Poor Antibody Validation Wastes Millions of Biological Samples, but Solutions Exist
Two linked studies provide effective recommendations for publishers, funders, institutions, and manufacturers
A widespread failure to validate research antibodies before use is estimated to lead to the avoidable waste of millions of animal and human tissue samples worldwide, and an international expert panel has reached consensus on how to address the problem, according to two studies published October 6th in the open access journal PLOS Biology by Harvinder Virk of the University of Leicester, UK, and colleagues.
Antibodies are critical reagents that enable researchers to detect, quantify, and isolate specific proteins in biological samples. However, research antibodies do not always bind their intended targets, or may bind additional unintended targets. Studies have suggested that many antibodies do not bind as advertised. This lack of specificity can misdirect biomedical research across fields.
In the first study, Virk and first author Michael Biddle combined data from focus groups (12 researchers), a survey (107 researchers), and an analysis of 785 publications linked to antibodies that had failed rigorous, knockout-controlled testing. Among 760 publications where validation status could be determined, only 120 (15.8%) presented any validation evidence, despite 72.0% of surveyed researchers reporting having used at least one recommended validation method. The papers lacking antibody validation used a minimum of 8064 animal samples and 4424 human tissue samples. Extrapolating, the researchers 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.
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 to rate proposed reforms for antibody validation. 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; a further 15 actions were judged effective but of uncertain feasibility. Participants pointed to diffuse ownership of the problem, and market incentives that fail to reward antibody quality as key barriers.
“The findings lend themselves to a programme of targeted stakeholder consultation,” the authors say. “To support this, we have prepared separate documents for each stakeholder group – publishers, funders, institutions, and manufacturers – presenting consensus recommendations alongside implementation options derived from the panel’s qualitative feedback. These present options rather than prescriptions, recognising that the optimal approach will vary across organisations, countries, and contexts.”
Harvinder Virk (corresponding author on both papers) says, “Around ten years ago I discovered that data I had submitted in a grant application relied on an antibody that did not detect its intended target. The data included staining of bronchial biopsies from patients who had given informed consent. They would not have expected their donation to be wasted. That has driven this work ever since.”
Michael Biddle (first author, “Inadequate antibody validation places substantial numbers of animal and human tissue samples at risk of waste”) adds, “Researchers told us they validate their antibodies: 72% reported using at least one recommended method. But only 120 of the 760 papers we could assess showed any validation evidence. The other 640 studies reported at least 8,064 animal and 4424 human tissue samples used with antibodies that had failed independent testing; we describe these samples as at risk of waste. In the clearest cases – where the antibody has since been withdrawn from sale, so the work cannot be reproduced at all – 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.”
Katherine Blades (first author, “Actionable solutions to address antibody validation failures”) states, “What struck us was the level of agreement once researchers, funders, publishers, institutions and manufacturers were brought into the same process. The panel reached consensus on 15 actions that are both effective and achievable by 2030. 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.”
Harvinder Virk notes, “Together these papers show the problem has significant impact with ethical dimensions, and is solvable. Since completing this work, we have 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. We are working with two national funders – the NC3Rs and Cancer Research UK – on implementation solutions, and have built free tools publishers can use to protect the integrity of what they publish.”
Provided by PLOS
