China bets big on brain research with massive cash infusion and openness to monkey studies | Science

After 5 years of planning and debate, China has finally launched its ambitious contribution to neuroscience, the China Brain Project (CBP). Budgeted at 5 billion yuan ($746 million) under the latest 5-year plan, the CBP will likely get additional money under future plans, putting it in the same league as the U.S. Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which awarded $2.4 billion in grants through 2021, and the EU Human Brain Project, budgeted at $1.3 billion. The project “is really on the move,” says one of its architects, neuroscientist Mu-ming Poo, head of the Chinese Academy of Sciences’s (CAS’s) Institute of Neuroscience (ION).

The details of the project remain murky. But China’s researchers “seem to be building on their strengths, which is great,” says neuroscientist Robert Desimone of the Massachusetts Institute of Technology, who collaborates with colleagues in China. The CBP focuses on three broad areas: the neural basis of cognitive functions, diagnosing and treating brain disorders, and brain-inspired computing. Monkey studies will play a key part in the research, and project leaders hope the virtual absence of animal rights activism in China will help lure talent from overseas. (Poo himself studied and worked in the United States for 40 years, including a decade at the University of California, Berkeley, and moved to China full-time in 2009.)

Neuroscience was first identified as a priority in China’s 2016 Five-Year Plan, but soon became “a very contentious project,” says Denis Simon, a China science policy expert at Duke University. “There was hefty debate and discussion about how to choose projects, set priorities, and allocate funds,” Simon says. Deliberations dragged on until brain science was again designated as a priority field in the 2021 Five-Year Plan, adopted in March 2021. Funding for the CBP finally started to flow in December 2021, Poo says.

The acrimony continued. The money will be shared among 11 designated centers and about 50 research groups selected by an organizing committee that Poo heads. Neurobiologist Yi Rao, president of Capital Medical University, told Science all 11 selected institutes are represented on the committee, which creates conflicts of interest. “Everyone tends not to oppose the targeted projects proposed by others, so that the projects they support can also be adopted smoothly,” he wrote in a 23 January social media post. Poo declined to comment on the criticism; several other neuroscientists in China did not answer emails seeking comment on the CBP.

Who will benefit most from the plan is hard to determine. Science could not find any official announcements of the awards to designated centers or grant recipients, and Poo declined to provide such numbers. Calls to China’s Ministry of Science and Technology seeking information proved futile.

Still, Desimone says it’s clear that the CBP, with its focus on treatments and basic work with primates, complements the EU and U.S. schemes. The BRAIN Initiative, announced in 2013, is more focused on tools and technologies. Europe’s Human Brain Project started off, also in 2013, as a plan to build a computer model of the human brain, although its research objectives were broadened after that goal was criticized as unrealistic.

One Chinese strength the CBP plans to expand on is imaging. A group led by Qingming Luo, president of Hainan University, has refined and automated a technique named fluorescence micro-optical sectioning tomography (fMOST) to slice and image microns-thick ribbons of tissue from blocks of mouse brains. Computers reconstruct the data into 3D views of neurons and their connections. fMOST “provided a foundational data set for understanding and identifying the diverse cell types in the mouse brain,” says Hongkui Zeng, director of the Allen Institute for Brain Science, which is collaborating with the U.S. BRAIN Initiative.

Now, Luo’s team plans to do the same for the macaque brain, which is 200 times bigger, aiming to produce a “mesoscale connectome”—something like a wiring diagram. The effort will complement new brain-mapping programs under the BRAIN Initiative, says the initiative’s director, John Ngai of the U.S. National Institutes of Health. He and Poo are discussing cooperation.

China is already a leader in another CBP focus area, the development of disease models in monkeys. Poo’s team made headlines in 2019 by combining cloning with gene editing to produce five genetically identical macaques that lacked a key gene regulating the circadian clock. The cloning proved inefficient; the group used 325 gene-edited embryos and 65 surrogate females to create the five animals. But the gene deletion had dramatic effects: The animals exhibit sleep disorders, increased anxiety, and depression. Poo’s group has also used gene editing to produce monkeys predisposed to Alzheimer’s disease. Other ION researchers are developing techniques for crippling genes in monkeys to induce symptoms of amyotrophic lateral sclerosis, says Stanford University neuroscientist Aaron Gitler, who studies ALS and has spent the past year on sabbatical at ION.

Poo intends to share his team’s animal models. But because major airlines no longer carry nonhuman primates as cargo, researchers will have to visit the International Center for Primate Brain Research, which receives funding from the city of Shanghai and CAS and is not part of the CBP. The center is led by Poo and neuroscientist Nikos Logothetis, who over the past 2 years moved most of his team from the Max Planck Institute for Biological Cybernetics after his lab was targeted by animal rights activists.

Logothetis, who declined an interview request, is unlikely to have similar problems in China. “There is some but not a lot of concern about animals used in research, but there is no animal rights group focusing on this area,” says Deborah Cao, an animal law and welfare expert at Griffith University, Nathan. Still, Chinese researchers are striving to “replace, reduce, and refine” animal experiments, says Ji Dai, a neuroscientist at CAS’s Shenzhen Institutes of Advanced Technology. Even in China, policies on handling animals are getting stricter, he says.

For now, China is expanding the number of nonhuman primates in its research centers. The Kunming Institute of Zoology is completing a new facility that, with space for 5000 monkeys, will be China’s largest, says Bing Su, a geneticist there. CAS institutes in Shanghai already have more than 1000 animals and may double or triple that number, Poo says. He adds a monkey breeding and research center in Hainan province may hold 20,000 animals a decade from now. For comparison, the United States’s seven National Primate Research Centers hold 18,000 to 20,000 nonhuman primates.

The CBP may face other challenges. China’s stringent zero–COVID-19 policy has led to draconian control measures; Shanghai, one of China’s top research cities, shut down entirely in April and May. Such restrictions have “expats bailing out of China,” Gitler says. “We’ll see how that affects the ability of Mu-ming and others to recruit people.”

Another question is whether political friction between China and the West will dent cooperation. Desimone sees little impact on life science collaborations at the moment. “But I don’t have a crystal ball about international tensions in the future,” he says.

After 5 years of planning and debate, China has finally launched its ambitious contribution to neuroscience, the China Brain Project (CBP). Budgeted at 5 billion yuan ($746 million) under the latest 5-year plan, the CBP will likely get additional money under future plans, putting it in the same league as the U.S. Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative, which awarded $2.4 billion in grants through 2021, and the EU Human Brain Project, budgeted at $1.3 billion. The project “is really on the move,” says one of its architects, neuroscientist Mu-ming Poo, head of the Chinese Academy of Sciences’s (CAS’s) Institute of Neuroscience (ION).

The details of the project remain murky. But China’s researchers “seem to be building on their strengths, which is great,” says neuroscientist Robert Desimone of the Massachusetts Institute of Technology, who collaborates with colleagues in China. The CBP focuses on three broad areas: the neural basis of cognitive functions, diagnosing and treating brain disorders, and brain-inspired computing. Monkey studies will play a key part in the research, and project leaders hope the virtual absence of animal rights activism in China will help lure talent from overseas. (Poo himself studied and worked in the United States for 40 years, including a decade at the University of California, Berkeley, and moved to China full-time in 2009.)

Neuroscience was first identified as a priority in China’s 2016 Five-Year Plan, but soon became “a very contentious project,” says Denis Simon, a China science policy expert at Duke University. “There was hefty debate and discussion about how to choose projects, set priorities, and allocate funds,” Simon says. Deliberations dragged on until brain science was again designated as a priority field in the 2021 Five-Year Plan, adopted in March 2021. Funding for the CBP finally started to flow in December 2021, Poo says.

The acrimony continued. The money will be shared among 11 designated centers and about 50 research groups selected by an organizing committee that Poo heads. Neurobiologist Yi Rao, president of Capital Medical University, told Science all 11 selected institutes are represented on the committee, which creates conflicts of interest. “Everyone tends not to oppose the targeted projects proposed by others, so that the projects they support can also be adopted smoothly,” he wrote in a 23 January social media post. Poo declined to comment on the criticism; several other neuroscientists in China did not answer emails seeking comment on the CBP.

Who will benefit most from the plan is hard to determine. Science could not find any official announcements of the awards to designated centers or grant recipients, and Poo declined to provide such numbers. Calls to China’s Ministry of Science and Technology seeking information proved futile.

Still, Desimone says it’s clear that the CBP, with its focus on treatments and basic work with primates, complements the EU and U.S. schemes. The BRAIN Initiative, announced in 2013, is more focused on tools and technologies. Europe’s Human Brain Project started off, also in 2013, as a plan to build a computer model of the human brain, although its research objectives were broadened after that goal was criticized as unrealistic.

One Chinese strength the CBP plans to expand on is imaging. A group led by Qingming Luo, president of Hainan University, has refined and automated a technique named fluorescence micro-optical sectioning tomography (fMOST) to slice and image microns-thick ribbons of tissue from blocks of mouse brains. Computers reconstruct the data into 3D views of neurons and their connections. fMOST “provided a foundational data set for understanding and identifying the diverse cell types in the mouse brain,” says Hongkui Zeng, director of the Allen Institute for Brain Science, which is collaborating with the U.S. BRAIN Initiative.

Now, Luo’s team plans to do the same for the macaque brain, which is 200 times bigger, aiming to produce a “mesoscale connectome”—something like a wiring diagram. The effort will complement new brain-mapping programs under the BRAIN Initiative, says the initiative’s director, John Ngai of the U.S. National Institutes of Health. He and Poo are discussing cooperation.

China is already a leader in another CBP focus area, the development of disease models in monkeys. Poo’s team made headlines in 2019 by combining cloning with gene editing to produce five genetically identical macaques that lacked a key gene regulating the circadian clock. The cloning proved inefficient; the group used 325 gene-edited embryos and 65 surrogate females to create the five animals. But the gene deletion had dramatic effects: The animals exhibit sleep disorders, increased anxiety, and depression. Poo’s group has also used gene editing to produce monkeys predisposed to Alzheimer’s disease. Other ION researchers are developing techniques for crippling genes in monkeys to induce symptoms of amyotrophic lateral sclerosis, says Stanford University neuroscientist Aaron Gitler, who studies ALS and has spent the past year on sabbatical at ION.

Poo intends to share his team’s animal models. But because major airlines no longer carry nonhuman primates as cargo, researchers will have to visit the International Center for Primate Brain Research, which receives funding from the city of Shanghai and CAS and is not part of the CBP. The center is led by Poo and neuroscientist Nikos Logothetis, who over the past 2 years moved most of his team from the Max Planck Institute for Biological Cybernetics after his lab was targeted by animal rights activists.

Logothetis, who declined an interview request, is unlikely to have similar problems in China. “There is some but not a lot of concern about animals used in research, but there is no animal rights group focusing on this area,” says Deborah Cao, an animal law and welfare expert at Griffith University, Nathan. Still, Chinese researchers are striving to “replace, reduce, and refine” animal experiments, says Ji Dai, a neuroscientist at CAS’s Shenzhen Institutes of Advanced Technology. Even in China, policies on handling animals are getting stricter, he says.

For now, China is expanding the number of nonhuman primates in its research centers. The Kunming Institute of Zoology is completing a new facility that, with space for 5000 monkeys, will be China’s largest, says Bing Su, a geneticist there. CAS institutes in Shanghai already have more than 1000 animals and may double or triple that number, Poo says. He adds a monkey breeding and research center in Hainan province may hold 20,000 animals a decade from now. For comparison, the United States’s seven National Primate Research Centers hold 18,000 to 20,000 nonhuman primates.

The CBP may face other challenges. China’s stringent zero–COVID-19 policy has led to draconian control measures; Shanghai, one of China’s top research cities, shut down entirely in April and May. Such restrictions have “expats bailing out of China,” Gitler says. “We’ll see how that affects the ability of Mu-ming and others to recruit people.”

Another question is whether political friction between China and the West will dent cooperation. Desimone sees little impact on life science collaborations at the moment. “But I don’t have a crystal ball about international tensions in the future,” he says.