How to solve scientific controversy – a case study

by Alexey Bersenev on August 30, 2013 · 0 comments

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Stem cell research field is full of scientific controversies, based on variability in reporting and lack of reproducibility. Just have a look at very recent one – about VSEL cells. Most of these controversies arise from different methodologies, applied in different labs to test the same hypothesis. The big question is how to resolve it. I’m trying to track all case studies on collaboration and standardization efforts in order to resolve controversies. While ago, I wrote about one such great effort – to define a role of N-cadherin in hematopoietic stem cells. Recently I came across one more interesting case study and I’m sharing it with you today.

Group of experts, representing 8 different labs has published a multi-center study to standardize reporting and analyses of murine intestinal epithelial cells. The controversy in this field was based on FACS sorting and some other methodologies for cell isolation and assays. And the way they solve it was development of very precise common protocol:

Detailed protocols, log sheets and protocol-associated information (Supplemental movie), were prepared to minimize errors and to ensure that sample isolation, collection, and handling were consistent. To control for as many variables as possible, the ISCC established experimental parameters, reporting criteria and threshold values to determine protocol compliance and subsequent inclusion of data in the analysis. Optimization of antibody saturation and gating strategy was established at Center 1. The standardized protocol was tested for consistency at Centers 1 and 2 prior to the study. An online training session, facilitated by the ISCC Coordinating Center, was conducted with laboratory staff from all 8 institutions to clarify critical points and establish consistency in protocol execution. A single operator performed all cell isolations at each center to help ensure intra-center consistency. All centers used antibodies that originated from the same vendor and lot number. Each center received pre-labeled vials containing cell lysis buffer for RNA isolation to minimize reagent variation and labeling errors. One center did not participate in FACS analysis due to incompatibility of FACS instrumentation.

This is excellent case study! It can be used as a framework for setting up collaborative studies in stem cell research and cell therapy translation. The main message for me that it’s doable! Instead of competition and “protection of your authority”, we should widely set up collaborations to resolve controversies. I also think, that as in this case, NIH can take initiative in setting up such collaborations.

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