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HeLa cells 50 years on: the good,
the bad and the ugly
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 competi-
tion among cancer-research scientists for
their laboratory to be the first to develop
‘human cancer in a test tube’. Rodent can-
cers had been cultured for many years by
Warren Lewis, without any appreciable
change in their appearance
1
. 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 old
2–4 and permanent cultures of animal cells had been established 5
, 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 ster-
ile 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 col-
lected and prepared on an almost daily
basis. Before starting work in the labora-
tory, a trip to the slaughterhouse was
needed in order to obtain plasma — taken
by plunging a needle into a chicken’s 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 ingredi-
ents was collected for the human cancer to
feed on, and this time — for George Gey —
it worked 6

7
.
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 can-
cer, 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 subse-
quently shown ‘without a doubt’ to be a
glandular cancer — a rare adenocarcinoma
8 — and not the usual epidermoid cancer of
the cervix, as the original publication on
HeLa 6 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

.
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To cancer research, HeLa is the equiva-
lent of the goose that laid the golden egg —
a constant supply of a precious and essen-
tial 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 can-
cer 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
changes
10
. Almost all of the continuous cell
lines are derived from high-grade, high-
stage 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
hurdles
11
. 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 sponta-
neous transformation in vitro to produce per-
manent 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 repair
12
.
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,
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 con-
fidentiality, 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 televi-
sion 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 dis-
covered — 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.
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 transforma-
tion; he also made some of the first phase-
microscope 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 laboratory’

TIMELINE (dates are after)

1907 Ross G. Harrison develops the ‘hanging
drop culture’ to study frog nerve-cell growth.
1910 Montrose T. Burrows
and Alexis Carrel grow
chick embryo cells in
tissue culture.
1940 Wilton R. Earle and
George Gey
generate a rodent
continuous cell line.
1951 Klaus H. Rothfels
and colleagues show
interspecies cross-
contamination.
1958 George and Margaret Gey
and Mary Kubicek develop
HeLa, the first human
cancer continuous cell line.
Walter Nelson-Rees
shows widespread
HeLa cross-
contamination.
Cross-contaminated
cell lines are used at
record levels.
Dennis Gilbert, Stephen O’Brien and
colleagues apply multilocus DNA
fingerprinting to cell-line authentication.
Stan Gartler shows
intraspecies cross-
contamination.
1907
1910
1940
1951
1958
1967
1974
1990
2002
Timeline | The development of human cancer cell lines
Figure 1 | George Gey. Courtesy of Alan Mason
Chesney Medical Archives.
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P E R S P E C T I V E S

The bad
Once George Gey had shown that it was
possible to culture human cancers, every-
one was able to do it. Suddenly, not only
human cancers could be cultured, but
also normal human cells became ‘sponta-
neously 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 estab-
lish 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 cells 18
.
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 dif-
ferent individuals of the same species. Stan
Gartler then introduced the concept of bio-
chemical polymorphism to the study of
human cell lines 19 : 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 individu-
als, 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 cells 20
.
So most of the new human cell lines that
had been established since George Gey’s
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 publi-
cations on the basis of the false cell lines
from the ATCC to admit that there might
be a problem. and have an endless supply of cells. Genetic
drift and phenotypic change will be minimal
within a laboratory 13 , provided that the cells
are not grown continuously — instead, the
cells should be replenished from frozen stocks
every few weeks — and standard quality con-
trol measures are used.
A chromosomal analysis has shown that
“the HeLa genome has been remarkably
stable after years of continuous cultivation”
14 . However, it is also relatively
easy to select strains of HeLa that have par-
ticular 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
test 15
. Large numbers of cells were needed to
grow the virus in order to produce the polio
vaccine that Jonas Salk subsequently devel-
oped. 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 dur-
ing shipment. Nevertheless, about 600,000
cultures had been shipped within two years 16
.
Jonas Salk even injected some patients with
HeLa cells, although at the time he thought
that he was growing the vaccine in normal
monkey cells 7
.
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 used
17
.
Perhaps the main reason underlying the
continued use of false cell lines is certain cell-
line banks. Despite being aware of the prob-
lem and being the most frequent source of
cells, some have continued to sell cells under
false descriptions. The small print has some-
times 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-contamina-
tion published in 1968, Stan Gartler summa-
rized the position. If the investigator’s
requirement was for any human cell line,
Stan Gartler has always felt that the iden-
tification of cross-contamination is rela-
tively unimportant, as any competent scien-
tist 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 devel-
oped techniques for authenticating cell lines.
With little consideration of the personal cost
or of the sensibilities of the people whose
mistakes and scandals he revealed
7
, Walter Nelson-Rees ruthlessly and relentlessly pur-
sued and exposed the HeLa cross-contaminants 21–23
. By the early 1980s, every human
cancer cell line, false or not, was a HeLa sus-
pect. So when Nelson-Rees retired in 1981, it
was a battle won. Or was it?

The ugly
Sadly, the battle was not won 24
. 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 scientists
25
. 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 lines 28–30. HeLa cells are used
under many other names with false descrip-
tions

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 use-
ful model of some other tissue. These find-
ings 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 spe-
cialized 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 break-
through has gone unrecognized.
Many journals do not want to take
responsibility for the widespread publica-
tion 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 avail-
able for this (trivial?) issue. Some journal
editors consider that it is not their responsi-
bility to set standards, referring to scientific
societies and funding bodies instead.
The peer-review process has almost com-
pletely failed in the respect of false cell lines.
If scientific journals required that each cell
line used was authenticated before publica-
tion, 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 problems
31
.

(BOX 1)
. Chaos reigns and fraud —
unwitting or deliberate — is condoned.

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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-Rees
21–23
. 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 cancer
33 . It was cited
more than 300 times during the period 1998–2000 in MedLine, and some of these studies used
the cells as a model of skin or head and neck cancer
34,35
. 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
larynx 36
. It was cited mre than 300 times during the period 1998–2000 in MedLine and is
frequently used by virologists as a human epithelial cell line 37,38
. 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 WISH 39
. 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 cells
40,41
.
•
HeLa (L132). The HeLa subline L132 was thought to be derived from normal human
embryonic lung cells 42
. These HeLa cells are sometimes described as being normal embryonic
human lung epithelial cells 43,44
.
•
HeLa (Intestine 407). The HeLa subline INT 407 was thought to be derived from human
intestinal epithelial cells 45
. Despite its origin from a cancer of the cervix, it is still used as a
model of normal human gastrointestinal cells 46,47
.
•
HeLa (Chang liver). The HeLa subline called Chang liver was thought to be derived from
normal liver cells 48
. Despite being cervical cancer cells, Chang liver cells are sometimes used in
studies of hepatic-cell physiology 49,50
.
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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 value 20
. There is, at present, a campaign to have the false cell lines renamed
with their correct designation 32
.
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
1.
Lewis, W. H. Malignant cells. The Harvey Lectures 31,
214–234 (1936).
2.
Harrison, R. G. Observations on the living developing
nerve fiber. Proc. Soc. Exp. Biol. Med. 4, 140–143 (1907).
3.
Carrel, A. On the permanent life of tissues outside the
organism. J. Exp. Med. 15, 516–528 (1912).
4.
Burrows, M. T. The cultivation of tissues of the chick
embryo outside the body. J. Am. Med. Assoc. 55,
2057–2058 (1910).
5.
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, 165–212 (1943).
6.
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,
264–265 (1952).
7. Gold,
M.
A Conspiracy of Cells. One Woman’s Immortal
Legacy and the Scandal it Caused (State Univ. New York
Press, New York, 1986).
8.
Jones, H. W., McKusick, V. A., Harper, P. S. & Wuu K. D.
The HeLa cell and a reappraisal of its origin. Obstet.
Gynecol. 38, 945–949 (1971).
9.
Masters, J. R. W. & Palsson, B. Ø. (eds) Human Cell
Culture Vol. 1–3 (Kluwer Academic, Dordrecht, 1999).
10. Masters, J. R. W. Human cancer cell lines: fact and
fantasy. Nature Rev. Mol. Cell Biol. 1, 233–236 (2000).
11. Wistuba, I. I. et al. Comparison of features of human
breast cancer cell lines and their corresponding tumours.
Clin. Cancer Res. 4, 2931–2938 (1998).
12. 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, 895–913 (1982).
13. UKCCCR guidelines for the use of cancer cell lines in
cancer research. Br. J. Cancer 82, 1495–1509 (2000).
14. Macville,
M.
et al. Comprehensive and definitive
molecular cytogenetic characterization of HeLa cells
by spectral karyotyping. Cancer Res. 59, 141–150
(1999).
15. Scherer, W. F., Syverton, J. T. & Gey, G. O. Studies on the
propagation in vitro of poliomyelitis viruses. J. Exp. Med.
97, 695–709 (1953).
16. Brown, R. W. & Henderson, J. H. M. The mass
production and distribution of HeLa cells at Tuskegee
Institute, 1953–55. J. Hist. Med. Allied Sci. 38, 415–431
(1983).
17. Arlett, C. F. The use of dubious cell lines in research: is
trust enough? Lancet Oncol. 2, 467 (2001).
18. 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.)
189–214 (Academic, New York, 1958).
19. Gartler, S. M. Genetic markers as tracers in cell culture.
Natl Cancer Inst. Monogr. 26, 167–195 (1967).

Figure 2 | Walter Nelson-Rees.
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44. Roos, W. P., Binder, A. & Bohm, L. Determination of the
initial DNA damage and residual DNA damage
remaining after 12 hours of repair in eleven cell lines at
low doses of irradiation. Int. J. Radiat. Biol. 76,
1493–1500 (2000).
45. Henle, G. & Deinhardt, F. J. The establishment of strains of
human cells in tissue culture. J. Immunol. 79, 54–59 (1957).
46. Takaishi,
S.
et al. Identification of a novel altrenative
splicing of human FGF receptor 4: soluble-form splice
variant expressed in human gastrointestinal epithelial cells.
Biochem. Biophys. Res. Commun. 267, 658–662 (2000).
47. Tsumura, T., Oiki, S., Ueda, S., Okuma, M. & Okada, Y.
Sensitivity of volume-sensitive Cl
–
conductance in human
epithelial cells to extracellular nucleotides. Am. J. Physiol.
271, C1872–C1878 (1996).
48. Chang, R. S. Continuous subcultivation of epithelial-like
cells from normal human tissues. Proc. Soc. Exp. Biol.
Med. 87, 440–443 (1954).
49. Li,
Y.
et al. A hepatocellular carcinoma-specific
adenovirus variant, CV890, eliminates distant human liver
tumors in combination with doxorubicin. Cancer Res. 61,
6482–6436 (2001).
50. Lee, Y. I., Kang-Park, S., Do, S. I. & Lee, Y. I. The
hepatitis B virus-X protein activates a phosphatidylinositol
3-kinase-dependent survival signaling cascade. J. Biol.
Chem. 276, 16969–16977 (2001).
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
33. Eagle, H. Propagation in a fluid medium of a human
epidermoid carcinoma, strain KB. Proc. Soc. Exp. Biol.
Med. 89, 362–364 (1955).
34. Kothny-Wilkes,
G.
et al. Interleukin-1 protects
transformed keratinocytes from tumor necrosis factor-
related apoptosis-inducing ligand. J. Biol. Chem. 273,
29247–29253 (1998).
35. Goan, Y. G., Zhou, B., Hu, E., Mi, S. & Yen, Y.
Overexpression of ribonucleotide reductase as a
mechanism of resistance to 2,2-difluorodeoxycytidine in
the human KB cancer cell line. Cancer Res. 59,
4204–4207 (1999).
36. Fjelde, A. Human tumor cells in tissue culture. Cancer 8,
845–851 (1955).
37. Galmiche,
A.
et al. The N-terminal 34kDa fragment of
Helicobacter pylori vacuolating cytotoxin targets
mitochondria and induces cytochrome c release.
EMBO J. 19, 6361 (2000).
38. Munger, J., Chee, A. V. & Roizman, B. The U(S)3 protein
kinase blocks apoptosis induced by the d120 mutant of
herpes simplex virus 1 at a premitochondria stage.
J. Virol. 75, 5491–5497 (2001).
39. Hayflick, L. The establishment of a line (WISH) of human amnion
cells in continuous cultivation. Exp. Cell Res. 23, 14–20 (1961).
40. Pavan, B., Biondi, C., Ferretti, M. E., Lunghi, L. &
Paganetto, G. 17
b-estadiol modulates prostaglandin E2
release from human amnion-derived wish cells. Biol.
Reprod. 64, 1677–1681 (2001).
41. Gayraud, B., Keene, D. R., Sakai, L. Y. & Ramirez, F. New
insights into the assembly of extracellular microfobrils
from the analysis of the fibrillin 1 mutation in the tight skin
mouse. J. Cell Biol. 150, 667–680 (2000).
42. Davis, E. V. & Bolin, V. S. Continuous cultivation of
isogenous cell lines from the human embryo. Fed. Proc.
19, 386 (1960).
43. Kasper,
M. et al. Induction of apoptosis by glyoxal in
human embryonic lung epithelial cell line L132. Am. J.
Respir. Cell Mol. Biol. 23, 485–491 (2000).
20. Gartler, S. M. Apparent HeLa cell contamination of human
heteroploid cell lines. Nature 217, 750–751 (1968).
21. Nelson-Rees, W. A., Flandermeyer, R. R. & Hawthorne, P. K.
Banded marker chromosomes as indicators of
intraspecies cellular contamination. Science 184, 1093
(1974).
22. Nelson-Rees, W. A. & Flandermeyer, R. R. HeLa cultures
defined. Science 191, 96–98 (1976).
23. Nelson-Rees, W. A., Daniels, D. W. & Flandermeyer, R. R.
Cross-contamination of cells in culture. Science 212,
446–452 (1981).
24. Nelson-Rees, W. A. Responsibility for truth in research.
Phil. Trans. R. Soc. Lond. B 356, 849–851 (2001).
25. Editorial. Responsibility for trust in research. Nature 289,
211–212 (1981).
26. Markovic, O. & Markovic, N. Cell cross-contamination in
cell cultures: the silent and neglected danger. In Vitro Cell
Dev. Biol. 34, 1–8 (1998).
27. MacLeod, R. A. F. et al. Widespread intraspecies cross-
contamination of human tumour cell lines. Int. J. Cancer
83, 555–563 (1999).
28. Dirks, W. G., MacLeod, R. A. & Drexler, H. G. ECV304
(endothelial) is really T24 (bladder carcinoma): cell line
cross-contamination at source. In Vitro Cell Dev. Biol. 35,
558–559 (1999).
29. Drexler, H. G., Uphoff, C. C., Dirks, W. G. & MacLeod,
R. A. F. Mix–ups and mycoplasma: the enemies within.
Leukemia Res. (in the press).
30. Drexler, H. G., MacLeod, R. A. F. & Dirks, W. G. Cross-
contamination: HS-Sultan is not a myeloma but a
Burkitt lymphoma cell line. Blood 98, 3495–3496
(2001).
31. Masters, J. R. W. et al. STR profiling provides an
international reference standard for human cell lines.
Proc. Natl Acad. Sci. USA 98, 8012–8017 (2001).
32. Stacey, G. N. et al. Cell contamination leads to
inaccurate data: we must take action now. Nature 403,
356 (2000).