✔Good day fellow Dukies.
The big news -- first reported by Fact Checker early Thursday evening but now with stunning new detail:
✔✔✔✔✔ The mentor of Dr. Anil Potti -- after four years of defending their joint research and claims to a break-thru in cancer treatment -- has stated their work has no validity. Or in the mentor's words, "no meaning."
The mentor is Dr. Joseph Nevins, a heavyweight in Duke medicine, Barbara Levine Professor of Breast Cancer Genomics and director of Duke's Center for Applied Genomics and Technology.
Nevins has sent an e-mail to the Journal of Clinical Oncology (JCO) requesting that it retract a 2007 research paper that he co-authored. The editors have yet to respond.
This paper claimed that locked in the DNA and RNA of each individual -- and in their cancer -- was information that revealed which form of chemotherapy would work best. Up until then, it was hit or miss; this was a major advance, major. Think Lasker, think Nobel Prize.
✔✔✔✔✔ Immediately, as news of Nevins' retraction request rippled thru the scientific community, a new storm engulfed Duke.
Experts say that Nevins has admitted that the clinical trials that followed the laboratory research -- more accurately described as experiments with human beings -- harmed patients. Up until this moment, Duke has steadfastly denied this; and in a Halloween statement, Duke affirmed "we do not believe that patients were endangered."
This sets up an interesting confrontation: who do you believe? The faculty member who was involved in the trials? Or the administrators responsible for oversight?
✔✔✔✔✔ Nevins revealed one aspect of Potti's research involved 59 samples of ovarian cancer. Or what was supposed to be ovarian cancer.
16 of those samples are not this kind of cancer at all. Nevins: "At this point, I cannot trace the origin or nature of these samples."
✔✔✔✔✔ Of the remaining 43 samples, the news is not much better. "The tumor ID labels for these samples are incorrect. In a large number of these cases, the mis-identification results in reversal of the clinical annotation of response vs. non-response."
Translation: with the tumors being mis-identified, no one could tell what was what. In fact Potti concluded some patients were helped when they were not. He concluded some patients were not helped but they were. And out of this crap, he developed his theories about unlocking secrets contained in DNA and RNA and was allowed to experiment with human beings.
The Cancer Letter -- which has broken most of the news in the Potti scandal -- turned to Dr. George Sledge, the President of the American Society of Clinical Oncology, a professor at Indiana University, for interpretation. "It is safe to assume that patients might have been assigned to treatments that were unlikely to benefit them and possibly even to harm them."
And Dr. David Carbone, chair of cancer research at Vanderbilt: because of errors in Potti's research, "you may be withholding an effective treatment from some people or giving an ineffective targeted drug" suggested by the research. And "there is the possibility of patient harm."
From Dr.John Ruckdeschel, director and CEO of the Nevada Cancer Institute: "The potential for patients to have been treated differently than they might have otherwise been is present."
✔✔ There's more: Duke's first official review of the Potti mess finally came last winter (after almost four years of questions, not one as the Chronicle states). This was a hush hush behind closed doors internal review; Fact Checker alone has reported it was led by Dr. John Harrelson, professor of orthopedic surgery and associate professor of pathology. A Deputy Fact Checker found he is a double Dukie, Trinity '61 and MD '64, who also stayed on at Duke to train on the House Staff. He is now retired.
Duke occludes this internal review, by mentioning its outside consultants -- and inferring it was an outside review. Wrong.
During this review, Potti was not suspended but he was not allowed to recruit more volunteers for his experiments. The people already in the trials were allowed to remain.
This weekend, Duke's medical PR man, Douglas Stokke, was sent out after Nevins denounced his own work to concede that the same 59 samples that Nevins looked at anew, had been analyzed last winter and found OK.
Dr. Sally Kornbluth, Duke Medical School vice dean for research, said last year's investigation did not "drill down" to re-check the actual raw data. She said the review team was "not aware that there were data integrity issues with the work."
Whoa. Whoa. Whoa.
We turn to the intrepid bio-statisticians at the M D Anderson Comprehensive Cancer Center, Keith Baggerly and Kevin Coombes, in a guest editorial in The Cancer Letter:
"In November, 2009, we identified and reported the exact problems now cited for retracting the paper.... Given that Duke knew of these problems, why were (Potti's) clinical trials reopened in January 2010?"
Kornbluth was one of two vice deans who signed off on the winter-time investigation. So she's got a lot at stake in its scoope and integrity. And that was just one of four investigations that we know of into the Potti mess.
Nevins' retraction request is not part of any of those investigations. So where did it come from? How did it occur? From Duke PR: "We cannot speak for Dr. Nevins and his team who analyzed the data and came to the conclusion regarding the need to request a retraction."
Keep reading, there's more.
✔ Speed check number one involves other Duke scientists who co-authored the JCO (Journal of Clinical Oncology) article that Nevins wants withdrawn. Where do they stand? Why are they silent?
These include two big shots: Dr. David Harpole, professor of cardiovascular and thoracic surgery, and vice chief of the entire Division of Surgical Services. And Dr. Phillip Febbo, a specialist in prostate cancer who has since left Duke for the University of California - San Francisco. There are also other junior Duke physicians and scientists, several of whom have left for other places including UNC.
✔ Speed check number two involves the request to retract the JCO paper. It's rather unusual -- to say the least -- for a co-author to initiate a retraction request -- and even more unusual for one co-author to proceed unilaterally without consent of all the other authors.
The Cancer Letter -- whose original reporting on the Potti mess has prompted, forced and embarrassed Duke into action and is fully worthy of major awards for investigative journalism -- says that Nevins sent an email October 22 to his 13 co-authors to advise them. That's a whole lot different from their consent.
Key issue: Did Potti respond? Did he agree to sign this correspondence? Did all of the co-authors sign? Are all of the co-authors in agreement that the paper should be retracted?
Key issue: Over the Halloween weekend -- yes some of this stuff is so scary that I threw that in again -- Chancellor Victor Dzau sent all medical personnel an E-mail. He referred to "A scientific misconduct investigation regarding Dr. Potti that began several weeks ago." In fact, while the Institute of Medicine has agreed to do this external, unfettered, complete investigation, it will not begin until next year.
Yes this is the same Dr.Dzau who told us in an earlier e-mail that the very investigation would be into "the science conducted by Drs. Potti and Nevins."
Or as they'd say in Brooklyn, hey Victor, what happened to Joe?
FC does not believe the above Chronicle article is correct when it states Nevins is not under investigation.
Or for that matter, what happened to William T. Barry, who received his Ph.D. at Carolina in 2007 and is an assistant professor of bio-statistics and bio-informatics, working in the cancer center? Loyal Readers will remember FC's taking the wraps off Duke's secret report dated last December. That's when welearned tdhat Barry -- along with Potti and Nevins -- was investigated.
✔ ✔✔✔ Speed check number three involves the tests that were run to confirm Potti's data -- the precise time-line being in question.
What a tug of war it must have been between Nevins and his superior, Huntington Willard, Ph.D., Vice Chancellor for Genome Sciences and Nanaline Duke (James B's widow)Professor in the Institute for Genome Sciences & Policy!!!!!
(Nevins has refused all media requests for an interview; Willard responded immediately to a Fact Checker inquiry over the weekend on another aspect of the Potti matter. We are still at work trying to sort out other things to ask Willard who has indicated he would respond. Monday morning Duke PR announced Willard will take on new duties as senior adviser to the king of undergraduate deans, Steve Nowicki)
A consistently reliable mole tells FC that Willard called a meeting with everyone in Potti's lab -- believed to be about 20 people, a total derived from pictures of those attending the annual Christmas party that Potti has thrown. Willard said he was taking over as Principal Investigator for Anil’s grants.
(This is more than a technicality. The rules for most grants provide that the Principal Investigator -- PI -- cannot be absent for more than three months. One key grant for this research expires November 1 and it will be interesting to see how Duke handles continuing the lab. If some disgruntled employees are let go, FC wants to hear from them!!!!).
And Willard put Bala Balakumaran, Ph.D., Research Associate, Senior Staff, Center for Applied Genomics & Technology in charge of repeating the Potti experiments -- with specific instructions to report to him, Willard.
Nevins apparently contradicted that, telling Balakumaran that only portions of the Potti experiments should be repeated -- and forget Willard, the results should be given to him.
The mole tells FC there were several rounds in the tug of war with Balakumaran being "cajoled" by Nevins and receiving "conflicting orders" from two superiors.
Loyal Readers, this is not a novel. All this is going on in Fitzpatrick!!
✔✔The FC mailbox overflowed this weekend. Here are some excerpts:
"Is Nevins falling on his sword or throwing Potti under the bus?"
"The rest of the investigation will determine who was responsible and if deliberate fabrication or falsification were involved. Admission of reckless incompetence may be the only way out for Potti and Nevins."
✔✔ Potti remains on administrative leave. Paid. "No change" in status, said Michael Schoenfeld, Duke PR in response to the latest outrages. Loyal Readers, I do not know what a Duke faculty member, Duke researcher, or Duke doctor has to do to get canned.
Nor do I know who is protecting this clown.
✔✔✔About 25,000 people in the medical enterprise at Duke, and their continuing discoveries and care have earned this university renown. As the Chronicle notes, they are led by Chancellor Dzau, and FC expresses complete confidence in his integrity.
He alone among Duke's administrators has kept his pledge to keep the Potti mess "transparent."
FC and he have had substantial discussions of not only this, but other issues, with FC given more time than ever anticipated, allowed to explore every angle.
Unfortunately our essay this morning -- as happens so often in journalism -- is not about the good being done by so many but about a few who are sinking their ship. The only issue on the horizon is how many will go under with the vessel.
✔ Thank you for reading Fact Checker on good days and bad.