ABSTRACT
Despite the dominance of animal cell culture in the production of biopharmaceuticals in recent times, this technology was not consolidated into standardized large-scale bioprocesses until the 1990s. Nevertheless, the first experience with animal cell culture can be traced back to the beginning of the 20th century. By the use of the hanging drop technique and frog heart lymph, Ross Harrison, at Yale, tried between 1906 and 1910 to elucidate how the nervous fiber is originated (Witkowski, 1979). He considered three hypotheses: (i) in situ formation from the nerve sheath; (ii) preformed protoplasmic bridges; or (iii) as a result of the nerve cell growth itself. When Harrison demonstrated the validity of the third hypothesis, he also confirmed the cell as the primary developing unit of multicellular organisms. An early pioneer of cell culture was the French surgeon Alexis Carrel,
who won the Nobel prize in Medicine in 1912 for his research at the Rockefeller Institute (Spier, 2000). Harrison was, above all, the inventor of analytical solutions, while Carrel, with his extensive clinical practice experience, sterility concerns, and capacity to develop appropriate culture media and culture flasks, created the change in the technological paradigm that led to the start up of animal cell technology. By careful manipulation, Carrel insured the maintenance of chicken embryo cells for several decades in culture. Spier (2000) lists some essential differences between cells in an organism
(in vivo) and cells in culture (in vitro), particularly the following;
(i) Tissues are three-dimensional, while cell cultures are of zero dimension (monodispersed in suspension culture) or two-dimensional (monolayer growth). However, some culture techniques exploit three-dimensional systems (Alves et al., 1996; Powers et al., 2002).
