oversight

Data Tampering / Sabotage / Fabrication

Published by the National Science Foundation, Office of Inspector General on 2007-03-19.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

                                                        NATIONALSCIENCE FOUNDATION
                                                         OFFICE OF lNSPECTOR GENERAL
                                                          OFFICE OF INVESTIGATIONS

                                                 CLOSEOUT MEMORANDUM

                                                                                      11          Page 1of 1



                     We learned fiom a university1 that it had completed an inquiry into an allegation of
             research misconduct by an ~ ~ F - f u n d postdoctoral
                                                         ed~           fellow (the subje~t)~ and that it was
             proceeding with a detailed investigation. The allegation involved the fabrication andlor
             falsification of data in a published journal article.4 After we concurred and referred the matter to
             the university for a detailed investigation, the university reversed its opinion, doing so without
             sufficient reason to dissuade us fiom the need for a complete investigation. We conducted our
             investig&on and determined that the evidence showed that the subject had falsified the
             published data. We prepared the attached investigation report recommending that NSF: make a
             finding of research misconduct; send a letter of reprimand to the subject; debar the subject for a
             period of 2 years; require the subject to submit certifications and assurances by a responsible
             official of his employer that his submissions to NSF do not contain research misconduct for 3
     .   '
             years after the debarment period; require the subject to certify completion of a course covering
             research misconduct before applying for NSF funding again; require the subject to certify
             retraction of the article containing the falsified data; and bar the subject fiom sewing as a
             reviewer of NSF proposals for a period of 3 years. The NSF Deputy Director made a finding of
             research misconduct in the attached letter and adopted our recommendations.

                     Accordingly this case is closed.




1INSF OIG Form 2 (11/02)
                                  NATIONALSCIENCE FOUNDATION
                                      4201 WILSON BOULEVARD
                                     ARLINGTON, VIRGINIA 22230



                                           MAR     9 2007

    OFFICE OF THE
   DEPUTY DIRECTOR




CERTIFIED MAIL -RETURN RECEIPT REQUESTED

Dr. Juan Carlos Jor~e-Rivera




       Re: Debarment

Dear Dr. Jorge-Rivera:

On January 11, 2007, the National Science Foundation ("NSF") sent you a Notice of Proposed
Debarment in which NSF proposed to debar you from directly or indirectly obtaining the benefits
of Federal grants for a period of two years. The Notice sets forth in detail the circumstances
giving
-    - rise to NSF's decision to propose your debarment. Specifically, NSF indicated in the
Notice that the proposed debarment is based upon your falsification of results from experiments
conducted on the impact o-receptors,                      and the publication of these results i n a
scientific journal. In that Notice, NSF provided you with thirty days to respond to the proposed
debarment.

Over thirty days have elapsed and NSF has not received a response. AccordingIy, you are
debarred until January 11, 2009. Debarment precludes you from receiving Federal financial and
non-financial assistance and benefits under non-procurement Federal programs and activities
unless an agency head or authorized designee makes a determination to grant an exception in
accordance with 45 CFR Section 620.215. Non-procurement transactions include grants,
cooperative agreements, scholarships, fellowships, conhacts of assistance, loans, loan guarantees,
subsidies, insurance, payments for specified use, and donation agreements.

In addition, you are prohibited from receiving Federal contracts or approved subcontracts under
the Federal Acquisition Regulations ("FAR") at 48 CFR Subpart 9.4for the period of this
debarment. 45 CFR Section 620!110(c). During the debarment period, you may not have
supervisory responsibility, primary management, substantive control over, or critical influence
on, a grant, contract, or cooperative agreement with any agency of the Executive Branch of the
Federal Government.

Lastly,       note that, in the Notice of Proposed Debarment, NSF also took the following
actions against you, which continue to remain in effect:

       By June 30,2007, you must retract the publication containing the falsified data, and
       certify to the OIG that you have done so.

       For three years from the end of your debarment period, you are required to certify that
       proposals or reports you submit to NSF do not contain plagiarized, falsified, or fabricated
       material.

       For three years from the end of your debarment period, you are required to submit
       assurances.by a responsible official of your employer that any proposals or reports you
       submit to NSF donot contain plagiarized, falsified, or fabricated material.

       You are prohibited from serving as an NSF reviewer, advisor, or consultant through
       January 1,2010.

       You are required to complete an ethics training course on research misconduct by
       December 3 1,2007. You must certify in writing to the OIG that such training has been
       completed.


If you have any questions regarding the foregoing, please contact          , Assistant General
Counsel, National Science Foundation, Office of the General Counsel, 4201 Wilson Boulevard,
Room 1265, Arlington, Virginia, 22230.



                                                     Sincerely,



                                                     Kathie L. Olsen
                                                     Deputy Director
                                                 NATIONALSCIENCE FO1I.NDATION
,                - --- --   -- - . - -. .   ..      4201                       .   . .   - .   - -. . .   .   .   ..


                                                   ARLINGTON, VIRGINIA 22230

                                                           JAN 1 1 2007


        OFFICE OF THE
       DEPUTY DIRECTOR




    CERTIFIED MAIL --RETURN RECEIPT REQUESTED

    Dr. Juan Carlos Jorge-Rivera




           Re:      Notice of Proposed Debarmerrt and Notice of Misconduct in Science
                    Determination

    Dear Dr. Jorge-Rivera:



                                     As documented in the attached investigative report, you
    knowingly falsified the results of experiments conducted on the impact o                                  v
    D    n     d published the falsified results in this article.

           In light of your misconduct, this letter serves as formal notice that the National Science
    Foundation ("NSF") is proposing to debar you from directly or indirectly obtaining the benefits
    of Federal grants for a period of two years. During your period of debarment, you will be
    precluded from receiving Federal financial and non-financial assistance and benefits under non-
    procurement Federal programs and activities. See 45 CFR Pad 620, Subpaits A, B and I. In
    addition, you will be prohibited from receiving any Federal contracts or approved subcontracts
    under the Federal Acquisition Regulations ("FAR"). See 45 CFR 620.125. Lastly, during your
    debarment period. you will be barred from having supervisory responsibility, primary
    management, substantive control over, or critical influence on, a grant, contract, or cooperative
    agreement with any agency of the Executive Branch of the Federal Government. See 45 CFR
    620.1 15.
.           . ...       .   .     .   .         .   .-- ....-.   .-   .   .   .   . .. . . . .   .   .-        -   -- .-- .. ,., ,
                                                                                                      Page 2
             In addition to proposing your debarment, I am requiring that, by June 30,2007, you
    retract the article containing the falsified data and certify in writing to NSF's Office of Inspector
    General ("OIG") that you have done so. I also am prohibiting you from serving as an NSF
    reviewer, advisor, or consultant until January 1,2010. Furthermore, for three years after the
    period of debarment expires, I am requiring you to certify that any proposals or reports that you
    submit to NSF do not contain plagiarized, falsified, or fabricated material. For this same period
    of time, you must submit assurances by a responsible official of your employer that any such
    proposals or reports do not contain plagiarized, falsified, or fabricated material. Lastly, by
    December 3 1,2007, you must complete an ethics training course on research misconduct, and
    certify in writing to the OIG that you have done so.

    ScientiJic Misconduct and Sanctions other thanDebarment

           Under NSF's regulations in effect at the time of your misconduct, "research misconduct"
    was defined as "fabrication, falsification, plagiarism or other serious deviation from accepted
    practices in proposing, carrying out, or reporting results from activities funded by NSF." 45
    CFR 5 689.1(a). Falsification is defined as "manipulating research materials, equipment, or
    processes, or changing or omitting data or results such that the research is not accurately
    represented in the research record." 45 CFR tj 689.1(a)(2). A finding of research misconduct
    requires that:

            (1) There be a significant departure from accepted practices of the relevant research
                community; and
            (2) The research misconduct be committed intentionally, or knowingly, or recklessly;
                and
            (3) The al.legationbe proven by a preponderance of evidence.

    45 CFR 5 689.2(c).

            As the OIGYsreport demonstrates, you manually changed the gain setting on the-
    d e v i c e so that the Variant 1 cells appeared to exhibit results in support of the hypothesized
    change in obsented current. You engaged in similar misconduct with respect to the Native 2
    cells. Thus, your conduct unquestionably constitutes falsification. I therefore conclude that your
    actions meet the applicable definition of "research misconduct" set forth in NSF's regulations.

            Pursuant to NSF's regulations, the Foundation must also determine whether to make a
    finding of misconduct based on a preponderance of the evidence. 45 CFR tj 689.2(c). After
     reviewing the Investigative Report, NSF has determined that, based on a preponderance of the
     evidence, your falsification was committed knowingly and constituted a significant departure
     from accepted practices of the relevant research community. I am, therefore, issuing a finding of
     research misconduct against you.
. . ..       .   ..,..   -.   ...   .   .   .... . -. .- .. .   .   -.... .-
                                                                      -, ,     .   ..   .   - ..-   . . .   . . ... -   - --.. - .   .   ,   -   ....   ,   . . .

                                                                                                                                             Page 3
                  NSF's regulations establish three categories of actions (Group I, 11, and 111) that can be
         taken in response to a finding of misconduct. 45 CFR §689.3(a). Group I actions include issuing
         a letter of reprimand; conditioning awards on prior approval of particular activities from NSF;
         requiring that an institution or individual obtain special prior approval of particular activities
         from NSF; and requiring that a i institutional
                                            ~            representative certify as to the accuracy of reports
         or certificationsof compliance with particular requirements. 45 CFR §689.3(a)(l). Group I1
         actions include award suspension or restrictions on designated activities or expenditures;
         requiring special reviews of requests for funding; and requiring correction to the research record.
         45 CFR §689.3(a)(2). Group I11 actions include suspension or termination of awards;
         prohibitions on participation as NSF reviewers, advisors or consultants; and debarment or
         suspension from participation in NSF programs. 45 CFR 689.3(a)(3).

                In determining the severity of the sanction to impose for research misconduct, I have
         considered the seriousness of the misconduct; our determination that it was knowing;the impact
         your misconduct had on the research record; and the determination that it was an isolated
         incident. I have also considered other relevant circumstances. 45 CFR 689.3(b).


                  I, therefore, take the following actions:

                  By June 30,2007, you must retract the publication containing the falsified data, and
                  certify to the OIG that you have done so.

                  For three years from the end of your debarment period, you are required to certify that
                  proposals or reports you submit to NSF do not contain plagiarized, falsified, or fabricated
                  material.

                  For three years from the end of your debarment period, you are required to submit
                  assurances by a responsible official of your.employer that any proposals or reports,you
                  submit to NSF do not contain plagiarized, falsified, or fabricated material.

                  From the date of this letter through January I , 2010, you are prohibited from serving as
                  an NSF reviewer, advisor, or consultant.

                  You are required to complete an ethics training course on research misconduct by
                  December 31,2007. You must certify in writing to the OIG that such training has been
                  completed.
             .         ..........   .......   ...   --   _       ..........   ......   _. .   .. - .            ..   - .......

                                                                                                       Page 4
Regulatory   arbfor Debarment
       Pursuant to 45 CFR 620.800, debarment may be imposed for:


       @)        Violation of the terms of a public agreement or transaction so serous as to affect
                 the integrity of an agency program, such as -


                 (1)       A willful failure to perform in accordance with the terms of one or more
                           public agreements or transactions; or



                 (3)    A willful violation of a statutory or regulatory provision or requirement
                 applicable to a public agreement or transaction


       In any debarment action, the government must establish the cause for debarment by a
preponderance of the evidence. 45 CFR 620.850. In this case, you knowingly falsified data in
connection with research experiments and published the falsified data in a scientific journal.
Thus, your actions support a cause for debarment under 45 CFR 620.800(b).


Length of Debarment

       Debarment must be for a period commensurate with the seriousness of the causes upon
which an individual's debarment is based. 45 CFR 620.865. Generally, a period of debarment
should not exceed three years but, where circumstances warrant, a longer period may be
imposed. 45 CFR 620.865. Having considered the seriousness of your actions, as well as the
relevant aggravating and mitigating factors set forth in 5 CFR 620.860, we are proposing
debarment for a period of two years.


Procedures Governing Proposed Debarment

        The provisions of 45 CFR Sections 620.800 through 620.855 govern debarment
procedures and decision-making. Under our regulations, you have 30 days after receipt of this
notice to submit, in person or in writing, or through a representative, information and argument
in opposition to this debarment. 45 CFR 620.860. Comments submitted within the 30-day
period will receive full consideration and may lead to a revision of the recommended disposition.
IfNSF does not receive a response to this notice within the 30-day period, this debamlent will
become final.
-.-   .   .-. .   - .. .          -
                           ..-.,. , .... . ..., .-. .-                        -
                                                     .. . .. . -.... - . ...,,.. ..   .,   .   .   .           -
                                                                                                       . . . . .. ...               --.
                                                                                                                        .- - -..-. ..     ...   .   ,   ..   - .- ..-.   ,   ..   .,   .- -..   .   .

                                                                                                                                                                                          Page 5
         Any response should be addressed to Lawrence Rudolph, General Counsel, National
  Science Foundation, Office of the General Counsel, 4201 Wilson Boulevard, Room 1265,
  Arlington, Virginia 22230. For your information, we are attaching a copy of the Foundation's
  research misconduct regulations, its regulations on non-procurement debarment, and FAR
  Subpart 9.4.



                                                                                                            Sincerely,



                                                                                                           Kathie Olsen
                                                                                                           Deputy Director




          -
  Enclosures:

  hvestigative Report
  Nonprocurement Debarment Regulations
  45 CFR Part 689
  FAR Regulations


  cc:
     CONFIDENTIAL




             National Science Foundation
1
I            Office of Inspector General
I
I
I
m
I
II
a                            Confidential
1                        Investigation Report
I                      Case Number A03070041
1                           Volume 1 of 2
a                       Report and Tabs 1-38
a                             26 July 2006
     CONFIDENTIAL


a    NSF OIG FORM228 (1103)
                                                    Summary

        The Office of Inspector General (OIG) has concluded that the subject1 committed
research misconduct2by knowingly falsifying data for a series of experiments published in a
journal article (the          As part of its procedures,4 the university5 conducted an inquiry6
and notified OIG and also the Department of Health and Human Services (DHHS), Office of
Research Integrity ( 0 ~ 1 of) ~its intention to proceed with a detailed investigation.' However,
the University, after accepting our investigation referral, re-opened its inquiry and reversed its
decision to proceed with an i n ~ e s t i ~ a t i o nBased
                                                      . ~ on the evidence from the inquiry, we did not
agree with the University's decision to forego a detailed investigation. lo We conducted our own
investigation1' , I 2 h m which we concluded that the evidence supports a finding of research
misconduct. We recommend that NSF:

                  send a letter of reprimand to the Subject informing him that NSF has made a
                  finding of research misconduct;

                  debar the Subject from receiving federal funds for a period of 2 years
                  commencing on the date of NSFYsfinding of research misconduct;

                  require the Subject to certify to NSF that the publication containing the falsified
                  data has been retracted;




n
' Dr. Juan Carlos Jor e-Rivera a/k/a Dr. Juan Carlos Jor e), presently Assistant Professor- o
NSF-funded Minori Postdoctoral Fellow
                                                           At the time of the alleged misconduct, the Subiect was an
                                                            in the NIH-funded laboratory o

  The alleged conduct in this case occurred before April 17,2002. Therefore, we apply the definition of misconduct
from the pre-April 17,2002, regulation and use the procedures in the current, post-April 17,2002, regulation.
Misconduct under the pre-April 17,2002, regulation means: (1) Fabrication, falsification, plagiarism, or other
serious deviation from accepted practices in proposing, canying out, or reporting results from activities funded by
NSF; or (2) Retaliation of any kind against a person who reported or provided information about suspected or
alleged misconduct and who has not acted in bad faith.




                                                   This is the institution where the alleged m~sconducttook place.
   University's First Inquiry Report, Tabs 3-16.
7
   See footnote 1 for ORI's jurisdictional basis.
8
   University's Letter to OIG and ORI, Tab 18.
   University's Second Inquiry Report, Tabs 21-23.
l o OR1 concurred in our assessment of the evidence and the need to proceed with a detailed investigation.
I I OR1 provided assistance to OIG with regard to the experimental technique involved in this case because OR1 staff
had particular expenence with the fundamental technique. ORI's role was limited to an advisory capacity due to
differences between OIG's and ORI's authorities.
l 2 An NSF expert with relevant scientific experience read and commented on the sc~entificaspects of the Draft
Investigation Report (Draft). ORI's experts also read and commented on the Draft, concumng with our assessment
of the scientific-technical aspects of the case.
                     require the Subject to certify completion of an ethics course covering research
                     misconduct before submitting any proposals to NSF on which he is a principal
                     investigator (PI), co-principal investigator (Co-PI), or otherwise a participant;

                     require the Subject to certify each time he submits a proposal or report to NSF
                     that the proposal or report does not contain fabricated or falsified material for 3
                     years after the debarment period;

                     require the Subject to submit assurances by a responsible official of his employer
                     each time he submits a proposal or report to NSF that the proposal or report does
                     not contain fabricated or falsified material for 3 years after the debarment period;
                     and

                     bar the Subject from serving as a reviewer of NSF proposals for 3 years
                     commencing on the date of NSF's finding of research misconduct.


                                   The University's First Inquirv ~ e p o r t ~

        The University conducted an inquiry into the Subject's actions in response to an'
allegation of data fabrication and falsificationI4in accordance with its policies and procedures.'5
The University's inquiry committee (the Panel) determined that a detailed investigation was
warranted. The data in question'6 involved a series of experiments on cells isolated from tissue
from different regions of rat brains (Native cells) and cells modified through genetic
manipulation (Variant cells) to mimic the cells taken from the different rat brain regions. The
data for one type of Variant cells appeared to have been manipulated to achieve a desired result.

       At the time of the data collection, NSF provided funding for the Subject's postdoctoral
fellowship at the university.I7 Consistent with the NSF's Research Misconduct regulation,'* the
University notified us of its determination to proceed with a detailed investigation and forwarded
a copy of the inquiry report for our review. l 9 The Panel concluded:

                1. The charges raised are serious and not frivolous.

                2.   It appears unlikely, and perhaps physically impossible, hta-t
                     could have been conducted as quickly as indicated on some of the computer




l3   See Tabs 3-16 (First Inquiry Report).
14
     Tab 4, Initial Allegation Letter.
     lau   L.

                                                             nsisted of the following experiments:-
                                                             ee Tab 7, "Appendix 3."

I*45 C.F.R. 5 689.4@)(2).
19
  Tab 1. ORI was also notified because the allegation involved work published with an acknowledgement to the
NIH award funding the laboratory.
                   changescod-uli                         occur without a change in the experimental
                   conditions.

               3. It is hi hl unlike1 that the changes in current reported to be secondary to
                  p r e s e n t s physical phenomena. The Inquiry Panel could not
                  rule out the possibility that changes were made in amplifier gain but not
                  recorded in the lab notebook. However, the Panel felt this was unlikely.

               4. The allegations warrant further investigation.[201


                                 OIG's Assessment of the First Inquiry Report

        We reviewed the substance of the allegation and the inquiry report. We concurred that a
detailed investigation was warranted to determine the facts surrounding the questioned data in
the Paper. Consistent with NSF's Research Misconduct regulation,21 we referred the matter to
the University for a detailed investigation, deferring our investigation pending completion of the
~niversity's.~~


                                    The University's Second Inquirv ~ e p o r t ~

        Following acceptance of our referral, the University engaged in a series of
communications with the Subject's attorney.24 In response to objections the Subject's attorney
raised, the University re-opened its inquiry to receive additional written comments from the
Subject and to allow him to make a visit to the campus to address the Panel in person.25 We
notified the University that our referral of investigation would continue until we had received its
report, at which time we would review the matter in total and determine how to proceed.26

        At the end of the reopened inquiry, the University notified us that it had concluded: "this
matter does not warrant Detailed                     In its second inquiry report the Panel noted
the following as reasons to reverse its previous determination:

                       1. Some of the experiments could not have been done correctly in the time
                          interval noted in the computer logs. However, there are reasonable
                          explanations for how this error could have occurred.

                   2.      The changes in-current         can be explained by variables in the
                           experimental conditions other than deliberate manipulations in gain.




20 Tab 3, page 4.
" 45 C.F.R. 4 689.5(d)(2).
22 Tab 17.
23
   See Tabs 21 -23 (Second Inquiry Report).



26   Tab 19.
27
     Tab 21, page 1.
                       3. The work flow in the laboratory in regards to data analysis and presentation
                          was such that it would be very difficult for [the Subject] to single-handedly
                          manipulate data used in the paper.

                       4.   Replicating the exact recording conditions in which [the Subject] did his
                            studies would be very difficult and would not likely resolve the issue of
                            scientific fraud.

                       5. The allegations. . . were well intentioned and were serious enough to
                            warrant this Inquiry.

                       6. Based on the review, it does appear that some of the data used in the [Plaper
                          . . .were flawed since [the Sub'ect] noted that it would have been
                          impossible to make the-changes             as quickly as noted on the time
                          stamps. It will be the responsibility of the authors to review all the data
                          used in the paper to determine whether the results remain valid.[2s1


                                 OIG's Assessment of the Second Inquirv Report

        We reviewed the University's second inquiry report and requested clarification from the
University on several points.29 The University's response30provided no additional clarity to the
rationale behind its decision to forego a detailed investigation. Thus, the second inquiry report
did not dispel the need for a detailed investigation.

        While it is true that explanations other than data fabrication and falsification could
account for the questioned data, the allegations remained unresolved by the evidence the
University gathered during the inquiry, thereby necessitating an investigation. The purpose of an
investigation is to gather information and evaluate that information in total to determine which of
the possible explanations, including data fabrication or falsification, is supported by a
preponderance of the evidence. The second inquiry report erroneously concluded that the
existence of alternative explanations rendered unnecessary an assessment of the evidence related
to the allegations. We determined that neither inquiry report provided a sufficient basis for
dismissing the allegation. Because the University had not completed the referred investigation
within the 180-day referral period and because it had expressed its intention not to proceed,31we
notified both the University and the Subject that we would continue with our investigation.32




     Tab 22, page 3.
''Tab 26.
30 Tabs 27 and 28.
   Tab 29.
32
   Originally, this case was a joint effort between our office and ORI. ORI's Division of Investigative Oversight
took the lead. When the University decided not to proceed with its investigation, ORI concurred with our
assessment that issues remained warranting a detailed investigation. However, OR1 lacked the authority to
investigate. In order to protect NSF's interests and the general federal interest, we assumed the lead. Because the
Subject asserted that the experiments involved were particularly complex (see Tab 30, pages 1-2), and ORI staff had
particular experience with the experimental techniques involved, OR1 staff participated in a limited advisory role
with respect to the experimental techniques and DHHS's interests.
                                              OIG's Investigation

        Consistent with NSF's Research Misconduct regulation,33we proceeded with an
investigation into the allegation that the Subject fabricated andlor falsified data that he published
with two coauthors (CoAuthor 1" and CoAuthor 235). During the course of the investigation,
we reviewed the evidence collected by the Panel, interviewed several individuals including the
Subject, collected supplementary documentation, and visited the laboratory where the Subject
collected the data.

                                           Basics of the Experiment


                                                                                                  are part of the

                                                    receptor. When the channel is open, ions flow
between the interior and exterior of the cell. The ion flow is observable as an electrical current
that can be measured in the laboratory using electrophysiological methods. Such methods
require attaching microelectrodes to the neurons whether the cell is an isolated individual or an
integral part of a tissue sample.

        In this particular case, the Subject and his coauthors published electrical current data
collected from tissue samples as well as isolated individual cells c o n t a i n i n g 3 '
The Subject initially collected data on tissue                        from two different regions of
rat brains. The tissue slices from one region                   Tissue 1)39had a higher proportion
o l e c e p t o r s with a particular                                     to the tissue slices from




Subject.
35

36Receptors are the structural part of a cell located in the cell membrane, often bridging between the interior and
exterior of the cell. They are generally made up of protein subunits. Molecules referred to as ligands, such as drugs
and neurotransmitters, can bind to receptors to tngger the receptor and cause a response (i.e.,change in the
receptor). A receptor and a ligand are analogous to a lock and key, respectively. Other molecules, generally
referred to as modulators, can facilitate or hamper the ligand's ability to bind to the receptor and produce the
response. In the case at hand, the response of interest is the ability of the ligand to cause the receptor to open a
channel in the cell membrane that allows charged particles (ions) to flow between the interior and exterior of the




postsynaptic currents (sIPSCs).
39 These were tissue slices from t            h             e             o             f ars-t
theother region-th issue 2)," which had a higher proportion o e c e p t o r s
with a different subunit (Subunit 2).42 The Subiect observed different effects on the ain~litudes




receptors in each tissue type were the underlying explanation for the different responses to the
application of the modulator. 46



          We refer to these isolated cells as the Native 1 and Native 2 cells, respectively,
because they are cells containing the receptors as they are found in nature (i.e., in their native




        To further test the h othesis, the Subject and Coauthor 2 decided to use isolated cells
that did not contai-             in their native form.48 Through a process known as
transfecti~n;~CoAuthor 1 genetically modified these cells to produce cells containing-




                                                                        cells. The DNA coded for each of
                                        collected data on isolated Native and
                                                  a microelectrode to individual cells
                                                      current^.'^ ~ h e t e c h n i ~ allowed
                                                                                       ue     the
Subject to rapidly appl           to a cell in either the presence or absence of a modulator in order
                               -- - - - -


to observe the electrical current and record it digitally by a computer.

         A s i n g l e x p e r i m e n t consisted of several successive data acquisitions (traces) on a
single cell. Each trace spanned a two second time frame. Near the beginning of the trace a
computer-controlled actuator toggled a pipette that was bathing the cell with one solution rapidly
(2-3 milliseconds) to a second position and back to the first thereby briefly bathing the cell in a
second solution. Exposure of the cell to the second solution for that short duration produced a
change in electrical current that appeared in the trace as an abrupt change in current in the
negative (downward) direction, as shown in Figure 1. Because the cell's exposure to the solution
is brief, the observed electrical current returns (decays) back to the starting (holding) current
over the two-second acquisition period.




                  Figure 1. Basic Features of an Experimental race." The black
                  portion represents the measured current collected over time. The
                  blue line represents the baseline of zero current. We have added
                  the red elements for illustrative purposes.

50 The Subject and CoAuthor 2 chose to use t h e m e t h o d . Other methods of attaching the cell to the electrode
are used in this field of research, in fact when CoAuthor 2's lab attempted to re eat the results reported in the Pa er,
the electrode was attached to the cells in a different manner. Regardless of t h e m e t h o d used,i                 s
as much an art as science with respect to the skill involved m creating- a seal between the cell and the electrode that
will remain intact during the course of the experiment.
5' Adapted from one of the Subject's experimental t      r a c e s , w h i c h is not at issue in this
case.
known as curve-fitting provided the means of determining the TTP. Curve-fitting results in the
calculation of a mathematical equation(s) or curve(s) thatbest represents the dat;collected. Not
all of the data points collected will lie on the curve because of background noise that is inherent
in the instrumentation andlor other conditions of the experiment will offset them from the curve,
giving the plotted data its irregular appearance suggestive of static interference (Figure 2).




                Figure 2. Expanded view of the peak region of the trace in Figure 1.53
                We have added the orange elements to illustrate the time-to-peak (TTP),
                which is the time from the beginning of the rise to the tip of the peak. The
                noise is the observed variation in the data not attributed to the signal
                (current) of interest. Portions of observed current are shown as line
                segments in red along with the associated noise level bracketed with the
                green line segments. It is customary to evaluate signals in terms of the
                signal-to-noise ratio with respect to a specific point in time. The noise
                level remains relatively consistent across the entire trace while the signal
                is strongest at the tip of the peak and approaches the holding current level
                by the end of the trace. Because the end of the trace provides (not shown)
                the lowest signal-to-noise ratio, it is a suitable and convenient measure for
                the changes in noise between traces in an experiment on a single cell.

" Tab 33, page 6; Tab 35, page 3; and Tab 37, page 13.
'3Adapted from one of the subject's experimental t r a   c   e   s   j   w   h   i   c   h is not at issue in this
case.
         A single completemexperiment involved only one cells4 and consisted of three
phases55(Figure 3). In the first phase, the Subject usually acquired two traces fiom the cell
under control conditions, i.e., without a modulator present (the Control Phase). The Subject then
acquired a series of traces of that same cell exposed to a modulator (the Drug Phase). Finally, he
acquired traces under wash conditions (the Wash Phase), wherein that cell was again exposed to
the initial control conditions. A cell could only be used for a ~ i n ~ l e x ~ e r i m eThe
                                                                                          nt.~~
mechanism for changing the conditions during a single experiment is known as solution-
switching. Concerns about the Subject's data related to solution-switching and TTP are
discussed below under their respective headings.




                                            -                                 -
                                                                                 -
                                              CT,                               0
                                             .-C                                .C
                                             L                                  L
                                             w
                                              0                                 0

                                             *                                  *'6
                                                                                +d


                                             '6
                         Control Phase                 Drug Phase                     Wash Phase
                          r        r       g- r               r         r       -0g         r         r
                                              C                                  c


                                            *0
                                            -                                  -V)




                       Figure 3. Schematic Representation of a s i n g l e x p e r i m e n t (not to
                       scale with respect to time). The traces were collected in 2 second periods
                       while solution-switching times varied, based on timestamps, from 4 to
                       more than 30 seconds.




54It appears that on at least two occasions the Subject reported data in the Paper for successive experiments on the
same cell, when a cell could only have been used for one experiment casting further doubt as the actual exposure of
the cells to the experimental conditions. According to the Subject, a cell could not be used more than once;-
                                          and it took at least ten to fifteen minutes t o ( ~ a 37,bpage 9.)




                                                                                             was only 250, also an
impossibly short time



"    Tab 37, page 9.
        CoAuthor 2 provided us with copies of the data traces and data logs for the Native 1,
Native 2, Variant 1, and Variant 2 experiments along with a spreadsheet identifying the specific
traces reported in the         We have confirmed that the data and subsequent calculations
correspond with the data reported in the         Three figures in the Paper included data from
the questioned experiments and are discussed below (Figures 8,9, and 10).




                                                                                                               0

The Subject was particularly interested in the behavioral aspects of the research, which according
to the Subject reflected his training and interests in psychology and biology.61 The second




       The allegation involves primarily the data for two particular sets of experiments: one set
supporting the structure-function relationship; and the other supporting the behavioral
conclusions of the Paper. The initial allegation had three basic facets: 1) apparent instrumental
gain changes to produce the hypothesized results; 2) questionable solution-switching times; and

57 We received the data in its raw form and as screenshots archived in Powerpoint. Relevant experiments and traces
are included in this report at Tabs 39,41,43,45, and 46. We have archived the remainder as part of the
investigation case file. Those data logs and traces are available for review on request.
58
   We correlated the aggregate results presented in the Paper with the spreadsheet calculations provided by
CoAuthor 2. The data values from the spreadsheet were then correlated with the curve-fitting values that
CoAuthor 1 wrote on the data logs for the experiments.
                                                      ) ( (desu
                               questioned data, the Subject


     Tab 37, page 4.
3) review of the data using time-to-peak (mP)selection criteria. Of these three, the instrumental
gain changes are directly relevant to the data fabricatiodfalsification allegation, while the
remaining two facets (as well as other facts) relate to the circumstances surrounding the data
fabricatiodfalsification as well as the Subject's intent.

                                               1. Gain Changes

        The gain setting on an instrument, such as t h e d e v i c e used in the Subject's
data collections, functions much like the volume adjustment on a radio, with the same effect on
the signal (i.e., current or sound volume) observed. For example, music playing on the radio
increases or decreases in volume (amplitude) in response to and in proportion to the change in
the volume setting in a particular direction. The amplitude of the signal transmitted from the
radio station does not change, only the listener's perception of it based on the volume setting of
the radio receiver. Similarly, the listener's perception of the background noise (static)
accompanying the music would increase or decrease in proportion to the change in volume
setting while the actual amplitude of the transmitted noise relative to the music would not
change.

       Similarly in the ~ u b j e c t ' s e x ~ e r i m e n tts ,h e d e v i c e measures the current
observed by the electrode, and the computer records the signal. The subject's-
device had an articulated knob for adjusting the gain in discrete incremental units (Figure 4).




                            Figure 4. Articulated gain knob on the-device
                            that the Subject used, showing incremental settings.63

~ h d e v i c ethe, gain knob, the perceived signal (i.e., recorded current and noise),
and the computer are analogous to the radio receiver, the volume knob, the speaker output (i.e.,
music and static), and the listener, respectively. While the actual signal remains unchanged, an

  For larger views of the e n t i r e d e v i c e see Tab 33, Photos taken on OIG visit to the lab, images 4
and 5.
adjustment to the gain knob will change the amplitude of the signal as perceived by the computer
in proportion to the adjustment of the knob. In this case the gain knob has pre-defined
incremental settings labeled 0.5, l , 2 , 5, 10, 20, 50, 100,200, 500, and 1000 ~ V / ~ A which
                                                                                          ,@
required modest force to change. Therefore, an adjustment of a single increment results in an
incremental change in the perceived signal by the same relative proportion.65

        In the Subject's experiments, the gain knob was set at the beginning of each experiment66
and should have remained unchanged through the final trace. The actual setting used was
dependant upon the cell and other experimental conditions such as the strength of the actual
current being measured. The use of different gain settings between experiments (i.e.,for
different cells) was accounted for during data processing, which determined the vertical scale bar
displayed for each trace in the experiment. In this particular case, the instrumental configuration
required that the Subject manually input the gain setting from t h e d e v i c e into the
software on the computer as well as on the data log sheet because an automated system for
recording the gain value from t h e d e v i c e on the computer was not a~ailable.~'

         In an ideal experiment, a constant electrical potential (V) is maintained across the cell
membrane. In the Subject's experiments, this was denoted as eithe-on                    the computer
on-              the data log sheet. The basic relationship between electrical potential (V), current
 (I), and resistance (R), is expressed as V = IR. Generally, the resistance in these experiments is
 sufficient1 1ar e that any changes are relatively negligible. When the V is held c o n s t a n d
                      the I consequently remains constant and is referred to as the holding current.68
As demonstrated in Figure 1, the holding current is reflected in the data as the distance between
the baseline (I = 0) and the observed signal before the pulse or after the
                                                                         -. signal decayed. The




example shown in Figure 5. '"'"




64 Each incremental change on the dial results in a perceived, not actual, change in the signal amplitude on the
millivolt (mV) or picoampere (PA) scale. The data traces in the Subject's experiments were plotted with respect to
pA against time. See Figure 1.
65 For example, changing the gain setting from 2 to 5 will result in an increase in the perceived amplitude by a factor
of 2.5; or changing the gain setting from 1 to 0.5 will result in a decrease in the perceived amplitude by one-half.
P6 Tab 37, page 15.
67 Tab 32, page 1; Tab 33, page 4; and Tab 37, pages 15-16.
68
   The resistance, R, remains virtually constant in these experiments.
69 Biological vanability recognizes the fact that all biological systems are not uniform and measurements on such
systems will demonstrate some inherent variability within certain limits. ~h-variability                  observed for
the Subject's unquestioned experiments is much less than the-variability                   observed between traces
where improper gain changes appear to have occurred.
70 Tab 37, page 17.
" Based on the traces (Tabs 39 and 41) and the data log sheets (Tabs 40,42 and 46) there remains some question as




e
to whether -ctualljl           remained constant across the traces in slngle experiments and across the experiments
in eneral. According to the subject (Tab 37, page 18) data can only be compared to other data collected at the same
the current scale bar overlain onto the traces did not change during the course of the experiment.
The software generated this scale as a function of the gain setting, which the Subject manually
entered into the software at the beginning of the experiment.72




           Control Phase                      Drug Phase                             Wash Phase

           Figure 5: Representative traces from an experiment on -reported                       in
           the paper." Note that the-current         and signal noise remain consistent
           across the series of traces.




           Control Phase                       Drug Phase                            Wash Phase



                            a
           Figure 6. Representative traces from a single experiment74demonstrating the
           observed change in             urrent and noise amplitude between phases of the
           experiments on a                   The current scale ba-remained
           constant across the series of traces indicating that no change in gain was recorded

          w5
           in the software. The gain setting manually entered into the software was




72 Tab   37, page 15.
73   The traces are t   r      a      c       e       s We selected these traces based on the Subject's own
                                             # 1,4,6." (See Tab 45.)
74   See Tab 39
75   See Tab 39,
         The combination of the change in-current                          amplitude was
consistent with a manual change in the gain setting on                  device resulting in an
artificial change in the perceived current amplitude in the             In fact, in the course of
the experiment that rovided the traces shown in Figure 6, the instrument captured what appears
to be the change in&current          and noise amplitude in mid-trace (Figure 7).




                  Figure 7. Experimental trace showing the apparent mid-trace
                  change in holding current and noise amplitude resulting from an
                  improper gain change. The trace is the last trace of the Drug Phase
                  on the experiment.76


        O f the twelve experiments in which gain changes between traces were originally
questioned during the University's inquiry,77the one in Figure 7 was the only one that appeared
to catch the manual gain change while the computer recorded the trace. The holding currents
before and after the apparent gain change in this experiment were in a 2.5: 1 ratio, although the
gain setting entered into the computer for all traces in this experiment was "2"; thus, the change
in holding current is consistent with the Subject having changed the gain switch from "2" to "5"
for the Drug Phase and then back to "2" for the Wash Phase.



76 Tab   39-,
                         included traces reported in the Pape

                     Tabs 41 and 42)) and cell experiments
                                 these traces during the University inquiry as "contain[ing] notable evidence of gain
manipulation". We have independently evaluated the twelve as well as all of the data traces reported in the Paper
for both Native and Variant cell experiments. Those cells showing indications of improper gain changes are
identified in Tables in Tab 5 1.
        We showed the Subject the.traces from this experiment one at a time and in chronological
order for his comments. When he saw the trace in Figure 7, the Subject said that it showed that
he had lost the cell at the break in the line78and that the entire experiment should have been
excluded from the published data set.79 The phrase lost the cell means that the cell is no longer
viable for collecting data, yet the traces and data log showed that the Subject continued to collect
traces in this experiment, which he could not have done if he had lost the cell. Furthermore, he
wrote "Gorgeo;s! Gorgeous!                     on the data log for this experiment after collecting
the traces: and used the data from the later traces in this experiment in making thA-

                                       )
                                In fact, the Sub'ect reported in the Paper a total oi
                                                       All complete Variant 1 experiments and one
                                         ed symptoms of gain adjustments during the course of the
experiment."




                                                            Figure 8                        ~orting
                                                            agETega1                         from the
                                                            question                        nents. 83




78   Tab 37, page 19.


"' Tab 37, page 19.
   We note that one of the five    experiments (Tab 39               to be incomplete consisting only of
traces collected unde                                          experiments (Tab 4 1      , also
appeared
83
   Tab 5, page 3306.
        In another particular Variant 1 experiment,84the Subject not only appeared to have
changed the gain setting between the Control and Drug Phases but also appeared to have
changed the gain between each of the traces in the Drug              The control traces showed
very weak currents relative to the noise amplitude, such that the currents were almost
indistinguishable from the                                      the holding current and noise both
increased dramatically in                                        noise amplitude returned to control
trace levels in the next                                         the following t r a c e o n l y to
decrease again in the next trace                                      above in Figure 7 shows an
experiment from the previous day in which the Subject appeared to have changed the gain in the
middle of a drug trace, the pattern of apparent gain changes in this experiment suggests that the
Subject observed the traces on the computer monitor directly as they were recorded. The pattern
of alternating gain changes suggests that he increased the gain to view the weak current but
returned to the lower gain setting in the next trace, knowing that the gain level should remain
constant throughout the experiment.86 The Subject's comments on the data log sheetg7suggested
that the data were not optimal, further indicating that he had reviewed the traces for quality
before including them in the Paper.

         The Subject prepared all of the figures for the Paper including those that presented the
Variant 1 and Variant 2 datag8 The highlighted traces shown in Figure 9 represent selected
traces from a complete Variant 1 experiment. As described above, each of the Variant 1
experiments reported in the Paper appeared to contain improper gain changes based on changes
in holding current and noise amplitude. To have produced the highlighted figure, the Subject
must have aligned the traces vertically to achieve overlap in the holding current between the
phases of the experiment.89 The Subject told us he edited the traces to align them horizontally to
achieve overlap in the l T P but not to aligning them vertically.90 Although such editing appears
.to be consistent with the practices of researchers in this field, the Subject would have needed to
select the traces to use and in making the figure observed the differences in the holding current
for the different phases of the experiment chosen for the figure.




84 ~ x ~ e r i m eTabs       n t 39 and 40. The file designatio-indicates          that this experiment was the third
experiment on the da following the experiment shown in Figure 7.
"  E x p e r i m e n t ~ a e 2,3,4,5,
                                   s       and 6 Tabs 39.
86 The data log indicates that there were 2(and                    & ( T a b 40.) Thus, we have t r e a t e a
as if it were part of the-although               it appears that the gain setting was at the lower, original level for this

n ' m m e n t s on the log sheet included: "UGLY but effect on [illegible]"; "Serpentine stream!"; and -was
 --
 dying!"; "last 2 were supposed to b e ( ? ) " , Tab 40.
"'ab     37, page 19.
 89 It was not necessary to
 a s t r a c e s from the                                                                           eported in the
                                                                  current) betwee
 used one of the                                                                               experiment reported in
                                    figure.
 90 Tab 37, page 19.
                      A
                                                [Native I ]
                                                 m                         -
                                                                          [Native 21




                                           I                        I

                                                [Variant 11               [Variant 21




                 Figure 9. -showing                a composite of traces from the
                 Variant experiments, with the questioned Variant 1 results


        The experiments with the Variant 1 and the Variant 2 cells were crucial to sugporting the
structure-function relationship hypothesized from the Native cell and Tissue studies. The
Native cells contained receptors of both types in differing pro ortions. Variant 1 and Variant 2
cells were prepared from cells, which did not have any of t h e b e e p t o r s of interest prior
to transfection. Through the transfection process only one form of the receptor was conferred in
each Variant ce11.93'94With the Variant 2 cells, the hypothesis indicated that the current
amplitude would decrease or not change as observed for the Native 2 cells and Tissue 2.
Therefore, it was the Variant 1 line of experiments that were the definitive experiments with
regard to the conclusions reached in the Paper with regard to the structure-function relationship.
Because all of the complete Variant 1 experiments show symptoms of improper gain changes


-- Tab 5, p   a g m
between phases, it appears that the resulting structure-function conclusion relies 'entirely on
falsified data.

          With regard to the Native cell experiments initially questioned
  of improper gain changes," six Native 2 cell experimentsg6appeared in
  aggregate
    -- -     datafor the data point highlighted
                                       -  -      in yellow in Figure       Five of those six Native 2
  cell experiments show distinct changes in holding current aid changes in noise amplitude
  between phases characteristic of a change in gai; setting and consistent with the hypothesized
  decreasei n current amplitude.98 ~ h e s e experiments
                                             s            appeared on the spreadsheet if calculations
                             the calculations supporting the right-most point of the lower curve in
                        This data point was the endpoint of the calculated S-shaped dose-res onse
  curve demonstrating the hypothesized
               That data point appears to have exerted a downward influence on the S-shaped
-ring              the curve-fitting procedure, thereby leaving the preceding data point the !utlier)
  above the curve. If the gain had not been manipulated for those experiments, thi               n
  intensity would have been slight or nonexistent. Consequently the endpoint would lie much
  closer upper curve, which depicted current amplitudein the absence-of the modulator. The
  curve that would fit the data with the non-fabricated endpoint would likely have included the
  Outlier. The downward shift in the curve correlates with the Subject's statement in the original
  draft of the Paper:




95CoAuthor 2, Grad Student 1, and Grad Student 2 initially identified for the Panel t h e m a p p a r e n t l y
                   e r changes (See Tab 7 and footnote 16). We have inde~endentlvassessed the data traces and
showing i m ~ r o ~gain




%remaining        one-is          more difficult to assess definitively; however, CoAuthor 2 andmcurrent graduate




''Tab 48, page 5.
loo During curve-fitting, the points at either end of the data set tend 'to exert the most influence on the ultimate shape
and slope of the curve calculated to fit the data.
lo' Tab 13, page 13.
This conclusion carried into the final published version of the Paper. 102,103


                                  A
                                               mative 11                           [Native 21




                            Figure 10. r e p o r t i n g aggregate data from.
                            the questioned Native 2 experiments, highlighted in
                            yellow.Io4 The Native 2 data highlighted in blue are not in
                            question.




                              -       -   -
Paper, relied i n these figures in preparing the subsequent drafts bf the Paper.
'04 ~ a 5-,b
        The remaining experiment initially questioned as showing changes in holding current and
noise amplitude between phases105does not appear to have been reported in the Paper. We
recognize that successful and unsuccessful experiments are recorded in general practice across
scientific disciplines. We have treated this Variant 2 experiment as data recorded but discarded
from use in the Paper. Based on our assessment of this experiment, we have determined that the
evidence is insufficient to include this experiment among those we have identified with
questionable gain manipulations.

        The proportion of traces ultimately reported as aggregate data in the Paper in relation to
the total data published in the Paper is summarized in Table 1.


                               Table 1. Relative Proportion of Questioned Traces.

                                            Total Number of                                                    % of
                        Total Number           Published    Total Number     Total                          Questioned
Cell type                     of             Experiments     of Traces in Number of                          Traces in
                        Experiments         with Questioned   Published   Questioned                        Published
                         Published             Traces Io6        Data      Traces lo7                          Data

Native 1                       31                     0                   27 1                0                 0


Native 2                       28                     7                   227                12                5.3

                                                      108
Variant 1                       5                                          39                13                33.3


Variant 2                       7                     1                    62



        The Subject said that he showed some traces with the increased noise level to Coauthor 2,
who, after consultation with a researcher at another university,109told him that the increased
noise resulted from channel opening.' lo Coauthor 2 remembered discussing the increased noise
with the other researcher in order to posit what could cause such an observed increase. ' I '


ol-            See Tab 46.
 106
       See Tables 1 and 2 at Tab 51 for specific details on the experiments containing questioned traces.




"O     Tab 8,page 8; and Tab 37, page 17.
Ill
       Tab 33, page 6.
                                                               '
Coauthor 2 and t w o L o m g r a d u a t estudents (Grad Student 1 l 2 and Grad Student 2' 13) have
subsequently analyzed the data and have been unable to identify any biological cause consistent
with the reported results. ' I 4

          The Subject did not admit to changing the gain during the experiments. He attributed the
changes in holding current and noise amplitude to factors such as the large size of the transfected
cells,' l5 the cell's position in the solution stream,' l6 and other factors. 'I7 The Subject's
explanations were inconsistent with the data. The factors the Subject cited would be random in
effect rather than producing changes in the data that were consistent with incremental changes in
the gain setting in each experiment and that were always consistent with the hypothesized
      '
result. lg Thus, the only remaining plausible explanation for the apparent changes in holding
current and noise amplitude across the entire set of questioned ex eriments is a manual,
unrecorded incremental change in the gain setting on thed e v i c e .

        The Subject collected the data, wrote the instrument settings on the data log, and entered
                                                               '
the parameters, including the gain setting, into the computer. l 9 The Subject set up the
experiments and made the necessary calibrations and adjustments. 120 Coauthor 1's primary role
in the data collection was to observe and learn the technique.12' After limited attempts to collect
data on her own, they determined that Coauthor 1 did not have the touch for it.'22 They
reallocated the workload such that Coauthor 1 fit the curves after the Subject collected the data




  Tab 33, page 8; Tab 35, panes 1-2; and Tab 37, pane 8.
'IY
 and entered the curve-fitting parameters onto the data log sheets under the heading "Analyzed
 ~ a t a . " Although
             '~~       Coauthor 1 was physical1 in the room while the Subject collected some of
 the questioned data, she was involved int          h       e cells, preparing for coursework, and
 other projects. '24 It is unlikely that she was positioned to see the Subject's access to
 knob or at that time fully understood any adjustments she saw the Subject make to the
e v i c e during the course of experiments. ' 2 5 Therefore, the Subject was the individual
 responsible for adjusting the gain to achieve the hypothesized results.

                                   2. Anomalous Solution-Switching Times

         An essential component of t h e m t e c h n i q u e is the ability to expose the outside of a cell




Iz3 The data collection and curve fitting were all done on a single, shared Macintosh computer; therefore, only one
person could work at the workstation at any given time.
Iz4 Tab 35. Dages 1-2. See also Tab 33. Dage 4.




fulfilling all of the roles ascribed by the Subject while maintaining a clear view of any adjustments the Subject made
to the instrumentation for the data collection.
'26 The instrument t                h             a             a              s seen pictured in lower part of images 4
and 5 at Tab 33.
'27 Gravity-fed solution transfer is similar to the process of siphoning a liquid from a tank or other reservoir with a
piece of tubing. Once the tube is filled with the liquid, the tubing will draw liquid out of the reservoir when one end
(the intake end) is placed in the reservoir and the other (the output end) is located somewhere below the level of the
reservoir. The speed of liquid flowing through the tubing will increase as the output end is moved farther below the
level of the reservoir. This increase in speed or flow rate occurs because of the longer distance through which
gravity can accelerate the liquid's flow.
12' Tab 33, page 2.
Figure 11. Diagram of thes y s        t   e   m adapted from
the diagram supplied by Coauthor 2.
           When the pulse was initiated, the computer began recording data including a
 for the trace. After two or three Control traces, the Subject would move the cell awa
i             t           h a micromanipulator, apply a vacuum to the tubing to remove the
  solutions, and move the feeder tubes to 'the reservoirs for the Drug Phase.132 After collecting the
  final trace of the Drug Phase, the Subject moved the feeder tubes back to the original solutions
  for the Wash Phase. It was the time necessary to change the solutions between phases (i.e.,the
  solution-switching time) that the University Inquiry Panel addressed when it wrote: "It appears
 unlikely, and perhaps physically impossible, that solution-switching could have been conducted
  as quickly as indicated on some of the computer time stamps."133

       The minimum amount of time required to execute all the necessary physical
manipulations to change the solution between a trace at the end of a phase and the beginning of
the next was 30-40 seconds.134,135 While the Subject explained at length why there was

13' Tab 37, pages 11-12.
'33      page
    Tab 3,     4.
'34 CoAuthor 2 a n d o t w o graduate students described their concerns after reviewing the time stamps on the




        m
at Tab 4, pages 5-6.
variability in the solution-switching times for his experiments, 136 he did not adequately explain
how he was able to perform the physical actions necessary for solution-switching in less than 30
seconds and as quickly as 4 ~ e c 0 n d s . lRather,
                                             ~~      he addressed, in general terms, several
"shortcuts" he developed such as shortening the solution delivery tubing and raising the
reservoirs to increase solution flow rates.13*

        In addition to the physical actions necessary for solution-switching, the experiment
                                                                                        -.

required a,sufficient amount of time to purge the previous solutions fiom the tubing139and to
reestablish a stable                                                             between the
solution streams (which was observable through the microscope). Coauthor 1 indicated that
waiting one minute would be necessary.O'      contrast, the subject said that after moving the
tubing and a 1 in the vacuum to clear the theta tube, he acquired the next trace as soon as he
observed th              He never measured how long it took for the solution to come through the
tube, because the change was "Very spontaneous."141 He did not know how long to wait; and he
never knew if the previous solution was coming out mixed with the new solution. The current
practice in Coauthor 2's laboratory is to wait 2 minutes to ensure a full purge of the tubing with
the new solution.

        Four of the Variant 1 and five of the Variant 2 experiments in the Paper involved
solution-switchingtimes of less than 30 seconds duration. We also identified short solution-
switching times in experiments that did not show changes in holding current and noise
amplitude.145These observations suggest that the Subject rushed through the experiments and
did not conduct the experiments as he reported in the Paper. The Subject's only explanation was
that the problem would average itself out.



135
    Tab 33, page 2; Tab 35, page 5; Tab 23page 5.
136
    Tab 8, pages 3-4 and Tab 23, page 4 ("I became very proficient with the process and, as explained in my.previous
letter to you, [Tab 81 I was able to shortcut some of the procedures that a less experienced and less confident
researcher might not be willing to do.")
13' See Tab 5 1, Table 1.
138
    Tab 8, pages 3-4 and Tab 23, pages 4-5. See also Tab 35, page 4; and footnote 127.
'39 The Subject minimized this time to some degree by the application of a vacuum to the system, thereby pulling the
solutions back through t h m t u b e . However, that process introduced solution from the dish holding the cell into
the tubes. Thus, it was still necessary to allow the new solutions to flow in order to purge the tubing and establish
the flow of the appropriate solutions for the particular phase of the experiment.
I4O Tab 35, page 5.
141
    Tab 37, page 20.
14' Tab 37, pages 12-13.
'43 Tab 33, page 2.
    Of the remaining experiments, one Variant -1            and one Variant 2 x p e r i m e n t contained only
Control traces therefore no solution-switchingtook place in those experiments. In the remaining Variant 2
experiment-           solution-switching appeared to have taken place in 128 seconds, although we deduced this
conclusion from conflicting information found on the data log sheet and the data traces with regard to which trace
was the first Drug Phase trace. We have tentatively resolved the conflict in favor of the explanation most likely
consistent with the published results and have not included it as one of the five experiments with solution-switching
times < 30 seconds.
145 ~ a 51.
          b
146
    Tab 37, page 13.
        Thus, the evidence shows that although the Subject collected data on cells, he did not do
so according to the method reported in the Paper because he either did not actually perform the
physical manipulations required to establish the conditions for those experiments or provide
sufficient time for the solutions to flow such that the cells were exposed as reported. This is
consistent with the alleged improper gain manipulations discussed above, because the Subject
created the desired experimental results by changing the gain setting. Thus, it did not matter
whether he exposed the cells to the correct experimental conditions.


                                       3. The Subject's Review o f the Data

        The Subject asserted that he did not review the traces or perform the curve-fitting.147He
has both denied and claimed responsibility for the data used in the publication.148He placed the
responsibility for these activities on CoAuthor 1, a graduate student he was assigned to
mentor.149Our reviews of the Subject's laboratory notes 150,151 and his assessment of data during
our interview152demonstrated that he possesses the capability for all the functions he attributed
to his mentee. Additionally, even if CoAuthor 1 was responsible for these data analyses and


147
      Although he did h o w how to fit curves, he relied exclusively on CoAuthor 1 to fit the curves because she had




gain knob during data collection and not through the mathematical analysis conducted by his inexperienced
subordinate.
148
     CoAuthor 2 assigned the Subject the responsibilities of supervising CoAuthor 1 as part of his training in her
laboratory. Tab 37, pages 5-6.
149
     The Subject explained to us that he used CoAuthor                         to d     o     a    n     d other parts of
the experiments he did not want to do, particularly the                          the curve-fitting. (Tab 37, pages 13
and 19).
I SO
     The Subject recorded his experhental notes on loose-leaf pages bound in three-ring binder, which was consistent
with the practice of that laboratory.
Is' On data logs for other experiments, the Subject made specific notations about baseline, curve shape, and TTP,
sometimes rejecting the use of those data sets. For example_"nice           TTP r n a y b e m n l y " (Tab 40);
         quality!!!" (Tab 42
          ' (Tab 46); andG a r b a g e anyway baseline change for each trace            !?!b9
                                       "too bad, do not use. No wash. Nice kinetics and hu e effect though . .

also Tab 35, page 3 and CoAuthor 1's annotations in green to the data sheet fo-dentifying
                                                                                                          (Tab 46). See
                                                                                                        the Subject's
handwriting including comments such as                                  "TAKE sweeps #1,9, 11, 13."
Is2 The Subject and Coauthor 1 each told                      as the primary criterion for identifying the useful data but
that-the criteria were relaxed with regard to the                        Tab 33, page 6; Tab 35, page 3; and Tab 37,
page 13. When we showed the Subject the series of traces from the experiment shown in Figures 6 and 7 one at
time and in sequence, he determined by visual inspection within the first four traces that the traces were "bad data"
and that the experiment should not have been incorporated into the Paper (Tab 37, page 19). In explaining his
rationale for that conclusion, he indicated that based on his experience ("you train you[r] eye to detect good and bad
current'' (Tab 37, page lo)), the shape of the peak, including t h e was not acceptable and he would not have
included the data in the Paper (Tab 37, page 19). He made this assessment visually before we showed him trace 5,
which contained the mid-trace change in gain. Then the Subject contradicted this by answering affirmatively when
we asked, hypothetically, if trace 5 did not exist, would he have included the experiment as good data for the Paper.
The Subject appeared shocked to learn that the experiment had been included in the Paper, but also confirmed to us
that he wrote "Gorgeous! Gorgeous! Gorgeous!" (Tab 40-                on the data log.
selection activities, it does not mitigate the Subject's manipulation of the articulated gain knob to
gather data that conformed with the theory to be presented in the Paper.

        The Paper presented both structure-function and behavioral relevance of the observations.
According to the Subject, his primary interests were in the behavioral aspects of the study, and
the structure-function information was of primary importance to CoAuthor 2. 153 The Subject
has asserted that he gathered the structure-function information to satisfy CoAuthor 2's interests.
While this appears to be true, it again does not mitigate the Subject's manipulation of the gain
knob to acquire data that conformed with the theory to be presented in the Paper.

        The Subject has asserted that both CoAuthor 1 and CoAuthor 2 154 had delineated roles in
the data preparation and analysis,155and in writing the paper,156respectively. We accept his
assertions. Any roles CoAuthor 1 or CoAuthor 2 may have had in these efforts or any
differences the Subject may have had with CoAuthor 2 about research interests do not alter the
Subject's manipulation of the gain knob to acquire data that conformed with the theory to be
presented in the Paper and that the two coauthors were involved in the analysis of already altered
data.


                                                OIG's Assessment

        The Subject's actions in this case took place before April 17,2002; therefore, the
definition of misconduct that was contemporaneous with his actions applies. 157 In all other

     Although the Subject and CoAuthor 2 decided together that the experiments on-would                   be a good
 experimental approach to pursue, the Subject asserts that their interests ultimately diverged. (Tab 37, page 4.) This
 divergence manifested itself,.according to the Subject, when he refused to do the
( " I wasn't going to do it " which made CoAuthor 2 "upset.") (Tab 37, page 8.) The Subject has distanced
 himself from the Pa e r ' s ~ c o n c l u s i o n based   s     on the data that he collected by armbuting the interest
 in t h e e l a t i o n s h i p to CoAuthor 2:

                   [Tlhis is a hypothesis developed by [CoAuthor 21. Thus, it is she who rightly
                   receives the accolades when research such as that which I conducted in her Lab,
                   confirms her previous hypothesis. Thus I am not an important player in the
                   finding that                                             as that was a known
                   fact in the Lab by the time I arrived. [Tab 23, page 8.1

See also Tab 8, page 10 and Tab 37, page 5, particularly the discussion of CoAuthor 2 wanting the
paper finished for inclusion in her tenure review package.
    CoAuthor 2 was the Subject's postdoctoral advisor. She treated the Subject as a colleague rather than as a
student, as expected in the mentor-postdoctoral fellow relationship. (Tab 37, page 6. See also Tab 33, page 7.) As
such CoAuthor 2 reviewed data only when the Subject showed it to her and did not have day-to-day review of the
data as it was being collected. (Tabs 37, page 14. See also Tab 33, page 4.)
155
    See footnotes 147 through 149.
    The final version of the Paper was a remarkably different document with respect to writing style reflecting
CoAuthor 2's role as the lead in editing and revising the,drafts. (Tab 33, page 8.) CoAuthor 2's primary role was
preparation of the draft for submission, in part because the Subject's first language was not English. CoAuthor 1
was involved only to the extent of reviewing for grammer and clarity. However, the pertinent experimental details
and data remained consistent between the first draft as prepared by the Subject and final versions of the Paper. (Tab
5 and Tab 13.)      .
157
    See footnote 2.
respects, NSF's current research misconduct regulation applies to this case. A finding of
misconduct requires (1) an act that constitutes "fabrication, falsification, plagiarism, or other
serious deviation from accepted practices in proposing, carrying out, or reporting results from
activities funded by NSF"; (2) the act constitutes a significant departure from accepted practices
of the relevant research community, (3) the act was committed intentionally, knowingly, or
recklessly, and (4) the facts are proven by a preponderance of the evidence.158

                                                    The Act

         We have concluded that the Subject manually changed the gain setting on t h e m
d e v i c e so that the Variant 1 cells appeared to exhibit results in support of the hypothesized
 change in observed current. We have concluded similarly for the Native 2 cells used to support
the highlighted data point in Figure 10. The relative changes in amplitude of both the holding
 current and the noise were consistent with incremental adjustments in the gain setting. The
 timing between solution switches, in most instances, was unreasonably short for the steps
necessary to execute not only the physical actions necessary for a solution-switch but also to
 allow sufficient time to ensure that the neurons were exposed to the solutions exiting t h e m
a      s reported. Fabrication and falsification of data fall under the definition of research
 misconduct. '51 Fabricating and falsifying data strike at the heart of research, and the extent of
 the Subject's falsification constitutes a significant departure from accepted practices.

                                                     Intent

         A change in the gain setting would of necessity be a knowing act because the ain knob
 had discrete incremental settings that required more than negligible force to change.
                                                                                     ' l   The
 necessary gain settings to achieve the desired results also required changes between specific
 traces in the experiments in specific directions, because the Wash Phase required the traces to
 return to the conditions of the Control Phase. Such actions were necessarily calculated rather
 than random or accidental. We conclude that the Subject knowingly changed the gain on the
-device               during the data acquisition in order to support the desired hypothesis. The
 Subject reviewed, selected, and incorporated the data into the manuscript for the Paper. We
 conclude that the Subject knowingly reported falsified data in the original manuscript, which
 ultimately became the Paper.

                                              Standard o f Proof

      We conclude that a preponderance of the evidence shows that the Subject has knowingly
committed data falsification in reporting results in the Paper.




Is8   45 C.F.R.5 689.2(c).
Is9 The falsification occurred prior to April 17,2002, therefore we use the definition of research misconduct as
described in footnote 2.
160
    OIG investigators manually adjusted the gain knob during their visit to the lab where the equipment is housed
today. The laboratory has upgraded the equipment since the Subject has left the group. Tab 32, page I, and Tab 33,
page 1.
                                      OIG's Recommended Disposition

       When deciding what appropriate action to take upon a finding of misconduct, NSF must
consider:

                   (1) How serious the misconduct was; (2) The degree to which the misconduct
                   was knowing, intentional, or reckless; (3) Whether it was an isolated event or
                   part of a pattern; (4) Whether it had a significant impact on the research record,
                   research subjects, other researchers, institutions or the public welfare; and (5)
                   Other relevant circumstances. [I611


                                                    Seriousness

        The Subject's actions were very serious because they demonstrated his disregard for the
accurate reporting of experimental results, with a negative effect on the literature in this field.
Although the Subject has admitted that there were "some flaws in the data," he has asserted that
these flaws "averaged out" in the data analysis, attributing the idea of averaging out the flaws to
CoAuthor 1. However the entire data set for Variant 1 was created by a mechanical
manipulation of the-device,                undermining the validity of the average of the data from
the outset. The conclusions derived from these data were a significant achievement reported in
the Paper. 16' Similarly, for the Native 2 cells whose data were aggregated as the endpoint which
deflected the dose-response curve in Figure 4 exaggerating the effect of the modulator on
isolated Native cells. Therefore, we conclude that the Subject's actions were very serious.


                                                  Degree o f Intent

        The Subject's intent exceeded the reckless intent that the regulation requires for a finding
of research misconduct. The Subject knowingly adjusted the gain during the experiments
discussed above to produce results consistent with the hypothesis and knowingly incorporated
those results into the Paper.




16'   45 C.F.R. $689.30).
'62   Tab 37, page 13.
163
      See footnote 62.
CONFIDENTIAL


                                             Pattern

      We concluded that there was insufficient evidence to support a pattern of misconduct
beyond the activities covered in this report.


                                 Impact on the research record

        The fabricated data have had a significant impact on the published research record. The
data provided substantial support for the structure-function hypothesis that explained the
observations in the Tissue studies. We identified twenty-seven papers in the Science Citation
Index that cited the Paper, of which twenty were by authors other than the Subject and/or his
 coauthor^.'^^ We also note that Grad Student 1 and Grad Student 2 have had manuscripts with



contrary results have been delayed in reaching the broader research community.


                                        Recommendation

       Based on the evidence, OIG recommends that NSF:

               send a letter of reprimand to the Subject informing him that NSF has made a
               finding of research misconduct;

               debar the Subject from receiving federal funds for a period of 2 years
               commencing on the date of NSF's finding of research misconduct;

               require the Subject to certify to NSF that the publication containing the fabricated
               and falsified data has been retracted;

               require the Subject to certify completion of an ethics course covering research
               misconduct before submitting any proposals to NSF on which he is a principal
               investigator (PI), co-principal investigator (Co-PI), or otherwise a participant;

               require the Subject to certify each time he submits a proposal or report to NSF
               that the proposal or report does not contain fabricated or falsified material for 3
               years after the debarment period;

               require the Subject to submit assurances by a responsible official of his employer
               each time he submits a proposal or report to NSF that the proposal or report does
              not contain fabricated or falsified material for 3 years after the debarment period;
              and

              bar the Subject from serving as a reviewer of NSF proposals for 3 years
              commencing on the date of NSF's finding of research misconduct.


                  The Subiect's Response to the Draft Investigation Report

       The Subject did not submit a response to the Draft Investigation Report directly nor did
he respond through his attorney.