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 five-year plan, CBP is likely to receive additional funding under future plans, putting it in the same league as US 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,” said one of the architects, neuroscientist Mu-ming Poo, head of the Institute of Neuroscience (ION) at the Chinese Academy of Sciences (CAS).

The details of the project remain obscure. But the Chinese researchers “seem to be building on their strengths, which is great,” said neuroscientist Robert Desimone of the Massachusetts Institute of Technology, who works 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 role in the research, and project leaders hope the virtual absence of animal rights activism in China will help attract talent from abroad. (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 it quickly became “a highly controversial project,” said Denis Simon, a China science policy expert at Duke University. “There was a strong discussion and discussion about how to choose projects, prioritize and allocate funds,” says Simon. The deliberations dragged on until brain science was redesignated as a priority area in the 2021 Five-Year Plan, which was adopted in March 2021. Funding for the CBP finally started flowing in December 2021, Poo says.

The bitterness continued. The money will be distributed among 11 designated centers and about 50 research groups selected by an organizing committee that Poo leads. Neurobiologist Yi Rao, president of Capital Medical University, said: Science all 11 selected institutes are represented on the committee, creating a conflict 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 Jan. 23 social media post. Poo declined to comment on the criticism; several other neuroscientists in China did not answer emails requesting comment from the CBP.

It is difficult to determine who will benefit most from the plan. Science could find no official announcements of prices to designated centers or grant recipients, and Poo declined to provide such numbers. Calling the Chinese Ministry of Science and Technology to ask for information proved futile.

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

One of the Chinese strengths that the Dutch DPA wants to expand is imaging. A group led by Qingming Luo, president of Hainan University, has refined and automated a technique called fluorescence micro-optical section tomography (fMOST) to cut and image micron-thick tissue ribbons from blocks of mouse brains. Computers reconstruct the data into 3D representations of neurons and their connections. fMOST “provided a fundamental dataset for understanding and identifying the different cell types in the mouse brain,” said Hongkui Zeng, director of the Allen Institute for Brain Science, which works with the US BRAIN Initiative.

Now Luo’s team plans to do the same for the macaque brain, which is 200 times larger, with the goal of producing a “mesoscale connectome” — something like a wiring diagram. The effort will complement new brain mapping programs under the BRAIN initiative, said the initiative’s director, John Ngai of the US National Institutes of Health. He and Poo discuss 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 that regulates the circadian clock. 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 show sleep disturbances, increased anxiety and depression. Poo’s group has also used gene editing to produce monkeys prone to Alzheimer’s disease. Other ION researchers are developing gene paralysis techniques in monkeys to induce symptoms of amyotrophic lateral sclerosis, says Stanford University neuroscientist Aaron Gitler, who studies ALS and spent the past year on a sabbatical at ION.

Poo plans to share his team’s animal models. But because major airlines no longer carry non-human 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 has spent the past 2 years moving 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 face similar problems in China. “There is some, but not much, concern about animals being used in research, but there is no animal rights group focusing on this area,” said Nathan Deborah Cao, an animal rights and welfare expert at Griffith University. Still, Chinese researchers strive to “replace, reduce and refine animal testing,” said Ji Dai, a neuroscientist at CAS’s Shenzhen Institutes of Advanced Technology. Even in China, animal handling policies are getting stricter, he says.

For now, China is expanding the number of non-human primates in its research centers. The Kunming Institute of Zoology is completing a new facility that, with room for 5,000 monkeys, will be China’s largest, said Bing Su, a geneticist there. CAS institutes in Shanghai already have more than 1,000 animals and could double or triple that number, Poo said. He added that a monkey breeding and research center in Hainan province could house 20,000 animals in 10 years. By comparison, the United States’ seven National Primate Research Centers contain 18,000 to 20,000 non-human primates.

The Dutch DPA may be faced with other challenges. China’s strict zero-COVID-19 policy has led to draconian control measures; Shanghai, one of China’s most important research cities, is completely closed in April and May. Such restrictions have “expats leaving China,” Gitler says. “We’ll see how that affects Mu-ming and others’ ability to recruit people.”

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