Orangutan Health Offers Insights for Human Respiratory Disease | 2024 ATS

Ecosystem health, animal health and human health are closely intertwined. Interdisciplinary collaboration between veterinarians and physicians can help each understand the larger picture of disease, said speakers at a plenary session at the 2024 American Thoracic Society (ATS) International Conference in San Diego.

Joining forces has been especially helpful when it comes to efforts to diagnose and treat the respiratory illnesses of orangutans, many of which mirror the lung-related illnesses that affect people, said the experts who spoke at the plenary session.

Human and orangutans share about 97% of their genome with humans and have similar medical physiology and disease processes. Orangutans can contract human respiratory pathogens, resulting in acute and chronic airway disease, said Nancy Lung, V.M.D., M.S., editor in chief of the Journal of Zoo and Wildlife Medicine.

Orangutans are native to the Southeast Asian islands of Sumatra and Borneo. But the orangutan population has declined significantly over the past 50 years, and they are listed as endangered. This is mostly due to deforestation of their natural habitat, Lung said.

Much of the rainforest where orangutan live have been lost to plantations of oil palm trees that yield palm oil, a versatile vegetable oil that is prized partly because it has a long shelf life. Palm oil is in many foods, including pizza dough, chocolate, ice cream, cookies and packaged bread, and soaps, detergents and lipstick.

“What's happening in Indonesia and more recently, in Africa and in South America, is a well-organized, multibillion dollar corporate takeover of the rainforest to replace those forests with monocultures of oil palm,” Lung said during her ATS presentation.

She said that between zoos around the world and rescue centers, the orangutan population is about 2,000 worldwide. But about 20% of orangutans experience a respiratory disease similar to human cystic fibrosis. The disease, which is called orangutan respiratory disease syndrome (ORDS), is a chronic condition that affects the sinuses, the air sacs and lungs and is the leading cause of death among adolescent and adult orangutans.

Jennifer Taylor-Cousar, M.D.

“Orangutan respiratory disease syndrome is a constellation of recurrent infections in the sinuses in the airways of these animals. Over time, these recurrent infections lead to progressive airway destruction and early death,” said Jennifer Taylor-Cousar, M.D., MSCS, ATSF, pediatric and adult pulmonologist at National Jewish Health, a leading respiratory hospital in Denver.

She said animal health researchers have had some theories about the causes of ORDS, ranging from exposure to toxins or people to disease spread through fecal matter that is the result of overcrowding in zoos and rescue centers to the the stress of captivity causing immunosuppression and greater chances of respiratory infection

Now investigators are looking at whether ORDS results from variants of the cystic fibrosis transmembrane conductance regulator (CFTR). In people, patients with cystic fibrosis inherit two copies of a mutated CFTR gene. These mutated genes disrupt the function of the CFTR protein found in lung cells, which leads to a build-up of mucus and lung infections, as well as destruction of the pancreas.

Taylor-Cousar, along with Garry R. Cutting, M.D., in the McKusick-Nathans Institute of Genetic Medicine of the Johns Hopkins University School of Medicine, published a study in January 2020 of 50 orangutans, 10 of which had chronic respiratory signs and symptoms. They found one potentially lethal variation of a CFTR allele in a healthy orangutan that is not found in humans. This altered gene was also found in the orangutan’s offspring that had died before birth.

But Taylor-Cousar and her colleagues did not find any other cystic fibrosis disease causing CFTR mutations in the remaining population studied. “The fact that we did not find CFTR mutations in the 10 animals with the respiratory disease does not diminish the possibility of having mutations elsewhere in the genome,” they wrote.

During the ATS meeting, Taylor-Cousar said that in the future, they plan to do a genomewide association study on these animals to try to identify what exactly is causing this respiratory disease.

Diseases in animals can provide insight about human health and vice versa, both Taylor-Cousar and Lung said during the session. “This is something we are beginning to understand, even more so because of climate change and its impact on environment and human health,” Taylor-Cousar said. “Interdisciplinary collaborations are necessary in the long run.”