Scientists release controversial genetically engineered mosquitoes in a highly secure laboratory

Scientists have launched a major new phase in testing a controversial genetically modified organism: a mosquito designed to quickly spread a deadly genetic mutation for its own species, NPR has learned.

For the first time, researchers began large-scale dissemination of modified insects in a high-security laboratory in Terni, Italy.

"It will be a truly revolutionary experience," says Ruth Mueller, an entomologist who heads the lab. "It's a historic moment."

The goal is to see if mosquitoes could possibly be a powerful new weapon to help eradicate malaria in Africa, where most cases occur.

"It's very exciting," says Mueller.

NPR was the only press organization allowed to enter the lab to attend the launch of the press releases in early February.

NPR health correspondent Rob Stein was the only journalist in the laboratory in Italy when a major new experiment testing modified mosquitoes began. Ruth Mueller directs the laboratory. (Pierre Kattar for NPR)

The laboratory was specially built to evaluate modified insects in as natural a environment as possible without the risk of by releasing them into the wild, which raises serious concerns about unforeseen effects on the environment.

"This is an experimental technology that could have devastating effects," says Dana Perls of Friends of the Earth, an environmental group belonging to an international coalition that fights against this new generation of organisms. changed.

To prevent any unforeseen effects on the environment, scientists have always tried to prevent genetically modified organisms from spreading their mutations.

But in this case, the researchers want the change to spread. So they made mosquitoes with a "genetic drive".

"A gene drive is like a" selfish gene, "says Mueller, because it does not follow the normal rules of genetics – normally, traits are only transmitted to half of the children. , almost all descendants inherit the change.

"All children, all children – mosquito children – have this change," says Mueller.

A technician begins the experiment by placing dishes containing dozens of modified mosquitoes at the stage of pupal development in large cages containing hundreds of their unmodified counterparts. (Pierre Kattar for NPR)

The researchers created the mosquitoes using the powerful new gene editing technique called CRISPR, which Mueller likens to a "molecular scissor capable of cutting at a specific site of DNA".

The cut has altered a gene called "double sex", implicated in the sexual development of mosquitoes.

The modified adult mosquitoes appear in a few days and begin to mate with their unmodified counterparts. Scientists hope to be able to transmit their mutation, thus sterilizing mosquitoes that spread malaria. (Pierre Kattar for NPR)

"Women are getting a little more masculine," says Mueller. "A kind of hermaphrodite."

Although genetically feminine, transformed insects have a mouth that look like the mouth of male mosquitoes. This means that they can not bite and therefore can not transmit the malaria parasite. In addition, the reproductive organs of insects are deformed, which means that they can not lay eggs.

As more and more female mosquitoes inherit two copies of the modification, more and more become sterile.

The idea is that if these modified mosquitoes eventually prove safe and effective, they could one day be released in African villages hit by malaria. The hope is that they propagate their mutation and eventually sterilize all females. This would crush – or significantly reduce – local populations of the main mosquito-spreading mosquito species known as Anopheles gambiae.

"Malaria is a huge problem that probably affects two-thirds of the world's population," said Tony Nolan, who contributed to mosquito development at Imperial College London. He is now at the Liverpool School of Tropical Medicine.

Tony Nolan (left) of the Liverpool School of Tropical Medicine and Andrew Hammond of Imperial College London participated in the creation of modified mosquitoes. (Pierre Kattar for NPR)

Malaria strikes more than 200 million people each year and kills more than 400,000 people, mostly young children.

Scientists believe that genetic organisms could help solve many problems, including the elimination of other diseases transmitted by insects such as Zika and dengue fever. Genetic creatures could also save endangered ecosystems by eradicating invasive rodents. They could help feed the world by creating more efficient crops.

But critics fear that genetic organisms will go crazy and wreak havoc if released into the wild. Insects could inadvertently have a negative effect on crops, for example, by eliminating important pollinators, they fear. The fall of the insect population could also bring other mosquitoes to come with other diseases, critics say.

"We can not take this extermination technology lightly," says Perls. "We have to slow down, we have to press the pause button on the gene drives."

Some activists in Africa are in agreement.

Scientists use a microscope to see if genetic modification is spreading. Modified immature mosquitoes glow with yellow eyes when they are illuminated by laser. (Pierre Kattar for NPR)

"It's a technology where we do not know where it's going to end, we need to stop where it is," said Nnimmo Bassey, director of the Mother Earth Health Foundation in Nigeria. "They are trying to use Africa as a large laboratory to test technologies at risk."

The experience is a key milestone of the Target Malaria project. The main funder of the project is the Bill & Melinda Gates Foundation, which also supports NPR. and this blog.

Nolan and Mueller said the project was working methodically and cautiously to evaluate mosquitoes in close consultation with scientists, government officials and local residents in Africa. In addition, genetic mosquitoes would affect only one of hundreds of mosquito species.

"There will be problems with any technology, but I do not think you should throw away technology without doing your best to understand its potential for transformation into medicine." And if it worked, it would be revolutionary, "Nolan said.

Other experts are in agreement.

Genetically modified mosquitoes can quickly transmit their mutation. Normally, traits are only transmitted to half of the children. With the gene reader, almost all the descendants inherit the modification. (Pierre Kattar for NPR)

"If my children were living in Africa, I would say, 'Go as fast as you can,'" says Kevin Esvelt, an evolution engineer at the Massachusetts Institute of Technology.

Esvelt is a gene-dependent pioneer who has repeatedly advised scientists to be cautious in the use of this technology because it is so powerful. But Esvelt thinks that Target Malaria acted responsibly.

"The known damage from malaria outweighs the combined damage of all that has been postulated, which could go wrong ecologically," Esvelt said.

The project provides for years of additional studies to assess mosquitoes and their potential impacts on the environment, as well as social and political consultations with a view to reaching consensus on cases in which release would be permitted. It's probably in at least five years, says Nolan.

On the day of NPR's visit to Terni's lab, Mueller introduced several levels of safety at the lab to prevent mosquitoes from escaping. She noted that the experiment is conducted in Italy, where this species of mosquito could not survive the climate, even if the insects had escaped.

"We really want to show that we are working very seriously and responsibly with this new technology," said Mueller.

To get into the safest part of the installation, Mueller grabs a security code into a keypad to open a sliding glass door. When the door closes, a powerful fan prevents the escape of genetically modified mosquitoes. Anyone who comes in should put on a white coat to help identify mosquitoes that might come out of the lab and go through a second sealed door and a fan.

Once inside, Mueller points a small container in white mosquito net. Inside are dozens of mosquitoes.

"Here we have genetically modified mosquitoes – these genetically modified mosquitoes," she says.

The insects quickly crushed populations of their natural counterparts in small cages in a secure laboratory in the basement of Imperial College London. The new experiment is designed to test them in a hot, humid environment that looks more like their natural habitat in the African countries where this species of mosquito lives.

"It helps us better understand the actual workings of a gene publication," she says.

Mueller goes to a large, thick metal door.

"We will now enter the experimental room where the release is taking place today," she said.

The room houses six huge "cages". The walls of the cage, from a height of 9 feet, are made of white mosquito net to contain insects. The net extends from floor to ceiling. Each cage contains hundreds of unmodified mosquitoes.

Technicians add modified mosquito nymphs and warm cow blood into large unmodified mosquito cages to begin the experiment for a period of one year. (Pierre Kattar for NPR)

Each cage is equipped with several features designed to replicate the conditions in which mosquitoes live in the wild. The idea is to encourage the natural behavior of mosquitoes.

The characteristics of the cages include piles of hollow cylinders made of moist clay that mosquitoes can use as shelters. In addition, large black boxes with a white background are inside the cages. Contrasting colors stimulate swarming, ie mating of mosquitoes.

A computer precisely controls the light in the room to simulate sunrise and sunset and natural changes of intensity and color throughout the day.

"OK, we can start," Mueller says as several of his colleagues gather in the room.

After donning rubber gloves, Chief Technician Tania Persampieri carefully picks up a tray of glass dishes, each containing dozens of modified mosquitoes at the stage of pupa development. They wriggle in the water.

Persampieri slowly walks towards the first cage, squats and picks up one of the dishes containing the nymphs. She gently slips the dish through an opening in the net that prevents insects from escaping and places the boat on the ground.

Within a few days, the modified mosquito pupae will appear as adult mosquitoes and begin to propagate their lethal change. (Pierre Kattar for NPR)

"The experiment has now begun," says Mueller. "It's very exciting."

Persampieri and his colleagues move slowly to avoid unnecessarily stressing mosquitoes.

Persampieri releases immature genetically-driven mosquitoes in four of the six cages. Two cages receive amounts equal to 25% of the unmodified populations already present in the cages; two cages receive amounts equal to 50 percent. The remaining two cages will be used for comparison purposes and will not receive any modified insects.

Other technicians slide cans of warm cow blood into each cage.

"We heat the blood because it's attractive to mosquitoes, they do not like cold blood, they want to have a live animal where they can bite," says Mueller.

As the researchers finish, the lights in the cage chamber begin to go out.

"It's a slow gradation but also a specific light color – very orange, very hot – so that they really feel like [they’re] to have a sunset, "says Mueller.

This is essential because the sunset is when the male mosquitoes start their mating dance.

"Males make swarms – a lot of male mosquitoes move around," says Mueller. "It sounds a bit like dancing."

When males swarm, females arrive and choose a male; then the pair flies to mate.

"They make a couple and make babies," says Mueller.

Mueller and his colleagues collect thousands of eggs in the cages each week to monitor the progress of the sterilizing mutation.

The researchers hope to know in six months to a year if the modified mosquitoes are dancing well enough to effectively propagate their lethal modification in the wild.

"Maybe you can already see if you get closer," said Mueller, pointing to some mosquitoes that started flying in the black boxes.

It turns out that Terni is home to a Valentine's Day sanctuary. And the experience begins just before Valentine's Day. Thus, the annual celebrations of the basilica for Valentine's Day are just beginning with a religious service in his sanctuary.

While she's watching the modified mosquitoes start their first mating ritual in her lab, Mueller laughs, laughing: "It's very romantic."

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