Charles Darwin had no idea what a gene was. If we dropped the father of evolution into 2019, the idea that humans can willfully alter the genes of an entire species would likely seem like wizardry to him.
Humans have been interfering with genetics for millennia. We domesticated dogs, we bred gigantic chickens. But during the 20th century, we learned genes were made of DNA and created tools that allowed us to tinker with them. By the 1970s, that had opened up a new field of research. the discovery of the CRISPR, genetic engineering became cheaper, faster and more efficient.
Now scientists possessed a robust molecular tool that could reliably alter genes in almost any organism. It was touted as a revolution in 2013 — and it has been, enabling genetic modification of crops, potential new cancer treatments, refining antibiotics and new ways to create animal models of disease. Anopheles mosquito, combatting a disease that according to the World Health Organization kills almost half a million people every year. Meanwhile, in Australia, a scourge of poisonous cane toads hop their way across the continent, endangering native species. Researchers hope to render their toxins inert and control their spread, giving the natural flora and fauna a chance to bounce back.
For 80,000 years, one particular monster has terrorized human beings. Plasmodium, a single-celled parasite that infects the liver and bloodstream. It causes malaria, a disease that can be fatal, particularly in children. The parasite hides in oxygen-carrying red blood cells and multiplies, eventually exploding out of the cell, destroying it in the process. the disease infected 216 million people, killing 445,000. Over 90 percent of those cases occurred in Africa, while 70 percent of deaths occurred in children under five.
To infect humans, Plasmodium relies on the female Anopheles mosquito. The parasite dwells inside the mosquito and is transferred to humans when a mosquito plunges her needle-like mouth into the skin. Anopheles mosquitoes — introducing DNA from other organisms into their genome that would help prevent the parasite’s spread. that inactivated Plasmodium or stopped its development altogether. However, by adding the extra genes, scientists had made the lab-grown insects weak and less likely to survive in the wild. That prevents them from spreading their anti-malaria genes because they die out too quickly, before they have the opportunity to breed.
The origin of changing species
The power to change a species begins with sex.
Genes exist in pairs. When two organisms mate, they hand down one copy each to their offspring. They don’t choose which gene gets inherited. It’s a genetic coin-toss: each gene has a 50 percent chance of being passed down.
However, some genes are selfish. They use molecular tricks to ensure they’re passed down with a greater than 50 percent chance. Breaking the rules of inheritance like this, these selfish genes can survive and spread throughout populations over time, even if they make an organism weaker.
Scientists htoyed with the possibility of modifying selfish genes to control insect species since the 1960s, but in 2003, Austin Burt, from Imperial College London, penned a seminal paper that first conceptualized the gene drive.
He suggested that a particular kind of selfish gene could be engineered to deliberately bias inheritance, allowing scientists to not just edit the genes of individuals, but entire populations. Burt and his colleagues developed the idea over eight years, eventually showing it was possible in 2011 but cautioning there were still “technical hurdles” that needed to be addressed.
Walking over a footbridge in Massachusetts’ Emerald Necklace, a historic stretch of parks and waterways that curl through Boston, Kevin Esvelt stared into the serene, still water and noticed a turtle, sparking a groundbreaking idea: Combining CRISPR with the concept of a gene drive would create an unimaginably powerful genetic engineering tool.
went to press in 2014, before his lab had even developed a working CRISPR gene drive. That paper, published in eLife, suggested a number of applications for the technology: eradicating insect-borne diseases such as malaria, sensitizing agricultural pests to pesticides and controlling invasive species.
In September 2018, a research team at Imperial College, London, led by Andrea Crisanti and featuring pioneer Austin Burt, revealed it had generated a CRISPR gene drive that caused a total population collapse in lab-bred Anopheles gambiae mosquitoes.
After starting with 600 mosquitoes, the gene drive spread through the population within 7 to 11 generations, causing a total collapse. The research team had created a similar drive in 2015 targetting a different gene, but it hadn’t been as successful in crashing the population because genetic mutations arose over time. This, then, was the most powerful drive yet.
“The most important and surprising thing is that doublesex can not be changed without altering its function. A lot of mutations were generated, but none were functional,” Crisanti explains.
“Now we’re trying to understand if this region is really ‘resistance-proof’ and if it is, we really have a tool that has the potential to be used in the field — and solve the problem of malaria.” Anopheles mosquitoes thrive and examining how the gene drive fares under such conditions.
The toxic toad
In the arid northern plains of Australia, an invader slowly hops its way west, across the continent. Rhinella marinus.
The biggest toad species in the world, the cane toad is a toxic, randy trespasser. In 1935, a state government-owned sugar industry body introduced the species into Australia’s north-west as a biological control measure — a way to stop cane beetles from damaging their crops. But the toad thrived in the Australian tropics, reproducing quickly and wreaking havoc on the natural ecosystem by competing for food and killing off any predator that might try to eat it with a cocktail of deadly toxins. Anopheles mosquitoes. They aren’t dangerous to humans (unless you should, for whatever reason, decide to lick one) but they cause a great amount of suffering to native fauna and flora. For the past 83 years they’ve been nearly impossible to contain and have been linked to dwindling numbers of Australia’s native lizards, snakes and frogs. Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Australia, believes his team can use CRISPR to genetically modify the toad to prevent it from producing the lethal toxins.
Nuts, bolts, warts and all
At first, it might seem like the CRISPR gene drive is a perfect machine to combat the toad, just like it would be the malaria-carrying mosquito. However, the cane toad provides an example of where the self-propagating gene drives, like the one being developed in London, may be overkill.
Esvelt doesn’t believe a self-propagating drive should be used to alter invasive species like the toad. Rather, he believes that such a drive is only viable in four specific cases that cause great human or animal suffering: the Anopheles gambiae mosquito, the New World Screwworm, whose larvae feed on the tissue of living mammals, and two parasitic worms that cause the majority of schistosomiasis cases, which the WHO estimates affects over 200 million people a year.
That a gene drive can self-propagate presents a unique experimental problem: It cannot be trialled in the field. It is impossible to guarantee the engineered organisms will stay in a controlled zone. Once unleashed, it would eventually spread to every organism of the species.
From the very beginning, Esvelt, who now heads up MIT’s Sculpting Evolution group, has championed scientific responsiveness when dealing with gene drive technologies. He believes the technology has such far-reaching effects that the scientific community must engage and interact with the community openly, from the earliest stages of a project.
In June 2018, Esvelt and his associates at MIT published a paper in the journal eLife, highlighting some of the potential risks of introducing self-propagating gene drives into wild populations. Their mathematical modelling showed that “even the least effective drive systems reported to date are likely to be highly invasive”. we must use safeguards. Anyone building a potentially invasive gene drive system should be extraordinarily careful to use safeguards beyond simple walls and cages.”
The game of genomes
Almost every two minutes another child dies of malaria. invested $100 million into development of gene drive technology, spurring advocacy groups to fight against further research over fears of militarization.the United Nations rejected those calls last November, they did suggest “parties and other Governments… apply a cautionary approach” and evaluate gene drive projects on a case-by-case basis.
In many ways, scientists working on gene drives, such as Esvelt, Crisanti and Tizard, have been on the front foot from the beginning, building in physical safeguards and working to educate communities about the potential risks and benefits of the technology well before any potential release.they could bias inheritance in lab mice. another form of gene drive, known as a “daisy drive”, designed to contain the release within a local environment for a limited time, rather than spread indefinitely. In January, a team from Cornell University described another set of safeguards they could build into the drives that would also prevent unintended spread.
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