Health & Medicine

A revolutionary genetic experiment is coming to rural Burkina Faso

Lede STAT.jpeg

Kadidia Ouattara, who lives in the city of Bobo-Dioulasso, teaches her neighbors about genetically engineered mosquitos that might eliminate malaria.
Credit:

Ike Swetlitz/STAT

This story was originally published on STAT.

BANA, Burkina Faso — This small village of mud-brick homes in West Africa might seem the least likely place for an experiment at the frontier of biology.

Yet scientists here are engaged in what could be the most promising, and perhaps one of the most frightening, biological experiments of our time. They are preparing for the possible release of swarms of mosquitoes that, until now, have been locked away in a research lab behind double metal doors and guarded 24/7.

The goal: to nearly eradicate the population of one species of mosquito, and with it, the heavy burden of malaria across Africa.

These scientists are planning to release mosquitoes equipped with “gene drives,” a technology that overrides nature’s genetic rules to give every baby mosquito a certain trait that normally only half would acquire. Once such an insect gets out into the wild, it will move indiscriminately and spread its modified trait without respect for political borders.

No living thing — no mammal, insect, or plant — with a gene drive has ever been set free. But if all goes as planned, it might happen here, in a remote village of about a thousand people, where the residents don’t even have a word for “gene.”

Despite such barriers, this is in some ways the most logical place to carry out the experiment. Nowhere does malaria exact a higher toll than here in sub-Saharan Africa, where hundreds of thousands die from the disease every year. And Burkina Faso already houses one of Africa’s highest-profile malaria research laboratories.

It may be six years before the gene drive mosquitoes are actually released in Burkina Faso, but scientists are already working around the clock to prepare the community for their release. Researchers in Mali and Uganda are also working toward the same goal under the banner of the “Target Malaria” project, propelled by $70 million from the Bill and Melinda Gates Foundation and support from research laboratories in England and Italy.

Speaking through interpreters, residents across Burkina Faso told STAT that they are grateful for the scientists’ work, and are eagerly looking forward to eliminating the dreaded disease.

But scientists still face a challenge: making sure that people understand and accept the newfangled genetic technology behind it all. That means building trust and doing basic education — explaining not only the impact of genetically engineered insects arriving in their homes, but also what genetics is in the first place.

                                                               *****

Driving west from Bobo-Dioulasso, the sleepy regional capital that is Burkina Faso’s second-largest city, the pavement fades away into an undulating dirt path. Traffic dissolves into a trickle of motorbikes whose drivers wear surgical-style masks to protect them from the dust. Donkey carts plod along under the weight of flattened grass, outpacing camels weighed down by saddlebags.

At the height of the dry season in late December, eight scientists and social scientists pulled off the dirt road, carrying a box of a hundred adult mosquitoes and a 1-liter bottle filled with wriggling larvae.

For the past few years, the scientists from the Institut de Recherche en Sciences de la Sante (IRSS) in Bobo-Dioulasso, where the country’s Target Malaria team is based, have been teaching Bana residents basic mosquito facts, including that the bugs transmit malaria. Many in Burkina Faso believe that malaria can be spread by eating too many greasy or sweet foods, said Lea Pare, the anthropologist who is leading a national effort to engage local citizens in Target Malaria.

Beyond live mosquitoes, the team also uses pictures to help explain the complicated scientific information: a set of thirteen cards, laminated like giant placemats, which detail the different phases of the project. In Bana, they talk through the first four of these cards, which show gigantic female mosquitoes biting humans, with small red squiggles flowing through the proboscis and into the person’s body. On the fourth card, a scientist wearing a white coat is looking at those mosquitoes under a microscope.

White coats are very familiar to residents of Bana. For the last three years, a team of researchers has lived part-time in the village, sleeping in an old cement house retrofitted into a scientific base camp. These technicians, with the help of local volunteers, count the number of mosquitoes in the homes, observe the mating swarms at dusk, and dust mosquitoes with colored powder to track where they travel around the village.

They are gathering data on the mosquito population to feed into intricate computer models that will help them determine how the gene drive mosquitoes should be released.

When the technicians stepped into one home on a recent day, they laid thick sheets across the floor of a bedroom and filled it with acrid-smelling insecticide spray. After 10 minutes, they hauled the sheets out, opened them up, and crouched over a small pile of dirt specks: only one male mosquito.

For low mosquito season, it wasn’t surprising. During the rainy season, however, which starts in June, there might be a few hundred mosquitoes in each room, said technician Ibrahim Diabate.

Men living in the treated homes were excited, even jubilant, that the researchers were working in the village. They understood that the scientists had a longer-term plan to battle the mosquitoes, but they were also happy for the insecticide spray in the present moment.

“Since you started this work, praise God, malaria has been reduced, because mosquitoes don’t bite us anymore,” said Ali Ouattara, one elder in the community.

In the next phase of the project, scientists will have to explain to Ouattara why they’re actually releasing more mosquitoes.

Going straight from zero to gene drives would be too extreme, so scientists are planning to release “regular” genetically engineered mosquitoes first — either here in Bana or in one of two other villages nearby.

Those mosquitoes, which could be released next year, are “sterile males”: Most of them are male, and they cannot have offspring. A field release is not intended to reduce the prevalence of malaria; rather, it is to prepare the scientists and the locals for the eventual arrival of the gene drive mosquitoes, said Delphine Thizy, who directs the work of engaging local, national, and international leaders for the project.

The outreach teams have started talking about DNA with their flash cards. But they aren’t saying anything yet to the locals about the much more powerful, and complicated, idea of a gene drive.

Partly that’s because researchers didn’t want the residents of Burkina Faso to expect that a miracle solution to the malaria epidemic is just around the corner, Thizy said. Scientists in London haven’t yet created the gene drive mosquitoes that would be used, and field trials of such mosquitoes are years away.

Also, she said, gene drives are hard to understand.

“To be fair, even in Europe and in North America, it’s complex to understand gene drives in one shot.”

If gene drive mosquitoes arrive in Burkina Faso, it will be thanks to the vision of Abdoulaye Diabate, a soft-spoken medical entomologist with a singular mission: to stop malaria.

The disease is ever-present in this country — mosquito nets hang for sale by the roadside, and hotel proprietors lay out smoldering coils in the courtyards to ward off mosquitoes as dusk falls.

Diabate, who is deeply involved in malaria eradication efforts worldwide, became dismayed when, in the 1990s, he realized that mosquitoes were building up resistance against the insecticide used on bed nets here.

“If this is the only tool we have in hand, then forget about malaria elimination,” Diabate said.

But, in 2012, he received an invitation to a meeting about the Target Malaria project, which was focused on solutions involving genetic engineering. He jumped at the chance.

Today he is leading the Burkina Faso team, trying to get the whole world — from remote villages to international diplomats — on board with his ambitious research.

Meanwhile, thousands of miles away in the United Kingdom, geneticists at Imperial College London are working on designing the gene drive mosquitoes. Specifically, they’re studying two different ways to disrupt the reproductive system of one particular species, Anopheles gambiae: reduce the number of female babies (only females bite and spread the disease) or stop the mosquitoes from having offspring in general.

To make the population predominantly male, Austin Burt, Target Malaria’s primary investigator, and collaborators are studying an “X shredder” — a gene that destroys the X chromosome in sperm, making all offspring males. Alongside that, they’re looking at reducing the number of mosquitoes of both sexes by creating genes that make them sterile.

Either approach might lead to massive population collapse within two to eight years, according to Charles Godfray, a University of Oxford professor and biologist who works on modeling for the Target Malaria project.

But the insects wouldn’t go extinct, scientists say. The gene drive mosquitoes currently under consideration would only reduce the population of Anopheles gambiae enough to stop the transmission of malaria.

“The foundation is not interested in eliminating Anopheles mosquitoes,” said Dr. Scott Miller, who leads malaria research and development for the Gates Foundation. “We’re interested in eliminating malaria.”

It will take years to reach the point that scientists will be ready to test the gene drive mosquitoes in the wild. In the meantime, they are facing the challenge of winning over local residents who might be wary of these new creatures.

Mariam Pare was initially frightened. A commanding woman who teaches in a Koranic school, Pare lives across the street from the IRSS in Bobo-Dioulasso. She said that when she first heard about mosquito research going on at the lab, she feared that the scientists were breeding mosquitoes to let loose on the locals. But after meetings and discussions with project staff, she came to understand that they are instead trying to fight against the mosquito.

She even took a tour of the insectary that currently holds the gene-edited sterile male mosquitoes, and could eventually hold the gene drive ones. She saw fans that would suck away mosquitoes if they happened to escape from their cages, and a hot water bath where unnecessary mosquitoes go to die.

“Because I saw what was going on in there, I believe and trust the people that work in there,” she said.

Earning Pare’s trust was particularly important for the team — because she lives so close to the insectary, her consent was required to import the sterile male mosquitoes. That requirement isn’t a legal one, but one that the Target Malaria project has put in place. The Gates Foundation has also said that gene drive mosquitoes will only be released if the host country agrees.

Lassina Diarra, a tailor whose turquoise-walled shop is down the road from the research lab, also had to give his consent. Sitting on the corner of a table among scraps of fabric and hand-tailored suits, he said that he was impressed by the scientists’ transparency and reliability. Two outreach workers recruited him to serve on a group of 12 local leaders who communicate information about the project to the city’s residents, dubbed the “relay group,” along with a different committee to address community grievances. Every few weeks, he knocks on doors up and down the streets, updating his neighbors on the scientists’ progress.

In June, Diarra and Pare both signed off on the arrival of the sterile males. So did Kadidia Ouattara, one of the relay group members and the president of multiple neighborhood associations. She recalled a joyous gathering filled with dance and song.

“Ni fonyon douma ni bora mi?” they sang in Dioula. “Ni fonyon douma ni bora mi?”

The song translates to, “Where did this good air come from?” and, more colloquially, means, “This is too good to be true!”

Ouattara said that it is a traditional song commemorating good news — a wedding, the birth of a baby, the success of a student in her exams. And on that day, it was celebrating the impending arrival of genetically modified mosquitoes.

Burkina Faso has experience with genetically modified organisms. One of the first associations some residents make with genetic engineering is Monsanto, which has been selling genetically modified cotton seeds to Burkinabe farmers since the 2000s. But the country’s grower’s association stopped buying the seeds in 2016 in the wake of concerns about the cotton’s quality and country-wide protests against the company.

One resident of Bobo-Dioulasso complained that genetically modified food rots quickly, and said that he hopes the mosquitoes suffer the same fate: an early death.

“The fight against malaria is a big concern, but the solutions are sometimes scary,” said Sylvestre Tiemtore, the director of an organization that represents over half of the nongovernmental organizations in Burkina Faso. The group met with Target Malaria in July, a discussion which “was very heated,” he said.

“In movies” — he cited “Jurassic Park” — “we’ve seen some research that went out of control,” he said.

Anopheles gambiae

The mouthparts of a female Anopheles gambiae mosquito. (Jim Gathany/CDC)

Scientists familiar with the effort here say defining the idea of “genetically modified” to residents here might be of limited use, because it won’t help people understand what the mosquitoes are or what they will really do, said Javier Lezaun, deputy director of the Institute for Science, Innovation, and Society at the University of Oxford, who is not involved in the Target Malaria project. In fact, the phrase might just serve to distract and scare — he spoke of another community in Tanzania who thought that a swarm of mosquitoes that invaded a hospital were genetically modified (they weren’t), and of others in Brazil who thought that Zika arrived as a result of genetically modified mosquitoes (it didn’t).

“As long as you explain something about the specific capabilities of the mosquitoes, or the limitations of these particular mosquitoes and how they’re supposed to behave in the wild or in the facilities, I think that serves the purpose of explaining genetic modification,” Lezaun said.

And that’s what many people are curious about. At the July meeting with NGOs, hosted by the Secrétariat Permanent des Organisations Non Gouvernementales (SPONG for short), attendees wanted to know: What would happen to the local ecosystem? And might these engineered mosquitoes be able to transmit other diseases?

Some of these questions don’t yet have answers, but others do. A risk assessment commissioned by the Foundation for the National Institutes of Health, a US nonprofit that supports the federal agency, found that the risk of the sterile mosquitoes currently in Bobo-Dioulasso transmitting other diseases was incredibly low; the modified mosquitoes probably won’t spread more malaria than their wild cousins; and the genetic modification probably won’t spread from the mosquito to other animals.

Outside scientists, convened by the FNIH in May, had previously concluded that Anopheles gambiae is not a “keystone” species, meaning that if its population shrank dramatically, the ecosystem would not be substantially impacted.

But the meetings continue. Tiemtore, SPONG’s director, said that he would like to have a meeting with representatives of different health-related NGOs that are based in Burkina Faso’s 13 different regions, to educate them about the project. But that requires money — to bring them to the capital, and to cover the costs of the meeting itself.

“They might need to rent a room,” Tiemtore said. “They might need to offer some coffee breaks. That costs money. Who pays for that? If you don’t do all of those things, your mosquitoes are going to come out, but they won’t be released in the regions, because the people will not agree with it, because they didn’t have enough information on it, and they will have the right to be afraid.”

The development of powerful new genetic engineering technologies, often outstripping regulators’ ability to keep up, is forcing scientists to reckon with the ethics of their work in a new way.

Of course, humans have been making potentially irreversible changes to our environment for a long time: clearing forests for farming, building power plants that change the composition of the atmosphere, and producing untold tons of synthetic materials like plastic that will stay in the environment for hundreds of years.

But gene drives lend these questions a different sort of urgency. The genetic technology can quickly change the properties of an entire population of a species, undoing millennia of evolution in a handful of years. And once you let them out of the cage, there’s no going back — other world-altering technologies have not been self-perpetuating like gene drive animals would be.

So scientists are treading carefully and doing what they can to keep the rest of the world involved. This has led to difficult questions: Who needs to give them permission to do certain things? What does it mean for residents to be fully informed? In answering them, there aren’t a lot of models to follow. There are only a few gene drive projects underway in the world, and none has yet resulted in the release of the animals into the wild.

Academic research on how to effectively include non-scientists in global health decisions is also lacking, said Jim Lavery, an Emory University professor of global health and ethics who has worked with the Target Malaria project in the past.

Right now, Lavery said, scientists can count the number of phone calls they make and the number of people who show up at community meetings, “but we don’t even have an understanding at a proxy level of what those things are supposed to represent in terms of effectiveness of engagement.”

While researchers like Lavery are trying to determine how to measure success, research is plowing ahead. Some scientists are thinking about releasing gene drive mice halfway across the world, in New Zealand, to eliminate invasive species. And Kevin Esvelt, a gene drive guru based at the Massachusetts Institute of Technology, is flying to Argentina in September to talk about using gene drives to get rid of flesh-eating flies.

He has said that gene drives are more important as a societal tool to change the way that science is done — it should be open to and inclusive of the people it will impact. To that extent, he praised Target Malaria’s community work. “I honestly don’t see how you could do it any other way,” he said, citing the language and cultural barriers that the project is working to overcome.

How the project is going to introduce gene drive mosquitoes, though, is an open question. National regulators and international organizations like the World Health Organization are still working on developing guidelines for introducing gene drive animals.

And in Burkina Faso, Thizy said she hasn’t even yet put a lot of thought into what it will mean for local leaders to understand a release of gene drive mosquitoes. She said it will probably include knowing that the modified mosquitoes will stay in the environment and grow in number, until some point at which the population of Anopheles gambiae will be reduced.

But, said Thizy, exactly how the gene drive works may matter less to the people than the impact it will have on them and their lives.

She pointed, by way of analogy, to her previous work as a consultant for a mining company in the Ivory Coast: It wasn’t “how big is the hole, how many holes, and how does the machine work” that the area residents were worried about, she said, but rather how they would be compensated and what jobs would be created.

On a dusty Wednesday morning earlier this year, Kadidia Ouattara arrived at an outdoor market, eager to chat with the vendors about genetically engineered mosquitoes.

Kadidia Ouattara market
Kadidia Ouattara talks to neighbors at a vegetable market in the city of Bobo-Dioulasso about research on genetically engineered mosquitos that might eliminate malaria.
Credit:

Ike Swetlitz/STAT

As a woman spooned tomato sauce from a gigantic aluminum can onto plastic sheets for individual sale, Ouattara told her about the insect lab just a few minutes’ walk down the street.

The researchers who work there are trying to reduce the population of mosquitoes, she said. Don’t be afraid — I saw the inside of the lab and all of the research. There are public meetings where they explain what they are doing, and if there is another one, I will let everybody know.

The woman was delighted. May God help the project be a success, she said.

Farther along, she came upon a butcher who she knew to be particularly recalcitrant. He thinks we’re getting money from the white people, Ouattara said. But that’s not true — she’s a volunteer.

Ouattara walked up to the man, who was hacking at a piece of meat with a foot-long knife, bits of gristle flying everywhere and flies swarming. Rivulets of blood ran along the dusty ground.

If there is a meeting about the project, I am begging you to come, she said.

Scarcely taking his eyes off of the meat, the butcher mumbled some kind of assent.

Ouattara’s enthusiasm was undimmed; she strode off to a woman selling onions. And she’d be back soon with more news to share.

Eric Boodman and Kate Sheridan contributed reporting.

Special thanks to Housmane Sereme and Steve Sanou for translation services.