Should Apes Be Saved From Ebola?
Scientists and conservationists can't agree on which is a bigger threat to chimpanzees: the disease, or the medical research that might lead to an animal vaccine for it.
Flat on her back on a gurney, the chimpanzee is an unsettling sight: Around 130 pounds, the animal is limp, with drool pouring from corner of her mouth, a common side effect of sedation. She looks helpless, like a patient laid out on a hospital bed. But this chimp isn’t hurt; she’s been anesthetized, knocked out so a veterinarian can give her an experimental vaccine against Ebola—a disease that’s been quietly devastating Africa’s primate population since long before last year’s outbreak began.
The most recent Ebola epidemic is the largest in history, but smaller outbreaks have been erupting at least since the 1970s. Ebola is a zoonosis, a disease that can be transmitted from animals to people, and by some measures its impact on animal populations has been even more dramatic than its effect on the people of west Africa. Hard numbers are hard to come by, but some conservationists estimate that Ebola has wiped out around a third of the world’s wild chimpanzees and gorillas over the past few decades.
Peter Walsh, the wildlife biologist spearheading this vaccine project, is trying to find a way to protect the rest. Walsh is a professor of biological anthropology at the University of Cambridge, but to do this work he’s come to the New Iberia Research Center, part of the University of Louisiana at Lafayette. It’s the largest primate-research facility in the United States, with more than 6,500 animals on site. Around 230 of those animals are chimpanzees; the rest are mostly macaques, capuchins and green monkeys.
With its low brick buildings and long rows of cages outside, New Iberia resembles a tidy, well-run prison. Security is tight—around the United States, animal-testing facilities have been the target of vehement protests. In 2009, the Center was the subject of an undercover operation by the Humane Society of the United States; hidden-camera videos captured monkeys and chimpanzees in what appears to be severe psychological distress, in some cases biting themselves bloody in cramped isolation cages. (Since the Humane Society videos, living conditions at New Iberia have gotten an upgrade: The chimps are mostly kept in groups of six to 10 in enclosures dubbed “Primadomes,” round cages about 20 feet high and twice that across, filled with tree limbs for climbing.) The sting came at a time when primate-research centers were already facing fierce criticism from advocates like the primatologist Jane Goodall, who during a debate on the Irish radio station RTE last year told Walsh that her first glimpse of chimps in a medical-research center “nearly destroyed” her.
But Walsh isn’t one to shy away from an argument. On RTE, he told Goodall that she was “dead wrong” to think vaccines could be developed without testing in live animals. And this spring he went to a conference to give a talk about Ebola’s emergence in West Africa, titling his address, “I Told You So.”
Now he’s leading a research project that many believe shouldn’t exist. 2011, the Institute of Medicine issued a report concluding that most biomedical research using chimpanzees was unnecessary. In 2013, the National Institutes of Health announced it would sharply limit research with chimps, and retire most of its animals. (All the chimpanzees currently at New Iberia are owned by the University). The next and most drastic move came in June, when the U.S. Fish and Wildlife Service classified captive chimpanzees as “endangered,” a move that forbids scientists to use them for medical research. The rule goes into effect on September 14.
One key difference: Walsh’s chimpanzees aren’t being poked and prodded in the service of human medicine. The work is on behalf of the chimps themselves, part of a plan that Walsh believes may be vital to the survival of their species. With the new Fish and Wildlife rule, though, the future of that plan is uncertain.
In the late 1990s and early 2000s, scientists’ field reports were noting die-offs of chimpanzees and a sharp decrease in the number of gorillas living in the jungle that straddles Gabon and the Republic of Congo. Several corpses that biologists found tested positive for Ebola. Walsh and his colleagues estimated that between 2002 and 2003, the virus wiped out 5,000 gorillas around the Lossi Sanctuary in Congo, or around 90 percent of the sanctuary’s population. In the same period, human outbreaks were traced to the handling of infected chimpanzee carcasses.
Before the outbreak, biologists believed that apes simply picked up the virus in the environment, perhaps eating fruit tainted by bat guano. But Walsh showed that to a large extent, gorillas were infecting each other. As he wrote in 2007, “Some gorilla social units may play a disease-transmission role analogous to that of prostitutes in the spread of HIV in southern Africa.”
Fearing that even more devastating outbreaks were on the way, Walsh began to investigate the possibility of animal vaccination. At New Iberia in 2011, he injected six chimpanzees with an experimental Ebola vaccine that had been in development for human use. (Although the virus was affecting both chimpanzees and gorillas, vaccination work has focused on chimpanzees, as no U.S. facilities keep medical-research gorillas.) The chimps developed a strong immune response and suffered no ill side effects. The results were published last year.
Despite the vaccine’s promise, there were several disadvantages to the approach. Most importantly, the vaccine could only be injected, either by capturing the apes or shooting them with darts from a distance. To try and vaccinate all the members of a wild population one by one wasn’t a viable solution.
More viable, it turned out, was an oral Ebola vaccine, one inspired by another animal disease a continent away. In the 1970s, there was raging epidemic of rabies in Europe’s forest creatures, most notably in red foxes. Officials tried without success to control the outbreak by trapping and shooting foxes, but in 1978 they turned to a new strategy. Scientists in Switzerland started sprinkling the woods and fields with a special snack: severed chicken heads, loaded with an anti-rabies vaccine. The foxes lapped it up. Over time, 24 more countries introduced similar oral-vaccine programs of their own. As more and more foxes became immune to rabies, the westward spread began to slow, then stopped altogether. Today, rabies has been eradicated from most of central and western Europe.
In Walsh’s current study at New Iberia, 10 chimpanzees are getting a version of this rabies vaccine, modified by the addition of an Ebola protein. In theory, it should protect against both diseases, though at this stage the team is only testing for safety and immune response. What they won’t do is jab the chimps with Ebola to see if the vaccine actually protects them.
In a medical suite the size of a small operating room, the unconscious chimps are wheeled in two at a time. A veterinarian performs a quick medical exam on each animal. She and the vet techs move quickly, minimizing the time each chimp must be sedated. A tech sweeps away rivers of drool. Of the 10 animals who come through, six receive an oral vaccine, a quick squirt on each side of the mouth. As a comparison group, four animals receive the vaccine via an intramuscular injection to the thigh.
Observing the action are Walsh and Matthias Schnell, a virologist at Thomas Jefferson University in Philadelphia, who developed and produced the vaccine being used in the trial. He’s been working with the rabies vaccine since the 1990s and says it’s been given to tens of thousands of animals thus far without any serious safety issues. (Schnell says he and colleagues at the National Institutes of Health are also developing a human version.)
There are several practical hurdles to vaccinating apes. Chimpanzees can be aggressive, while gorillas are intensely shy—both traits that would make an animal difficult to dart with a vaccine, explains Chris Whittier, a veterinarian at Tufts University who spent years working with wild gorillas. Another problem is that gorillas are notoriously picky eaters. Walsh has done experiments looking at potential baits, but hasn’t yet hit on anything that the animals can reliably be induced to eat, as the foxes were with their chicken heads.
Whittier is currently working on a vaccine project run by Michael Jarvis, a molecular virologist and immunologist at the University of Plymouth. Instead of setting out bait to inoculate apes one by one, Jarvis wants to spread protection like a brushfire: He wants to pack an Ebola vaccine on the back of a virus that would spread from ape to ape, an infectious outbreak that would shield the animals rather than sicken them.
Jarvis has a particular virus in mind: the herpes virus cytomegalovirus, or CMV. It’s generally benign, although in human infants or people with weakened immune systems, it can cause a mononucleosis-like illness or even developmental disabilities. CMV has also been studied as a delivery vehicle for contraceptives in mice and targeted cancer drugs in people. Jarvis spent a big piece of his career growing and manipulating CMV for use in vaccine development, targeting simian immunodeficiency virus (SIV) as a step towards a human HIV vaccine.
To produce an Ebola vaccine with CMV as the “vector,” Jarvis explains, take a surface protein from an Ebola virus—the same protein used in the Ebola-rabies combo—and insert it into a CMV virus particle. The immune system recognizes the Ebola protein and becomes primed to attack anything similar that comes along (like an actual Ebola virus). Meanwhile, the modified CMV replicates, spreading not just within the body but to other animals as well, through bodily fluids or direct contact.
The CMV vaccine, in theory, may dramatically reduce the need for bait: Infect a few animals, and they’ll spread it to the rest on their own. To some, that makes it an exciting possibility. To others, it’s alarming.
Ken Cameron, a veterinarian who heads the WCS efforts in Brazzaville, Republic of Congo, is leery of Jarvis’ work. “Non-target species are a big concern,” he says; what if a modified CMV spread to non-ape species? “What effect could this possibly have on them?”
Jarvis isn’t worried. “CMV is incredibly specific,” he explains. “There’s a chimpanzee version, a gorilla version, a people version. As far as we know, it doesn’t cross the species barrier.”
But not everyone finds that comforting. “You’re introducing a genetically modified organism,” says Sarah Olson, an epidemiologist with the WCS’ Wildlife Health and Health Policy Program. “It could be something eventually seen as a mistake.”
For animal-rights activists, the end of testing on captive chimpanzees is cause for celebration. For Walsh and the team at New Iberia, it’s a calamity, halting their work right as they are—they believe—on the cusp of developing a workable vaccine.
Spokespeople for the U.S. Fish and Wildlife Service and the National Institutes of Health each say that Walsh’s vaccine study might be allowable even under the new rules, which permit work on captive chimps as long as it supports “enhancement or survival of the species by providing a conservation benefit to species in the wild.” To continue its work, though, the team at New Iberia would have to apply for a special license under the new law.
But for Walsh, the assurance rings hollow. “In principle we’d be allowed,” says Walsh, “but who’s going to pay for that maintenance?” Once New Iberia loses the ability to study chimpanzees for human-health-related purposes, he argues, funding to keep the animals will likely dry up.
Some conservationists say it doesn’t matter, that the work could be done just as well in African sanctuaries, where chimpanzees are cared for in a semi-natural environment. One proponent of that view is Brian Hare, an evolutionary anthropologist who has worked with bonobos at sanctuaries in the Republic of Congo . He began his career at Emory University’s Yerkes Primate Center, a medical research facility, but became disillusioned with the way the animals were treated.
“We’ve published tons of papers out of these sanctuaries on a whole host of topics,” including a test of a polio vaccine, Hare says. “We can do all the types of research that used to be done in laboratories in the United States.” Walsh, though, argues that sanctuaries don't provide enough of a controlled environment for a scientifically rigorous study.
At least three major U.S. primate research facilities—Yerkes, the Southwest National Primate Research Center in San Antonio, and a center run by MD Anderson in Bastrop, Texas—say they’re keeping their chimpanzees for the foreseeable future, until they get a better picture of whether federal funding will be available for continued work. Officials at New Iberia haven’t yet decided whether they’ll apply for the license that will allow them to maintain a chimp research program. Without a new license, the researchers will still be allowed to conduct some non-invasive testing—like collecting feces—but the chimps’ career in medical research is effectively over.
Walsh collected the most recent round of blood samples for his study on September 9, around week before the law takes effect. It takes two to four weeks to complete the analysis that shows whether the vaccine produced a strong immune response. So far, the chimps’ experience has been happily uneventful: “All the clinical findings are in the normal range,” Schnell told me in early September. After giving their last blood samples, they were taken out of isolation and returned to their Primadomes to wait for whatever comes next.