Luke Alphey

Genetically-modified mosquitoes to control dengue fever

Technical field
Isis Innovation Limited, Oxitec
Dengue fever is an excruciatingly painful – and sometimes fatal – disease that affects millions of people each year. The culprit behind its spread is a mosquito that has proven tricky to keep in check. That is until now. British scientist Luke Alphey has come up with a way to use the mosquito as a tool to control its own species. By programming an extra gene into the mosquitos’ DNA, he has ensured that the resulting mosquito larvae never reach reproductive maturity.

Finalists for the European Inventor Award 2015

For more than ten years, Alphey has been supercharging a decades-old method known as the “Sterile Insect Technique” (SIT) to turn mosquitoes’ natural reproductive instincts against them. Through research Alphey conducted at Oxford University along with fellow scientist Dean Thomas and later at their university spin-off company, Oxitec, Alphey developed a method to use genetic engineering to ‘sterilise’ maleAedes aegypti mosquitos so that when released, these modified mosquitos breed offspring that do not survive to adulthood.

With successive releases, the invasive mosquito population is reduced, leading to fewer biting mosquitos and lower risk of disease transmission. This ingenious technique can reduce mosquito numbers by more than 90% in target populations – far better than current methods – offering viable mosquito control that does not rely on toxic pesticides.

Societal benefit

After malaria, dengue fever is the second-most widespread mosquito-borne disease in the world. The World Health Organisation (WHO) estimates that every year, between 50 and 100 million people suffer, and about 25,000 die, from the disease. Worse still, the rate of new infections is rising. Since the 1970s, the number of countries affected by dengue outbreaks has risen tenfold, making dengue the fastest growing mosquito-borne disease in the world.

One of the biggest problems facing public health officials is that there is currently no cure for dengue, nor any way to protect a population from getting sick in the first place. An effective vaccine has so far proven elusive because dengue is caused by four different types of the virus. In fact, when someone becomes infected with one strain of the virus, they actually increase the risk of developing a more severe form of the illness if they are infected with another strain later in life.

Economic benefit

According to WHO, as much as 40% of the world’s population – or 2.5 billion people – are at risk of contracting dengue. The economic burden of the disease has been estimated to be around € 1.72 billion (US$ 2.1 billion) per year in the Americas alone. Oxitec has the support of the Biotechnology and Biological Sciences Research Council (BBSRC), the largest funder of non-medical bioscience in the UK, as well as the Bill and Melinda Gates Foundation. In June 2014, a € 7.7 million (£ 6.1 million) investment round was completed and the technology is now on the brink of commercialisation In what may likely be the largest test of sterilized mosquitoes to date, The Florida Keys Mosquito Control Department (FKMCD) has requested approval from the US Food and Drug Administration for a test release in 2015.

How it works

Miniscule amounts of genetically modified DNA is injected into mosquito eggs, and the larvae inside absorb it into their cells, where it is subsequently copied into their genomes. The majority of the larvae won’t accept the foreign DNA, but only one out of a thousand eggs needs to absorb the DNA to breed an entire colony.

After the DNA has been copied into every cell, it spurs the production of a protein called tTAV that effectively stops the cells from working properly.

In captivity the mosquitoes are fed a diet containing tetracycline, an antidote that stops tTAV protein from working. This allows them to mature and breed as normal.

In the wild, the absence of tetracycline results in tTAV production which ties up the cell’s normal processes so genes that are essential for the mosquito cells to survive are switched off.

The inventors

Luke Alphey, along with Dean Thomas, was the first scientist ever to use genetically modified insects this way. The first patent for the transgenic mosquito technology was filed by Isis Innovation (the technology commercialisation company at Oxford University) in November 1999, with Alphey and Thomas listed as the inventors. Equivalent patents have been filed in other countries, including the US, Mexico and China. Alphey is also listed as the inventor on six additional patents relating to GM mosquito technology.

Alphey originally worked as the chief scientific officer at Oxitec, the company he co-founded, and is now one of its non-executive board members. Alphey received a PhD in biochemistry from the University of Dundee, followed by research posts at Imperial College London and the University of Dundee. In 1997, he became an MRC Senior Research Fellow and later Reader in Genetics at the Department of Zoology at the University of Oxford, where he is currently a visiting professor. He works at the Pirbright Institute, furthering research of genetic control for insect pests.

Did you know?

Aedes aegypti has several characteristics that make it difficult to control and a near-perfect vector for spreading dengue fever, yellow fever and chikungunya. Unlike many other mosquito species, it prefers to lay its eggs in shallow pools like those found in old tires and gutters. Sleeping under netting is no use either: unlike Anopheles, the mostly nocturnal mosquito which carries malaria, Aedes aegypti is active by day and has developed a taste for human rather than animal blood.


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Luke Alphey
Minute change, massive impact

While insecticides may help prevent the spread of mosquito‑borne diseases, Luke Alphey knows that better solutions lie in controlling mosquitoes at a genetic level. If you can stop the insects breeding or prevent them from contracting a disease in the first place, you can slow the transmission of yellow fever or Zika to humans.

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Half of the world’s population is at risk of contracting dengue, a deadly mosquito-borne viral infection. Luke Alphey has spent two decades developing DNA-based solutions to slow the spread of disease. His current research looks at gene drives and techniques that could ensure beneficial traits are passed on in mosquitoes.

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