When Shapiro and colleagues decoded the first passenger pigeon genomes in 2017, using tissue samples from museum specimens, they found a bizarre pattern—high diversity at the chromosome ends but surprisingly little variation in the middle, a pattern that might have contributed to the species’ rapid demise.21 Her colleague Ben Novak, who has been obsessed with these birds since he was a teenager, is leading “the great comeback.” A scheme to revive the passenger pigeon begins with the bird’s closest relative, the band-tailed pigeon.
At Monash University in Australia, Novak has taken the first steps, engineering a line of pigeons expressing Cas9, priming their progeny to receive select gene edits based on their passenger pigeon cousins.22 A best-case scenario suggests that changes in around thirty genes would confer many key traits such as coloring. But editing genes is just the beginning. Novak would have to raise enough birds to coax them to flock;23 one idea is to raise the first hybrid chicklets using surrogate homing pigeons painted to look like the Real McCoy. He’d also have to reproduce the birds’ natural habitat, perhaps the forests of the northeast United States. Novak proposes to calls his prize pigeon Patagioenas neoectopistes, or the “new wandering pigeon of America.”
“Humans have made a huge hole in nature over the last 10,000 years,” says Brand. “We have the ability now, and maybe the moral obligation, to repair some of the damage.” Revive & Restore supports projects led by Church, Shapiro, and many others. Hope for the de-extinction movement comes from the story of Celia, the last bucardo mountain goat, which roamed the mountains of Spain. Although Celia died in the wild, some of her cryopreserved ear tissue was used to produce a live animal. It was the first successful de-extinction in history, but unfortunately it died soon after birth from a lung abnormality.24
On Hawaii, mosquitoes carrying avian pox and malaria have wiped out more than half of the islands’ one hundred species of native birds. Most of the rest are endangered. A species called Culex quinquefasciatus was introduced to Hawaii on ships in the early 19th century. The islands’ native birds, including the honeycreepers, had no natural resistance to the avian malaria. And with climate change, mosquitoes are able to reach “upslope” to the higher elevations that serve as a natural sanctuary for surviving species. Revive & Restore is contemplating various strategies to reduce the mosquito population, including the sterile insect technique and the introduction of a natural bacterial predator, Wolbachia. Potentially the most effective technology involves CRISPR. It is also the most dangerous.
Eradicating diseases like Lyme disease, dengue fever, and especially malaria is a grand challenge on a global scale. And it is one where CRISPR offers a radical solution. What if CRISPR could have an impact on one of the most notorious killers on the planet? Mosquitoes don’t have an important role in ecology. They don’t pollinate plants or serve as an essential food source for anything. It is unlikely they would be missed, particularly in sub-Saharan Africa. “As the apex predator throughout our odyssey, it appears that her role in our relationship is to act as a countermeasure against uncontrolled human population growth,” observes Timothy Winegard.25
The solution on offer is called a gene drive; it gives researchers the power to warp the natural Mendelian pattern of inheritance, raising the prospect of halting the spread of devastating infectious diseases. A gene drive is like loaded dice, stacking the odds in favor of a particular copy or version of a gene being passed on to the next generation, rather than leaving it 50:50. Why is that interesting? For decades, biologists have tried to combat the spread of infectious disease or other pests by spraying tons of toxic chemicals or introducing a predatory species, often with dire consequences.
A gene drive offers a much more sophisticated strategy to combat deadly diseases such as malaria, which kills some 650,000 people every year. Scientists would introduce a special DNA element that would act as a sort of poison pill in the Anopheles gambiae mosquito. This selfish element can essentially clone itself by inserting a copy into the partner chromosome. The idea was first formulated B.C. (before CRISPR) in 2003 by Austin Burt at Imperial College, London. Burt suggested that a gene drive cassette introduced into 1 percent of the African mosquito population would quickly spread in a chain reaction, affecting 99 percent of insects within twenty generations.
Many observers are understandably scared that a gene drive in the wild could go awry, crossing geographic boundaries or spreading into unintended species, threatening the ecological balance of countries across the equator. Then again, trying to save the lives of more than 400,000 children who perish from malaria each year surely justifies some desperate measures.
Scientists have taken on and defeated malaria on a national scale before. In 1944, the Rockefeller Foundation and the United Nations initiated a program to eradicate malaria-carrying mosquitoes on Sardinia, which claimed 2,000 victims a year. The disease was probably introduced by North African slaves brought to the island after the conquest by the Carthaginians in 502 B.C.E. The peak assault came in the summer of 1948, likened to the Normandy landing, involving 30,000 men who sprayed more than 265 tons of DDT. The campaign eradicated three of the four zanzare—endemic species of mosquito—and wiped out malaria.26
In 2009, a British biotech company, Oxitec, launched a trial using three million genetically infertile male mosquitoes in the Grand Caymans to halt the spread of dengue fever. Following similar trials in Brazil and Malaysia, Oxitec has proposed a release for the Florida Keys, but some residents worry about inadvertent consequences of the modified mosquito release.IV
The use of a CRISPR-based gene drive allays some of these concerns as no foreign genes are inserted into the mosquito genome. With CRISPR’s ease and precision, researchers have conducted successful gene drives in small lab populations of mosquitoes. But it is one thing to perform a gene drive under the controlled conditions of a basement insectary in London or San Diego. It’s another to take this into the real world. The holdback is less technical than social.
Kevin Esvelt leads the Sculpting Evolution group at the MIT Media Lab—an institution, he says, for black sheep who don’t fit anywhere else.27 Esvelt is a leading evangelist in the potential use of CRISPR-Cas9 to develop strategies, including but not limited to gene drives, to combat diseases ferried by ticks and mosquitoes. But with the power of this approach comes tremendous responsibility. Esvelt takes this very seriously: his boyish appearance with sandy hair belies his eloquent intensity.
Esvelt’s interest in evolution began with a visit to the Galapagos Islands when he was in the sixth grade. “I wanted to know, how is it that so many marvelous creatures are created? Can we learn how that is done and create equally marvelous things ourselves?” In striving to answer that question, Esvelt has formulated a few ethical objections to the way that natural evolution does things, “the apparent total indifference to animal suffering, to any kind of notion of right or wrong. Evolution is amoral. I’m not saying it is immoral, because it is a physical process. But the fact that it does not care about or optimize well-being I view as a fundamental flaw in the universe.” That was just the first minute of our interview.