In a commentary published today in Science, top leadership from the National Institutes of Health (NIH) and the ASCB responded to the simmering “reproducibility” controversy by calling for broad reform across the biomedical research enterprise in standards and best practices for studies conducted on cultured cell lines.
The NIH itself “may require” all grant applicants to provide information on their handling of cell lines and key reagents similar to a requirement issued in 2004 for reporting on model organism-sharing, according to Francis Collins, NIH Director, and Jon Lorsch, Director of the NIH National Institute for General Medical Sciences (NIGMS). The third author of the Science commentary was Jennifer Lippincott-Schwartz, 2014 ASCB President and an investigator at the NIH Eunice Kennedy Shriver National Institute for Child Health and Human Development.
NIH is also considering issuing new standards for cell culture in consultation with scientific societies such as ASCB, other government agencies such as the U.S National Institute of Standards and Technology, as well as U.S. and international research funding agencies. Additional NIH investments in “faster, cheaper, and easier methods” of cell line “fingerprinting” are also under consideration, say the authors.
In their commentary, Lorsch et al. acknowledged persistent and unresolved problems surrounding the misidentification and contamination of cell lines used in published studies, some which were later challenged as unreproducible by other labs. They cited studies going back to 1960, identifying 400 cell lines widely used in laboratories that have been shown to be misidentified by human tissue type and even by species. They also cited a study of 122 different cell lines used in head and neck cancer studies that found 30% were misidentified. Such errors can be especially damaging, for example, in cancer research when drugs tested on a “misidentified” cell line turn out to be ineffective in wider trials, they contend.
NIH issued a “Guide Notice” in 2007, asking researchers to tighten controls and procedures over cell lines. Yet the problem persists, say the NIH and ASCB leaders. Reform will depend on cooperation from the entire biomedical research community—government and private research funders, professional groups, journal editors, manufacturers, suppliers, universities, research institutes, and bench scientists themselves. For its part, NIH plans on putting new emphasis on “best practices” in publication, laboratory training, and cell culture technology. NIH is also interested in basic research into experimental reliability due to variables introduced by different cell types and genetic drift.
The basic research community has not done enough to date in tackling the reproducibility issue, according to Lorsch, Collins, and Lippincott-Schwartz. “For example, it is hard for both individual scientists and their fields to accept that their work could be called into question because the wrong cell line was used. For some researchers, the problem may even seem insignificant in the context of their specific research focus; after all, all animal cells have microtubules, motor proteins, and ribosomes, which may lead some scientists to feel that the particular cell type they are studying is irrelevant.” With scientific credibility on the line, the NIH and ASCB authors now say those days are over.