How Mass Spectrometry Can Help Limit Reproducibility Problems
Antibodies are critical for biological and medical research. Yet, since early 2015, the state of the antibody industry has been described as being in a reproducibility crisis. One of the main issues is the improper characterization of primary antibodies. The health research industry is saturated with discrepant validation data on the sensitivity, specificity and reactivity of a variety of antibodies against the same immunizing agents (antigens). Aside from testing with a small number of assays, such as DNA sequencing, many vendors and manufacturers do not have a clear-cut quality assurance process for validating their antibody-based products such as commercial assay antibodies and/or therapeutics.
This inconsistency in data validation can cost researchers time and money, and in some extreme cases, their projects. In a Nature article in 2015, Andrew Bradbury and Andreas Plückthun estimated that in the United States alone, $800 million is spent on antibodies, and half of this sum accounts for improperly validated antibodies that lead to lengthy troubleshooting and delays for important research. One of the most prominent examples to date is that of a research group which hoped to develop a diagnostic assay against a novel ovarian cancer prognostic marker, CUZD1.
They ordered a kit that contained the antibody against their marker to validate their assay and spent two years of research work, thousands of patient samples and $500,000 on additional experiments only to realize that the kit’s anti-CUZD1 was actually anti-CA125, an antibody targeting another ovarian cancer prognostic marker, which was a product already in the diagnostic market. This situation could have been prevented if researchers safeguarded their work by testing against the right antigen prior to conducting experiments, by asking vendors how they routinely verify for the correct identity of their antibody products and/or by utilizing recombinant antibodies.