Terra Sigillata

This missive came in yesterday from NIH, apparently sent to all investigators funded by the agencies:

A recent open letter to Secretary Leavitt (PDF here) from Dr. Roland Nardone and several experts in cell biology highlighted an important methodological issue associated with research involving cultured cells. The letter identifies a number of instances in which research has been based on misidentified or contaminated cultures. In some cases, proper characterization would have altered the experimental outcome significantly. Improper characterization can impede efforts to replicate published findings and therefore the advancement of science. The letter goes on to indicate that there are relatively inexpensive ways to authenticate lines and characterize these experimental systems. Dr. Nardone recommends that granting agencies restrict funding to institutions that do not use available authentication procedures.

We are convinced by the body of evidence developed by Dr. Nardone and his colleagues that misidentification of cell cultures is a serious problem1. Because authentication methods can be quite specific and are continuously evolving, it would be impractical for the NIH to require application of particular methods in all grant applications. The peer review process has been designed to carefully examine the experimental approach and assure that the investigators propose appropriate methods and resources for the described study. A similar process is used to screen manuscripts for publication. Both review processes can accommodate improvements in methodologies and experimental systems in ways that would be difficult for the segments of a granting agency involved in making awards.

We believe that professional societies, researchers, and reviewers are continually working to establish a range of acceptable experimental practices. Grant applications that fail to employ such practices would not be considered of the highest quality and such manuscripts would not fare well in the journal review process. We encourage all reviewers to consider these issues carefully in order to protect and promote the validity of the science we support.

Norka Ruiz Bravo, Ph.D.
NIH Deputy Director for Extramural Research

Michael Gottesman, M.D.
NIH Deputy Director for Intramural Research

For further information contact Walter T. Schaffer, Ph.D., Senior Scientific Advisor for Extramural Research, Building One, Room 144, Bethesda, Maryland 20892
Phone 301-402-2725, Email: ws11q@nih.gov

1Chatterjee, R. Cell Biology: Cases of Mistaken Identity, Science (315) 928-931, 2007


Dr Nardone has also written a similar white paper to this effect that appeared in the May 2007 issue of Cell Biology and Toxicology.

I had been aware since graduate school that HeLa human cervical carcinoma cells are often found to contaminate cell stocks from various sources – this fact has been recognized since 1976 or earlier. In 2002, a common MDA-MB breast carcinoma cell line (MDA-MB-435) was recently found to be more likely a melanoma. More recently, an Adriamycin-resistant MCF-7 breast carcinoma line used by NCI was shown to be of ovarian origin.

Marc Lacroix has suggested that cell lines can be easily verified using short tandem repeat (STR) analysis but, correct me if I am wrong, that method will only define the species and not the tissue type; the STR method is also influenced by time-dependent drift in markers during long-term culture of these genetically-unstable cell lines, making it difficult to confirm the origin of the specific cellular subclone with which one is working. In the letter to Secretary Leavitt, Nardone and co-signers suggest more drastic measures that would have NIH withhold grant support for any group that did not provide authentication of the cell lines being used.

Certainly this should be an issue for cell banks who sell cell stocks to researchers or institutional cell culture facilities that distribute cell lines.

But do any researchers reading this blog routinely confirm the identity of the cell lines they use?

Comments

  1. #1 apalazzo
    January 15, 2008

    This story reminds me of the big “Hela contamination” scare that resurfaces every 5-10 years. I guess people need to pay attention.

  2. #2 Drugmonkey
    January 15, 2008

    “But do any researchers reading this blog routinely confirm the identity of the cell lines they use?”

    or the identity of the drugs they use, as with the Ricaurte/MDMA/Meth affair perhaps?

    I was struck by the pronounced tone of “We’re not going down that slippery slope” from Ruiz Bravo. You could see in many fields and with many techniques that someone could advance an argument that all NIH researchers “must” do something the OneTrueWay….”nightmare” doesn’t even begin to capture it.

  3. #3 PhysioProf
    January 15, 2008

    I never do, but the kinds of experiments I do (heterologous expression of membrane proteins) always have internal controls that obviate the need to do so.

  4. #4 Roland M. Nardone
    February 17, 2009

    The comments that referred to the blog by Abel Pharmboy in Terra Sigillato, Jan. 15, 2008, regarding cell line authentication reflects the broad picture I have encountered during a four-year study of the current status of cell line cross-contamination and misidentification of cell lines (see BioTechniques, 2008, vol.45,221-229). The article concludes: “…is there any quality/integrity issue confronting the scientific community more compelling—I don’t think so.”

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