G.D. Ball’s scientific contributions

This chapter discusses large-scale production of human interferon from lymphoblastoid cells. Samples are tested to demonstrate freedom from moulds, bacteria, mycoplasmas, and other infective agents. The frozen stock has subsequently been maintained as a Master Cell Bank from which fresh cells are withdrawn as needed for revival and establishment in culture. For production purposes, the cells are grown in tanks and stirred with an impeller, which is coupled magnetically to the drive motor, thus avoiding the need for a complicated gland and allowing the tank to be operated while completely sealed. Cultures are subjected to aeration to control the redox potential; temperature and pH are also controlled. At the end of the period of induction, purification begins with the removal of the cellular components of the culture to yield a crude solution of interferon. This step can be carried out either by the use of a sterilizable continuous centrifuge or by filtration. The former approach is convenient, but the equipment is complex, difficult to clean effectively without dismantling, and expensive to repair and replace. Filtration systems can be time consuming to develop and involve a significant operating cost in terms of preformed filters.

Excerpt Human proteins required for medical purposes, e.g., insulin, interferons, tissue plasminogen activator, and growth hormone, can now often be produced by recombinant DNA procedures. They can also be obtained by extraction from the appropriate human organ (e.g., growth hormone from pituitaries) or by stimulating human cells grown in culture to make the protein of interest. We pioneered production by the latter approach because we needed to make enough human interferon for large-scale clinical trials; we continue to use this route today, because we think it has certain advantages. To understand our reasons, some points from the history of interferons must be considered. Discovery and Development of Interferons Fifty years ago, Hoskins (1935) and Magrassi (1935) independently discovered the interference phenomenon: A virus replicating in an animal's organ, e.g., the brain, prevented that organ during the next few days from superinfection with any of a number of serologically unrelated viruses. Although...

Suspension cultures of mammalian cells can be used to produce virus vaccines, as a source of interferons, and as a host system for expressing inserted human genes. We will discuss the experience with this technology in our organisation over the past 18 years, during which we have progressively expanded our facilities for such work: we are now operating routinely with 8 000 litre fermenters. Information will be summarized in relation to the following topics: design of plant, medium and serum requirements, plant operation and product processing.