Stopping disease carrying mosquitoes 2: Gene Drive

Using molecular biology, scientists at Imperial College have created a method which may dramatically halt the number of malaria cases

When in 1880 a parasite was discovered in the blood of malaria patients by Charles Louis Alphonse Laveran a French army officer in Algeria, a scientific journey began. It would lead to the discovery of avian malaria’s transmission by a parasite in the anopheles mosquito by Ronald Ross (born in Almora, India) in 1897. Then in 1898 Italian Zoologist Giovanni Battista Grassi and his colleagues, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava discovered the life cyle of the malarial parasite and its transmission from mosquitoes to humans. The Italian scientists also confirmed similar infection transmission in humans as Ross discovered in birds, whereby mosquitoes feeding on infected human beings would then be carriers of the parasite, spreading it to others.  

‘It’s a fascinating area studying the molecular interactions between the mosquito and the parasite,’ says Dr Tony Nolan, Senior Research Fellow at Imperial College, London, ‘and trying to understand the biology of the mosquito in order to find ways to interfere with its ability to act as a vector for the malaria parasite.’ 

Dr Nolan explains that over the years there have been different control measures for the disease such as removing the habitat for the mosquitoes, insecticide spraying and bednets. But the scale of the problem remains intimidating. The World Health Organisation estimates that 3.3 billion people are at risk, with 1.2 billion people at high risk. New control methods are needed.

Genetic approach

The team at Imperial College identified genes in the mosquito Anopheles gambiae that when changed, makes the female mosquito infertile. ‘We disrupt these female fertility genes specifically that are responsible for female reproduction.’ 

If these genes are disrupted, then females can’t produce offspring and the number of mosquitos crashes, so the logic goes. However, under normal circumstances these disrupted genes that cause infertility wouldn’t be spread through the population.

This is where the gene drive comes in. The gene drive, explains Nolan, ‘refers to the ability to insure that a gene is transmitted to a disproportionately high number of offspring, much more than you would expect from the normal inheritance of a gene. As a result, that genetic element increases rapidly in frequency within a population, so we have designed that gene drive element to actually target female reproduction as it does so.’ 

Normal genetic inheritance

Mosquitos, like humans, have two copies of each gene in their cells. These can be the same or different versions. When mosquitos mate, each parent passes one of these two gene copies to their offspring. 

In order to be infertile, female mosquitos would need to inherit the disrupted gene version from their mother and father, so that they have two disrupted copies. Normally however, the gene that each parent passes down is randomly assigned, and so if each parent has only one copy of the infertile gene, then there is only a 1 in 4 chance of the offspring receiving both. That means that 75% of the offspring will inherit one or no disrupted gene copies, won’t be infertile, and the mosquito population can still be a menace.

Gene drive

The gene drive is a kind of molecular tool which works like the Find and Replace tool in a word processor. If a mosquito only inherits one disrupted version of the fertility gene, the gene drive will find the normal version inherited from the other parent, cut it, and copy and paste the disrupted version in its place.

So now the mosquito has two copies of the disrupted gene, and if it’s a female, it will be infertile. The idea then is to generate a population crash among Anopheles gambiae, to a level that malaria would no longer be transmitted. ‘From a relatively small release of these modified mosquitoes, you can rapidly spread through a population,’ says Nolan. 

Ecological concerns

Are there any issues for the wider ecology? ‘What is important to remember here is that it is targeting a specific species of mosquito that transmits human malaria, the predominant burden of human malaria is due to this mosquito. There are three or four thousand species of mosquito across the world, this is only one of them.’ They are still testing and modifying, doing field studies, and there is a relatively long timeline of perhaps 10 years – but no longer than normal.  But when the project is finally complete they anticipate the effect of releasing the modified mosquitoes to be quite quick. ‘In a small number of generations,’ says Nolan, ‘it could rapidly have an effect.’