GM flies promise a good night

Amid global protests, scientists find a new way to control malaria by modifying mosquito sperm to produce only male offspring

By Kundan Pandey
Published: Sunday 31 August 2014


The thought of the world being rid of mosquitoes is enough to give many a good night’s sleep. The idea is close to being a possibility. Scientists from Imperial College, London, have successfully demonstrated a genetic vector control strategy that wiped out most of the female mosquitoes in a cage. The experiment was part of a research on dealing with malaria, a vector-borne disease spread by the bite of female mosquitoes.

In June, their research paper, published in the journal Nature Communication, established that wiping out mosquitoes by sterile insect technique is possible. In the experiment, scientists inserted a DNA-cutting enzyme, called I-PpoI, into the Anopheles gambiae mosquito, the most efficient malaria vector known. In normal reproduction, half of the sperms bear the X chromosome and produce female offspring, and the other half bear the Y chromosome and produce male offspring. The enzyme that the researchers used ensured that almost no sperm carried the female chromosome. As a result, the offspring of the genetically modified (GM) mosquito was almost exclusively male.

The mosquitoes were tested in a lab and it was found that the method created a fertile mosquito strain that produced 95 per cent of male offspring. This is the first time scientists were able to manipulate the sex ratio of mosquitoes. It took the researchers six years to produce an effective variant of the enzyme.

Nikolai Windbichler, lead researcher from the department of life sciences at Imperial College, says, “What is most promising about our results is that they are self-sustaining. Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially they carry out the work for us.”

The result has generated hope as morbidity and mortality from vector-borne diseases have posed significant challenges to public health. According to the World Health Organization (WHO), vector-borne diseases account for 17 per cent of the global burden of all infectious diseases. The most deadly vector-borne disease, malaria, caused 627,000 deaths in 2012. Dengue—the fastest growing vector-borne disease in the world—has seen a 30-fold increase in incidence over the last 50 years.

India has a dubious distinction in this area. The country bears a huge burden of mosquito-borne diseases, contributing 34 per cent of global dengue and 11 per cent of global malaria cases.

Commercial use

In April 2014, Brazil became the first country to commercially use GM mosquitoes. There, the strain has been developed by Oxitec, a UK-based firm. The concept involves engineering male Aedes aegypti in such a way that their offspring die before reaching maturity. This is done by injecting a lethal gene in the mosquitoes that develops a protein called tTA. When these mosquitoes mate with females, the offspring die before reaching adulthood.

Responding to a mail sent by Down To Earth, Hadyn Parry, CEO of Oxitec, says: “We first developed the product in 2002 and started lab testing. We went into the open environment in 2009. In all open trials, we have shown we can reduce the Aedes aegypti population by more than 90 per cent.”

Oxitec is considering India for its future projects. “We formed a collaboration with Gangabishan Bhikulal Investment and Trading Ltd (GBIT), a privately held Indian company, in 2011 to work specifically on bringing this technology to India,” Parry says. “We hope to obtain this (permission to conduct trials) later this year.” GBIT develops novel technologies for the health and agriculture sectors.

Row over modification

In Florida, people had protested when the idea of field trials was mooted. In April 2012, an online petition floated by a Florida resident, Mila de Miler, gave voice to fears of unknown consequences of the trial. It gave examples of unintended consequences of GM technology. It highlighted the dwindling population of the monarch butterfly in areas where GM crops are doused with ultra-high levels of herbicides that wipe out the monarch’s favourite milkweed plant. There are concerns over the unintended effects that might occur when GM mosquitoes bite humans. Similar concerns were raised when the idea was introduced in Malaysia. The US is yet to give a nod to Oxitec to conduct field trials.

Parry claims these protests are due to the perception created by GM crops. He said that while GM crops’ traits stay in the environment, the mosquitoes modified by his company are self-limiting. The released mosquitoes die, the offspring die and the gene does not remain in the environment, explains Parry.

India story

India has been a controversial ground for GM mosquitoes in the past. In the 1970s, WHO, along with the Indian Council of Medical Research, had initiated a malaria control programme by introducing sterile male mosquitoes, says Sujatha Sunil, a research scientist with the International Centre for Genetic Engineering and Biotechnology. The project was stopped after stiff opposition. Sunil says GM mosquitoes are safe. “Even nature modifies species according to need,” she says, adding that GM mosquitoes have the potential to eradicate diseases.

B K Tyagi, director of the Centre for Research in Entomology, echoed similar views. According to him, India should seriously consider the scientific utility of GM technology dealing with vector-borne mosquitoes.

But Debal Deb, ecologist and founder-chair of advocacy group Centre for Interdisciplinary Studies, is sceptical of the idea. He says the Supreme Court has banned field trials of GM crops, so if Oxitec has applied for trials in India, all possible impact on the environment and health should be examined.

imageDNA solution
Scientists have for long believed GM mosquitoes can control diseases such as malaria, dengue

  • imageIn 1937, US etymologist E F Knipling for the first time tried to control insects by altering their reproductive process. He experimented with the screwworm fly by injecting them with chemicals, thus rendering the insects sterile. Between late 1930s and early 1970s, several attempts were made globally to develop GM mosquitoes. This led to sex-ratio distortion in many species

  • In 1970, a village in Myanmar successfully eradicated Culex mosquito through genetic modification
  • In 1971, India decided to conduct a trial on Aedes and Culex mosquitoes. WHO started a malaria control programme by introducing sterile male mosquitoes. But it was stopped after opposition
  • imageIn 1972, chemical sterilisation process was used to achieve 99.8 per cent sterility in male Anopheles mosquitoes. The successful trial was conducted in El Salvador, where 4.4 million sterile mosquitoes were released in a 1,500 ha area
  • In 1974, an experiment on Aedes was started in an isolated Kenyan village. Some 814 sterile male mosquitoes were released each day for nine weeks in the village. It was unsuccessful
  • The Cayman government completed a small-scale feasibility study with GM Aedes, which addressed how long GM mosquitoes lived, how far they flew and whether they would mate with female mosquitoes. About 19,000 sterile mosquitoes were released over 10 ha for a four-week period. It ran into controversies over methodology
  • In 2014, Brazil became the first country to commercially allow the use of GM mosquitoes. It used a mechanism in which male Aedesaegypti are injected with a lethal gene that results in the death of the offspring before it reaches adulthood
Source: Ecological Aspects for Application of Genetically Modified Mosquitoes, edited by W Takken and TW Scott, 2003

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