关键词: 生化工程, 生物制药, 生物反应器, 生化分离工程, 生化制剂工程

Abstract:

Professor Daniel I.C. Wang was the founder of the Biotechnology Process Engineering Center (BPEC) at Massachusetts Institute of Technology (MIT). Under his leadership, BPEC has made remarkable achievements. It is a historical monument with great influence on the development of biochemical engineering. The historical background, outstanding contributions, innovative mechanisms, and significant impact of BPEC, led by Prof. Wang, were reviewed in this paper. (1) Leading biochemical engineering into a new era of biopharmaceuticals. With the development of genetic engineering in the 1970-1980s, a new era of modern biopharmaceuticals emerged. Professor Wang acutely felt that the production of biomacromolecule medicines by genetic engineering must solve a series of engineering science problems, which was the opportunity and challenge of biochemical engineering. He proposed to the National Science Foundation of the United States (NSF) for establishing BPEC at MIT. It was approved by the NSF in 1985. Compared with the initial concept of biochemical engineering at that time, the focus of BPEC had a great shift. The target molecules were no longer limited to microbial fermentation or bioconversion of antibiotics, chemicals and fuels. The mission of BPEC was to solve the engineering problems encountered by the large-scale production of various protein pharmaceuticals. In doing so, BPEC has successfully led biochemical engineering into the new era of biopharmaceuticals and established a unique position in the development of modern biotechnology. (2) Launching animal cell culture engineering. Animal cell culture is required for production of very complex biomacromolecules. While cell biologists were busy to scale up production by increasing the number of roller bottles, BPEC started engineering approach by design of bioreactors and control strategies. Successful bioreactor cultivation of mammalian cells was realized by minimization of shear stress and diffusion limitation. The culture nutritional composition was optimized by stoichiometric calculation. The strategy of nutritional medium addition was set up by metabolism analysis. Through intelligent cell culture control strategy and optimized reactor configuration, post-translational modification of the target protein was controlled at the optimal level to effectively avoid the loss of target protein. (3) Innovating separation and purification techniques for high quality biomacromolecules. Prof. Wang is one of the pioneers of biochemical separation engineering. He proposed biochemical separation engineering as another main direction of BPEC. Novel approaches such as affinity membrane, reversed micelles, electric-assisted separation were set up. He and his students discovered the mechanisms of protein refolding and aggregation. Using quasi-elastic light scattering technique, they were able to invent a novel technique of stabilizing refolding intermediates with polyethylene glycol. The smart work was published in Nature Biotechnology, and initiated various approaches of protein stabilization by different research groups. (4) Establishing a collaborative innovation and education system for biochemical engineering talents. Prof. Wang actively promoted the spirit of collaborative innovation, encouraged close collaborations among BPEC members, worked closely with biotechnology enterprises, and held lectures on downstream processing courses for R & D personnel of biotechnology companies in the US and other parts of the world. BPEC also attracted many young talents worldwide. Prof. Wang made the academic atmosphere of BPEC extremely active. The scientific exchange brought about brain storming to solve scientific and engineering problems. Numerous graduates and visiting scholars from BPEC have become successful professionals and entrepreneurs. (5) The influence of Prof. Wang and BPEC on biochemical engineering development in China. The influence of Prof. Wang and BPEC on biochemical engineering in China is the spirit of innovation. This spirit has been embodied to the strategic planning of the key laboratories and research directions from bioreactor to biocatalysis, from biological separation/purification to bioformulation, from equipment, media, and technologies to intelligent scale up productions. Biochemical engineering has become the support for sustainable development of life science and biotechnology in this country. Not only that, biochemical engineering researchers have integrated themselves into synthetic biology, gene editing, vaccine development and other frontier life science research, playing increasingly important roles.

Key words: biochemical engineering, biopharmaceuticals, bioreactors, bioseparation, bioformulation