Animal Vegetable Criminal, page 25
“You tried it?” His look combines horror, confusion, and pity. “You want some gum?”
Like many people, I have some qualms about genetic engineering and its possible future. Also like many people, I know diddly about how it works. My plan for this afternoon is to become someone who knows a little more than diddly. I’m scheduled to meet with the Center’s wildlife genetics staff, upstairs in the Long Speak Room, which is an amusingly apt name for a government conference room (except that it isn’t—a realization that will dawn when I take note of the plaque by the door, which reads: Longs Peak Room).
I’m in the main lobby now, waiting for my escort. There is, yes of course there is, taxidermy. A family of monk parakeets is posed in and around a nest in the top segment of a power pole. The diorama takes up most of the surface of the small table beside my chair, forcing me to place my coffee directly beneath the birds and fostering a vague sense of unease.
My escort arrives and we make our way toward the stairwell. The corridors are hung with mounted research posters and color blowups of photogenic “nuisance” species: cormorants, ground squirrels, beavers. Wildlife management agencies and pest control websites do this too, and it always hits me as slightly off—it would be like the FBI decorating the hallways with headshots of goodlooking federal criminals.
Up in the Longs Peak Room, I take a seat next to Toni Piaggio, a conservation genetics specialist. Her own personal genetics have provided well. She received: graceful cheekbones, blinding intelligence, glossy black curls, deep reserves of patience. Toni introduces a young colleague, Kevin Oh, also a geneticist.
Before we get to the should and could of gene drives, a wobbly stab at the how. A gene drive is two unique manipulations. First, there is the one people are familiar with, at least in a general way: genetic modification, the GM in GMO. This is done using a technology called CRISPR-Cas (or CRISPER, for short). A target gene is selected—say, a gene for a trait that enables a mosquito to carry malaria—and then what Kevin calls the “molecular scissors” of CRISPR cut out and/or replace the target gene. The edit is done, in this case, early in the embryo’s growth—when it’s just a few dozen cells—so that the modified genome will be copied into every new cell going forward.
CRISPR-Cas is a natural element of bacteria, a part of the mechanism that serves as their defense against viruses called phages. This defense system includes an enzyme that cuts up the virus’s DNA, and as it does so, it retains a memory of it—a “molecular bar code,” as Kevin puts it. So if the virus returns, its specific genetic sequence will be recognized and cut up. Geneticists have harnessed the CRISPR scan-and-snip system as a way of precision-targeting and editing DNA.
“But how does the enzyme get in there?” I’m whining.
“They’re literally injecting mouse embryos,” says Kevin.
“Using, like, super-tiny dollhouse hypodermics?” I want to see these.
Toni steps in to move things along. “There are different methods. We sort of flood the embryo in its petri dish.”
The enzyme gets in. It scans, it finds a match, and beep, it does its thing.
So let’s say that you’ve managed, with your scissors and your bar code reader and your dollhouse drug paraphernalia, to manipulate the genome of a group of mice. And that now these mice cannot produce female offspring. If you set enough of them free on an invasive mouse-plagued island, the population will start to dwindle.
“Enough” is the challenge. This is where the gene drive element comes in. With normal Mendelian inheritance, this new trait would show up in 50 percent of the offspring, because half the offspring’s genetics are contributed by the male. What a gene drive aims to do is deliver the machinery to make that gene 100 percent heritable. So that now all mice born to the gene-drive mouse will carry the trait. A successful gene drive would speed the time it takes for a trait to spread through a population.
Here’s a hitch. In order to swamp an island population to a point where the gene-drive animals make sufficient inroads, scientists will have to release large numbers of the very species they seek to be rid of. Depending on the size of the island’s invasive population, it may take a considerable number of lab-born gene-drive animals to tip the balance. So before a gene drive can improve the situation, it will temporarily make it worse. Thus the first step, with rodents, would likely be an aerial drop of a rodenticide—the practice we’re trying to get away from. The gene-drive rodents would be released afterward as a sort of mop-up and maintenance program. So that any survivors, and any newly introduced future rodents, will peter out—rather than building up their numbers again and necessitating another hail of poison.
So far, the gene-drive element is proving tricky. The genedrive mechanism isn’t always copying correctly. And there seems to be a narrow window within the embryo’s development during which the manipulation will take. Too early and it kills it; too late and it doesn’t transform. The sexual practices of wild mice may also pose a challenge. Polyandry—whereby one litter may include offspring fertilized by multiple males—was recently shown to be more common among wild mice than previously thought. Thus it may take longer and require more gene-drive males to overtake the population.
On a more basic level, there’s a possibility that the invasive residents won’t breed with the genetically modified newcomers. In nature, mice from different islands or regions of the world begin to evolve separately. Not necessarily to the extent that they’re different subspecies, but different enough that they may not breed with one another. “You create these mice in the lab and then you have to make sure the wild mice on the island find them sexy,” says Katherine Horak, a toxicologist sitting a few seats to my right. Laboratory Mus musculus are surprisingly different from wild Mus musculus. “Lab mice want to just sit there and hang out in your hand. The first time I worked with a wild mouse,” Horak recalls, “I was like, What is that? It wanted to jump up and bite my face off.” (Thus the need for a high-security habitat.) One of the first things that will happen in the SNE are mating trials—backcrossing the gene-drive lab mice with wild mice to create a strain that’s sufficiently sexy to the invasives one wishes to control.
The big concern with gene-drive organisms is that they’ll make their way beyond the area—and the population—they’re intended to control. And that the locals wherever they end up will not hesitate to breed with them. Say you create a gene-drive “daughterless” feral pig and one of them mates with a domestic pig. Pig farmers would be undelighted. This is one reason scientists would plan to start with a physically isolated population— invasive rodents on a remote, uninhabited island, for instance. (Preferably an island no ships visit, because mice and rats are notorious stowaways.)
There is a way to avoid the concerning scenario. The same genetic drift that could prevent mice from different land masses from mating can be harnessed as a safety feature. Geneticists can target a genetic bar code unique to the population of the particular island or region. “So CRISPR can sit down and cut at this place in the genome that we only find in this population of mice,” Toni says. “So even if someone nefariously transported those mice somewhere”—or they transported themselves as stowaways—“we wouldn’t have to worry about it migrating into the local population.” In other reassuring news, research out of the University of California, San Diego, suggests it may be possible to halt or even reverse a gene drive. In a paper published in the fall of 2020, two new gene-drive control mechanisms were shown to work in fruit flies.
Katherine Horak has been working on something altogether different and less anxiety-provoking than gene drives. It’s called interfering RNA, or RNAi. Riddle me this: It’s a bait that kills, yet it contains no poison. It’s a species-specific genetic solution, yet it doesn’t modify the target species’ genome. That makes it an appealing package: doesn’t effect nontarget animals, safe for the environment, can’t go rogue. RNAi is based on a mechanism all organisms have: enzymes that patrol for viral RNA and destroy it. So you would choose a protein critical to your target animal’s life processes, dress it up like viral RNA, and let the interference mechanism destroy it. There are of course hundreds of proteins critical to life. Horak will look for one that would end it swiftly and without suffering, probably something neurological or cardiac.
The challenge with RNAi bait is that you’re sending delicate strings of genetic code through the acids and enzymes of a digestive tract. Horak is working with biochemists to design a carrier molecule. That will take a while, as will getting RNAi registered with the EPA. It’s at least a decade away from being something you’ll see at Home Depot.
The novelty of the approach may trip it up. “There’s a lot of talk in my world about perceived risk and actual risk,” Horak says. “People are more comfortable with the actual risk of anticoagulant rodenticides, which will kill anything if they eat enough. But because we’ve done it for so many years, that level of risk is somehow acceptable.” (In some places, and for some people, anyway.) “But the risks of RNAi are new risks, and so there’s hesitation around those risks.”
RNAi will face the inevitable challenge of any island eradication effort that relies on bait. The holdouts. The rodents that never encountered any bait. (Or, with poison bait, the ones that nibbled it, ate enough to feel sick but not die, and from then on steer clear.) Agencies can end up spending as much money tracking down the last ten of an invasive species—and monitoring for eleven, twelve, thirteen—than they spent eradicating the first ten thousand. This is going on right now in California’s Sacramento– San Joaquin River Delta, where nutria have been proliferating. Nutria are similar to beavers—big swimming rodents that like to manipulate the landscape in ways that can make them unpopular. But nutria breed faster, and they’re invasive. To find the holdouts, the California Department of Fish and Wildlife has been releasing neutered “Judas nutrias”—radio-collared individuals turned loose to betray their hidden kin.
A gene drive would have the rodents eradicate themselves. Without death or pain, and without killing any nontarget species.
And yet.
Here are some species the EPA, the USDA, and the Department of Health and Human Services consider “pests”: chipmunks, bears, raccoons, foxes, coyotes, skunks, flying squirrels, tree squirrels, little brown bats, rattlesnakes, coral snakes, cliff swallows, crows, house finches, turkey vultures, black vultures, and mute swans.
This is what troubles me, I say to Aaron. We’re back in his building now, watching rows of mice in stacked Plexiglas habitats, a Hollywood Squares of mice. Paul Lynde is doing backflips off one wall. What if a government agency eventually decides to go forward with gene drives on these other “pests”? What if economic considerations start to determine which species are next? What then? So long, pocket gophers? Toodle-oo, “nuisance beaver”? Right now, the focus is island conservation. It’s a more appealing and less worrisome application: saving endangered species in a geographically isolated location. So you try it out there, and it works well, and the native species recover and there’s good press. Now what? Where does the line get drawn, and who draws it? Let’s remember: The National Wildlife Research Center is part of the USDA. It’s not a conservation organization. “Aaron, the end point here, the ultimate target, is agricultural pests? Right?”
“That has been part of the discussion,” he allows.
This is where it gets scary to me. We’ve seen what happens when the deciding factor is agriculture’s bottom line. Will gene drive be a tidier rendition of the poisoning, shooting, trapping, bombing, wipe-’em-out campaigns of past centuries?
Aaron agrees that the decisions can’t be just financial. “It has to be tied to ethics. We feel like we’ve taken a lot of steps to be sure this is accepted on a lot of fronts and we’re not trying to go to third world countries to test it out.” But the United States is surely not the only country working on gene drive in mammals. If we’re on it, China is too. And China has not demonstrated a comforting abundance of oversight in the realm of genetic engineering.
Aaron was at the GBIRd meeting where Jane Goodall called for a moratorium on gene-drive research. GBIRd stands for Genetic Biocontrol of Invasive Rodents; it’s a consortium of five U.S. and Australian government agencies and universities, plus the nonprofit Island Conservation. I ask him what Goodall’s stated objection was. (Efforts to communicate directly with her were unsuccessful.)
“I think the concern is that the technology and the ability of people to experiment with it is moving way too fast, and the only way you’re going to slow it down is to shut it down completely,” he says. “And I think it’s good. If someone reputable like Jane takes a stand, people will stop and think, Maybe we need to establish some guidelines that we’ll all follow.”
Yes, please. Guidelines. Imagine if, rather than reducing the population or geographic distribution of a species, a gene drive wiped a species off a whole continent. Or an ecosystem was changed in some unanticipated and catastrophic way. It’s the unknown unknowns that trouble some biologists. I spoke with Will Pitt, a former project leader at NWRC and now deputy director of the Smithsonian Conservation Biology Institute. Rather than any specific fallout scenario, he expressed a general wariness. “People always say, ‘We’ve thought of everything that might be a problem.’ Well, it’s probably one of the things you haven’t thought of that’s going to be a problem.”
In a corner habitat on the top row, Charles Nelson Reilly is pirouetting on his hind legs. Look how clever we are. See how we dance! Don’t wipe us out! Personally I would hate for mice to disappear. As would species for whom they’re a common bill of fare. Who knows what defenseless small meat they’d turn to instead? But I suspect I’m not in the majority opinion as regards small rodents. I think plenty of people would be a-okay with, say, a global Mus musculus extinction.
“Right?”
“You mean if you asked a farmer or rancher who has a mouse problem?” Aaron chews his gum and considers this. “And you said, ‘What if mice were eliminated from the planet, even from places where they have some important function?’ ”
“Yeah.”
“Yeah, they might be like, ‘I don’t care.’ ”
Aaron knows a Big Agriculture guy with a lot of mice on his property. His name is Roger and he runs a feed lot where beef and dairy operations send their cattle to be raised. They’re fed different diets depending on what they’re being raised for, milk or beef or breeding more beef. The mice enjoy all of the diets. When Aaron needs wild mice for the SNE, he drives out to Roger’s place. Roger surely has opinions about bothersome rodents and what their fate should be. Aaron agrees to drive out there with me after lunch.
Roger arrives to greet us driving a bulldozer-sized forklift. His cowboy hat is white felt, and the rest is mostly denim. He steps down and extends a hand. His grip is strong, but not in the manner of a person who’s been coached on the importance of a firm handshake. More in the manner of a person who uses hand tools a lot. “Glad to meet you,” Roger says.
Aaron hasn’t been out here in a while, so he reintroduces himself. “I know who you are,” Roger says. “You guys are the ones that let that elk out.” Aaron lets this drift.
We follow the hat into the interior of Roger’s grain elevator. As our eyes adjust to the dim, we start to see them. Every half minute or so, a mouse races along the base of a wall or shoots across the floor and disappears beneath a pile of metal machine parts. They say if you see twenty mice, there are two hundred more you’re not seeing.
We go back out into the sun to continue the conversation. Above us is a silo of cracked corn and, I’m guessing, those other two hundred mice.
“Nah, that’s pretty much mouseproof,” Roger says. The top button on his shirt is open, and a long white chest hair quivers when the wind rises. “They could go up there, but why? They don’t have to go very far to find something to eat.” He scuffs the ground with one boot. There’s enough spilled corn that the driveway crunched like gravel when we pulled up.
Other feed ingredients are stored out in the open. At the end of the drive is a low mountain range of brewer’s grain and barley hops. I ask Roger to estimate the percentage that’s lost to mice.
“Well, it comes in twenty-five-ton lots. How do you know if mice ate fifty pounds of that?” He removes his hat with one hand and with the other, wipes away sweat. His face is tanned up to where the hat begins, then not. “In the grand scheme of things, the wind probably blows away more than that. You know, so. I’m not sure that’s a huge problem.”
Roger’s quibble with the mice is that they like to nest in the engines of his vehicles and sometimes they chew the wiring. But he doesn’t set out traps or poison. “I try to keep barn cats. Though they keep going out there on the yellow line and getting run over. Or the barn owls get them.”
I ask if he puts up nest boxes to encourage the barn owls, which also eat mice. This is a dumb question. Roger has barns. He doesn’t need boxes. Though he has heard about the practice. “They’re doing that out in California. Man, they eat a lot of mice.” He surmises the reason he has no rat problem is that the foxes around his farm keep the population down. Probably so. In the late 1950s, overexuberant slaughter of foxes and coyotes in Oregon contributed to a massive mouse infestation. In California, circa 1918, one bounty program begat a second: three cents per ground squirrel tail or, in some counties, scalp.*
In the sky over a corral of Holsteins, twenty or so black birds wheel east. Aaron asks about bird-hazing strategies. “There’s guys that’ll come in and shoot at the starlings,” Roger says. He doesn’t use them, he adds, because it’s not effective. The birds take off, circle around, and quickly come back. “It’s more of a psychological benefit. To feel like you’re doing something.” He watches the birds disappear behind a stand of trees. “It’s not a huge problem.”
