Chinese Academy of Sciences Academician Zhao Guoping Highlights Lack of Predictability as Key Challenge in Synthetic Biology
“Technological breakthroughs in synthetic biology represent only the first step in a long journey. The integration of proof-of-concept studies with real-world investigations is key to translating innovative scientific research into products that meet market demands.”——“Only with them can one cross the ‘Valley of Death’; without them, one can only stop here.”
According to information from Made in China (operated by the News and Publicity Center of the Ministry of Industry and Information Technology),12Month18Day, in2025At the Bio-Manufacturing Conference, Zhao Guoping, an academician of the Chinese Academy of Sciences and a professor at Fudan University, stated in his keynote speech.
Academician Zhao Guoping further pointed out that this“Death Valley”"The setting sun was as red as blood."Moreover, even after crossing the “Valley of Death,” products must still undergo engineering translation, pilot-scale process validation, and clinical trials, which is akin to scaling“Shangganling”。
When the industry truly enters the stage of comprehensive industrialization and marketization, it will still face stringent regulations, fierce competition, and involution; this is a landscape rife with rivalry.“Darwin Sea”。Only by crossing this sea can synthetic biology ultimately form industrial clusters and achieve societal applications.
It is understood that Academician Zhao Guoping20Age of being sent to the countryside,30Age at college,35Went to the United States for study at the age of,42Graduated with a Ph.D. at the age of44returned to China at the age of46At the age of , he/she served at the Chinese Academy of Sciences,57Elected as an academician at the age of [X], his life journey can be described as legendary, with every step filled with challenges and struggles.
Academician Zhao Guoping participated in launching research on genomics, bioinformatics, proteomics, and transcriptomics in China, cloned several disease-causing genes for genetic disorders, and conducted sequencing of microbial genomes in China. He has made pioneering contributions in fields such as protein acetylomics, gut microbiome, and synthetic biology.
According to reports, the development of synthetic biology is actually rooted in the evolution of life sciences.
Academician Zhao Guoping has outlined that, at the beginning of this century, engineering science concepts were gradually integrated into the field of life sciences, driving synthetic biology to shift from hypothesis-driven to goal-oriented approaches, undergoing20Over the years of development,Significant progress has been made in pathway engineering, metabolic engineering, genome engineering, and cell engineering.
According to an article previously published by Academician Zhao Guoping in the journal Acta Sinica of Academia Sinica, the core of synthetic biology can be summarized with two keywords:
One is "convergence,"Synthetic biology converges the “discovery capability” derived from scientific research, the “construction capability” inspired by engineering principles, and the “invention capability” driven by disruptive technologies, thereby comprehensively enhancing society’s “innovation capability.”
One is the "engineering essence,"For example, component standardization→Module Construction→Chassis adaptation, including the understanding of pathways in life processes, network composition, and their regulation, and“Orthogonalized Life”The design and construction of [systems/organisms] constitute the core research focus of synthetic biology.
Past20Over the years, synthetic biology has made significant advances in component engineering, circuit engineering, metabolic engineering, genome engineering, and cell engineering.5Significant progress has been made in this major field, yet multiple challenges remain.
In the view of Academician Zhao Guoping, the main challenges currently facing synthetic biology areLack of rational design capability and predictability.
“The era of big data and the engineering-oriented research system bring new opportunities: through ‘black box”+Research on “quantitative synthetic biology” through “white-box” or “black-box-to-white-box” approaches, ultimately leading to engineering applications for understanding, modifying, designing, and synthesizing life.”
Academician Zhao Guoping has stated that the emergence of cross-level functions in living systems is accomplished during the growth, differentiation, and development of organisms from single cells to multicellular individuals, with its biological laws being those that nature has employed30Over hundreds of millions of years, across countless units of life—from molecules and cells to individuals and populations“Evolution”(including neutral evolution and natural selection), within the genome that we have yet to decipher“Genetic Language”Coding completed.
“Currently, we are attempting to use ‘synthetically engineered life’ to explore the underlying physical and chemical laws. Only by understanding these laws can ‘rational de novo design’ truly establish a predictive foundation.”Academician Zhao Guoping pointed out.
According to an article published by Academician Zhao Guoping in the journal *Bulletin of the Chinese Academy of Sciences*, living organisms exhibit a high degree of complexity, making it difficult for artificially designed genetic circuits to function entirely as intended; they often require prolonged and iterative tuning. The most effective approach to overcoming this challenge is to establish an engineered research platform that enables large-scale testing of various combinations of components, circuits, and chassis, thereby generating massive amounts of experimental data to guide further engineering optimization and rational design.
And the core of the engineering platform isAutomated Facilities for Synthetic Biology Research, also known as a biofoundry, according to“Design—Construction—Test—Learning”closed-loop strategy to organize technological processes for engineering implementationMassive Trial-and-Error, thereby rapidly obtaining synthetic life forms with desired functions.
such as the United StatesLawrence Berkeley National Laboratoryof Agile BioFoundry, University of Illinois iBioFAB, from the Massachusetts Institute of Technology in the United States MIT-Broad Foundry, Imperial College London's London DNA Foundry, and the industry'sAmyris Company,Zymergen Company,Ginkgo companies, etc.
In this context, China has planned for the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, to undertake the construction of the world’s largest major scientific and technological infrastructure facility for synthetic biology research.
It is worth noting that,From original discovery to industrial application, relying solely on automated facilities is insufficient.
For example, the production of artemisinin by artificial yeast cells is currently the most successful case of industrialization in the field of synthetic biology. The project leader, the United StatesJay KeaslingProfessor, a complete R&D system has been established around the engineering platform.——Upstream original discoveries are led by Lawrence Berkeley National Laboratory, in collaboration with the Joint BioEnergy Institute (JBEI) responsible for midstream technology development, Amyris The company oversees the innovation chain for downstream industrial applications.
These institutional and mechanistic innovations centered on the engineering platform warrant in-depth research and reflection.To provide important reference for fully leveraging the significant role of China’s major scientific and technological infrastructure in driving research, innovation, and industrial development in synthetic biology.
“To promote the efficient development of synthetic biology, it is necessary to integrate the guidance of national scientific and technological innovation policies with the operational needs of enterprises. Financial resources and other mechanisms should serve as bridges to foster deep integration between the innovation chain and the industrial chain. We must uphold the philosophy of conducting genuine research on real issues and solving practical problems, approaching all tasks with a commitment to truth-seeking and diligent work,” emphasized Academician Zhao Guoping.
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