial College London.
Doublesex, as the name implies, controls how mosquitoes differentiate into male and female. Females with two copies of the mutated gene didn’t develop properly and couldn’t reproduce, while males developed normally and continued spreading the mutation. Mutant females also failed to develop the long, needly proboscis they need to bite humans and suck blood.
What’s more, the experiment seemed to succeed where others have failed — the spread of these mutant genes was not thwarted by the mosquitoes developing resistance.
‘We have selected a target site that cannot be mutated or changed by the mosquito without paying a high price,’ Crisanti said.
The researchers note this doesn’t necessarily prove their methods are ‘resistance-proof.’ Experts say this could play out very differently outside small, confined spaces and among many other species of mosquitoes — only some of which carry the parasite that causes malaria.
But even when it comes to suppressing or extinguishing a species of mosquito, are we opening Pandora’s Box and releasing something into the world we don’t fully understand? Or will the only major impact be a positive one for humans while other organisms — less harmful ones, ideally — take these bugs’ place in the ecosystem?
‘That’s an open question,’ said Catherine Hill, professor in the department of entomology at Purdue University. ‘We’re very interested in protecting human health, but at the same time protecting the environment.’
Hill said we’re still untangling how mosquitoes fit into the food web and environment at large. Larvae, for example, are sources of food for some fish — including the mosquitofish. ‘I don’t believe that we know the answers to these questions yet,’ Hill said. ‘We try to anticipate unintended consequences.’
But a gene like doublesex, while ubiquitous among insects, has evolved differently across species, so it may be possible to launch a genetic attack on one species without affecting another. Experts say the focus, then, is not on swatting down all mosquitoes — just the small fraction that pesters humans and transmits debilitating and deadly diseases.
‘There are more than 3,000 species of mosquitoes in the world, most of which do not feed on people,’ Bob Peterson, professor of entomology at Montana State University and vice president of the Entomological Society of America, said in an email. ‘It is not practical or desirable — indeed it’s not even possible — to wipe out all populations of all mosquito species. No one is seriously contemplating that.’
‘The African malaria mosquito is the most dangerous animal on earth,’ said Conor McMeniman, assistant professor at the Johns Hopkins Malaria Research Institute. ‘New technology that could help to specifically and efficiently control this plague on humanity is welcomed, but I would caution that we need to carefully test this and also engage communities at risk to see what their attitudes are.’
The World Health Organization estimates 216 million cases of malaria in 2016 and 445,000 deaths, with children under age 5 among the most susceptible.
HISTORY OF FIGHTING INSECT DISEASE CARRIERS
Health experts and entomologists have long been focused on fighting disease-causing mosquitoes, but ‘insect pests have the uncanny ability to adapt to and overcome our best efforts to manage them and the harm they cause,’ Peterson said.
In recent years, scientists have infected another mosquito species with Wolbachia bacteria, sterilizing them. Many efforts have traditionally involved insecticides, which are far less targeted and can have detrimental impacts on surroundings and species nearby, McMeniman noted.
While experts are calling the new study a big leap in a positive direction, some anticipate ‘growing pains and unexpected results,’ in the words of medical entomologist Donald Yee, associate professor at the University of Southern Mississippi.
‘It’s going to be nearly impossible to eliminate mosquitoes of any species, given that doing so requires coordinated efforts of governments, scientists, and the public,’ Yee said. ‘With very few exceptions in human history, humans just have not been very good at eliminating mosquitoes, even for short periods of time.’
Yee said that the mosquitoes we’re really concerned about — the major vectors for diseases such as yellow fever and dengue — aren’t native to many places where they spread disease to humans. While few studies have held a magnifying glass to mosquitoes’ importance to their habitats, he doesn’t expect that eliminating them would hugely affect those environments.
Crisanti said he’s part of upcoming research on where mosquitoes sit in the food web, as well as how this gene-editing technology will work in spaces that better mimic tropical conditions — though it could be years before this is ever brought to market.
And time is of the essence, Hill said. In the next five to 10 years, she says scientists ‘absolutely have to come up with new technologies that are replacements for those earlier conventional strategies’ and that work in concert with each other.
With climate change and a growing human population, ‘I think we are going to see more epidemics’ of mosquito-borne illness, Hill said. ‘And we will see those diseases in places where we haven’t seen it before.’
‘It is a constant arms race between us and the mosquito and the pathogens it transmits,’ she added. ‘I don’t think it’s ever going to go away, and I don’t see one magic bullet.’