Committees

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Committees

Sometime in 1998, the research space in the department of radiology was reassigned. I was given an office immediately opposite that of my young colleague, Roger Howell, and a small laboratory nearby. The larger laboratory was to be shared by my colleague, his postdoctoral fellow, Anupam Bishayee, and myself.

Truth even unto its innermost parts

As our interests were somewhat similar, I volunteered to work with Howell to help him get government funding. He applied for a grant from the National Cancer Institute which he submitted for the November 1 deadline in 1999. I was a co-investigator on that grant application. Bishayee had been working in the lab for about 2 years and it was his research that formed the experiments reported in several research papers published between 1998 and 2002. My expertise was in DNA damage and mutagenesis. Howell asked me to work with Bishayee on an experiment which he had devised to determine whether the experimental model that he had designed would provide adequate oxygen to the cells that he was studying. The model involved incubating several million mammalian cells in loose pellets which Howell termed "clusters". Bishayee performed the first part of the experiment and then passed dishes containing mammalian cells to me to study for mutations. My results showed that it was likely that the cells were not getting adequate oxygen. Howell then had Bishayee repeat both parts of the experiment by himself. During the course of his experiment I examined dishes that I was quite certain were his from that experiment. I believed those dishes were empty, that is, they did not contain the colonies that were expected and were later reported to contain. I was suspicious of the results and related my concerns to Howell. Bishayees results supported Howell's hypothesis regarding oxygen whereas my results did not support that hypothesis. Howell used Bishayees results in Figure 7 of his grant application, although he knew -- because I had told him -- that my outcome conflicted with that of Bishayee.

To my knowledge, that experiment has never been repeated although good scientific practice would require that the conflict between the two outcomes be resolved. Scientific misconduct was not of much concern in those days. I wrote a memo to myself (lab problems) about my suspicions but did nothing further. Howell's grant application was successful and the monies ($1.42 million over 5 years) started flowing July 1, 2000. Howell hired a new postdoctoral fellow, Marek Lenarczyk, in the fall of 2000. Lenarczyk worked closely with me and voiced concern about Bishayee's integrity. One evening in March of 2001, Lenarczyk came to me because he was concerned about an experiment that Bishayee was carrying out. We determined to follow that experiment which would last for another 10 to 12 days, believing that experiment was contaminated with mold which would show up in the end. In actual fact, a couple of other events that made us additionally suspicious occurred. Lenarczyk photographed samples in the incubator that we believed should not have been there because the protocol called for them to be processed in another laboratory (see photo). Furthermore, Bishayee had obtained fresh cultures from Lenarczyk and we believed he used those to simulate the desired results.

Unbeknownst to me, Howell became aware of the shadowing of Bishayee and went to the department chairman, Dr Stephen Baker. He sent Baker a memo the same day, April 6, reflecting their conversation (Howell-Baker memo 4.6.01) . The memo indicates that I had made "accusations of falsification of data" although I was not to do so until the following week. It also states that "I [Howell] have requested that my post-doctoral fellow Marek Lenarczyk, PhD repeat some of Dr. Bishayee's experiments as a check of the validity of the data", when, at this time, Lenarczyk had already performed 11 experiments that had failed to reproduce Bishayee's results (non-replication experiments). There were to be in all 22 experiments that followed the same 2 protocols precisely and that failed to reproduce Bishayee's findings. Howell would acknowledge in his deposition that his failure to reproduce was never reported to Dr Baker, Dr Putterman, the Vice-President for Academic Affairs, the NIH or to the journal, Radiation Research, that had published 2 papers based on Bishayee's data. Furthermore, he had felt no obligation to do so (Howell dep part 1 and part 2). Lenarczyk took a number of pictures of the contents of various incubators, but the most significant were of the 10.5 degree centigrade incubator which housed the slender "Helena" tubes due to be processed on Friday, March 30 and should, we were certain, have been gone that day (see photo taken on 04.04.01 above and The Saga of the Mysterious New Cell Line (NCL) That Comes and Goes, below). They remained there until the following Thursday. Unfortunately, earlier in the week, Lenarczyk moved the tubes for reasons that are not clear, took pictures and moved them back. This was to allow the Campus Committee on Research Integrity (CCRI) to conclude that we were lying. I reported my suspicions regarding this experiment to Howell, to my department chairman, Baker, and to the chairman of the CCRI. The CCRI was composed of 3 Deans, 1 vice president, 1 department chair, 1 lawyer, 1 staff for the vice president and 1 administrator. The chair, Elizabeth Raveche, was the only member without an administrative appointment. None were qualified in radiation biology and, in fact, one was a midwife. The committee interviewed me, Howell, and the two postdoctoral fellows. During the course of the investigation, I told them about the experiment that had concerned me in 1999.

In the end, the committee ruled that there was insignificant evidence for research misconduct (1st Committee Minutes, Report and letter: CCRI-1, CCRI-2, CCRI-3, CCRI-4, CCRI-5, CCRI-Hill docs, CCRI final report, Saporito letter 7.2.01). This is the first of 3 learned bodies whose rulings the judge thought I should have accepted. I did not accept their ruling, and after it came down, I was subjected to retaliation by being locked out of the shared laboratory and being defamed by Dr Howell (Howell Memo 07.30.01, Howell Memo 07.31.01, Baker email to Howell 07.02.01, List of Recipients, Grievance Memo) and later on by another member of the division, Dr Edouard Azzam. The events around this time are recorded in the Time Line found in the Supplement to the Written Disclosure filed with the Court on 4/4/04.

NB: The first committee's report along with the minutes of the various meetings were made available during Discovery several years later. The retaliation was recorded in the initial charges in the qui tam law suit (Original Complaint, attachments to Original Complaint).

Because I was not satisfied with the ruling of the first committee, I reported my observations to the Office of Research Integrity (ORI) of the United States Public health Service. The ORI took nearly a year to come to the same conclusion as the first committee. The case was managed by Dr. Kay Fields. Dr. Fields, in actual fact, supported my findings. However, when she reported her results to her board, she was overruled and, as she related to me, she was taken off the case and stormed out of the room. Fields report was redacted by her boss Dr. Alan Price. Both of these reports became available during the discovery period of the qui tam case which did not become known to me for several years (Fields' Report, Price's revision of Fields' Report). Just before the ruling by the ORI board, Dr. Fields told me about a statistical method for analyzing the rightmost terminal digits of numbers that should be random or uniform as an indication of potential scientific misconduct. These were numbers recorded from the LED screen of the Coulter Counter, a counter used for quantifying the cell numbers in virtually all of the experiments done in Howell's lab. The ORI had analyzed the numbers in that first experiment in 1999 and found that they were highly unlikely to be, as they should have been, random or uniform (cf Exhibits 10 and 11 in the attachments to Original Complaint). Fields told me how to perform the analysis which I did and found, indeed, that the Coulter counter numbers that Bishayee had produced in that 1999 experiment had a probability of being random on the order of 1 chance in 10,000,000,000,000. This method is now posted on the ORI website as a forensic tool to use when scientific misconduct is suspected (www.ori.dhhs.gov/statistical-forensics-check). Both Dr. Fields and Dr. Price indicated that I should return to the University and present to them this latest analysis (Price Letter 09.05.02). Dr. Fields also indicated to me in a phone conversation that she thought I had a good case for qui tam. I did apply again to Vice President Dr Karen Putterman and a new investigation was undertaken. This second committee was made up primarily of members who had served on the first committee. In her opening remarks to this second CCRI, Dr. Putterman insinuated that Dr. Fields and I had some sort of a relationship (CCRII-1).

The second committee was presented with my statistical analysis and also with a graph that I had constructed from the results that Lenarczyk had sent to me that demonstrated dramatically his failed attempts to replicate in eight experiments the results generated by Bishayee. Lenarczyk would also indicate in his deposition that he sent all of his experiments to the second committee, although they do not acknowledge this in their list of articles examined and there is no record in the minutes that they discussed these experiments (CCRI2-2, CCRI2-3, CCRI2-4). Having been made aware of the statistical anomalies in Bishayee's results, the second committee initiated a telephone conversation with members of the ORI. In her report, Dr. Fields had noted that she believed that the first committee thought that I had been lying to them. In his record of this telephone conversation, Dr. Price recorded his insinuation that I lacked integrity (Price note re phone call). Dr. Price also stressed that proper controls for the Coulter counter were not available and probably would never become available. Neither he nor the committee considered the possibility that others in the laboratory might have used the same Coulter counter and would therefore provide controls. During discovery, I found numerous controls produced by others in the lab using the same instrument. The second committee came away from the telephone conversation with ORI with the message that statistics alone were not sufficient indication of scientific misconduct. Relying on this, the second committee therewith backed up the ruling of the first committee. In doing so, the second committee completely ignored the evidence presented by me and by Lenarczyk that Bishayees results could not be reproduced. This evidence clearly showed that there was more than just statistics alone.

After the judge came down with his opinion in 2010 that there had been no violation of the false claims act, I decided to go back to both the CCRI and the ORI and present the new information that I had garnered as a result of Discovery. Perhaps there was no violation of the False Claims Act but I might now, with all the new information, be able to get a ruling of Scientific Misconduct and, better still, clean up the scientific literature by getting the 8 papers co-authored by Bishayee retracted.

I sent the same materials to both committees along with identical cover letters. In the letters, I emphasized that I was presenting new material that was distinct from the 2 instances that both groups had examined earlier. I enclosed a memory stick that contained the PDF files I had access to from Discovery, an Excel sheet of the Coulter counter terminal digit data, copies of the 8 papers co-authored by Howell and Bishayee, expert reports of Pitt and Robbins, Robbins Figures, the memo of Howell to Baker and notes that Vice-President Putterman wrote to herself that showed that Howell concealed from her the fact that Lenarczyk had been unable to replicate Bishayee's experiments, the "Summary of Experiments" document written by Howell in 2004 acknowledging 10 unsuccessful attempts to repeat Bishayee's results, a preprint by me summarizing the statistical and radiobiological findings that are covered in the 2 expert reports and finally copies of pages from Howells grant renewal showing data that could not be replicated and noting that he cited at least 20 times the two Radiation Research papers that contained the unsubstantiated data.

On January 7, 2011, I met for several hours with Drs Pranela Rameshwar and Vivien Bellofatto, members of the current CCRI. Both are basic scientists: Rameshwar a professor in the department of Medicine and Bellofatto in the department of Microbiology and Molecular Genetics. I thought at last I would be getting a fair evaluation of my findings. How wrong I was. They questioned me at length about my charges and the findings and it really seemed that they were coming around to supporting my findings. The session was recorded (available on request). Rameshwar closed the meeting saying "There is a big discrepancy and in summary we believe that this warrants for further investigation, a full investigation". On March 1, Rameshwar called to tell me that the CCRI had, again, decided not to go forward with the investigation. Rameshwar had turned 180 degrees. Even though I had new information, how could it be used to show fraud? They were concerned that there were no print outs of the Coulter raw data. She said that the CCRI had met with the University lawyer after they had interviewed me. I expect that that was what turned the tide. They had not interviewed Howell, called in a statistician and, of course, the full committee did not interview me. I asked how she had voted and she said they did not take a vote. That same day I passed in the hallway Dr Leroy Sharer, a Pathologist and member of the committee. His head was down and his eyes were averted. Is it possible he felt ashamed? About a month later, I received a very informal letter from Rameshwar, not a formal letter from the Vice President as had been done in the past. In it, she said that the Committee members "unanimously decided that an inquiry is not warranted".

I had about the same success with the ORI. The letter from Acting Director Wright states that I had presented nothing new and the judge had dealt with all the pertinent issues. This was not the case because the judge drew the line at November 1, 1999, the submission date of the grant application. This allowed the judge (and the ORI) to completely ignore everything I had uprooted during Discovery. The judge had barely acknowledged the expert reports and stated that "the fact that the results could not be replicated is proof only that the results could not be replicated" and the statistical analysis done by Dr Joel Pitt, was done subsequent to the ORI investigation, and therefore could not have contributed to Defendant Howell's knowledge as of October, 1999. Furthermore, although "it was biochemically and radiobiologically impossible for the outcome of Bishayee's 100% experiments to occur" these "were likewise not known to Dr Howell when he applied for the NIH grant". This decision by Cavanaugh could have enormous implications regarding the False Claims Act (FCA). Supposing a contractor builds a bridge for the federal government that subsequently collapses killing several people and it becomes known that the contractor had at some time earlier become aware that a subcontractor had watered the concrete. Cavanaugh's decision would absolve both the contractor and the subcontractor from responsibility because the contractor was not scienter (did not know about the watered concrete when the bridge was constructed) and the subcontractor was neither scienter (did not know he was cheating the government), nor material (did not sign the original contract). Neither one would be held responsible for violating the FCA.

The Saga of the Mysterious New Cell Line (NCL) That Comes and Goes: as reflected in the minutes of 4/27/01 of the CCRI1. See photo above taken on 4/3/01.

If the protocols had been followed (as recorded), there should have been 1 rack of 7 Helena tubes from Tuesday, March 27 until Friday, March 30; no tubes (or rack) from that Friday until Tuesday, April 3, then 1 rack of 7 tubes until Friday, April 6. There was, in fact, as expected, one rack of 7 tubes from Tuesday, March 27 to Friday, March 30. The number of tubes dropped from 7 to 6 between 3 and 5 PM and this mystery rack of 6 tubes (the NCL?) remained until Thursday, April 5. A new rack appeared in front of the mystery rack on Tuesday, April 3 (see photo above, presumably, the next experiment, for which there is a record).

BISHAYEE: [The mystery] NCL was put in the incubator between Monday and Friday, March 26-30 [i.e. a second rack should have appeared because there was already an on-going experiment, but it didn’t]. Was not in his notes, was preparing for freezing but got contaminated

RAVECHÉ: When?

BISHAYEE: 1.) After April 5 (Thursday) the day HILL and LENARCZYK observed the disappearance of the mystery rack in the back (see photo)

2.) Monday after

3.) April 9 (Monday)

RAVECHÉ: When were extra cells in the incubator?

BISHAYEE: Between April 4 and 6 (HILL and LENARCZYK observe them from 3/30 to 4/5)

COMMITTEE: thought it was the week of March 26

BISHAYEE: Between 3/27 and 3/30

RAVECHÉ: Why didn’t you freeze the NCL?

BISHAYEE: Getting ready to go to Puerto Rico (for a meeting), looked at them and threw them out

COMMITTEE: How many Helenas on 3/30/01?

BISHAYEE: 7

(HILL notes 8:30 AM. 12:54 and 3:00 PM, there are 7. At 5:00 and 6:00 PM there are six, tube number seven is gone)

COMMITTEE: Where did he throw them out?

BISHAYEE: in the trash

FINE: Was there contamination?

BISHAYEE: Did not check them (but note the first statement above that says they got contaminated)

COMMITTEE minutes: BISHAYEE had 2 sets of 7 on Thursday 3/29 (This is incorrect. On that day, he had only one, the second one (in front) appeared on Tuesday, 4/3/01, see photo).

COMMITTEE: What time on Friday, 3/30 were there none?

BISHAYEE: Possibly mid-day (but see HILL notes above: there were never “none”)

RAVECHÉ: Was he sure he had 7 tubes for the NCL?

BISHAYEE: “for the other study…I probably had 5”

COMMITTEE: Had he previously tested the NCL?

BISHAYEE: tested it a month earlier, record in his lab binder #9 which they have

COMMITTEE: Why throw out the tubes of the NCL without recording the results?

BISHAYEE: Wanted to do other things, was not a crucial experiment

COMMITTEE: what did he do with the tubes of the 3/26 experiment?

BISHAYEE: Threw them out (confusion in COMMITTEE about where)

COMMITTEE: What time did he go to the Fluorescence-Activated Cell Sorter (FACS)?

BISHAYEE: 2-2:30 Friday. Sorting takes 4 hours

RAVECHÉ: Did he look at the NCL before or after going to the sorter?

BISHAYEE: Probably

RAVECHÉ: What did he do after sorting?

BISHAYEE: Plated the cells – into incubator between 7 and 8 PM (HILL & LENARCZYK leave at 6:30, BISHAYEE is not around)

COMMITTEE: Anything else in the 37 degree incubator?

BISHAYEE: “other things on top”

Starts new experiment Monday, 4/2 with 7 tubes.

COMMITTEE: anything else in the incubator?

BISHAYEE: not sure

COMMITTEE: When did he look at his 3/26 dishes?

BISHAYEE: Takes 7 days = 4/6

COMMITTEE: What did he find for plates?

BISHAYEE: All dyed contaminated, undyed OK

BISHAYEE to RAVECHÉ: Didn’t look at tubes from 3/27 (Tuesday) to 3/30 (Friday). Also did not look at the NCL but cf above COMMITTEE minutes say he had 2 sets of 7 on 3/29

Show him the photos: rack is his, contains 6 tubes. Doesn’t know when taken or why location changed

COMMITTEE: What happened to 7th tube?

BISHAYEE: “no idea”

COMMITTEE: Did he ever take one tube out and leave the others?

BISHAYEE: “no” should have been 7 according to the protocol

COMMITTEE: Is it possible to tell whether cells are contaminated?

RAVECHÉ: Would not be visible in the Helena tubes

RAVECHÉ: Would he continue experiment with contamination?

BISHAYEE: He would not

Re: cells from LENARCZYK (clean cells received Thursday evening, March 29 – FACS processing was March 30)

BISHAYEE: Yes, he got them, doesn’t know what for

COMMITTEE: Could he have used them in the sort?

BISHAYEE: Why?

Final statement: Victim of a conspiracy. Had problems with Dr Hill for 2 yrs. HILL had problem because HOWELL didn’t want to incorporate her work into his grant. Fought with LENARCZYK who has conflict of interest by living in HILL’s house

COMMITTEE concludes: BISHAYEE had no motive

NON SEQUITUR

Helene Z. Hill, Ph.D.

Photo of 2 sets of tubes

where should be only one