PERSPECTIVES

every country that previously used asbestos

now has a rising trend of mesothelioma
deaths32 (FIG. 2), and the mineral is as
controversial as ever.
As with other industrial cancers, an
awareness of the cancer risk of asbestos has
been hindered by powerful vested interests
and sometimes bitter controversies among
scientists with the polarities of the scientific debate often reflecting who had commissioned the research. In 2001, a line was drawn
when the World Trade Organization stated
that there is no safe level of asbestos exposure, that all types of asbestos are carcinogenic, and that controlled risk in manufacture, product use and disposal is
unachievable33. Nevertheless, asbestos manufacture continues in parts of the developing
world. Canada still exports (though does not
use) chrysotile, and its mining companies
continue to proclaim that it is harmless and
indispensable (see Asbestos Institute web
site). Even countries that have banned the
material still have to devise strategies to cope
with the asbestos that remains in place. The
asbestos industry is in retreat, but the health
effects of its products will stay with us for
some time to come.
Geoffrey Tweedale is at the Centre for Business
History, Business School,
Manchester Metropolitan University,
Aytoun Street, Manchester M1 3GH, UK.
e-mail: G.Tweedale@mmu.ac.uk

16. Tweedale, G. Science or public relations?: the inside

story of the Asbestosis Research Council. Am. J. Indust.
Med. 38, 723734 (2000).
17. Enterline, P. E. Changing attitudes and opinions regarding
asbestos and cancer 19341965. Am. J. Indust. Med.
20, 685700 (1991).
18. McCulloch, J. Asbestos Blues (James Currey Publishers,
London, 2002).
19. Wagner, J. C., Sleggs, C. A. & Marchand, P. Diffuse
pleural mesotheliomas and asbestos exposure in the
North-Western Cape Province. Br. J. Indust. Med. 17,
260271 (1960).
20. Selikoff, I. J. & Lee, D. H. K. Asbestos and Disease
(Academic, New York, 1978).
21. Newhouse, M. L. & Thompson, H. Mesothelioma of
pleura and peritoneum following exposure to asbestos in
the London area. Br. J. Indust. Med. 22, 261269
(1965).
22. Johnston, R. & McIvor, A. Lethal Work: A History of the
Asbestos Tragedy in Scotland (Tuckwell, Glasgow,
2000).
23. Proctor, R. Cancer Wars (Basic Books, New York, 1995).
24. Smith, A. H. & Wright, C. C. Chrysotile asbestos is the
main cause of pleural mesothelioma. Am. J. Indust. Med.
30, 252266 (1996).
25. Stayner, L. T., Dankovic, D. & Lemen, R. A. Occupational
exposure to chrysotile asbestos and cancer risk: a review
of the amphibole hypothesis. Am. J. Public Health 86,
179186 (1996).
26. Epstein, S. S. The Politics of Cancer Revisited (East
Ridge Press, New York, 1998).
27. Doll, R. & Peto, J. Asbestos: Effects on Health of
Exposure to Asbestos (HMSO, London, 1985).

28. Dalton, A. Asbestos Killer Dust (BSSRS Publications,

London, 1979).
29. Tait, N. Asbestos Kills (privately published, London,
1976).
30. Peto, J., Hodgson, J. T., Matthews, F. E. & Jones, J. R.
Continuing increase in mesothelioma mortality in Britain.
Lancet 345, 535539 (1995).
31. Peto, J., Decarli, A., La Vecchia, C., Levi, F. & Negri, E.
The European mesothelioma epidemic. Br. J. Cancer 79,
666672 (1999).
32. Health & Safety Commission. Health & Safety Statistics
(HSE Books, Norwich, annual).
33. World Trade Organization. European Community
Measures Affecting Asbestos and Asbestos-Containing
Products. Report of the Appellate Body,
WT/DS135/AB/R, 12 March 2001.

Online links
DATABASES
The following terms in this article are linked online to:
CancerNet: http://www.cancer.gov/search/
lung cancer | mesothelioma
FURTHER INFORMATION
Asbestos Institute web site: www.asbestos-institute.ca
British Asbestos Newsletter: www.lkaz.demon.co.uk
Health & Safety Executive: www.hse.gov.uk
International Labour Organization: www.ilo.org
Trades Union Congress: www.tuc.org.uk
White Lung Association: www.whitelung.org
Access to this interactive links box is free online.

TIMELINE

HeLa cells 50 years on: the good,

the bad and the ugly

DOI: 10.1038/nrc774
1.
2.

3.

4.

5.
6.
7.
8.

9.

10.

11.

12.

13.
14.

15.

Health & Safety Commission. Health & Safety Statistics

200001 (HSE Books, Norwich, 2001).
Wikeley, N. J. Asbestos and cancer: an early warning to
the British TUC. Am. J. Indust. Med. 22, 449454
(1992).
Wood, W. B. & Gloyne, S. R. Pulmonary asbestosis: a
review of one hundred cases. Lancet 2, 13831385
(1934).
Lynch, K. M. & Smith, W. A. Pulmonary asbestosis. III.
Carcinoma of the lung in asbestos-silicosis. Am. J.
Cancer 24, 5664 (1935).
Proctor, R. The Nazi War on Cancer 108111 (Princeton
Univ. Press, Princeton, New Jersey, 1999).
Ministry of Labour & Factory Inspectorate. Annual Report
for 1947 7980 (HMSO, London, 1949).
McLaughlin, A. I. G. The prevention of the dust diseases.
Lancet 2, 49 (1953).
Schepers, G. W. H. Changing attitudes and opinions:
asbestos and cancer 19341965. Am. J. Indust. Med.
22, 461466 (1992).
Wyers, H. That Legislative Measures Have Proved
Generally Effective in the Control of Asbestosis. Thesis,
Glasgow Univ. (1946).
Tweedale, G. Magic Mineral to Killer Dust: Turner &
Newall and the Asbestos Hazard 146 (Oxford Univ.
Press, Oxford, 2000).
Castleman, B. I. Asbestos: Medical and Legal Aspects
4th edn 69 (Aspen Law & Business, Englewood Cliffs,
New Jersey, 1996).
Lilienfeld, D. E. The silence: the asbestos industry and
early occupational cancer research a case study. Am.
J. Public Health 81, 791800 (1991).
Doll, R. Mortality from lung cancer in asbestos workers.
Br. J. Indust. Med. 12, 8186 (1955).
Greenberg, M. A study of lung cancer mortality in
asbestos workers: Doll, 1955. Am. J. Indust. Med. 36,
3147 (1999).
Ministry of Labour & Factory Inspectorate. Annual Report
of HM Chief Inspector of Factories 39 MHSO, London,
1965).

NATURE REVIEWS | C ANCER

John R. Masters
HeLa cells the first continuous cancer
cell line have been a mainstay of cancer
research ever since their isolation from the
aggressive glandular cervical cancer of a
young woman more than 50 years ago.
Knowledge of almost every process that
occurs in human cells has been obtained
using HeLa cells and the many other cell
lines that have since been isolated. So why
does fraud an ignorance surround the use
of these and other human cancer cell lines?

Fifty years ago, there was intense competition among cancer-research scientists for
their laboratory to be the first to develop
human cancer in a test tube. Rodent cancers had been cultured for many years by
Warren Lewis, without any appreciable
change in their appearance1. But, despite
thousands of attempts, nobody had grown
human cells in the laboratory for more than
a few weeks. Tissue culture was nearly 50
years old24 (see TIMELINE) and permanent
cultures of animal cells had been
established5, so surely it was possible?

The breakthrough came on 8 February

1951 at The Johns Hopkins Hospital in
Baltimore, Maryland. George Gey (FIG. 1)
was given a small sample and took it back
to his laboratory. It was not a tissue-culture
laboratory as we know it today. There were
no laminar-flow cabinets or bottles of sterile culture media and sera. Tissue culture
was done on the open bench, with the help
of a bunsen burner to give a small window
of relatively sterile air, using materials collected and prepared on an almost daily
basis. Before starting work in the laboratory, a trip to the slaughterhouse was
needed in order to obtain plasma taken
by plunging a needle into a chickens heart.
A visit to the abattoir was next, as calf
embryos were collected, which could later
be homogenized for extract. Finally, a trip
to the labour ward was made, to suck off
human placental blood from umbilical
cords. This gruesome mixture of ingredients was collected for the human cancer to
feed on, and this time for George Gey
it worked6.

VOLUME 2 | APRIL 2002 | 3 1 5

PERSPECTIVES

Figure 1 | George Gey. Courtesy of Alan Mason

Chesney Medical Archives.

George Gey was a brilliant and highly

respected scientist. By 1951, he had been
growing cells for nearly 30 years, and until
1937 had worked with Warren Lewis. He
was the first to show in vitro transformation; he also made some of the first phasemicroscope time-lapse films of living cells
and developed roller tubes for culturing
cells. His goal was to cure cancer, and he did
not take time out to write papers. Crucially
for the success of HeLa cells his wife
Margaret was the chief technician and the
meticulous director of day-to-day operations
in the laboratory7.
The cancer sample came from the cervix
of a young black lady called Henrietta Lacks,
a 30-year-old mother of five living on New
Pittsburgh Avenue in Baltimore. Cervical
cancer is normally slow growing, and most
patients survive for at least five years after
diagnosis. But this was not an ordinary cancer, according to the gynaecologist Howard
Jones. It was purple and soft, and he had
never seen anything like it before (or since,
according to a television interview screened
in the United Kingdom in 1997). It did not
respond to radiotherapy and was subsequently shown without a doubt to be a
glandular cancer a rare adenocarcinoma8
and not the usual epidermoid cancer of
the cervix, as the original publication on
HeLa6 incorrectly described it.
On 4 October 1951, eight months after
her cancer was diagnosed, Henrietta
Lacks died, leaving her husband, David, a
widower, and her children motherless. The
autopsy report stated that her abdomen
was filled with cancer deposits and her

316

| APRIL 2002 | VOLUME 2

bladder was almost entirely replaced with

the tumour. By this time, her cancer was
also growing like wildfire in the laboratory.
The cell line was called HeLa, taken from
the first two letters of Henrietta Lacks names.
The failure to preserve complete anonymity
was regrettable, but, to give a measure of confidentiality, the donor was said to be Helen
Lane or Helen Larson. It was not customary
then to ask for written permission to obtain
such samples for research purposes, and there
is no record that Henrietta Lacks consented to
the use of her cells. Attitudes were different
then prison inmates were shown on television being injected with HeLa cells, proud
that they were repaying some of their debt to
society (The Way of All Flesh, BBC TV
documentary screened on 19 March 1997 in
the United Kingdom).
When Mrs Lacks children eventually discovered more than 20 years later what
had happened to her tissue, they were
shocked that cells from their mother had
been distributed worldwide and no one had
ever sought their views or permission. The
requirement today for documented patient
consent for research samples is, in part, a
consequence of the HeLa cell story.
The good

Fifty years ago, the HeLa cell was seen as a

great breakthrough, and possibly even the
key to a cure for human cancer. The war on
cancer and the worldwide hunt for the virus
that was believed by some scientists to cause
human cancer was soon to follow.
Our knowledge of every fundamental
process that occurs in human cells whether
normal or abnormal has depended to a large
extent on using HeLa and other cell lines as a
model system. Much of what we know today,
and much of what we do tomorrow, depends
on the supply of HeLa and other cell lines.

To cancer research, HeLa is the equivalent of the goose that laid the golden egg
a constant supply of a precious and essential resource. Within a few years, HeLa cells
had been distributed worldwide and
became the laboratory model of the cancer
cell that would be used for much of cancer
research. But they are not just used for cancer research HeLa cells are used
throughout biomedical research to study
the biochemical pathways of normal and
diseased tissue in human cells. Although
thousands of continuous cell lines from
almost every type of human cancer have
since been established mainly in the
1970s and 1980s (REF. 9) HeLa is still the
most widely used human cancer cell line.
What was special about the cancer from
which HeLa cells were grown? Generally,
the human cancers that grow permanently
in culture are a selected group of very
aggressive cancers that have acquired the
necessary phenotypic and genotypic
changes10. Almost all of the continuous cell
lines are derived from high-grade, highstage cancers. It is possible to grow some
less aggressive cancers permanently, but
very few scientists have had the patience,
tenacity or skills to overcome the technical
hurdles11. A short cut is to immortalize the
cells with viral genes, the products of which
bind and inhibit key proteins such as p53
and retinoblastoma (RB).
So why do normal human cells usually
senesce and die, rather than undergo spontaneous transformation in vitro to produce permanent cultures, as normal rodent cells so
often do? One possibility is that the difference
is related to the higher capacity of human cells
for DNA repair12.
Why was human cancer in a test tube such
an important goal? With cell lines, it is possible
to go back to the same cancer again and again,

Timeline | The development of human cancer cell lines

Ross G. Harrison
develops the hanging
drop culture to study
frog nerve-cell growth.

1907

1910

Montrose T. Burrows
and Alexis Carrel grow
chick embryo cells in
tissue culture.

Wilton R. Earle and

George Gey
generate a rodent
continuous cell line.

1940

1951

Klaus H. Rothfels
and colleagues show
interspecies crosscontamination.

1958

George and Margaret Gey

and Mary Kubicek develop
HeLa, the first human
cancer continuous cell line.

1967

Walter Nelson-Rees
shows widespread
HeLa crosscontamination.

1974

Stan Gartler shows

intraspecies crosscontamination.

1990

Cross-contaminated
cell lines are used at
record levels.

2002

Dennis Gilbert, Stephen OBrien and

colleagues apply multilocus DNA
fingerprinting to cell-line authentication.

www.nature.com/reviews/cancer

PERSPECTIVES

Box 1 | A sample of the better known HeLa cell cross-contaminants

Comprehensive lists of ~100 early examples of cross-contamination are given in the references of
Walter Nelson-Rees2123. The cell lines described briefly in this box are authentic HeLa cells, and
there is no evidence that they contain any genetic information from any other cell type. As a result
of genetic drift and being subjected to different conditions in various laboratories, each strain
might have genetic and phenotypic differences. There is no common stock of HeLa cells, and
consequently every batch from each source will be slightly different. The differences between the
various cell stocks labelled HeLa are probably as great as the differences between these various
strains given different names. Within the last year, some of the false cell lines listed below were
catalogued and sold by some cell banks under the false name and false description.
HeLa(KB). The HeLa subline KB was thought to be derived from an oral cancer33. It was cited
more than 300 times during the period 19982000 in MedLine, and some of these studies used
the cells as a model of skin or head and neck cancer34,35. Few of the papers mention or seem to be
aware that the cells are derived from a glandular cancer of the cervix.
HeLa (HEp-2). The HeLa subline HEp-2 was thought to be derived from a cancer of the
larynx36. It was cited mre than 300 times during the period 19982000 in MedLine and is
frequently used by virologists as a human epithelial cell line37,38. Usually, there is no mention
that these cells are a HeLa subline and are derived from a cervical cancer.
HeLa (WISH), HeLa (AV3) HeLa (FL). These three sublines of HeLa were all thought to be
derived from amnion cells, the most well-known and widely used one being WISH39. Despite
their origin from cervical cancer, these cell lines are sometimes used in the fields of
reproduction and endocrinology, and are described as being normal human amnion cells40,41.
HeLa (L132). The HeLa subline L132 was thought to be derived from normal human
embryonic lung cells42. These HeLa cells are sometimes described as being normal embryonic
human lung epithelial cells43,44.
HeLa (Intestine 407). The HeLa subline INT 407 was thought to be derived from human
intestinal epithelial cells45. Despite its origin from a cancer of the cervix, it is still used as a
model of normal human gastrointestinal cells46,47.
HeLa (Chang liver). The HeLa subline called Chang liver was thought to be derived from
normal liver cells48. Despite being cervical cancer cells, Chang liver cells are sometimes used in
studies of hepatic-cell physiology49,50.

and have an endless supply of cells. Genetic

drift and phenotypic change will be minimal
within a laboratory13, provided that the cells
are not grown continuously instead, the
cells should be replenished from frozen stocks
every few weeks and standard quality control measures are used.
A chromosomal analysis has shown that
the HeLa genome has been remarkably
stable after years of continuous
cultivation14. However, it is also relatively
easy to select strains of HeLa that have particular properties by applying selection
pressures deliberately or accidentally
simply by altering the culture conditions,
such as the medium or serum. For example,
it is possible to select HeLa cells that grow
in suspension rather than attached to the
culture dish, or HeLa cells that are resistant
to cancer drugs.
One of the first applications of HeLa cells
was in the fight against polio. George Gey and
colleagues in Minneapolis showed that polio
virus grew easily in HeLa cells, and killed the
cells, which provided a simple diagnostic
test15. Large numbers of cells were needed to
grow the virus in order to produce the polio

NATURE REVIEWS | C ANCER

vaccine that Jonas Salk subsequently developed. A HeLa production facility was set up at
the Tuskegee Institute in Minnesota which
was not ideal, as both the summer and winter
temperatures could be lethal to the cells during shipment. Nevertheless, about 600,000
cultures had been shipped within two years16.
Jonas Salk even injected some patients with
HeLa cells, although at the time he thought
that he was growing the vaccine in normal
monkey cells7.
HeLa cells are even more important
today than when they were first described.
Every year for the past 20 years the number
of citations for HeLa on MedLine has
increased, with more than four times as
many hits in the year 2000 as in 1980. Many
more publications use HeLa cells without
acknowledgement (see BOX 1). HeLa and the
other human cancer cell lines that have been
established since 1951 are the bedrock of
laboratory cancer research. Analysis of the
frequency of use of cell lines in papers that
were published in one recent issue of Cancer
Research indicated that three-quarters of the
publications used cell lines, and, in total,
more than 112 cell lines had been used17.

The bad

Once George Gey had shown that it was

possible to culture human cancers, everyone was able to do it. Suddenly, not only
human cancers could be cultured, but
also normal human cells became spontaneously transformed and proliferated at
great speed in the laboratory. The number
of cells could double about every 24 hours,
and soon this was happening in biomedical
laboratories worldwide.
But of course it was not that easy to establish a cell line from a human cancer it
remains very difficult to this day for most
types of cancer and normal human cells
almost never spontaneously transform. It
soon became clear that many of the cell lines
were not what they were claimed to be.
Monkey cells turned out to be human cells;
human cells were shown to be mouse cells18.
But it took more than 15 years before the
full extent of the problem was revealed. Until
1967, it had not been possible to distinguish
between cell lines that were derived from different individuals of the same species. Stan
Gartler then introduced the concept of biochemical polymorphism to the study of
human cell lines19: some proteins have several
different forms, and these forms can differ
between individuals.
In 1962, the American Type Culture
Collection (ATCC) was set up to collect
authentic cell cultures. Stan Gartler was
supplied 18 supposedly unique human cell
lines by the ATCC and other sources, and
investigated the expression of the enzyme
glucose-6-phosphate
dehydrogenase.
Individuals have either the A or the B form
of the enzyme, and these are distinguished
according to mobility in a gel. The A form is
almost exclusively found in black individuals, at an incidence of ~30%. HeLa and the
other 17 cell lines that were tested expressed
the type A form, and also had an identical
phenotype for another polymorphic
enzyme, phosphoglucomutase 1. Stan
Gartler suggested that perhaps all of these
cell lines were HeLa cells20.
So most of the new human cell lines that
had been established since George Geys
success back in 1951 were not new, they
were just more HeLa cells. Scientists in
dozens of laboratories had been careless
and mixed up the cells. But Stan Gartler
might as well have talked to himself even
scientists who must have known that his
conclusions were correct attacked him. Too
many people had written grants and publications on the basis of the false cell lines
from the ATCC to admit that there might
be a problem.

VOLUME 2 | APRIL 2002 | 3 1 7

PERSPECTIVES

Figure 2 | Walter Nelson-Rees.

Stan Gartler has always felt that the identification of cross-contamination is relatively unimportant, as any competent scientist can easily authenticate the cells. But
because many scientists did not seem to be
making these checks, one man went into
open battle to expose the problem. Walter
Nelson-Rees (FIG. 2) was head of the Oakland
Cell Culture Laboratory and Bank, part of
the University of California at Berkeley.
In the 1970s, Walter Nelson-Rees developed techniques for authenticating cell lines.
With little consideration of the personal cost
or of the sensibilities of the people whose
mistakes and scandals he revealed7, Walter
Nelson-Rees ruthlessly and relentlessly pursued and exposed the HeLa cross-contaminants2123. By the early 1980s, every human
cancer cell line, false or not, was a HeLa suspect. So when Nelson-Rees retired in 1981, it
was a battle won. Or was it?
The ugly

Sadly, the battle was not won24. In 1981, the

editor of an influential journal described
individuals such as Walter Nelson-Rees as
self-appointed vigilantes and said it would
be tragic if they corrupted the civilized
habits of scientists25. With such attitudes
holding sway, and Nelson-Rees retired, the
civilized habits of ignorance, complacency
and deception were, again, unchecked.
Today, it is estimated that ~20% of cell
lines are falsely labelled (mainly due to
intraspecies contamination) 26,27 and the
problem has spread to many other human
cancer cell lines2830. HeLa cells are used
under many other names with false descriptions (BOX 1). Chaos reigns and fraud
unwitting or deliberate is condoned.

318

| APRIL 2002 | VOLUME 2

Continued use of a cell line that has been

contaminated with HeLa cells is often based
on claims that the HeLa cells have acquired
the specialized properties of the other cell
type, making the false cell line despite
being composed of HeLa cells alone a useful model of some other tissue. These findings are remarkable, as the HeLa cells would
have shared the same substrate as the other
cell type for only a few days, if at all. There is
no evidence that the cross-contaminated
sublines have a mixed parentage, underwent
any form of somatic cell hybridization or
exchanged any genetic information.
How could HeLa cells have acquired specialized characteristics of normal and cancer
cell types, such as lung, amnion, liver and
heart? If it is possible for one cell type to gain
characteristics of another cell type, simply by
growing the two cell types together for a
short period, an important scientific breakthrough has gone unrecognized.
Many journals do not want to take
responsibility for the widespread publication of false data. The usual excuses are that
the problem is already widely known (so
should it continue to be ignored?), the
information is not of sufficient scientific
interest or there is not enough space available for this (trivial?) issue. Some journal
editors consider that it is not their responsibility to set standards, referring to scientific
societies and funding bodies instead.
The peer-review process has almost completely failed in the respect of false cell lines.
If scientific journals required that each cell
line used was authenticated before publication, all but the most deliberate fraud would
disappear. DNA profiling provides a simple
and cheap method of authentication, it is
available to everyone and could prevent
most of the problems31.
Perhaps the main reason underlying the
continued use of false cell lines is certain cellline banks. Despite being aware of the problem and being the most frequent source of
cells, some have continued to sell cells under
false descriptions. The small print has sometimes indicated that the false cell line might
have HeLa characteristics, which in itself is
misleading of course HeLa cells have
HeLa characteristics.
What is the significance of the rising
mountain of incorrect data? The implication
is that ~20% of publications using cell lines
contain false data, but that does not mean
that all of these publications are misleading.
In the description of HeLa cross-contamination published in 1968, Stan Gartler summarized the position. If the investigators
requirement was for any human cell line,

whether or not it was HeLa or another cell

line does not seem important. However, in
those cases in which the investigator has
assumed a specific tissue origin of the cell
line (such as liver or lymphocytes), the work
is of dubious value20. There is, at present, a
campaign to have the false cell lines renamed
with their correct designation32.
The future

HeLa cells are even more important today

than they were when first grown by George
Gey 50 years ago. Cell lines have been, and
will continue to be, the model system of
the cancer cell that is used by most cancer
research scientists. However, the HeLa
story also shows the consequences when
peer review fails and there is a lack of
quality control.
John R. Masters is at the Institute of Urology,
University College London,
67 Riding House Street,
London W1W 7EY, UK.
e-mail: j.masters@ucl.ac.uk
DOI: 10.1038/nrc775
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Lewis, W. H. Malignant cells. The Harvey Lectures 31,

214234 (1936).
Harrison, R. G. Observations on the living developing
nerve fiber. Proc. Soc. Exp. Biol. Med. 4, 140143 (1907).
Carrel, A. On the permanent life of tissues outside the
organism. J. Exp. Med. 15, 516528 (1912).
Burrows, M. T. The cultivation of tissues of the chick
embryo outside the body. J. Am. Med. Assoc. 55,
20572058 (1910).
Earle, W. R. et al. Production of malignancy in vitro. IV.
The mouse fibroblast cultures and changes seen in
living cells. J. Natl Cancer Inst. 4, 165212 (1943).
Gey, G. O., Coffman, W. D. & Kubicek, M. T. Tissue
culture studies of the proliferative capacity of cervical
carcinoma and normal epithelium. Cancer Res. 12,
264265 (1952).
Gold, M. A Conspiracy of Cells. One Womans Immortal
Legacy and the Scandal it Caused (State Univ. New York
Press, New York, 1986).
Jones, H. W., McKusick, V. A., Harper, P. S. & Wuu K. D.
The HeLa cell and a reappraisal of its origin. Obstet.
Gynecol. 38, 945949 (1971).
Masters, J. R. W. & Palsson, B. . (eds) Human Cell
Culture Vol. 13 (Kluwer Academic, Dordrecht, 1999).
Masters, J. R. W. Human cancer cell lines: fact and
fantasy. Nature Rev. Mol. Cell Biol. 1, 233236 (2000).
Wistuba, I. I. et al. Comparison of features of human
breast cancer cell lines and their corresponding tumours.
Clin. Cancer Res. 4, 29312938 (1998).
Sanford, K. K. & Evans, V. J. A quest for the mechanism
of spontaneous malignant transformation in culture with
associated advances in culture technology. J. Natl
Cancer Inst. 68, 895913 (1982).
UKCCCR guidelines for the use of cancer cell lines in
cancer research. Br. J. Cancer 82, 14951509 (2000).
Macville, M. et al. Comprehensive and definitive
molecular cytogenetic characterization of HeLa cells
by spectral karyotyping. Cancer Res. 59, 141150
(1999).
Scherer, W. F., Syverton, J. T. & Gey, G. O. Studies on the
propagation in vitro of poliomyelitis viruses. J. Exp. Med.
97, 695709 (1953).
Brown, R. W. & Henderson, J. H. M. The mass
production and distribution of HeLa cells at Tuskegee
Institute, 195355. J. Hist. Med. Allied Sci. 38, 415431
(1983).
Arlett, C. F. The use of dubious cell lines in research: is
trust enough? Lancet Oncol. 2, 467 (2001).
Rothfels, K. H., Axelrad, A. A., Siminovitch, L.,
McCulloch, E. A. & Parker, R. C. in Proc. 3rd Canadian
Cancer Research Conference 1958 (ed. Begg, R. W.)
189214 (Academic, New York, 1958).
Gartler, S. M. Genetic markers as tracers in cell culture.
Natl Cancer Inst. Monogr. 26, 167195 (1967).

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PERSPECTIVES
20. Gartler, S. M. Apparent HeLa cell contamination of human
heteroploid cell lines. Nature 217, 750751 (1968).
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Online links
DATABASES
The following terms in this article are linked online to:
CancerNet: http://www.cancer.gov/search/
cervical cancer | head and neck cancer | laryngeal cancer | oral
cancer | skin cancer
LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/
glucose-6-phosphate dehydrogenase | p53 |
phosphoglucomutase 1 | RB

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