Three years later, Korch’s colleague, Andy Bradford, a molecular
biologist who studies gynecologic cancers, ordered three samples of the
line. He sent them to Korch for fingerprinting as a matter of course. “I
was very disappointed when they turned out to be breast cancer cells,”
Bradford says. “Sometimes the truth sucks!” He asked Klonisch for
another batch, hoping that perhaps his own lab had contaminated the
first ones. But the new samples Klonisch sent were also breast cancer
cells. After that, Korch and Bradford say, repeated emails to Klonisch
went unanswered. During that time, research groups in at least three
countries unwittingly studied and published papers on the line.
Klonisch struggles to explain why he did not immediately pay to
fingerprint the line himself. One reason, he says, was the cost. At that
time, the cost ranged from $67 to $475. “I offered to profile their
samples as blind samples, with the identities sent to a neutral party
‘arbitrator,’ ” Korch says.
Klonisch felt he had a reasonable alternative. “We went through very
extensive functional testing, and our data seemed to contradict that of
Dr. Bradford. The uniqueness of our line meant that a lot was at stake.
And our line did not seem to behave like breast cancer.”
How can scientists be so easily fooled by the behavior of a cell?
“It’s the same concept as raising identical twins in different
environments,” says Bradford. “They will look and behave differently,
but their DNA remains the same.” If a breast cancer line had silently
contaminated Klonisch’s cell culture early on, it would have been
subject to the usual technique for immortalizing a normal cell (which
involves applying enzymes, antibiotics and antibiotic-resistant genes).
The only breast cancer cells that would proliferate would survive every
one of those chemical manipulations. They would emerge functionally
different than an untouched breast cancer cell because their environment
had so radically changed.
In 2012, Korch, Bradford and colleagues published a paper detailing
their false line and its breast cancer provenance. By May 2013, Klonisch
did what a good scientist must: He offered corrections to the relevant
journals, which have since published them. “My reputation was
tarnished,” says Klonisch soberly, “and all my research in this field
has been shut down. And we never intended any of this.”
Winds of Change
A global correction for cell line science has begun. In 2012, Korch,
Masters and 16 other scientists formed the International Cell Line
Authentication Committee (ICLAC). They agreed on STR fingerprinting as
the global standard for authenticating cell lines. The committee also
set up a public database (found at iclac.org) of all known false lines,
which numbers more than 400.
Recently, the top four cell line repositories, in America, Germany and
Japan, made plans to merge their online databases of cell lines
validated through STR fingerprinting, with each fingerprint converted to
a searchable genetic “bar code.” The consortium’s online tool (known as
OSTRA, for Online STR Analysis) can be accessed online
As of this writing, at least 22 journals now require cell line
authentication from authors. Norbert Fusenig, the Germany-based
associate editor of the International Journal of Cancer, notes that the
journal has had a steady increase in submissions since 2012, when it
began to require authentication. “Our impact factor, a common measure of
a journal’s success, has increased,” he says.
In April 2013, Nature published more stringent requirements, in which
every author had to report the source of a study’s cell lines and
whether the lines had been verified recently.
Immunologist Linda Miller, whose 2009 Nature editorial called for a
global database of STR-fingerprinted lines, says, “Encouraging the
community to authenticate, that’s the first step, but not the final
step. Ultimately, it must become a requirement. Science, and the flow of
money to scientists, depends on the public trust.”