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Austin Burt

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Insecticide

It was a typically anodyne statement by the World Health Organisation: “Given the magnitude of the Zika crisis, WHO encourages affected countries and their partners to boost the use of both old and new approaches to mosquito control.” Anodyne, that is, until you realise what they mean by “new approaches”.

Zika is a mosquito-borne virus that is spreading panic around the world. It was first linked to hydrocephaly – a developmental defect in infants that results in abnormally small heads, severe learning difficulties, and often early death – only last year in Brazil. WHO estimates that it may infect 3 to 4 million people in the Americas alone this year – and its “new approach” is to exterminate the mosquitoes. Literally.

An alternative approach would be to develop a vaccine for the Zika virus – but that would take up to ten years, and the crisis is now. Zika has already been detected in 30 countries, and Brazil is investigating more than 4,300 suspected cases of microcephaly. The pressure is on to do something fast.

By the wildest of coincidences, something fast is available. It’s only twelve years since Austin Burt, an evolutionary geneticist at Imperial College in London, raised the idea of a “gene drive” that would spread some desirable quality (like immunity to malaria) through an entire population in a relatively short time. With a population of mosquitoes, whose generations are only a month long, you could do it in only a year or two.

Mosquitoes were the obvious first target for the new technology, since their bite transmits lethal diseases like dengue fever, chikungunya and, above all, malaria, which still kills 600,000 people a year. But “editing” a gene was a long, difficult process until CRISPR/Cas9, a fast, accurate, cheap gene-editing tool that was developed in 2012.

Scientists immediately set to work on mosquito genes, and by last year they had a genetically modified (GM) mosquito whose offspring do not survive into adulthood. They die as larvae, before they can breed.

By an even wilder coincidence, the species of mosquito whose genes they edited was Aedes aegypti, best known as a vector for dengue fever. But Aedes aegyti is also the main transmitter of the Zika virus, and Oxitec, the British-based company that was created to exploit this new technology, is already field-testing the GM version of the insect – in Brazil, as luck would have it.

In the town of Piracicaba, Oxitec has a “factory” that produces 800,000 mosquitoes each week that carry the OX513A gene, and a white van that sets them free all over town. In theory they should mate with the local females of the same species, whose children will never grow up to mate themselves, so the local population should go into steep decline. And in practice, it works.

It’s actually a rather labour-intensive process, and the little prototype “factory” is only producing enough GM males to cover a town of 10,000 people. To completely eradicate the local population of Aedes aegypti would take several dozen generations – that is, a couple of years – even if it was not replenished by fertile males from the surrounding area.

Obviously, the enterprise could be scaled up to cover all of Brazil, or even the whole world. The question is: should it be?

Human beings have wiped out entire species in the past, starting with the big animals that were wiped out in the “New World blitzes” when human hunters first arrived in the Americas, Australia and various ocean islands. But we never actually intended to exterminate a species before. This time it’s different.

Some environmentalists have already attacked the idea, ostensibly on the grounds that removing an entire species of mosquito would upset the ecological balance and possibly cause further extinctions among the animals that feed on them, or maybe open up an ecological niche that would be filled by an even nastier species.

But one suspects that their real worry is the “slippery slope”. If we edit Aedes aegypti out of existence today, what species will we next choose to remove for our own convenience? That is a legitimate concern, but nothing can make mosquitoes cuddly, whereas healthy babies definitely are cuddly. The threat of Zika will trump all their arguments.

Besides, there are some 3,000 species of mosquitoes (only 200 of which bite human beings), so some other species will just fill the niche left empty by Aedes aegypti and no other bird, fish or insect will go hungry. If you are still upset about “playing God”, keep a small breeding population of Aedes aegypti alive in captivity so you can repopulate the planet with the little pests if you need to.

The great American biologist and champion of biodiversity E.O. Wilson gets the last word on this. In his book “The Creation: An Appeal to Save Life on Earth”, he makes a exception for Anopheles gambiae, the mosquito that spreads malaria in Africa. “Keep their DNA for research,” he writes, “and let them go.”

The same goes for Aedes aegypti. We are going to commit insecticide. And we should.
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To shorten to 725 words, omit paragraphs 5 and 9. (“Mosquitoes…2012″; and “It’s actually…area”)

Gene Drives

Most powerful new technologies are double-edged. Cars are a vast improvement on horses as a means of transportation, but they also kill more than three thousand people a day and they are a major source of pollution.

So here comes another double-edged technology, and its edges are very sharp. Gene drives can spread an engineered mutation through an entire species with amazing speed, which means that you could, for example, make the breeds of mosquitoes that transmit the malaria parasite to human being immune to the parasite themselves. (You could also just wipe those species of mosquito out, but then a lot of birds and bats would starve.)

The idea of a gene drive was first suggested twelve years ago by Austin Burt, an evolutionary geneticist at Imperial College in London. What drew his attention were certain naturally occurring “selfish” genes, known as homing endonuclease genes, that can get themselves passed on to the next generation more than the usual fifty percent of the time.

Burt suggested that you might use those genes to build a “gene drive” that would spread some desirable quality (like immunity to malaria) through an entire population in a relatively short time. But back in 2003 the task of manipulating genes was still difficult, lengthy, and unreliable.

It took Burt and his colleagues another eight years to create a homing endonuclease that could find and cut a gene in mosquitoes. Other scientists were working to make artificial protein systems that would do the same job, but it was slow and painful work.Then came CRISPR.

CRISPR (it stands for “clustered regularly interspaced short palindromic repeats”, but never mind) refers to bits of viral DNA that bacteria carry in their genomes. With the help of an enzyme called Cas9, these CRISPRs protect the bacteria from attacks by hostile viruses. In 2012 researchers managed to modify this CRISPR/Cas9 system into a gene-editing tool.

CRISPR/Cas9 has transformed the business of genetic engineering, making it fast, accurate and cheap. It allows researchers to cut and paste practically any gene into any organism, and it has spread through the world’s biology labs like wildfire.

Almost immediately Kenin Esvelt of Harvard University recognised that CRISPR is basically a homing endnuclease, and in July of last year he and his colleagues publicly proposed turning it into a gene drive and listed some of the possibilities that opened up.

It could, Esvelt said, “potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species.” Sick of the cane toads that infest Australian fields? Modify them so that their skin is no longer poisonous to predators, and watch the problem go away.

“Since the 1970s we’ve been able to genetically engineer individual organisms,” Burt said. “With gene drive, we could change the genetics of vast populations.” And we have gone from zero to 60 in less than a year.

Last January, Esvelt’s lab made a gene drive in yeast. In March, biologists Valentino Gantz and Ethan Bier at the University of California, San Diego reported online in Science that they had created a gene drive in fruit flies. They had introduced a drive for yellow colour into females, bred them with normal males – and between 95 and 100 percent of the offspring were yellow.

They then started collaborating with Anthony James, a molecular biologist at the University of California, Irvine who has been working for thirty years on genetically modifying mosquitoes so they can’t pass on malaria. Using CRISPR/Cas9, the team are now within a year of a non-malaria-carrying mosquito ready to be released into the wild – but they won’t do it.

James’s team have no intention of doing that it until there are clear and agreed rules for this sort of thing. They are well aware of the risk of unforeseen side-effects: “We’re not about to do anything foolish,” says James.

One of the precautions James took was to work with an Indian breed of mosquito, so that if one escaped from his California lab it wouldn’t find anyone to mate with. In the same spirit, as soon as Esvelt created a gene drive for a species of yeast he immediately set to work creating another drive that could over-write the first, cancelling the genetic changes it made. If things went wrong, the second one could be released and would spread just as fast.

As Esvelt said, “the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application.” You bet your boots it does.

This is a technology that can change the entire character of a wild species very quickly (or wipe it out) if just one individual that has been genetically altered in the lab accidentally escapes and breeds, because the mutation will be passed on to ALL its descendants, and all of theirs, ad infinitum.

And, of course, we are also talking about the possibility that people with evil intentions might take common, harmless insects and make them lethal to human beings. This technology will have to be handled with very great care.

To shorten to 725 words, omit paragraphs 13 and 14. (“James’s…fast”)