On the occasion of “Cambridge Nanjing Forum 2021 – Summit of Brain Science and Brain-inspired Research”, Cambridge University - Nanjing Centre of Technology and Innovation interviewed Professor Heping Cheng, Professor of College of Future Technology, Peking University, and President of Nanjing Molecular Medicine Transformation Institute, Peking University, and he elucidated his understanding of brain science and brain-inspired research through our dialogue. Now, we would like to share Professor Cheng’s profound insights with all readers.
-Part 1 Academic Experience of Heping Cheng -
1. Would you please briefly introduce your academic course and main research fields?
Heping Cheng: I originally majored in mathematical physics and took a second degree in biology at Peking University. After obtaining my master’s degree in 1987, I worked as a teaching assistant in the Department of Radio Electronics of Peking University for two years, mainly assisting in digital circuit teaching. In 1990, I went to the University of Maryland to study for a doctorate in physiology and biophysics, and in 2006, I worked as a senior researcher at the National Institutes of Health (NIH). Since 1998, I have started the working mode of travelling between China and the United States, and in 2005, I participated in the establishment of the Institute of Molecular Medicine, Peking University.
My research focuses on cell biology and biophysics. In general, I have been working on calcium sparks for nearly 30 years, mitochondrial dazzle for nearly 20 years, and imaging instruments for nearly 10 years. At present, the research and development of miniaturized two-photon microscope is an important task of our team.
2. In what kind of opportunity you started to explore the world of life sciences?
Heping Cheng: When I studied in Peking University, I was an “experimental product” trained by tutors from different directions. After studying physics and biology, I realized the importance of cultivating experimental techniques, and then went to the Radio Department for further study. In the third year of college, Physiology, an introductory course, really aroused my interest in exploring life sciences. The logical and mathematical thinking contained in this course are very consistent with my background, and make me feel the intimacy and interest of life sciences. Therefore, I shifted my academic interest to this field, and determined it as my lifelong research direction.
-Part 2 Talks of Heping Cheng about Brain Science Research-
3. In recent years, what progress has been made in brain science and brain-inspired research in the world? What are the key scientific problems and challenges to be overcome?
Heping Cheng: From my personal experience, I summarize brain science research into four words, namely “reading”, “interpretation”, “writing” and “imitation”, which are all in progress at present.
As for reading, the brain is the most complex regionalized network in the universe, with tens of billions of neurons and their connections (a thousand times more than neurons). It is dynamic, not static, and its activity is not random, but meaningful. How to read its structure and obtain its functional image is a research direction;
Then, interpretation. For the acquired brain structure imaging and functional data, how to understand the organization and working principles of the brain from different levels, from the smallest cell to a neural loop for controlling depression to the whole brain, and how it works? When depression occurs, what problems exist in the corresponding neural circuits? All these need to be explored.
And writing means, on the basis of interpretation, physical or pharmacological means or their combination is adopted to regulate the abnormal state of the brain or enhance the brain function;
Imitation is mainly for brain-inspired research. Natural brain is the greatest miracle created by nature, and as Engels said, “Thinking is the most beautiful flower on the earth”. How to apply the principle of brain to artificial intelligent system? For our current intensive study on the neural network, we just apply individual principles of the brain. Many principles are used by natural brain, but have not yet been involved in artificial intelligence.
4. What kind of interdisciplinary subject is brain science and brain-inspired research? As an interdisciplinary field, what are its development directions and applications?
Heping Cheng: Brain science is the frontier of scientific research, just as “jewel in the crown”. It transcends life science and interweaves humanities, society, computation, information, psychology and many other disciplines closely. In the ongoing research on brain science, I think it mainly involves four aspects:
The first part involves optoelectronic, physical, mechanical and bioengineering technologies. As a research tool, it covers the fields of deep brain stimulation, intervention, imaging and regulation realized by using electrical, magnetic and ultrasonic technologies, among which optics, magnetic resonance, brain slices and other brain imaging researches occupy an important position. Following the structural imaging, functional imaging research is actually more important. A miniature two-photon fluorescence microscope that I am presiding over belongs to a brain-related functional imaging research.
The second part is the combination of mathematical methods and information technology, which uses mathematical tools to encode and decode massive data and extract meaning from it.
The third part involves clinical medicine, neuroscience and cognitive science, and includes the construction of the whole brain model, how the brain as a whole thinks and perceives stimuli and environment;
The fourth part can be extended to the humanities. The essence of how our culture is formed and how our language evolves is related to the brain.
5. Compared with traditional brain imaging technology, what are the advantages of your project "Multimodality and Trans-Scale Biomedical Imaging Facility"?
Heping Cheng: The project "Multimodality and Trans-Scale Biomedical Imaging Facility" is located in Huairou, Beijing. It is a general platform and integrates dozens of imaging modalities. As the chief scientist, I am responsible for the construction of the national imaging platform. The benefits of establishing such a large-scale comprehensive platform are obvious.
On the one hand, the brain is a more complex structure than the universe, and it is a dynamic and functional information processing structure. To study this complex structure integrated in less than one liter of volume, there is no tool that can solve all problems. We need to develop different tools, including simulation and integration, and describe our "brain universe" comprehensively by various means of photoelectromagnetic nucleus from different levels of micro, meso and macro. Any single means and scale of description are limited.
Moreover, we should not only "read" the data of brain, but also fuse the data of different scales through traditional mathematics, brain-inspired, artificial intelligence and other technologies. Therefore, we also designed a corresponding large-scale intelligent data analysis and processing platform.
We hope to reveal the rules of multiple scales and the relationship between them through the method of "imaging omics", which is the advantage of this platform and is especially suitable for brain science research. Expect more scientists to participate in the construction and solve the most concerning problems in human brain science.
6. What is your outlook and opinion on the development of brain science in the next five to ten years?
Heping Cheng: I think the last century was "the century of neuroscience". Compared with neuroscience, which focused on the molecular level and intracellular process, the current brain science research turned from the cell to the whole level, focusing on the whole concept from the cell to the neural circuit and then to the network. With the development of information technology, physical technology, computing ability, especially magnetoencephalogram (MEG), electroencephalogram (EEG) and other imaging technologies, brain science research that was previously not allowed to enter the door can be carried out. In the process of explosive development of brain science, we only see the beginning now. I believe this process will last for the next ten, twenty or even fifty years. Perhaps the 21st century we are experiencing will be named "Century of Brain Science".
If we look forward to the time scale of five to ten years, I think that on the one hand, we need to continue polishing research tools, and there is a very interesting analogy between the brain and the universe. At present, astronomy has a complete set of observation tools, and brain science also needs to build tools for obtaining brain information such as observation and imaging; On the one hand, we should increase our understanding of the brain and build analytical tools, especially the mathematical theory and calculation methods of the brain. Although the existing technology can observe the simultaneous activities of thousands of neurons, the mathematical theory of understanding the simultaneous activities of these neural networks needs to be strengthened, and it needs the continuous promotion of this generation and the next generation of scientists.
What's particularly interesting is that the brain-inspired intelligence we invented through the study of the brain will in turn help us analyze our own brain. Therefore, I think that in the next five to ten years, there will be some opportunities to promote brain research through brain-inspired research, and new tools will emerge, such as brain analysis tools at large network level. This is also the research point I want to pursue.
7. Broaden the time scale to the next 30 years, what is your outlook for the development of brain science?
Heping Cheng: By about 2050, firstly, I believe that we will have the technology to describe the brain state very accurately and non-destructively, and realize the closed-loop regulation of "reading" and "writing" on the brain operation. This closed-loop is very significant, for example, depression can be identified and regulated by drug assistance and brain-inspired technology (even without drugs), which is expected to fundamentally solve the depression problem.
Second, on the scale of thirty years, the development of brain science is expected to understand our thoughts, concepts and consciousness. At that time, disabled patients such as aphasia and stroke will be able to communicate with the world better, and patients with paralysis and limb injury will also be able to achieve healthy and happy normal life through brain-inspired regulation exoskeleton technology. It remains to be seen whether the connection between brain and brain-inspired can produce other new intelligence.
--- PART3 Grasp the opportunity of the times, promote the research and construction of brain science in China. ---
8. Advanced countries and regions all carry out "brain project". Compared with the brain projects of the United States, the European Union and other countries and regions, what is the uniqueness of China's brain project?
Heping Cheng: The American brain project focuses on creating tools and doing "reading" work; The European Brain Project focuses on brain-inspired intelligence and does "imitation". The project adopted by China Brain Project is to strive for balanced development in all work, and impartiality is its characteristic. To sum up, the layout of China's Brain Project is "one body and two wings". The so-called "one body" refers to understanding the principle of brain work, and the so-called "two wings" refers to focusing on the treatment and research of brain diseases and the integration of brain and brain-inspired intelligence.
In the specific research path, the China Brain Project emphasizes that primate brains should be used as a bridge between human brains and lower animal brains. The research on "Meso-neural connectivity map of the whole brain" promoted by Muming Pu, Academician of Chinese Academy of Sciences is also very distinctive. At the cell level and below, he paid attention to the microscopic electron micrographs of synapses and molecules, and the macroscopic atlas of brain functional connection established by nuclear magnetic resonance. The mesoscopic optical microscope atlas with both structural and functional imaging, which is horizontal and more accurate, is constructed, and the corresponding analytical techniques of structure and function are extended. This strategy is suitable for the current development stage.
9. At present, two brain science and brain-inspired research centers have been established in Beijing and Shanghai. What advantages and opportunities do you think Nanjing has in developing brain science and brain-inspired research?
Heping Cheng: The Nanjing Municipal Government is very wise in treating the layout of brain science and brain-inspired research, with special emphasis on building industries of brain and brain-inspired research, focusing on combining basic research with application scenarios, medical needs and serving the society, and transforming them into industries and trades. In particular, Jiangbei New Area, Nanjing, which aims to "recreate a new main city", is laying out "City of Genes" and "City of Chips", while brain science and brain-inspired research are just at the junction of the two and can be integrated into the industrial matrix of "City of Chips" and "City of Genes". At the same time, Jiangbei New Area has active capital elements and sustained attraction of high-end talents, and its prospects are widely optimistic and will be further improved. The opportunity to develop brain science and brain-inspired research in Nanjing may not be in basic research, but I think Nanjing has a very good vision and pattern in application and industrial layout.
10. What is the main work of Nanjing Brain Observatory which you presided over in Jiangbei New Area?
Heping Cheng: Compared with the national platform in Huairou, Beijing, which emphasizes general needs, the Nanjing Brain Observatory led by me in Jiangbei New Area focuses on brain science and specializes in brain imaging. I hope to promote the development of corresponding fields and industries through this platform.
The mission of Nanjing Brain Observatory is to study the function and structure of the brain on the mesoscale, with more emphasis on functional description. It integrates advanced equipment such as Fast High-Resolution, Miniaturized Two-Photon Microscopy (FHIRM-TPM), ultra-sensitive structured light super-resolution microscope and new Volumetric Imaging with Synchronized on-the-fly-scan and Readout (VISoR).
Among them, FHIRM-TPM can monitor the dynamic activity of neuron network in the state of natural operation of brain, and observe the relationship between "spatio-temporal association" and behavior among neurons. Super-resolution microscope can track the micro-level structures such as molecules and synapses for a long time under ultra-high time and space resolution, and monitor the changes of structures after behavioral activities, such as plasticity and migration. On the basis of FHIRM-TPM observation, Nanjing Brain Observatory also introduced VISoRs technology taught by Guoqiang Bi, Professor of University of Science and Technology of China, which made the brain transparent, marked small-scale active neurons, and further revealed how they projected on the whole brain, thus establishing the relationship between structure and function, local and macro.
The mission of Nanjing Brain Observatory is to provide observation ability for brain scientists all over the country and all over the world, and provide tools for drawing mesoscopic map of China Brain Project, so that researchers can use the most advanced technology and data analysis tools, and promote the development of brain science and brain-inspired research. Through this platform, laboratories and young scientists in need do not need to buy complete sets of equipment or apply for scientific research funds, but can communicate with our team with research problems and topics. Through the operation of specialized assembly lines and technical factory-style training, high-throughput equipment and data analysis tools are available and affordable, thus reducing the barriers to entry, shortening the research cycle of scientific problems and accelerating the process of transforming ideas into discoveries. This is my dream, and Jiangbei New Area is helping me realize this dream.
11. From your scientific research experience, what do you think should be done to build a benign relationship between scientific and technological innovation and application transformation?
Heping Cheng: From my personal experience, if China wants to do original-created science, it must have its own instruments. Under the background of "Special Project for Developing Major Scientific Research Instruments and Equipment", I led the interdisciplinary team of Peking University to develop a miniature two-photon fluorescence microscope. Only by transforming the prototype into a product can more scientists and laboratories use high-end technology, but this cannot be done in laboratories. With the help of school authorities, government policies, capital and other factors, as well as the entrepreneurial enthusiasm of young workers, the team set up an innovative company to promote the industrialization and productization of this imaging equipment, which was initially recognized by the market. It is planned to be gradually applied to clinical medical scenes such as obstetrics and gynecology, dermatology and pathology laboratory.
Among them, the government's support is very important for the scientific and technological innovation with high investment in the early stage. With the support of Jiangbei New Area, Nanjing Brain Observatory has carried out alpha and beta test on the products that have not yet been finalized, and built a demonstration area that serves science and product iteration simultaneously. At present, the products have been tested for a long time, which has strengthened the confidence of the team in transforming their achievements and serving more scientists.
Concerning the promotion of the research into brain science and brain-inspired science, as an open and cooperative platform gathering international and domestic academic and scientific research resources, what role do you think the Centre will play or what function it can provide?
Heping Cheng: I think the establishment of Cambridge University - Nanjing Centre of Technology and Innovation is a very beneficial attempt. On the one hand, Cambridge University has a great vision for the development of the “Future New Main City” in Jiangbei New Area, and has placed the Centre here. Jiangbei New Area has the conditions for the development of brain science such as industrial layout, capital, talents and policies. On the other hand, I admire the long academic tradition and profound theoretical thinking of Cambridge University, which will exert influence upon the Centre, its surroundings and its partners (including me). I have discussed with the Centre about brain science and brain-inspired research. I think the Centre has good conditions in clinical diseases, development research and tool making with a complete range of disciplines. At the same time, the Centre has cooperated with many domestic universities such as Peking University and Nanjing University. We look forward to the great achievements of the Centre in Jiangbei, Nanjing and China.
Specifically, we hope to seize the opportunity of common development with the Centre and jointly launch international, bilateral or multilateral large-scale scientific and engineering projects to overcome theoretical and application problems. In this process, partners of the Centre such as Nanjing Brain Observatory and Peking University can join it to make pioneering and contemporary work in the field of brain science.