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Dividing HeLa cells as seen by scanning electron microscopy

A HeLa cell (also Hela or hela cell) is a cell type in an immortal cell line used in scientific research. It is the oldest and most commonly used human cell line.[1] The line was derived from cervical cancer cells taken on February 8, 1951[2] from Henrietta Lacks, a patient who eventually died of her cancer on October 4, 1951. The cell line was found to be remarkably durable and prolific as illustrated by its contamination of many other cell lines used in research.[3][4]

George Otto Gey and Henrietta Lacks

HeLa cells stained with Hoechst 33258

The cells were propagated by George Otto Gey shortly before Lacks died in 1951. This was the first human cell line to prove successful in vitro, which was a scientific achievement with profound future benefit to medical research. Gey freely donated both the cells and the tools and processes his lab developed to any scientist requesting them, simply for the benefit of science. Neither Lacks nor her family gave Gey permission to harvest the cells, but, at that time, permission was neither required nor customarily sought.[5] The cells were later commercialized, although never patented in their original form. Then, as now, there was no requirement to inform a patient, or their relatives, about such matters because discarded material, or material obtained during surgery, diagnosis, or therapy, was the property of the physician and/or medical institution. This issue and Mrs. Lacks' situation was brought up in the Supreme Court of California case of Moore v. Regents of the University of California. The court ruled that a person's discarded tissue and cells are not their property and can be commercialized.[6]

At first, the cell line was said to be named after a "Helen Lane" or "Helen Larson", in order to preserve Lacks' anonymity. Despite this attempt, her real name was used by the press within a few years of her death. These cells are treated as cancer cells, as they are descended from a biopsy taken from a visible lesion on the cervix as part of Mrs. Lacks' diagnosis of cancer. A debate still continues on the classification of the cells.[citation needed]

HeLa cells are termed "immortal" in that they can divide an unlimited number of times in a laboratory cell culture plate as long as fundamental cell survival conditions are met (i.e. being maintained and sustained in a suitable environment). There are many strains of HeLa cells as they continue to evolve by being grown in cell cultures, but all HeLa cells are descended from the same tumor cells removed from Mrs. Lacks. It has been estimated that the total number of HeLa cells that have been propagated in cell culture far exceeds the total number of cells that were in Henrietta Lacks' body.[7]

Use in research

HeLa cells were used by Jonas Salk to test the first polio vaccine in the 1950s. Since that time, HeLa cells have been used for "research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and many other scientific pursuits".[8] According to author Rebecca Skloot, by 2009, "more than 60,000 scientific articles had been published about research done on HeLa, and that number was increasing steadily at a rate of more than 300 papers each month."[6]

Telomerase

The HeLa cell line was derived for use in cancer research. These cells proliferate abnormally rapidly, even compared to other cancer cells. In Rebecca Skloot's The Immortal Life of Henrietta Lacks, she explains that HeLa cells have an active version of telomerase during cell division, which prevents the incremental shortening of telomeres that is implicated in aging and eventual cell death. In this way, HeLa cells circumvent the Hayflick Limit, which is the limited number of cell divisions that most normal cells can later undergo before dying out in cell culture.

Chromosome number

Horizontal gene transfer from human papillomavirus 18 (HPV18) to human cervical cells created the HeLa genome which is different from either parent genome in various ways including its number of chromosomes. HeLa cells have a modal chromosome number of 82, with four copies of chromosome 12 and three copies of chromosomes 6, 8, and 17.

Human papillomaviruses (HPVs) are frequently integrated into the cellular DNA in cervical cancers. We mapped by FISH five HPV18 integration sites: three on normal chromosomes 8 at 8q24 and two on derivative chromosomes, der(5)t(5;22;8)(q11;q11q13;q24) and der(22)t(8;22)(q24;q13), which have chromosome 8q24 material. An 8q24 copy number increase was detected by CGH. Dual-color FISH with a c-MYC probe mapping to 8q24 revealed colocalization with HPV18 at all integration sites, indicating that dispersion and amplification of the c-MYC gene sequences occurred after and was most likely triggered by the viral insertion at a single integration site. Numerical and structural chromosomal aberrations identified by SKY, genomic imbalances detected by CGH, as well as FISH localization of HPV18 integration at the c-MYC locus in HeLa cells are common and representative for advanced stage cervical cell carcinomas. The HeLa genome has been remarkably stable after years of continuous cultivation; therefore, the genetic alterations detected may have been present in the primary tumor and reflect events that are relevant to the development of cervical cancer.[9]

Contamination

Because of their adaptation to growth in tissue culture plates, HeLa cells are sometimes difficult to control. They have proven to be a persistent laboratory "weed" that contaminates other cell cultures in the same laboratory, interfering with biological research and forcing researchers to declare many results invalid. The degree of HeLa cell contamination among other cell types is unknown because few researchers test the identity or purity of already-established cell lines. It has been demonstrated that a substantial fraction of in vitro cell lines — approximately 10%, maybe 20% — are contaminated with HeLa cells. Stanley Gartler in 1967 and Walter Nelson-Rees in 1975 were the first to publish on the contamination of various cell lines by HeLa.[10]

Science writer Michael Gold wrote about the HeLa cell contamination problem in his book A Conspiracy of Cells. He describes Nelson-Rees's identification of this pervasive worldwide problem — affecting even the laboratories of the best physicians, scientists, and researchers, including Jonas Salk — and many, possibly career-ending, efforts to address it. According to Gold, the HeLa contamination problem almost led to a Cold War incident: The USSR and the USA had begun to cooperate in the war on cancer launched by President Richard Nixon only to find that the exchanged cells were contaminated by HeLa. Gold contends that the HeLa problem was amplified by emotions, egos, and a reluctance to admit mistakes. Nelson-Rees explains:

It's all human - an unwillingness to throw away hours and hours of what was thought to be good research...worries about jeopardizing another grant that's being applied for, the hurrying to come out with a paper first. And it isn't limited to biology and cancer research. Scientists in many endeavors all make mistakes, and they all have the same problems.[11]

Rather than focus on how to resolve the problem of HeLa cell contamination, many scientists and science writers continue to document this problem as simply a contamination issue — caused not by human error or shortcomings but by the hardiness, proliferating, or overpowering nature of HeLa.[12][13][clarification needed] Recent data suggest that cross-contaminations are still a major ongoing problem with modern cell cultures.[3][14]

Helacyton gartleri

HeLa cells
Scientific classification
Kingdom:
Phylum:
incertae sedis
Class:
incertae sedis
Order:
incertae sedis
Family:
Helacytidae
Genus:
Helacyton
Species:
H. gartleri
Binomial name
Helacyton gartleri

Due to their ability to replicate indefinitely, and their non-human number of chromosomes, HeLa was described by Leigh Van Valen as an example of the contemporary creation of a new species, Helacyton gartleri. The species was named after Stanley M. Gartler, whom Van Valen credits with discovering "the remarkable success of this species."[15] His argument for speciation depends on three points:

  • The chromosomal incompatibility of HeLa cells with humans.
  • The ecological niche of HeLa cells.
  • Their ability to persist and expand well beyond the desires of human cultivators.

This definition has not been followed by others in the scientific community, nor, indeed, has it been widely noted.[citation needed]

As well as proposing a new species for HeLa cells, Van Valen proposed in the same paper the new family Helacytidae and the genus Helacyton.[15] Recognition of Van Valen and Maiorana's names, however, renders Homo and Hominidae paraphyletic because Helacyton gartleri is most closely related to Homo sapiens.

See also

References

  1. ^ Rahbari R, Sheahan T, Modes V; et al. (2009). "A novel L1 retrotransposon marker for HeLa cell line identification". Biotechniques. 46 (4): 277–84. doi:10.2144/000113089. PMC 2696096. PMID 19450234. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Scherer, William F. (20). "STUDIES ON THE PROPAGATION IN VITRO OF POLIOMYELITIS VIRUSES : IV. VIRAL MULTIPLICATION IN A STABLE STRAIN OF HUMAN MALIGNANT EPITHELIAL CELLS (STRAIN HELA) DERIVED FROM AN EPIDERMOID CARCINOMA OF THE CERVIX". The Journal of Experimental Medicine. 97 (5): 695–715. doi:10.1084/jem.97.5.695. PMC 2136303. PMID 13052828. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  3. ^ a b Capes-Davis A, Theodosopoulos G, Atkin I; et al. (2010). "Check your cultures! A list of cross-contaminated or misidentified cell lines". Int J Cancer. 127 (1): 1–8. doi:10.1002/ijc.25242. PMID 20143388. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  4. ^ Watts, Denise Watson (May 9, 2010). "HeLa Cancer Cells Killed Henrietta Lacks. Then They Made Her Immortal". The Virginian-Pilot. pp. 1, 12–14.Note: Some sources report her birthday as August 2, 1920 vice August 1, 1920.
  5. ^ Washington, Harriet "Henrietta Lacks: An Unsung Hero," Emerge Magazine October 1994
  6. ^ a b Skloot, Rebecca (2010). The Immortal Life of Henrietta Lacks. New York: Crown/Random House. ISBN 9781400052173. {{cite book}}: Check |isbn= value: checksum (help)
  7. ^ Sharrer T (2006). ""HeLa" Herself". The Scientist. 20 (7): 22. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ Smith, Van (April 17, 2002). "The Life, Death, and Life After Death of Henrietta Lacks, Unwitting Heroine of Modern Medical Science". Baltimore City Paper. Retrieved 2 March 2010. {{cite news}}: Cite has empty unknown parameter: |coauthors= (help)
  9. ^ Macville M, Schröck E, Padilla-Nash H; et al. (1999). "Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping". Cancer Res. 59 (1): 141–50. PMID 9892199. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Masters JR (2002). "HeLa cells 50 years on: the good, the bad and the ugly". Nat. Rev. Cancer. 2 (4): 315–9. doi:10.1038/nrc775. PMID 12001993. {{cite journal}}: Unknown parameter |month= ignored (help)
  11. ^ Gold, Michael. A Conspiracy of Cells: One Woman's Immortal Legacy and the Medical Scandal It Caused. ISBN 9780887060991.
  12. ^ Wang H, Huang S, Shou J; et al. (2006). "Comparative analysis and integrative classification of NCI60 cell lines and primary tumors using gene expression profiling data". BMC Genomics. 7: 166. doi:10.1186/1471-2164-7-166. PMC 1525183. PMID 16817967. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
    Publications that cite the Geys and Kubicek
  13. ^ Louis Pascal (1991) "What happens when science goes bad" in Science and Technology Analysis Working Paper #9 University of Wollongong online
  14. ^ Roland M. Nardone (2006) "Eradication of Cross-Contaminated Cell Lines" white paper, Society for In-Vitro Biology online
  15. ^ a b Van Valen LM, Maiorana VC (1991). "HeLa, a new microbial species". Evolutionary Theory & Review. 10: 71–4. ISSN 1528-2619.

Further reading