BBC File On 4 recently learned that “millions of pounds
of charity donations and taxpayers’ money have been wasted on worthless cancer
studies”. Labs have been using contaminated cell lines – rather than
experimenting on the cancer cells they thought they had researchers have been
studying other kinds of cancers or even mice cells. Perhaps the most remarkable (and newsworthy)
aspect of the whole affair is that it is not a recent surprise: researchers
sounded the alarm bell – repeatedly – in the early 1970’s. Science noted in
1974 that “a lot of people may have been spending a lot of time and money on
misguided research.” That was 33 years ago, a millennium of time in cell
biology.
That contamination occurs is not surprising
but it is disturbing how widespread it is. 18-36% of cell lines submitted to
cell banks were found to be misidentified. Several hundred scientific papers
last year used cell lines known to be contaminated. Yet only about 50% of
researchers regularly verify the identities of their cell lines.
This is not a cause of deliberate fraud or
stinginess (testing costs as little as $30), but persistent sloppiness. No
researcher wants to waste effort on erroneous research, yet checking that the
cells the whole lab uses are valid risks upsetting everybody’s research and
careers. No wonder many prefer not to rock the boat and hope the professor had
someone check the cells when they arrived.
In a recent call to arms Roland M. Nardone (a cell biologist
and professor emeritus at the Catholic University of America) argues that
journals and funding agencies should impose rules on researchers, forcing them
to submit proof of cell line identity along with their manuscripts and grant
proposals, respectively. But funding agencies appear slow in reacting, possibly
out of fear of upsetting many of their already funded projects. Journals appear
to think it is up to the researchers.
The Ethics of Contamination Control
The pursuit of better understanding is
fundamental to science. As a corollary,
it is against the goals and ethics of science to mislead both oneself and
others. Everybody involved in science should hence be trying to prevent
contamination. But do certain groups have more responsibility because they are
well positioned to stop it?
Cell banks noticed the problem early and now
increasingly check submissions as well as stopping delivery of contaminated
cell lines. But many cell lines are shared between researchers before being
submitted. The cell banks can not stem the contamination, just monitor it.
Funding agencies – often representing the
public – have an interest in producing the best and most useful research, so
they should pursue contamination checking. It is both the right thing and
cost-effective. But while they can demand checking in the grant contracts, they can only control that this has been done after the fact.
Science is a very collective activity,
despite appearances. While researchers ought to do their best that is not
enough. Even excellent researchers with the highest standards make mistakes or
pursue the wrong theories. Science works thanks to the different error-checking
methods built into the system rather than individual perfection. The main form
of error checking is replication of experiments. While not glamorous, it is
necessary to check that findings are not flukes. Unfortunately contaminated
cell-lines can be widely spread, undermining replication as a tool to notice
the problem.
Peer review is another form of error
correction: it should be harder to publish a finding that is erroneous than a
correct one. This is where scientific journals can play a key role, by
demanding that the researchers check for contamination. But the journals may
not regard themselves as guardians of scientific truth, preferring to set the
reviewers in that role. Reviewers on the other hand will not do more work than
necessary and are not always reliable.
Perhaps the most serious problem today is that
many researchers and journals appear to be unaware of which cell lines are
known or suspected to be contaminated, long after this has been announced. Contamination
is often reported in little read specialist journals. This suggests an additional strategy to promote contamination checking.
Much would be won if there was a clear, conveniently available repository of
contamination warnings. Reviewers should check that papers do not use cell
lines from the list, and the reputation of journals that publish papers using
such cell lines should suffer – a credible incentive for the journals to behave, since in scientific
publishing reputation is everything. Establishing official contamination lists
and fingerprints identifying “clean” strains would be a natural job for funding
agencies and cell banks. By making blame clearer it makes it harder to hide systematic sloppiness.
References
Rhitu Chatterjee, Cases of Mistaken
Identity, Science, 315:5814, pp. 928-931, 16 February 2007
Marc Lacroix, Persistent use of “false” cell lines,
International Journal of Cancer, 122:1, Pages 1–4 2007
Roland M. Nardone, Eradication of
Cross-Contamination: A Call for Action, Society for In Vitro Biology, 2007