In September 2025, David Amaral’s team celebrated a long-awaited milestone: the birth of their first macaque with a variant in the CHD8 gene, which is linked to autism and co-occurring intellectual disability and macrocephaly.
The team had been working to create this model with collaborators at the Oregon National Primate Research Center since 2020. It could help them understand the condition’s neurobiology better than existing CHD8 mouse models can, and it might reveal, for example, what cell types contribute to the overgrowth of the brain, says Amaral, professor of psychiatry and behavioral sciences at the University of California, Davis.
His team has been meticulously genotyping and phenotyping that first animal, logging in-depth behavioral records and longitudinal MRI scans, and they are creating a second animal. He estimates that they need 10 genetically modified monkeys to adequately explore the causes of megalencephaly.
But Amaral says he worries about the future of this work. After negotiations earlier this year about potentially converting the Oregon primate center into an animal sanctuary, the facility plans to downsize and pivot to nonanimal models—and it’s unclear which monkey research will continue. The center, home to an artificial reproductive technology core that doesn’t exist at other primate centers in the United States, is essential to his project, Amaral says. “A lot of what we’re doing in terms of genetically modified monkeys is being done at the Oregon National Primate Research Center.”
For now, the team is proceeding as if the Oregon center will keep being able to produce genetically modified macaques—but if they lose access to the facility, the project could end prematurely, he says.
There are now more than half a dozen monkey models of autism and related conditions, based on natural social variation, maternal infection and genetic modification. And more are in the works. But even as these projects show promise, researchers express a mix of concerns about the future, including how to maintain the international collaborations, resources and technical expertise required to run these efforts—particularly in the U.S., amid cuts to primate research funding and a broader push to move away from animal models. Some say they are already feeling the effects: One researcher, who requested anonymity because of concerns about their continuing work and funding, said that these changes have led them to put their work in nonhuman primate autism models on hold. Three other scientists who work with monkey models of autism in the U.S. did not respond to The Transmitter’s interview requests, and another declined.
Funding cuts and delays have the potential to cause long-lasting problems. Running out of cash could require letting go of people with specialized expertise or even depopulating a primate colony—and rebuilding after such losses would be “extremely difficult,” says Michael Platt, professor of neuroscience at the University of Pennsylvania, who has studied social behaviors in monkeys.
Those changes could also affect the pipeline. “It’s hard to be optimistic,” Amaral says. “I’d love to see some younger investigators take up the idea of doing nonhuman primate models of autism, but it would be a very hard sell at the moment because it is so difficult to get grants and because of the perception that maybe this is not something that is going to be funded long term.”
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growing body of evidence suggests that using monkey models can address some of the limitations of other animal models for studying autism and related brain conditions, says Guoping Feng, professor of brain and cognitive sciences at the Massachusetts Institute of Technology (MIT). Mice lack some autism-linked brain regions, such as the dorsolateral prefrontal cortex, for instance, and they don’t reliably model social deficits.One of the first genetically modified primate models of autism originated in China. More than 10 years ago, Feng and his colleague Robert Desimone, professor of brain and cognitive sciences at MIT, began a collaboration with researchers at the Shenzhen Institutes of Advanced Technology to create macaque monkeys with variants in SHANK3, a gene strongly linked to autism.
Heterozygous SHANK3 monkeys, unlike heterozygous SHANK3 mice, exhibit characteristics—sleep disturbances, abnormal social interactions, cognitive impairment, repetitive behaviors, altered functional connectivity in the brain—that parallel those seen in people carrying SHANK3 variants, the team has found.
These macaques remain in China, because MIT—like most U.S. research institutions other than the seven federally supported primate research centers—lacks the space and facilities to house the large number needed for this type of work, Desimone says. But he and Feng brought the knowledge gained from this work back to the U.S. to establish a SHANK3 model in marmosets.
“Macaque transgenic work is very difficult in the U.S.,” Desimone says, because it requires large numbers of animals, as well as people with gene-editing expertise. Marmoset work is also expensive but is “much more feasible,” because the animals are smaller and easier to handle and breed, he adds.
Desimone currently uses marmosets to study the effect of SHANK3 variants on face-processing areas, which don’t exist in mice. And Feng has used both the macaque and marmoset SHANK3 models to test a novel therapy, injecting a functional SHANK3 “minigene” directly into the central nervous system. Although Feng developed that treatment in mice, he says the monkey models have provided critical insights into safety and efficacy.
“We’re not saying that a monkey model is required for clinical trials, but these studies do give us confidence that these treatments are safe and effective,” Feng says. (Feng’s SHANK3 gene therapy has been licensed to a biotechnology company, Jaguar Gene Therapy, which is investigating the therapeutic in a clinical trial.)
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esimone and Feng both say they have sufficient financial support from the U.S. National Institutes of Health and philanthropic organizations to keep their studies going, but they have concerns about the broader landscape: In addition to potential losses in government funding in the U.S., attitudes toward collaborations—like their own—with other countries that do invest in this research, especially China, have also shifted dramatically in recent years.“If it turns out in the future that [monkey models] are critical for developing medicines for brain disorders,” Feng says, “then other countries will be way ahead of us.”
Indeed, neuroscience research in nonhuman primates remains active in other countries, including China and Japan, where there are permissive attitudes toward animal research. The China Brain Project, a 5 billion yuan (about $750 million) initiative launched in 2022 to boost neuroscience in China, put nonhuman primate studies at its core. In addition to using SHANK3 monkeys, Chinese scientists have genetically engineered monkeys with other autism-related variants, such as MECP2 and CHD8.
Policymakers in Japan have generally supported primate work. That country’s national brain project focused on mapping the marmoset brain and using those animals to generate models of neurodevelopmental and neurodegenerative diseases. Although the latest iteration of that initiative puts more emphasis on human research, “nonhuman primate research is still quite active,” says Noritaka Ichinohe, senior researcher at the National Center of Neurology and Psychiatry in Japan. Ichinohe’s group has developed a marmoset model of autism based on valproic acid exposure and is using these animals to study underlying neurobiology, potential biomarkers and interventions.
“Nonhuman primate research, especially neuroscience research, looks more active in China than the other countries, and several primate models of neurodevelopmental disorders have been established and published,” says Yongchang Chen, principal investigator in nonhuman primate models of CNS disease at the Kunming University of Science and Technology, who has developed macaque models of MECP2, the Rett syndrome gene that has also been linked to autism.
Even so, Chen adds, the number of research groups doing this type of work is still small, and these studies require experienced scientists, specialized facilities and complex platforms for collecting behavioral, imaging and other data. On top of that, this type of research is costly—these studies typically involve a large number of animals and big teams of researchers, according to Zhonghua Lu, professor at the Shenzhen Institutes of Advanced Technology, who collaborates with Feng and Desimone. The latest SHANK3 monkey study, which involved collecting extensive behavioral phenotypes and neuroimaging data for 15 animals, required eight full-time technicians and engineers, Lu says. Even in China, the funds needed to support these kinds of primate projects can be increasingly difficult to come by, particularly as the government favors brain-computer interface research, he adds.
Looking ahead, many autism researchers have been turning to organoids and other complex in-vitro models and intraoperative recordings in humans. Although these technologies have advanced over the past decade or so, some studies, such as those that involve testing novel gene therapies, require living animals—at least for the time being. “Each model, whether it is a single cell, yeast, rodents, primates or humans, is a good model for certain questions,” Feng says. “No model is perfect. Not even a human is a perfect model for another human.”
