By Dr. Alyssa Master

There is an inherent risk in utilizing cell culture media supplements that originate in animals. However, researchers can easily reduce their risks by understanding where their products are sourced and the history of that country of origin.

Bovine Spongiform Encephalopathy: What Is It?

Bovine spongiform encephalopathy (BSE) is a progressive neurodegenerative disease that affects cattle [1]. BSE, known more colloquially as Mad Cow Disease, was originally discovered in the United Kingdom in 1986. The disease has since gained world-wide focus due to the need to maintain clean and safe products in all industries involving cattle. BSE is caused by aberrant proteins called prions, which are resistant to most biological responses that typically destroy pathogens. These prions stimulate other proteins in the brain to misfold into atypical shapes which, upon replication, cause plaque buildup, leading to degradation of neural tissue [2]. BSE is believed to have transferred to humans as Creutzfeldt-Jakob disease (CJD) through the import of corrupted cattle product [3]. Because of this jump across the species barrier, BSE is a global concern that predicates safe sourcing of bovine products imported into the US.

Cell and tissue culture is an essential technique that allows for cost effective understanding of how cells respond to various stimuli in vitro. Fetal Bovine Serum (FBS) is the most common media supplement used in cell culture media because the hormone, protein, and macromolecule levels instigate rapid cell growth. The safety and purity of FBS is threatened by the risk of infection by bovine viruses and other diseases such as BSE since contamination can adversely affect cell culture experiments. FBS is a byproduct of the meat and dairy industry and thus supply can fluctuate based on cattle supply. If BSE infects a particular source there will be a large reduction in cattle being slaughtered for meat and therefore a large reduction in the FBS supply [4]. To combat the threat of contaminated cultures and a constantly variable supply of this serum, a comprehensive method of assessing the risk of BSE worldwide is necessary to ensure that cell culture continues to contribute to medical breakthroughs.

The Geographical Risk Assessment

Because BSE is an issue with worldwide implications, regulatory organizations have been driven to monitor how all cattle industries import products. The Geographical BSE Risk Assessment (GBR) qualitatively evaluates the likelihood that an animal within a country or region is infected with BSE based on the probability that a BSE agent will enter the country (external challenge) and the probability that the agent would amplify and spread within a country (internal stability) [5]. This method strongly depends on the surveillance system of the World Organisation for Animal Health (OIE), which classifies the BSE risk in each country or region through the Terrestrial Animal Health Code, or Terrestrial Code [4]. The OIE assesses countries’ veterinarian services, ability to diagnose diseases, awareness of symptoms, and other factors as a well-rounded approach to solving and avoiding the spread of BSE. Since 2008 this system places countries in one of three categories: negligible BSE risk, controlled BSE risk, and undetermined BSE risk. The Terrestrial Code also enforces an awareness program for veterinarians, farmers, transporters, marketers, and all others involved in slaughter industries and requires them to report all potential cases [5-7].

Among other cattle commodities such as hides and skins, milk, and gelatin, the Terrestrial Code does not require these same conditions to be met for the import of “blood and blood by-products” [7]. However, the ability for the disease to be transferred via blood is still being researched. Recently a nine- year study conducted by the American Society of Hematology examined the transmission of BSE or scrapie, a variant of the disease in sheep, through blood transfusions from infected sheep. Transmission of BSE occurred mostly from donors with later stages of the infection but also from preclinical donors [8]. Although the code does not directly refer to serum as an unsafe risk within the cattle industry, the FBS industry is based on the many other cattle commodities. These commodities require a strict risk assessment by the OIE, which drives FBS production. It is important to understand the risks associated with FBS choices to ensure the success of experiments.

For many years, the United Kingdom was in the highest risk category while countries like Australia and New Zealand maintained the lowest risk category. Due to some Mad Cow Disease exposure, the United States was in the second category for several years [9]. The most recent GBR standings, as of May 2016, indicate that countries such as Australia and New Zealand still fall under the lowest risk category of “Negligible BSE Risk” [10].


  1. ”About BSE.” Centers for Disease Control and Prevention, 10 Feb. 2015. Web 01 Feb 2017.
  2. J. Collinge, “Human prion diseases and bovine spongiform encephalopathy (BSE).” Human Molecular Genetics. 6.10 (1997): 1699-1705. (page 1695)
  3. P. Brown, R. Will, R. Bradley, D. Asher, l. Detwiler, “Bovine Spongiform encephalopathy and Variant Creutzfeldt-Jakob Disease: Background, Evolution, and Current Concerns.” Emerging Infectious Diseases. 7.1 (2001): 6-16. (page 10)
  4. C. Rauch, E. Feifel, E. Amann, H. Spotl, H. Schennach, W. Pfaller, G. Gstraunthaler, “Alternatives to the Use of Fetal Bovine Serum: Human Platelet Lysates as a Serum Substitute in Cell Culture Media.” Alternatives to Animal Experimentation. 28.4 (2011): 305-316. (page 305)
  5. Scientific Steering Committee. Update of the Opinion of the Scientific Steering Committee on the Geographical Risk of Bovine Spongiform Encephalopathy (GBR). (2002): 3-10. (page 3)
  6. D. Heim, I. Gardner, E. Mumford, U. Kihm, “Risk assessment and surveillance for bovine spongiform encephalopathy.” International Office of Epizootics. 25.3 (2006): 937-950. (page 937)
  7. World Organisation for Animal Health, “Terrestrial Animal Health Code: Bovine Spongiform Encephalopathy.” 2016. Web 01 Feb 2017.
  8. S. Siso, L. Gonzalez, F. Houston, N. Hunter, S. Martin, M. Jeffrey. “The neuropathologic phenotype of experimental bovine BSE is maintained after blood transfusion.” Blood. 108.2 (2006): 745-748. (page 746)
  9. Asher, David M. Office of Blood Research & Review. “FDA TSE Advisory Committee Meeting” 2003. Web 06 Feb 2017.
  10. World Organisation for Animal Health, “Bovine Spongiform Encephalopathy (BSE)” 2016 Web 06 Feb 2017.