Reproducibility crisis: Blame it on the antibodies

Monya Baker in Nature:

AntibodyIn 2006, things were looking pretty good for David Rimm, a pathologist at Yale University in New Haven, Connecticut. He had developed a test to guide effective treatment of the skin cancer melanoma, and it promised to save lives. It relied on antibodies — large, Y-shaped proteins that bind to specified biomolecules and can be used to flag their presence in a sample. Rimm had found a combination of antibodies that, when used to 'stain' tumour biopsies, produced a pattern that indicated whether the patient would need to take certain harsh drugs to prevent a relapse after surgery. He had secured more than US$2 million in funding to move the test towards the clinic. But in 2009, everything started to fall apart. When Rimm ordered a fresh set of antibodies, his team could not reproduce the original results. The antibodies were sold by the same companies as the original batches, and were supposed to be identical — but they did not yield the same staining patterns, even on the same tumours. Rimm was forced to give up his work on the melanoma antibody set. “We learned our lesson: we shouldn't have been dependent on them,” he says. “That was a very sad lab meeting.”

Antibodies are among the most commonly used tools in the biological sciences — put to work in many experiments to identify and isolate other molecules. But it is now clear that they are among the most common causes of problems, too. The batch-to-batch variability that Rimm experienced can produce dramatically differing results. Even more problematic is that antibodies often recognize extra proteins in addition to the ones they are sold to detect. This can cause projects to be abandoned, and waste time, money and samples. Many think that antibodies are a major driver of what has been deemed a 'reproducibility crisis', a growing realization that the results of many biomedical experiments cannot be reproduced and that the conclusions based on them may be unfounded. Poorly characterized antibodies probably contribute more to the problem than any other laboratory tool, says Glenn Begley, chief scientific officer at TetraLogic Pharmaceuticals in Malvern, Pennsylvania, and author of a controversial analysis1 showing that results in 47 of 53 landmark cancer research papers could not be reproduced.

More here.