Experts Reach Consensus on Fixing a Decades-Old Antibody Problem

Two studies published in PLOS Biology by Harvinder Virk of the University of Leicester and colleagues quantify the scale of sample waste tied to inadequately validated research antibodies and present a set of consensus-backed reforms to address it.

Antibodies are used throughout biomedical research to detect, quantify, and isolate specific proteins, but they do not always bind their intended targets with the specificity researchers assume. In the first study, Virk and first author Michael Biddle drew on focus groups with 12 researchers, a survey of 107 researchers, and an analysis of 785 publications linked to antibodies that had failed knockout-controlled testing. Among the 760 publications where validation status could be determined, only 120 (15.8%) presented any validation evidence, even though 72.0% of surveyed researchers reported using at least one recommended validation method. The papers lacking validation evidence used a minimum of 8,064 animal samples and 4,424 human tissue samples, leading the researchers to estimate that millions of animal and human tissue samples have been consumed globally without adequate validation. 

“This study provides, to our knowledge, the first systematic quantification of biological sample waste attributable to the use of poorly performing antibodies without context-specific validation,” the researchers say. Biddle adds that in the clearest cases, where an antibody has since been withdrawn from sale and the original work cannot be reproduced, scaling to the commercial antibody market gives a lower-bound global estimate of 4 to 7 million animal samples and 6 to 11 million human tissue samples.

In the second study, Virk and first author Katherine Blades convened 32 international experts, including researchers, publishers, funders, antibody manufacturers, and institutional leaders, for a two-round Delphi consensus exercise. The panel agreed that 15 actions, including institutional training, dedicated validation budgets in grant applications, and publisher reporting requirements, were both effective and feasible for implementation by 2030, with 15 additional actions judged effective but of uncertain feasibility. Participants identified diffuse ownership of the problem and market incentives that fail to reward antibody quality as key barriers. “What struck us was the level of agreement once researchers, funders, publishers, institutions and manufacturers were brought into the same process,” Blades says. “Progress is held back not by disagreement about what to do, but because no single group owns the problem—so everyone waits for someone else to move first.”

Virk notes that since completing the work, the team has embedded champions for better practice in 14 UK research institutions, and the University of Leicester has made antibody validation training mandatory for its bioscience postgraduate researchers. The team is also working with the NC3Rs and Cancer Research UK on implementation solutions and has built free tools for publishers to use.