in vitro culture

In vitro Culture: How It All Began

The pioneering use of peptones and protein derivatives, such as peptone proteose from Witte’s peptone, in the in vitro culture of mammalian cells and tissues is mainly attributed to French biologist and surgeon Alexis Carrel and researcher and biochemist Lillian E. Baker at the Rockefeller Institute for Medical Research during the 1920s.

While Carrel was the visionary and surgical mind who had already won the Nobel Prize for his vascular suture and organ transplantation techniques, Baker brought the precision of organic biochemistry to answer a fundamental question: what exactly do cells feed on?

In the early days of in vitro culture, cells were maintained primarily using blood plasma and chick embryo extract, a method developed by Ross Harrison and further refined by Carrel. Although effective, these media were biologically “black boxes”: it was not known which components stimulated mitosis or in what proportions.

Carrel and Baker set out to fractionate and chemically analyze the substances that promoted massive cell proliferation, with the goal of creating an artificial, synthetic, or semi-defined culture medium.

Their Main Discoveries (1926–1928)

1. The Role of Peptones and Proteoses

They identified that mammalian cells, such as chick heart fibroblasts and epithelial cells, could not directly utilize intact high-molecular-weight proteins such as pure albumin or hemoglobin. Instead, they required the products of their partial digestion: proteoses and peptones, intermediate peptide chains.

2. The Free Amino Acid Paradox

They discovered that a simple mixture of pure amino acids alone could not sustain continuous cell growth in the same way as peptones or embryo extract. This demonstrated that certain oligopeptides played a key role in signaling and nutrition, something that the technology of the time was only beginning to reveal.

3. Inhibitors vs. Stimulators in Serum

They analyzed the lipid and protein fractions of blood sera and determined that adult serum contained growth-inhibiting factors, associated with cellular aging, while embryo extract and enzymatic digests such as peptones contained growth-stimulating factors.

Their joint publications in the Journal of Experimental Medicine between 1926 and 1930 laid the foundations for:

The development of chemically defined media: Decades later, researchers such as Harry Eagle built on this work to develop Eagle’s basal medium (MEM), identifying the exact amino acids, vitamins, and salts required by cells.

Modern bioprocessing: The concept of supplementing cell cultures with peptones and enzymatic digests to replace or reduce the use of fetal bovine serum remains an established approach in the biotechnology and industrial sectors, including the production of monoclonal antibodies and recombinant proteins in bioreactors.

Today, the innovation pioneered by Carrel and Baker is taking on new relevance through Biotecnica, a leader in the development and supply of high-purity peptones and extracts designed to enhance process productivity.

If you are looking to optimize cell culture performance, ensure batch-to-batch reproducibility, or develop customized formulations for your industrial bioprocesses, our team of specialists is ready to help you take your processes to the next level.

Contact us today to discover the nutritional solution that can unlock the full potential of your cell cultures.

References

Carrel A. and Baker L.E. The chemical nature of substances required for cell multiplication. J Exp Med, 1926, 44: 503–521.

Journal of Experimental Medicine – Article

Baker L.E. and Carrel A. Artificial maintenance media for cell and organ cultivation: II. The cultivation of organs in artificial media. J Exp Med, 1939, 70: 29–38.

Journal of Experimental Medicine – Article

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