Climate Conundrum

India ponders using GM mosquitoes to fight dengue – and climate change could make this necessary

But releasing genetically modified mosquitoes into habitations is an ethical issue that requires a serious debate, apart from biosafety regulations. The first part in a series on the challenges India faces from climate change.

In October, soon after a vicious dengue outbreak in Delhi had subsided, a small commission headed by Ashish Khetan of the state's ruling Aam Aadmi Party set out for Guangzhou, China. Their goal? To see whether genetically modified mosquitoes could possibly prevent a similar dengue outbreak next year.

They could well have gone to Jalna, Maharashtra.

A few hundred kilometres away from the small district headquarters in the heart of Maharashtra, a group of scientists is in initial stages of testing genetically modified mosquitoes that aim to control the dengue virus by directly attacking the Aedes aegypti mosquitoes that carry it. The testing site is owned by Mahyco, an Indian company perhaps best known for its joint venture with Monsanto Company that manufactures and tests genetically-modified seeds.

The technology

The technology being tested in Jalna was developed in the early 2000s by Oxitec, a company partly owned by the University of Oxford that worked on converting academic research into marketable products. In August, it was bought over by Intrexon Corporation, a leading global synthetic biology firm.

In theory, it is simple. Male mosquitoes of the Aedes aegypti species are engineered – or "modified" – with a lethal gene that is programmed to cause the death of their progeny before they reach adulthood. When these mosquitoes are released into the wild and procreate with untreated female mosquitoes, their offspring will not grow to carry the dengue virus and, over time, the population of Aedes aegypti will itself decline.

The effects of this gene can be reversed with tetracycline – also a key component of certain antibiotics for malaria. This is how Oxitec manages to sustain its initial population of mosquitoes and can continue to release more modified mosquitoes into the wild.

The Chinese mosquitoes that the Delhi government has considered using are genetically modified to be unable to carry the dengue virus at all. Their mosquitoes also have a shorter lifespan.

Oxitec has conducted tests at a small scale in four countries – Brazil, the Cayman Islands, Malaysia and Panama – and its technology has been cleared for commercial use in Brazil.

Its tests have been underway in India for at least seven years. Reports first emerged of initial stages of testing in 2008 from Tamil Nadu, when Oxitec announced that it was working in collaboration with the International Institute of Biotechnology and Toxicology near Chennai.

Oxitec returned to the news in 2011, when it formally announced its partnership with the elaborately named Gangabishan Bhikulal Investment and Trading Corporation, better known as GBIT. While the Oxitec partnership is formally with GBIT, the actual testing is taking place in the facility of GBIT’s subsidiary Mahyco.

At present, GBIT has “successfully conducted laboratory level studies required for the application of technology in India”, a spokesperson for the company said. The Review Committee of Genetic Manipulation under the Department of Biotechnology in the Ministry of Science and Technology, is considering their proposal for an open field trial at a limited scale.

Climate change

Innovations such as these are important aspects of the ongoing fight to reduce disease incidence and mortality. But they become even more relevant because of climate change and rising temperatures in India.

Vector-borne diseases such as dengue and malaria are perhaps the most sensitive indicators of the impact of climate change on health. These diseases are spread by mosquitoes, or vectors, from human to human. Mosquitoes also respond directly to changing temperatures.

The first signs of this are already visible.

In 2003-'04, Sikkim recorded its first case of dengue. From there, the disease moved to Bhutan. Dengue and Japanese encephalitis, a disease transmitted by the Culex mosquito, have been reported from the Terai region of Uttar Pradesh and Bihar.

These populations, particularly in Sikkim and Bhutan, have never been exposed to dengue before and so have little resistance to them.

There are other early signs of changing vector patterns. In its State Action Plan for Climate Change released in 2012, Madhya Pradesh pointed not only to an increase in the number of dengue and malaria cases but also that outbreaks of these diseases in urban areas were lasting longer.

If, as scientists have been predicting for decades now, global temperatures do indeed rise two degrees above the average recorded during last 150 years, mosquitoes will tend to have a longer life span over a larger area for a longer period of time.

Purely from the human perspective, that spells trouble for people in tropical regions such as India. It also means that plans must be made for long-term solutions, whether by addressing the pathogens that cause these diseases, as Oxitec and the Chinese company are doing, or by strengthening the public health system.

Mosquitoes and rising temperatures

Ramesh Dhiman, a scientist at the National Institute of Malaria Research in Delhi, explained the precise mechanism of how malaria incidence might change in India.

The body temperatures of mosquitoes respond to the climate and are not internally maintained. What is more, the pace of their development directly corresponds to outside temperatures. At cooler temperatures, their development slows, while the reverse happens at higher temperatures. The ideal temperature range for the Anopheles mosquito that transmits the malaria parasite ranges roughly from 16 to 32 degrees centigrade for various subspecies.

Mosquitoes live for an average of two weeks. When temperatures rise above 32 degrees centigrade, it is possible for a single mosquito to breed two generations in a single month, instead of one.

“At increased temperatures, the development of mosquitoes’ life cycle will be faster and the development of [malaria] pathogen in their body will also be faster,” he said. “However, there is an upper limit also beyond which a mosquito cannot survive.”

That limit is at 40 degrees.

Aedes mosquitoes that transmit the dengue virus are sturdier than Anopheles ones, with a survival range of 11.9 to 42 degrees. However, there has been negligible work done on them in India, let alone on the impact of fluctuating temperatures on them.

How might it be manifested?

North India is more at risk of increased malaria incidence than south India, Dhiman observed in a paper for the World Health Organisation in 2012, as temperatures there were more likely to increase. On the other hand, if temperatures in south India cross the 40-degree threshold, that region might see a great reduction in malaria cases as Anopheles mosquitoes cannot survive beyond that.

It is not possible to directly link every unusual occurrence of these diseases to climate change, scientists say. For instance, the severe dengue outbreak in Delhi this July might not necessarily have been linked to climate change, but to a more prolonged and scattered rainfall that enabled Aedes mosquitoes to breed for a longer period.

“Climate change does not work in isolation, but has to be linked to the social transition and impacts of phenomena like urbanisation, migration and globalisation,” wrote Anant Bhan, an independent researcher of global health and bioethics, in an email to “Madhya Pradesh for example is undergoing urbanisation in many parts – this leads to water collection at construction sites, influx of migrant labour – [and] a part of this population might be carriers of infection (malaria and dengue).

The conducive environment due to climate change including warm, humid conditions or excessive rainfall, he added, could then lead to outbreaks of infections.

What can we do about it?

On November 23, researchers at the University of California in the United States published a paper stating that they had created a genetically modified mosquito that can combat the malaria parasite. Their mosquitoes have genes with malaria antibodies that will immunise them to the parasites and make them unable to carry malaria. They will also be able to spread this to other mosquitoes during intercourse.

Oxitec, on the other hand, wants to eliminate mosquitoes altogether, an approach that is quite different from that suggested by the University of California or the Chinese company the Delhi government approached.

That said, the fact that genetically modified mosquitoes are being considered at all opens the debate for how diseases such as this might be tackled in the future. Apart from confronting the vectors of such diseases, as companies seek to do with genetically modified mosquitoes, it is still important to strengthen existing public health systems.

“It might be nearly impossible to avert all environmental impacts of climate change in the present scenario – but we can have better health system foresight and take preventive steps to prevent impacts on public health, and possibility of disease outbreaks,” Bhan wrote.

And what of the ethics?

The Delhi government might be searching for answers in China, but they will not find it as simple as buying a box of pumped-up mosquitoes and releasing them in the open. As with any other genetically modified mechanism, the government will have to bring back this technology to India and then subject it to rigorous testing.

“The release of GM mosquitoes into habitations would be an ethical issue and requires regulation of biosafety,” said Dhiman. “In India, this still needs to be debated.”

The questions here are not just of practicality or “make in India” but of ethics. There has as yet been little debate in India on the implications of aiming to eradicate an entire species of insects that has become inconvenient to humans, or whether this reasoning might extend to other species. The warmer India becomes, the more urgent it will be for intellectual debate on these issues as well.

This is the first part in a series on the challenges India faces from climate change.  

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