Biological Standards in Life Sciences – Enhancing Reproducibility

Cara N. Wilder, Ph.D.

With tremendous breakthroughs being made in the life sciences every day, it is critical that reported and published data are not only reliable and accurate, but reproducible as well. Unfortunately, with the inherent variability of biological materials and reagents, as well as the differences in analytical techniques and data reporting, irreproducibility is still a universal problem throughout both commercial and academic settings. In fact, this issue has resulted in significant, long-lasting effects including extensive losses in time and funding, perpetuation of false data, reputational damage, and impairment of professional relationships and collaborations. Here, we will briefly discuss how variations in biological materials can affect reproducibility and how the use of organisms as standards can help counteract these effects.

 Within the life sciences, irreproducibility can be caused by a number of underlying factors ranging from the biological materials and reagents used for a set of experiments to how the experiment is performed and analyzed. For instance, bacteria can vary quite a bit at the species level, which is why we often see further characterization at the subspecies and strain level. Within any given bacterial species, representative strains will exhibit similar phenotypic and genotypic traits, such as characteristic morphologies, similar metabolic requirements, and conserved ribosomal 16S sequences. However, as similar as these strains may be, selective and societal pressures can lead to genetic mutations or the acquisition of laterally transferred genetic elements that may result in significant phenotypic changes such as variations in serotype, intracellular signaling, protein expression, pathogenicity, or drug-resistance. In turn, this can affect experimental reproducibility between research facilities that are not using the same variant. Overall, the inherent differences of biological materials bring unique challenges to establishing reliable assays.

To help control for the intrinsic differences between the strains used within the life sciences, and thus enhance experimental reproducibility, the use of biological standards is recommended. Biological standards are defined as well-characterized, authenticated, purified biological reference materials – qualities of which are essential for their effective use in assay validation and calibration, research and development, diagnostics, etc. For example, when testing consumable or pharmaceutical products for specific microbial pathogens, the use of appropriate biological reference materials can ensure that the assay is sensitive and precise enough to detect the presence of objectionable microbial contaminants. The use of biological standards is equally important in clinical settings for the detection and identification of infectious agents. As you can image, the sensitivity and specificity of these assay can have a profound effect on public health.

Currently, biological standards are developed and produced by a number of entities, including government agencies, commercial companies, and non-profit institutions. ATCC, for example, produces both animal cell lines and microorganisms as Certified Reference Materials (CRMs). These biological standards are produced under an ISO Guide 34:2009 accreditation -- a process that offers confirmed identity, well-defined characteristics, and an established chain of custody. Moreover, ATCC CRMs are stable with respect to one or more specified properties, which makes them ideal for performing in challenge assays, verifying or comparing test methods, and benchmarking critical assay performance during assay validation or implementation.

Overall, the inherent variability of biological materials can significantly affect the quality and reproducibility of data. Through the use of standardized biological reference materials, assay consistency and accuracy can be improved.