Good Cell Culture Practice

Foreword

The US National Institute of Health (NIH; Bethesda, MD, US) has a new rule in place that requires grant applicants to describe methods for authentication of key resources, including cell lines.  Dr Roland M. Nardone of the Catholic University of America (CUA; Washington, DC, US) has played a vital role in this new development, publishing a 2007 call for action against misidentified cell lines that recommended authentication testing be performed as a condition of funding and publication. Dr Nardone has now celebrated NIH’s new rule for authentication of key resources by writing a “Snail Glide” memo that summarizes the last decade of effort and looks at the need for culture change.

Dr Amanda Capes-Davis

Honorary Scientist, CellBank Australia

Snail Glide: Personal Reflections of Dr Roland M. Nardone

1. Challenge from son, Mark: “Happy Birthday, Dad. What are you going to do with the rest of your life?” Challenge accepted, March 29, 2005.

2. Strategic White Paper calling for action against widespread use of misidentified cell lines is widely disseminated.

3. Open Letter sent on July 11, 2007 from ad hoc committee of concerned scientists to Michael Leavitt, Secretary of Health and Human Services, requesting his support.

4. The NIH promulgates Research Guidelines Notice NOT-OD-08-017, Authentication of Cultured Cell Lines, on November 27, 2007. The guidelines, signed by the Deputy Directors for Intramural and Extramural Research, urges added vigilance by researchers and peer-reviewers, but falls short of a zero tolerance policy.

5. For decades, the problem of misidentification and cross-contamination of cell lines was referred to as scandalous and the research outcome as pseudoscience and false. Yet the responses of the scientific community, including that of active researchers, officers of professional societies and funding organizations, publishers and editors of scientific journals, and directors of departments and research institutes, did not provide a proportionate response. With too few exceptions, the collective response was an exercise in pantomime.

6. The Snail Glide trajectory and accompanying velocity momentum has changed between 2009 and 2015. The MD Anderson Cancer Center promulgated an institution-wide cell line authentication policy. The American Association for Cancer Research requires authentication as a condition for publication in their six journals. The journals, Nature and Science, with NIH in a supporting role, lead adoption of this policy among about 200 other journals.

7. As strong evidence for a growing consensus, a standard, ASN-0002-2011, was developed and approved for authentication of human cell lines in 2011. ASN-0003, which deals with authentication of non-human cell lines, is now under final review.

8. The International Cell Line Authentication Committee (ICLAC) was established in 2012. This organization of volunteers maintains a database of misidentified cell lines, serves in an advisory capacity when requested, and initiates and coordinates a variety of other projects dealing with cell line authentication.

9. The contribution of misidentified cell lines to the major problem of non-reproducibility of preclinical research data is publicly recognized by Francis Collins. It is hoped that the outcome of an NIH-sponsored workshop (September 28-29, 2015) will help remedy the current situation.

10. Effective January 25, 2016, a new NIH mandate will become operational. NIH Guideline for Research NOT-OD-16-011 requires that grant applicants include specific information regarding the source of the cells to be used for the proposed research as well as how cell line authentication is to be performed before and during the research period. This zero tolerance mandate, when broadly adopted, will be a major transition point and hopefully mark the end of Snail Glide.

What comes next? A culture change broadly developed and supported by a variety of stake- holders who are intent on instituting and monitoring remedial policies that are effective and sustainable. Such an initiative will make the culture change transition effective because it will be consensus-based and provide for much needed institutional memory. The Snail Glide era has provided invaluable experience. We now recognize more fully how fragmented and diverse the stake-holders are and how narrow is their focus and how great is their inertia. We also recognize that persistent, fact-based calls for action, addressed to groups with a clear fiduciary responsibility, can elicit a favorable response.

Dr Roland Nardone

Catholic University of America

(Snail Image Credit: Modified from YouTube Images)