Nature vs. Nurture
The question of nature (cell-line engineering) vs. nurture (media, feed, and culture strategies) inevitably arises during any discussion of cell-culture optimization. “You can do a lot of things in the way of nurturing cells, but you cannot change the fundamental nature of a cell once it’s set,” notes Eileen Skaletsky, Ph.D., CEO of QED Bioscience, a contract cell culture services company.
“If it’s an inherently low producer, there’s only so much you can do to ramp that up because the cell probably lacks the signaling machinery required to pump out lots of product.” Media and feed strategies can help, but turning a poor producer into a high producer is unlikely to succeed.
Despite the homage paid to nature, most experts—Dr. Goldsborough included—believe that nurture has thus far paid the most dividends. “Nurture, including media, supplements, and control over bioreactor conditions, is still the predominant activity today.” Nevertheless, researchers are looking into “nature” as well as into cell processes and signaling, which has the potential to harness all the cell’s activities and recruit them toward production. “So it’s clear the two, nature and nurture, have to work together,” Dr. Goldsborough says.
“Nature and nurture go hand in hand,” adds Machielse. While cells are initially selected based on growth and productivity, “you can do a lot once you have selected them through the right feeding strategy. And with refined media the exercise becomes a lot more manageable.”
Machielse believes that in the future cell phenotype and genotype will help processors predict the type of feeding strategies that are likely to improve productivity. And at some point, those characteristics may be designed in.