StemCell Therapy

Fabian Leendertz has spent decades studying how diseases flow between humans and wildlife. Here, he and colleagues hunt for bats in Ivory Coast.

By Kai KupferschmidtJan. 28, 2021 , 12:05 PM

TA NATIONAL PARK IN IVORY COASTThe message arrived as Fabian Leendertz was watching what he calls breakfast TV: a troop of black-and-white colobus monkeys leaping acrobatically through the trees that tower above the remote field camp here near the Liberian border. A colleague had received word that the carcass of a duiker, a kind of antelope, had been spotted in the rainforest some 10 kilometers away.

The notification launched Leendertz, a wildlife veterinarian at the Robert Koch Institute, into a race against time. The jungle is a hungry place, and Leendertz and his team needed to hike to the carcass before it was hauled away by a leopard or consumed by smaller animals. If the researchers beat the scavengers, they could collect tissue and other materialsincluding maggots feeding on the carrionthat could help answer a fundamental question: What do animals in the jungle die of?

Leendertz and his colleagues have been chasing answers here in the Ta forest for the past 20 years, studying hundreds of carcasses and sampling living animals in one of the only long-term studies of its kind. Theyve found that poachers and predators arent the only deadly threat lurking in the rainforestinfectious diseases are a big killer, too.

A discovery that leprosy can infect wild chimpanzees broke new ground.

The findings have implications for both saving endangered animals, especially apes, and protecting human health. Leendertzs work has revealed, for example, that chimpanzees can die from common cold viruses introduced by humans, prompting scientists, conservation groups, and ecotourism firms to impose new requirements on people visiting the apes. His team has also discovered a previously unknown variant of anthrax that appears to pose a major threat to wildlife. And he and colleagues in Guinea-Bissau recently found that wild chimpanzees suffer from leprosy, suggesting apes might be a previously undetected reservoir of that disfiguring disease, which could spill over into human populations. Fabians work has really changed how we view biosafety and biosecurity around great apes in the wild, says disease ecologist Tony Goldberg of the University of Wisconsin, Madison.

Now, the 48-year-old Leendertz, who once investigated the animal origins of an Ebola outbreak in West Africa, has been asked to help to solve one of the great disease mysteries of the early 21st century: the origins of SARS-CoV-2, the coronavirus that originated in bats and has killed more than 2 million people worldwide. In November 2020, the World Health Organization (WHO) named him to a 10-person team that is examining how the COVID-19 pandemic emerged. At the same time, Leendertz is worrying about how the coronavirus might affect great apes if it spreads to those vulnerable species.

Just 30 minutesafter the message arrived, Leendertz and two other veterinarians, Penelope Carlier and Bernard Ngbocho Nguessan, set off to find the carcass. After a kilometre or so, they passed a group of sooty mangabey monkeys lounging on logs. The animals, even a mother hugging a baby to her belly, appeared undisturbed by the hikers. That is because the monkeys had been habituated; researchers followed them for years until they grew used to humans.

In 1979, primatologists Christophe Boesch and Hedwige Boesch-Achermann came to the forest, one of the last large swaths of rainforest in West Africa, to study chimpanzee behavior. Over years, they habituated chimps, mangabeys, and several other kinds of monkeys, and began documenting their lives. But then, in 1994, the chimpanzees started to die. Eight of 43 study animals turned up dead; four more disappeared.

Before necropsying wild animals, Fabian Leendertz and Kouadio Leonce don protective gear.

The researchers hauled one chimps body back to their camps sturdy dining table for dissection. They wore gloves, but no gowns or masks, and 1 week later one woman fell ill. She recovered, but scientists isolated a virus from her blood. It was a new species of Ebola, a group of viruses already known from human outbreaks elsewhere in Africa, and the dead chimp carried it, too. The discovery of what became known as Ta forest Ebola marked the first time an Ebola outbreak had been documented in nature.

The experience was a wake-up call from both a safety and a scientific perspective, says Boesch, who retired as director of the Max Planck Institute for Evolutionary Anthropology in 2019. In retrospect it is clear that we ran a risk; we were not prepared at all, we had no equipment. And it made the researchers realize that infectious diseases could be playing a larger role in wildlife mortality than they realized. We cannot go on like this, Boesch recalls thinking. They needed a trained veterinarian, and in 2001 Leendertz got the job.

It was the kind of position he had long coveted. Growing up in Krefeld, Germany, Leendertz had bred mice and toads and spent a lot of time at the local zoo. (The director was a friend of his parents.) At university, he began to study biology but grew frustrated. It was just way too much biochemistry, he recalls, including countless hours in the laboratory running polymerase chain reactions (PCRs) to amplify snippets of DNA. All these PCRs were so far removed from working with actual animals, he says, so he switched to veterinary medicine.

In 1999, after completing his undergraduate studies and working in Namibia for a few months, Leendertz reached out to Boesch, asking whether he could join the Ta project. The reply was yesif Leendertz found an academic laboratory that would help support his graduate studies.

That wasnt easy. But Beatrice Hahn, a virologist at the University of Pennsylvania, had just published work showing HIV, the virus that causes AIDS in humans, had come from chimpanzees. The discovery ignited scientific interest in zoonoses, diseases that jump from animals to humans. That was kind of the first big aha! moment about zoonotic disease, Goldberg says. It helped Leendertz find a home at the Robert Koch Institute and ensured that, from the start, he would focus on both veterinary and human medicine.

Researchers draw blood from a dog in a village in Ivory Coast as part of their efforts understand how pathogens move among species.

Starting in 2001, Leendertz spent 14 months at Ta, following chimpanzees through the forest, collecting feces, and conducting necropsies. That was the real starting point for my work, he says. The conditions didnt bother him. He was content to be outdoors and largely cut off from the world, able to send and receive emails just once a week though a satellite connection. Leendertz didnt see images of the planes hitting New York Citys twin towers in 2001 until the year after the attack, after he emerged from his sojourn in the forest.

After a long march,the team found what was left of the dead duiker, surrounded by buzzing flies. Leendertz and Carlier suited up: masks, body suits, face shields, layers of gloves. They filled a bucket of bleach to disinfect equipment. Then they began cutting snippets of tissue and collecting blood, even grabbing a few maggots, which would be liquefied and analyzed for any pathogens they carried.

Moving deliberately around the forest in their gleaming white suits, the researchers looked like investigators at a crime scene. They were, in a way, with the added complication that the killer might still be lurking nearby. Leendertz has been following one suspect in particular since his first stint in the Ta forest. He was watching a group of chimpanzees when an alpha male named Leo suddenly vomited. Then, He climbed on this low branch, toppled over, and died, Leendertz recalls. I was stunned.

The killer, Leendertz and his group reported inNaturein 2004, was anthrax. It later became clear, however, that the cause was not the usual anthrax bacterium, but an unusual variant ofBacillus cereus, a soil bacterium that is usually benign. But this variant had acquired two circles of DNA, called plasmids, that had turned it into a formidable killer.

Subsequent work showed the bacterium was attacking other Ta forest mammals, too, including monkeys, mongooses, and porcupines. In 2017, the team published evidencegathered from bones, carcasses, and even fliesthat it appeared to be associated with 38% of 279 deaths the team had investigated from 1996 to 2015. The work was a reminder, Leendertz says, that we understand very little about what animals really die of in an environment like this.

Most worrying, theNaturepaper presented simulations showing anthrax could help wipe out the Ta forests chimpanzees within 150 years. And anthrax is not the only disease threatening the chimps, other work by Leendertzs team has shown. On top of all of the deforestation, the poaching they are just getting bashed by these infectious diseases, says primatologist Kimberley Hockings of the University of Exeter.

Some of those deadly diseases come from humans, Leendertz and colleagues reported in 2008 inCurrent Biology. After investigating five respiratory disease outbreaks that had struck Ta chimpanzees between 1999 and 2006, killing at least 15 individuals, the researchers concluded they were linked to two viruses that commonly cause mild disease in humans: human respiratory syncytial virus and human metapneumovirus. Our results suggest that the close approach of humans to apes, which is central to both research and tourism programs, represents a serious threat to wild apes, they wrote.

In Ivory Coast, veterinarian Fabian Leendertz traps bats to test for Ebola virus.

The idea was not new. Jane Goodall, the prominent primatologist, had described a pneumonia outbreak that killed several chimpanzees; researchers believed it was caused by a human-introduced pathogen. But theCurrent Biologystudy, and a similar viral outbreak documented in Tanzania, highlighted the threat of what Goldberg calls reverse zoonoses. Its a world of viruses that are crossing species in every direction, he says. And whenever that happens, it can cause devastating losses. (Goldberg has shown that the most common human cold virus, rhinovirus C, caused a deadly 2013 outbreak among chimpanzees in Uganda.)

The 2008 study also presented a dilemma for primate researchers such as Boesch, who was one of the co-authors. It suggested that even as they studied and worked to protect apes, they might be killing them, too. So, to reduce the risk of future outbreaks, the Ta researchers imposed new restrictions: Incoming staff must quarantine at the camp for 5 days before going into the forest, and everyone must stay at least 7 meters from study animals as well as wear masks while observing. Leendertz, meanwhile, pushed hard for field sites and tourism firms elsewhere to adopt similar measures, co-authoring safety guidelines published in 2015.

Such efforts really opened peoples eyes [that we needed] to be a lot more careful, Hockings says. But, It was a very controversial thing before COVID, Goldberg adds. People were afraid that tourists would be angry if you tried to make them wear a mask, that the apes would be afraid of the masks and attack tourists that foreign governments would get less money from tourism.

Today, Leendertz says helping catalyze such practical, real-world change is among his proudest accomplishments. And he says the experience only underscored the value of long-term, multifaceted studies of wildlife mortality. The threat that infectious diseases pose to chimpanzees was long underestimated and hardly studied, he says. They were neglected for a long time.

DESPITE HIS LOVE of fieldwork, Leendertz is spending less time in the Ta forest these days, visiting just once or twice a year. When my feet are hurting because Im not used to the long distances anymore, and when I get up in the morning from that moldy mattress, I do think that time is over, he says. Still, he says, When I arrive it really is that feeling of coming home.

At the Robert Koch Institute, meanwhile, Leendertzs lab is busy with samples shipped by colleagues in the forest. Located in a brand-new building that also houses one of the worlds newest biosafety level four high-biosecurity labs, the lab uses state-of-the-art technologies to identify and characterize the pathogens found in the samples. Ironically, Leendertz notes, Im back to doing PCRs. Recently, for example, the samples collected from the dead duiker in 2019 were analyzed. The antelope was, as suspected, infected with anthrax.

A research team heads into Kanankru, Ivory Coast, to search for bats, which have been implicated in outbreaks of Ebola and other deadly diseases.

Such molecular sleuthing isnt just about identifying animal killers. Leendertz notes that, when paired with careful field observations, lab findings can yield important insights into protecting human health. In 2017, for instance, some Ta chimpanzees began to cough and display respiratory distress. Lab work showed the cause was monkeypox, a less deadly relative of smallpox that can move from primates to humans. In humans, monkeypox often announces itself through a skin rash, but Leendertzs work suggests coughing is an unusual symptom that health workers working in communities near primate populations should keep in mind.

More recently, Leendertzs team has discovered that leprosyanother disease with the potential to jump to humansaffects wild chimpanzees too. In 2017, Hockings, who studies chimpanzees in Guinea-Bissaus Cantanhez National Park, observed animals with lesions on their faces and hands. She shared her observations with Leendertz, and soon afterward he noticed similar lesions on Woodstock, a Ta chimpanzee. By analyzing fecal samples, the researchers confirmed the lesions were caused by leprosy, a disease never before seen in wild chimpanzees.

The discovery has highlighted how little is known aboutMycobacterium leprae, the bacterium that causes leprosy, says immunologist John Spencer of Colorado State University, Fort Collins. Researchers cant culture the microbe in the laboratory and, although they have found it circulating in armadillos and red squirrels, it hadnt been seen in apes. The chimp find suggests leprosy has other niches that it has adapted to, Spencer saysand adds one more pathogen to the growing roster of diseases that afflict both humans and other animals.

If Leendertz has builthis career on the dual concerns of human and chimpanzee health, then the emergence of SARS-CoV-2 has brought these two issues together with new urgency. The virus now rampaging through human populations is a potential threat to great apes as well, Leendertz and primatologist Tom Gillespie of Emory University warned in a letter published inNaturein March 2020. To reduce the risks, they asked governments to suspend ecotourism and researchers to reduce field research, and many complied.

Since then, gorillas at the San Diego Zoo have tested positive for SARS-CoV-2. They showed only mild symptoms, but that is not very reassuring, Gillespie says, because captive animals tend to be well fed and be less burdened with other infections. Its really hard to say from captive studies what we would see in the wild, he says.

Looking ahead, Leendertz says, The question is how to get back to a more normal situation for primate scientists. One concrete step could be to vaccinate researchers and people living around field sites like Ta, he suggests.

In the meantime, WHO has asked Leendertz to join its investigation into the origins of SARS-CoV-2. That appointment makes sense scientifically and politically, colleagues say. Leendertzs years of patient, intensive focus on understanding death in a single rainforest have given him a valuable perspective on how to investigate pathogens hopping from one species to another, as SARS-CoV-2 is believed to have done. And he represents the Robert Koch Institute, Germanys equivalent of the U.S. Centers for Disease Control and Prevention. I see the WHO mission as about 50% actual science and 50% building bridges with Chinese colleagues, Goldberg says. I think Fabian will do well on both fronts.

But Leendertz also knows from past experience with virus hunts that definitive answers can be hard to come by. In 2014, he led a team that traveled to Meliandou, Guinea, shortly after the start of an Ebola outbreak that ultimately killed some 1000 people. The researchers interviewed villagers, who told them about a hollow tree where the child who had been the first to get sick had played.

When the team visited the tree, they discovered it had burned (whether by accident or intention wasnt clear). On the blackened stump, they found traces of DNA left behind by bats that had apparently roosted in the tree. Had an encounter between the child and a bat sparked the outbreak? It was a plausible scenario, they concluded, but there would likely never be proof.

The chain of events that led to the COVID-19 pandemic is likely to be far more elusive. And the WHO investigation has gotten off to a bumpy start. When the team first tried to visit China earlier this month, officials barred several members from entering because of pandemic restrictions. Leendertz himself could not join the trip because of a family commitment. So, while his colleagues conducted Zoom meetings from the hotel rooms where they were quarantined after arriving in China, Leendertz joined from his home, where it was 2:30 a.m. It was another kind of breakfast TV, just not the episode he enjoys the most.

Read the rest here:
This wildlife vet tracks deadly microbes in the African jungle. Now, he's on the trail of COVID-19 - Science Magazine

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