“A billion here, a billion there, and pretty soon you’re talking real money” ~attributed to Everett Dirksen
Unfortunately for us, the phrase goes differently–and, in cancer research, we’re already talking about ‘real money.’
A retraction of a scientific paper on cancer here, a retraction there. . .and pretty soon you’re talking about a real fiasco–for scientists, researchers, clinicians, and–above all–the patients.
In yesterday’s post I raised the concern issue over staggering numbers of cancer research studies which cannot be replicated–until one frustrated scientist, trying to make a difference, claimed it was this lack of care taken in the lab that was preventing cancer treatment from making steps forward. Writes he:
The failure to win “the war on cancer” has been blamed on many factors, … But recently a new culprit has emerged: too many basic scientific discoveries… are wrong.
Pretty astounding–and sounds rather over the top. Until you really start to take a look at some of the ‘boo-boos’ that have occurred in cancer labs and journals–and that have required retractions, taking time and space from research that might actually have proven helpful.
Just to give you an idea of the gravity of the problem, I share with you several recent retractions of cancer studies from premier journals. I cherry-pick a few that stand out for humor, or moxie, or downright chutzpa.
Let’s start with one on an abstruse topic. We don’t know what they’re talking about science-wise, but they tell you in clear language how they goofed.
The authors conclude:
…in consideration of the aggregate data from our own laboratory and that of others, it is our current view that the [conclusion] has not withstood the test of time or of independent verification and that this association is now tenuous. Therefore, we retract the conclusions in our article.
This retraction has a certain panache. You see, the results simply had not “withstood the test of time.” It makes it sound like the original experiments had been done in the Paleolithic period, rather than a few months ago.
2. Researcher Retracts Cancer Biomarker Paper Cited by Lawsuit, January 4, 2012
This one tickles me in its very round-about way of saying very little about what led up to the retraction. It also amuses me how the lab can’t tell us anything–but they’re taking that undisclosable information [whatever it might be, if it even exists] ‘very seriously.’ The full statement from Hopkins reads:
We are aware that at Dr. Robert Getzenberg’s request, the journal Urology on Oct. 3, 2011, retracted his manuscript entitled, “EPCA-2: a highly specific serum marker for prostate cancer.” Johns Hopkins University takes the circumstances that led to the retraction extremely seriously. Although internal investigations of the kind that might be triggered by the issues that have been raised are confidential, we want to emphasize that matters of integrity in research are at the core of our mission and we are committed to ensuring that all research conducted under the auspices of Johns Hopkins University are conducted to the highest ethical and scientific standards.
Given that I’m not allowed to have the slightest insight into what they’re talking about, I’m glad they’ve emphasized that I should trust they’ll handle this matter better in the future than they’ve done so far.
3. This next one is truly in a category of its own. Dr. Anil Potti supposedly made the cancer discovery of a lifetime.
Potti “discovered” the ability to match chemotherapy to a patient’s genetic makeup, radically changing a cancer patient’s survival statistics. It’s only too unfortunate that scientists didn’t set aside time to verify his results–which were unreplicable–until much later.
At last count, Potti had retracted nine–count ’em–nine papers–and seemed to be working his way up, steadily, to the 13 expected retractions he’d have to make.
“Ninth Potti paper to date gets retracted,” February 7, 2012
The paper, “An Integrated Genomic-Based Approach to Individualized Treatment of Patients With Advanced-Stage Ovarian Cancer,” was published in the Journal of Clinical Oncology in February 2007. The research studied ovarian cancer patient responses to platinum-based therapy.
The retraction noted:
The majority of the authors wish to retract this article because they have identified several instances of misalignment of genomic and clinical outcome data. The authors deeply regret the impact of this action on the work of other investigators.
4. Not to be missed, for a certain element of amusement:
After Mistakes, Scientists Try to Explain Themselves from April 16, 2012, New York Times. Some researchers who had to retract papers go back to explain how things went, uh, wrong.
It begins with the story of one Naoki Mori, a Japanese cancer researcher who has had–sit down for this one–30 papers retracted by scientific journals. He did fess up that he and his co-authors “were lax in certain regards in the preparation of papers,” but he denied that it was any serious offense.
One of my favorite pieces of this article is that Mori et al used pictures from older papers to prove their points, rather than from the actual experiments they were describing in the paper.
Points for creativity, I say.
5. The long road to retraction 2003
Clever researchers see the handwriting on the wall, and, given little option, are the ones to retract their own papers. Not so quickly in the case of Alexander Kugler.
He held out–and the last laugh was nearly the journal’s, as they apologized for taking so long to retract the faulty science–and essentially blaming it on Kugler’s feet-dragging.
Acknowledging how damaging to a career a formal retraction by a journal is, they nonetheless threatened to pull the paper unless they got a formal, written retraction from every author. Write the editors of Nature Medicine:
In the current issue of Nature Medicine, we are publishing the retraction of a paper by Kugler et al., titled “Regression of human metastatic renal cell carcinoma after vaccination with tumor cell−dendritic cell hybrids.”
. . . . . .
A detailed look at the committee’s report exposed several deficiencies in the manuscript: inaccurate primary data in the publication, insufficient documentation of laboratory work and patient vaccination, and inclusion of patients that did not fulfill the criteria described in the Methods section. Perhaps the most significant fault was that the authors developed a protocol for using dendritic cells that was not approved by the ethics committee.
I hate it when you forget to consult the ethics commitee. That’s like not writing your name on the top of a test paper. Ten points off the top. And, the Journal continues, they want the paper to be as if it never was:
Many retracted articles continue to be cited and, in most cases, treat the retracted article as if it were valid research. We now look to the community to place the results of the Kugler article in the right context. Whether their method is a good cancer strategy is an important question. It may be, but this paper should no longer be cited as evidence.
This one tickled my funny-bone a bit, as I thought, upon reading about it–sure, you’ve got a good idea? It went over big? Why not see how far that can take you? I mean, who’s really going to notice? But someone, it seems, is.
Apparently the article, “Current concepts of surveillance and its significance in head and neck cancer” in Annals journal, looked mighty familiar to certain journal readers, but not because the authors had plagiarized other researchers’ work.
Oh, no! Far be that from them. Instead they merely re-phrased their own. I mean, wasn’t it good enough to achieve publication the first time?? And they already had it in front of them.
Wrote the Annals:
Recently the Editor received an enquiry from a reader concerning a paper published in the November 2011 issue of the Annals. This noted extensive similarities between the Annals paper and a publication by the same authors in 2009. The abstracts of the two papers are almost identical, the work reported concerns the same group of patients seen in an identical time period, many sections of the text are closely similar or identical, and several tables contain the same information, albeit sometimes in a different order.
And here comes the nail in the coffin:
The recent publication in the Annals has now been retracted. We regret the time and effort wasted in this matter by our reviewers and staff, and the lost opportunity to publish another paper in the space taken by this submission.
6. It’s hard to quit once you’ve been bit by the retraction bug, but I’ll leave you with a title that’s a sure winner:
Come on–how can you pass that one up?
Well, here’s the tale of woe behind the big bucks.
Here the authors of a 2009 study in the Proceedings of the National Academy of Sciences(PNAS) retracted a paper, with the compelling title “Wnt-5a signaling restores tamoxifen sensitivity in estrogen receptor-negative breast cancer cells,” which found a particular molecule could make breast tumors respond to a drug to which they’re not normally susceptible.
Another one of those ‘sounds too good to be true,’ Wnt-5a would, supposedly make breast cancer cells respond to tamoxifen in women who previously didn’t respond to the drug.
Pretty great, no?
Only–I’m sure you can guess it–it didn’t work like that at all, not in the slightest. So came time for retraction:
The authors wish to note the following: “During efforts to extend this work, we re-examined the laboratory records for all figures and found that the Excel files on which Fig. 4C was based contained serious calculation errors; the first author of the paper takes full responsibility for these inaccuracies. Considering the importance of this figure for the conclusions drawn, the authors hereby retract the work. We apologize for any inconvenience this may have caused.”
But the story doesn’t end there. The company responsible for this wonderful new responsiveness to tamoxifen is Wnt Research, which had been scheduled to go public on November 16, 2010. After the retraction appeared on November 11, the timing seemed less than ideal. So they postponed the IPO.
And then remember that ‘first author’ the retraction alluded to? She gave back all $24,000 worth of her shares–perhaps allowing this to become one of the most (directly) expensive retractions of a scientific paper to date.
I feel I should quit, while the quitting’s good, and while I’m not too terribly depressed about what I’ve written here. Plus, if I keep on going, I’ll be in danger of discovering–and having to update the post–Dr. Anil Potti tenth retraction. It’s coming any moment–best go to press.
http://retractionwatch.wordpress.com– A wordpress blog that keeps up on all the latest in scientific retraction of papers–a wealth of information.