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Target Malaria wants to end the disease transmitted by mosquitoes using genetic units



Mosquitoes are the deadliest animals in the world and kill millions of people each year by infecting them with diseases such as malaria, dengue fever, West Nile virus and Zika.

Malaria, the deadliest of these diseases, causes more than 430,000 deaths per year. It used to be even more common, but a combination of new drugs and insecticides led to a sharp drop in the early 2000s.

That fall has stagnated since then, according to the World Health Organization. The global malaria rate has not changed much since 2013, largely because the affected areas are not receiving sufficient funds to fight the disease. Over time, mosquitoes also develop resistance to existing insecticides.

Many scientists agree that a new approach is needed to eliminate the disease, and a group of nonprofit Target researchers think that genetic modification through "genetic units" is the way to do it. This process would reduce the number of female mosquitoes that transmit malaria.

Target Malaria is not the only organization that experiments with genetically modified mosquitoes, but its members believe that they will release their technology first. The group has already selected three locations in Africa as test sites.

Genetic units, which can change a gene to produce a specific trait that will be displayed in a population for many generations, have generated controversy in recent months. After much debate, a United Nations group ruled in November 2018 that genetic drive research could continue for the time being, although limitations have been established.

"We are on the cusp of a new biological revolution," a UN official who requested anonymity told The Guardian. "It's like we're using saws but now we're using scalpels, we can eradicate whole species and we can resurrect them like Jurassic Park, the change is amazing, but it does not always work 100%, there may still be unintended consequences."

Delphine Thizy, manager of stakeholder participation in Target Malaria, told Business Insider that the group will not change its work in the light of the UN resolution, as the language reinforces what its team is already doing .

"It is a good text because it is really balanced between these needs to continue the investigation and make sure that we can answer the questions, the very valid questions about safety and efficacy and, at the same time, provide some caution to ensure the risk The evaluation is done, "said Thizy.

People queue outside a health center while waiting to receive treatment for malaria, in San Felix, Venezuela, on November 10, 2017.
William Urdaneta / Reuters

How technology works genetic unit

There are thousands of mosquito species in the world, but very few represent a danger to humans.

Male mosquitoes do not bite humans; Only women infected with a virus or parasite can transmit this infection to people because they drink human blood to collect nutrients that help them produce eggs.

To reduce the number of female mosquitoes that infect people with malaria, Target Malaria scientists are focusing on a technology called CRISPR, which makes efficient DNA editing possible.

Generally, only 50% of the descendants of each generation inherit the DNA that is transmitted from one of the parents, which means that the frequency of a trait in a population of mosquitoes remains the same from generation to generation. Genetic units, however, are inherited by a higher percentage of descendants, which makes the modified trait more common as time passes.

Target Malaria aims to reduce the mosquito population without killing an entire species. The non-profit organization only chases the Anopheles gambiae mosquitoes that are responsible for the vast majority of malaria deaths in Africa, while leaving others alone.

"We are not trying to extinguish them, nor do we think it would be possible," said Thizy.

An Indian vegetable vendor sells potatoes during the spraying smoke that is being carried out to prevent the spread of mosquito-borne diseases in Allahabad, India, on November 1, 2018.
Ritesh Shukla / NurPhoto a via Getty Images

Target Malaria wants to test gene units in three African countries

Thizy's team is considering two main approaches: One could bias the sex ratio of mosquitoes to produce a population with at least 90% of men. Another objective would be the genes responsible for female reproduction to cause sterility.

These ideas are still being developed in the laboratories. So far, the group has succeeded in reducing the number of mosquitoes in a small cage, Thizy said.

Read more: Malaria mosquitoes disappeared in laboratory trials of the genetic unit technique

Finally, Target Malaria says it will apply a genetic unit in three African countries: Mali, Burkina Faso and Uganda.

In Uganda, the organization hopes to open a laboratory building soon, Thizy said. The group is also studying wild-type mosquitoes to better understand how they behave.

Regulators in Mali are reviewing the application of Target Malaria for the use of sterile male mosquitoes in a laboratory. Thizy said that these mosquitoes are not a tool to fight malaria, but introducing them now can help scientists prepare for the use of genetic units later on.

Target Malaria also obtained permission to import sterile male mosquitoes to Burkina Faso. About 10,000 male mosquitoes now await their release, and Thizy said he expects them to leave sometime this year. Regulators and local residents have approved the test, he said.

Thizy said Target Malaria will request permission to launch the first genetic unit in 2024 as soon as possible, adding that he does not know how long it will take officials to approve the request.

"We are not anywhere near making any version of genetic units in Africa or anywhere else," he said.

Bill and Melinda Gates Foundation co-chair Bill Gates speaks at the World Bank / IMF spring meetings in Washington on April 21, 2018. The Gates Foundation has donated approximately $ 2 billion in grants to help to fight malaria.
AP Photo / Jose Luis Magana

Other new companies are also developing ways to eliminate mosquito-borne diseases

Bill Gates is betting on Target Malaria to succeed, and his foundation has donated at least $ 75 million To the group.

But other companies are also competing to control mosquito populations and eradicate diseases caused by the insect, including dengue fever and West Nile virus.

Verily, the life sciences unit of Google's parent company, Alphabet, is targeting Aedes aegypti mosquitoes, which spread dengue fever and chikungunya in the tropics. Verily is infecting male mosquitoes with the Wolbachia bacterium, which prevents hatchlings from hatching.

Another company backed by Gates, Oxitec, is developing a male mosquito that can kill future generations of women who transmit malaria.

The most recent plan of the company based in the United Kingdom is based on its previous trials, which decreased the populations of mosquitoes that carry dengue, Zika and other diseases. Oxitec mosquitoes have been sent to Brazil, Panama and the Cayman Islands, and have reduced wild mosquito populations by around 90% in certain places.

However, these techniques are not perfect. In November 2018, the Cayman Islands suddenly suspended the future release of genetically modified mosquitoes in the area without giving a reason.

Some scientists say that malaria can be eliminated without genetic modification

Ify Aniebo, a molecular geneticist who focuses on resistance to anti-malarial drugs and has lived in Nigeria, wrote in Scientific American that Africans should Having been consulted before GM mosquitoes first developed, he added that scientists must complete more studies on the safety and consequences of this technology.

It is not clear if the introduction of these mosquitoes could cause the appearance of new diseases. Aniebo said that genetic modification is not necessary to eradicate malaria, pointing to Sri Lanka, which was declared malaria-free in 2016 without the use of such technology.

However, Thizy said it is imperative to develop a new tool for malaria control, since spending more money on insecticides and other existing methods will not work.

He said that Target Malaria asks the residents of the village to give their consent before performing any tests. There is no evidence to suggest that any species relies on mosquitoes as the main source of food, he added, although Target Malaria will work independently to confirm that.

"If there were one, suppose, the question for society and regulators would be: is this species that could be affected important enough not to try a new tool for a disease that kills half a million people?" Said Thizy. "And that's a social decision."


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