From Humble Beginnings to Scientific Luminary
In the world of molecular biology, where DNA and RNA form the blueprint of life, Dr. Debao Wang (王德å®) is celebrated as the pioneering force who laid the foundation for nucleic acid research in the People's Republic of China 1 . His journey, which began in the small town of Taixing, Jiangsu Province in 1918, would lead to a series of groundbreaking discoveries that forever changed China's scientific landscape. His work not only deciphered the fundamental codes of life but also translated them into practical innovations that benefited millions, from flavor enhancers in kitchens to tools for understanding deep biological processes 1 .
Dr. Wang's story is one of profound dedication. He once left a promising career abroad to return to his homeland with a singular mission: to build Chinese scientific capability from the ground up. He established the nation's first nucleic acid research group and dedicated his life to unlocking the secrets of RNA, inspiring generations of scientists to come 1 .
Developed industrial method adopted by pharmaceutical companies for three decades
Discovered nucleoside hydrolase, cytosine deaminase, and uracil oxidase
Established China's first nucleic acid research group in 1955
Dr. Wang's scientific acumen was evident early in his career. After graduating in 1940, he embarked on academic pursuits in the United States, where he made significant strides in biochemistry 1 . His work during this period was nothing short of revolutionary:
Returned to China and joined the Institute of Physiology and Biochemistry of the Chinese Academy of Sciences (CAS)
Became director of a dedicated nucleic acid research laboratory, formally launching China's nucleic acid research
Won the National Science and Technology Achievement Award for work on 5′-ribonucleotides
In 1955, driven by a deep sense of duty, Dr. Wang made the pivotal decision to return to China. He joined the Institute of Physiology and Biochemistry of the Chinese Academy of Sciences (CAS) and established China's first nucleic acid research group. In 1961, he became the director of a dedicated nucleic acid research laboratory, formally launching the nation's journey into the heart of the cell 1 .
His impact was both profound and practical. He and his team refined the production of 5′-ribonucleotides, leading to the creation of a powerful flavor enhancer for monosodium glutamate (MSG). This work, which won the 1978 National Science and Technology Achievement Award, cemented his status as a founder of Chinese industrial biochemistry 1 .
Among Dr. Wang's numerous achievements, the artificial total synthesis of yeast alanine transfer RNA (tRNAAla) stands as his magnum opus. In mid-November 1981, after 13 years of relentless effort, his team achieved a world first: the complete synthesis of a biologically active tRNA molecule 1 .
RNA is a notoriously fragile molecule. The presence of a hydroxyl group (-OH) at the second carbon of its ribose sugar makes it highly reactive and prone to unwanted side reactions, unlike the more stable DNA. The challenge was to build this complex chain, complete with its specific folded structure, without damaging its delicate components 1 .
To overcome this challenge, Dr. Wang's team devised a brilliant, multi-stage strategy:
Instead of building the entire 76-nucleotide chain at once, they broke it down into more manageable segments. They chemically synthesized smaller fragments.
These smaller fragments were then meticulously joined together to create two larger halves: the 3'-half molecule and the 5'-half molecule 1 .
In the final step, the two halves were ligated (connected) to form the complete, full-length yeast tRNAAla molecule 1 .
The team didn't just create the molecule; they proved it was correct. They demonstrated that their synthetic tRNA had the same chemical composition—including 9 modified nucleotides of 7 different species—and the same intricate three-dimensional structure as its natural counterpart 1 .
The ultimate test was function, and the synthetic tRNA passed brilliantly. It was biologically active, meaning it could perform its essential role in the cell: carrying the amino acid alanine to the growing protein chain during translation 1 .
A key finding was that the synthetic tRNA's anticodon loop (the part that reads the genetic code) was not involved in its interaction with the enzyme that attaches the alanine (alanyl-tRNA synthetase). This provided crucial insights into the molecular "handshake" that ensures the genetic code is translated accurately 1 .
This landmark achievement won the first prize of the National Natural Science Foundation and the Tan Kah Kee Award in Life Sciences 1 .
Announced China's arrival as a major power in the field of cutting-edge molecular biology.
This landmark achievement, which won the first prize of the National Natural Science Foundation and the Tan Kah Kee Award in Life Sciences, had profound implications 1 . It provided scientists with a powerful tool to probe the deepest questions of life:
The monumental task of synthesizing tRNA required a suite of specialized tools and molecules. The table below details some of the essential "research reagents" that were fundamental to Dr. Wang's work and remain staples in molecular biology today.
| Research Reagent | Function in Nucleic Acid Research |
|---|---|
| Ribonucleotides | The fundamental building blocks (A, U, G, C) used to chemically synthesize RNA chains 1 . |
| Protecting Groups | Special chemical groups used to temporarily shield the reactive -OH group on ribose, preventing unwanted reactions during synthesis 1 . |
| Enzymes (Ligases) | Biological catalysts that act as "molecular glue," joining together the synthesized RNA fragments to form the complete tRNA molecule 1 . |
| Modified Nucleotides | Rare, chemically altered nucleotides (e.g., inosine, pseudouridine) that are crucial for the proper structure and function of mature tRNA 1 . |
| Guide RNA | A synthetic RNA molecule that directs CRISPR-associated (Cas) enzymes to a specific DNA sequence for precise editing, a modern evolution of RNA's guiding role . |
Debao Wang's legacy extends far beyond his laboratory discoveries. He was a dedicated educator and institution-builder who understood that science thrives on shared knowledge. In 1961, he authored "Nucleic Acids-Structure, Function, and Synthesis," the first comprehensive nucleic acid textbook in China. This work had a profound impact, shaping the education and inspiring the careers of countless biochemists and molecular biologists across the nation 1 .
He mentored numerous students, many of whom became the backbone of nucleic acid research and teaching in China 1 . His former colleagues and students remember him not just for his intellectual brilliance, but for his personal integrity. Professor Youxin Jin's words capture this sentiment:
"The kindness of teacher Wang is hard to forget, and his qualities will be inherited forever" 1 .
"Nucleic Acids-Structure, Function, and Synthesis" (1961)
The first comprehensive nucleic acid textbook in China
His work on the structure and function of tRNA paved the way for modern research into non-coding RNAs, a vibrant area of study today. In a fitting tribute to his enduring influence, research in the same institute now explores tRNA-derived fragments (tRFs) and their role in cancer—a direct and contemporary extension of Dr. Wang's original vision 1 .
When Dr. Wang passed away in 2002 at the age of 84, the scientific community at home and abroad mourned the loss of a true giant. As Professor Boliang Li noted, "Whether it is learning or being a human being, Dr. Wang is an academic model and an example for the younger generations" 1 . He left behind a rich spiritual and scientific wealth that continues to guide and inspire, a permanent testament to the power of curiosity, perseverance, and love for one's country.
Yeast alanine tRNA (tRNAAla) consists of 76 nucleotides forming a cloverleaf structure with specific loops and stems.