The Extensive and Expensive Impacts of HEp-2 [HeLa], Intestine 407 [HeLa], and Other False Cell Lines in Journal Publications
Open accessAbstract
Cell lines are essential models for biomedical research. However, they have a common and important problem that needs to be addressed. Cell lines can be misidentified, meaning that they no longer correspond to the donor from whom the cells were first obtained. This problem may arise due to cross-contamination: the accidental introduction of cells from another culture. The contaminant, which is often a rapidly dividing cell line, will overgrow and replace the original culture. The end result is a false cell line, also known as a misidentified or imposter cell line. False cell lines may come from an entirely different species, tissue, or cell type than the original donor. If undetected, false cell lines produce unreliable and irreproducible results that pollute the biomedical literature and threaten the development of reliable drug discovery and meaningful patient treatments.The goal of this study was to ascertain how widespread this problem is and how it affects the literature, as well as to estimate how much funding has been used to produce pools of scientific literature of questionable value. We focus on HEp-2 [HeLa] and Intestine 407 [HeLa], two false cell lines that are widely used in the scientific literature but were shown to be cross-contaminated in 1967. These two cell lines have been used in 8497 and 1397 published articles and extensively described as laryngeal cancer and normal intestine, respectively, rather than their true identity: the cervical cancer cell line HeLa. Discussed are tools, approaches, and resources that can address this issue-both retrospectively and prospectively.
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Up to 30% of cell lines may be misidentified, leading to substantial financial losses.
“The prevalence of CCCM is alarmingly high, with estimates suggesting that up to 30% of cell lines may be misidentified, leading to substantial financial losses [2][3][4].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
The “Present Day: Cross-Contamination Persists and the Problem Is Worsening” section (page not provided) reports an average misidentification rate of 22.1% across 16 collections, but not an upper limit of 30%; it says reported proportions range from 10% to 100%. “What Is the Cost of This Type of Research?” (page not provided) estimates substantial research-funding costs associated with false cell lines, supporting the financial-loss portion. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA single lab published 2.65% of HEp-2 work, and although they ceased using the line after being alerted, none of their articles were retracted or labelled with alerts.
“A single lab published 2.65% of this work.Although they ceased using the line after being alerted, none of their articles were retracted or labelled with alerts.”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
In “One Laboratory’s Use of Intestine 407 [HeLa] Leads to 1212 Citations” (page unavailable), the paper says Lab X published 37 of 1,397 Intestine 407 articles (2.65%)—not 2.65% of HEp-2 work. The same section says the lab stopped publishing with Intestine 407 after being alerted and that the authors found no retractions, corrigenda, or letters of concern for those articles in PubMed or PubPeer. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe lab's publications received an average of 32.7 citations each, meaning that 45,682 papers were built upon their incorrect information.
“The lab's publications received an average of 32.7 citations each, meaning that 45,682 papers were built upon their incorrect information [2].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
The section “One Laboratory’s Use of Intestine 407 [HeLa] Leads to 1212 Citations” reports that Lab X’s publications averaged 32.7 citations each. It derives 45,682 by applying that average to all 1,397 publications using the cell line—not to Lab X’s publications alone—and describes the result as a possible number of citations to reports of questionable significance, not a count of papers built on incorrect information. (LLM, conf=0.94)
Experimental — accuracy not yet measuredIn 2021, Korch and Capes-Davis evaluated the research and economic impacts of CCCM by focusing on the HEp-2 and INT407 cell lines.
“In 2021, Korch and Capes-Davis evaluated the research and economic impacts of CCCM by focusing on the HEp-2 and INT407 cell lines [2].”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
HEp-2 and INT407 were used in 8497 articles and 1397 articles, respectively.
“These lines, known to be misidentified since the 1960s, were used in 8497 articles published on HEp-2 and 1397 articles on INT407.”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
If each article using HEp-2 and INT407 was cited 15 times, the cost could be as high as $14.8 billion.
“This represents an enormous waste of resources: if it is”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
37% of HEp-2 articles ascribed an incorrect origin to the cell line, with the number of manuscripts growing by 250 per year.
“37% of the HEp-2 articles ascribed an incorrect origin to the cell line, with the number of manuscripts growing by 250 per year.”
From The history, landscape, and outlook of human cell line authentication and security (2024) · cites this paper as [2]
Korch and Capes-Davis identified 8497 and 1397 published articles that used the HeLa derivatives HEp-2 and Intestine 407 extensively describing them as laryngeal cancer and normal intestine cells.
“They identified 8497 and 1397 published articles that used the HeLa derivatives HEp-2 (CVCL_1906) and Intestine 407 (CVCL_1907) extensively describing them as laryngeal cancer and normal intestine cells [19].”
From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [19]
In 2021, Korch and Capes-Davis estimated that roughly $990 million were spent to publish the 8497 HEp-2 and 1397 Intestine 407 studies in which these false cell lines were used.
“In 2021, Korch and Capes-Davis estimated the financial consequences of using the two HeLa contaminated cell lines HEp-2 and Intestine 407. They concluded that roughly $990 million were spent to publish the 8497 HEp-2 and 1397 Intestine 407 studies in which these false cell lines were used [19].”
From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [19]
Many human cell lines are known to be wrongly identified because of cross-contamination or uncertainty about donor origins.
“Finally, due to cross-contamination and/or uncertainty over donor origins, many human cell lines are known to be wrongly identified (21–25).”
From Misspellings or “miscellings”—Non‐verifiable and unknown cell lines in cancer research publications (2024) · cites this paper as [25]
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Self-citation
- Authors
- Korch, C. T., & Capes-Davis, A.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Korch, Christopher T.
- Venue
- SLAS Discovery
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 26
- Issue
- 10
- Pages
- 1268-1279
- ISSN
- 2472-5552 (ISSN-L)
- OpenAlex
- W3208168144
- Cited by
- 23
- References
- 59
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 1
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Decision Sciences › Information Systems and Management › Academic Publishing and Open Access
- Physical Sciences › Computer Science › Information Systems › Research Data Management Practices
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Keywords
- cell line misidentification, cross-contamination, HeLa, cervical cancer cell lines, laryngeal cancer, research reproducibility, research funding, cell line authentication
- MeSH terms
- HeLa Cells, Humans, Intestines, Prospective Studies, Retrospective Studies, Biomedical Research, Cell Line, Tumor, Drug Discovery
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