Department of Health and Human Services
Departmental Appeals Board
RESEARCH INTEGRITY ADJUDICATIONS PANEL
SUBJECT: John C. Hiserodt, M.D., Ph.D.
DATE: February 25, 1994
Docket No. A-93-117
Decision No. 1466
DECISION AS TO SCIENTIFIC MISCONDUCT; AND FINDINGS OF
FACT, PROPOSED CONCLUSIONS OF LAW, AND RECOMMENDED DECISION
FOR THE DEBARMENT OF JOHN C. HISERODT, M.D., Ph.D.
The Office of Research Integrity (ORI) of the Public Health Service
(PHS), Department of Health and Human Services (DHHS), determined that
John C. Hiserodt, M.D., Ph.D. (Respondent) had engaged in scientific
misconduct. The conduct in question concerned applications for research
funding which Respondent wrote and which were submitted to the PHS
National Institutes of Health (NIH) in February and October 1989. ORI
determined that Respondent had falsified data, fabricated figures and
tables in these applications, and misrepresented experimental results in
the applications. ORI proposed the following administrative actions be
taken with respect to Respondent: (1) Respondent be prohibited from
serving on PHS advisory committees, boards, or peer review groups for
seven years; (2) Respondent's PHS- sponsored research be monitored for
its accuracy by any awardee institution for seven years; and (3) the
article, "The Expression and Functional Involvement of Laminin-like
Molecules in Non-MHC Restricted Cytotoxicity by Human Leu-19+/CD3-
Natural Killer Lymphocytes," which appeared in the Journal of
Immunology, Vol. 141, 3318-23, 1988, be corrected to reflect that
Figure 2 of this publication may not be relied upon.
Based on ORI's determination of scientific misconduct, the DHHS Deputy
Assistant Secretary for Grants and Acquisition Management (Debarring
Official) proposed to debar Respondent from eligibility for, or
involvement as a principal in, non- procurement transactions (e.g.,
grants) of the federal government, and from contracting or
subcontracting with any federal government agency. The term of the
proposed debarment was five years. The Debarring Official informed
Respondent that his determination to debar Respondent will be made on
the basis of a recommendation of the Research Integrity Adjudications
Panel of the Departmental Appeals Board.
Respondent requested a hearing before this Panel to contest ORI's
determination of scientific misconduct, ORI's proposed administrative
actions, and the proposal to debar him. We conducted a de novo hearing
at which both ORI and Respondent presented evidence. 1/ Both ORI and
Respondent submitted posthearing briefs and reply briefs.
Thus, we have two distinct responsibilities in this appeal. First, we
must decide whether Respondent committed scientific misconduct. If we
find that Respondent has committed scientific misconduct, we must review
the administrative actions proposed by ORI and decide whether they
should be imposed. Our decision on the administrative actions is final.
Second, we are to make findings of fact and propose conclusions of law
in a recommended decision to the Debarring Official whether Respondent
should be debarred from receiving federal funds for a period of years.
In performing these separate responsibilities, we will be relying on the
same core findings of fact as to whether Respondent committed scientific
misconduct.
SUMMARY OF DECISION
We conclude that ORI established by the preponderance of the evidence
that Respondent committed scientific misconduct. We find that
Respondent knowingly presented falsified data and fabricated
experimental results to NIH in applications for funding for research
which Respondent proposed to conduct and that Respondent fabricated
results of experiments and falsified documents in an attempt to conceal
his misconduct. We do not reach the question of whether Respondent
committed scientific misconduct by failing to maintain primary data
since our other factual findings so clearly support our conclusion that
there was scientific misconduct under the applicable legal standards.
Moreover, even if we were to find that ORI's other allegations
concerning the retention of primary data were not substantiated, this
would not mitigate against our conclusion that Respondent committed
scientific misconduct.
Respondent engaged in the conduct which is at issue here prior to and
after the effective date of regulations that define scientific
misconduct. We find that Respondent's acts which occurred prior to the
regulations' effective date are scientific misconduct under applicable
and widely recognized professional standards which predated the
regulations. We find further that Respondent's acts which occurred
after the regulations' effective date are scientific misconduct under
the regulations. Furthermore, all of the conduct by
Respondent which we find to be scientific misconduct constitutes
scientific misconduct under the professional standards which predated
the regulations' effective date and under the regulations. We
accordingly uphold the administrative actions proposed by ORI, subject
to one minor modification.
We also make proposed conclusions of law determining that the alleged
cause for debarment of Respondent have been proven. In particular, we
find that the preponderance of the evidence establishes that Respondent
is not presently responsible to be a recipient of federal funding. We
recommend to the Debarring Official that, in light of our findings and
our proposed conclusions of law, a term of debarment of five years is
appropriate.
In making our decision concerning the administrative actions and our
findings of fact and proposed conclusions of law concerning Respondent's
debarment, we specifically address the issue of Respondent's
credibility. We find that Respondent is not a trustworthy individual
and that this lack of honesty provides additional support for the term
of debarment. Our recommendation of a five year debarment is in part
based on our conclusion that Respondent's persistence in attempting to
conceal his misconduct discredits his present responsibility to receive
federal funds.
Below, we provide a discussion of the factual and legal basis for our
decision as to misconduct and our proposed decision as to debarment. As
part of this analysis, we discuss the law which applies to scientific
misconduct and debarment. We address specifically, and reject,
Respondent's contention that we lack authority to conclude that the
conduct at issue in this case constitutes scientific misconduct, or to
propose debarment.
Background
Respondent and the activities he directed at the Pittsburgh Cancer
Institute of the University of Pittsburgh
In 1977, Respondent received a Ph.D. degree in the fields of immunology
and biochemistry from the University of California, Irvine. In 1983,
Respondent received a M.D. degree from the University of California, Los
Angeles, School of Medicine. In 1986, while at the University of
Michigan doing his residency training in pathology, Respondent was
invited by Ronald B. Herberman, M.D., to join the Pittsburgh Cancer
Institute (PCI) which was being formed at the University of Pittsburgh.
Dr. Herberman was then and remains the Director of PCI.
Respondent accepted Dr. Herberman's offer and, beginning in 1986, was
employed as an assistant professor in the Department of Pathology of the
University of Pittsburgh and as an associate member of PCI. Respondent
held these positions until he resigned them in January 1990.
Respondent's duties at PCI included heading a laboratory. The research
which he pursued at this laboratory included research concerning natural
killer (NK) cells. A NK cell is a lymphocyte or white blood cell that
floats in the blood and acts as part of the body's immunological
response to foreign substances. NK cells are unique because they have
an innate ability to recognize and kill tumor cells. Respondent
dedicated his research to discovering more about the mechanism by which
a NK cell kills a tumor cell.
In 1987 NIH awarded a three-year research grant (RO1 CA43765-01) to the
University of Pittsburgh to study the mechanism by which NK cells might
kill cancer cells. Respondent was the principal investigator for this
grant, and his laboratory at PCI was in part funded by it.
One of Respondent's principal research objectives was to discover the
interaction between NK cells and tumor cells which leads to the lysis of
tumor cells by NK cells. Lysis is a process whereby the integrity of
the tumor cell is disrupted, so that the tumor cell leaks its internal
contents and is no longer viable. Respondent's central theory was that
there was a basement membrane protein known as or similar to laminin
expressed on the surface of NK cells which was involved in NK cells'
ability to recognize and kill tumor cells. Respondent contended that
this laminin-like protein had a molecular weight of 48 kilodaltons;
hence, he referred to it as "p48."
Respondent also theorized that tumor cells were capable of producing an
antibody, another protein, which could bind itself to p48. The antibody
would thus block the interaction between the NK cell and the tumor cell
so that the NK cell would no longer be able to recognize and kill the
tumor cell. Respondent called this antibody to p48 "anti-laminin."
Respondent's laboratory at PCI was staffed by laboratory technicians,
graduate assistants, and post-doctoral researchers. The personnel who
were associated with Respondent's laboratory who were involved
significantly in the research projects led by Respondent into NK cells
included the following individuals:
-- Michael W. Olszowy, Ph.D. Dr. Olszowy began working for Respondent
as a laboratory technician in 1986. Beginning in 1986 or 1987, Dr.
Olszowy was formally accepted as a Ph.D. candidate at the Department of
Pathology of the University of Pittsburgh, with Respondent serving as
Dr. Olszowy's thesis monitor. As a graduate student working in
Respondent's laboratory, Dr. Olszowy conducted experiments in the area
of NK cells which he designed and which were agreed to by Respondent.
In 1987 and 1988, Dr. Olszowy and Respondent met almost on a daily
basis to discuss the progress of experiments conducted by Dr. Olszowy.
Dr. Olszowy received a Ph.D. degree from PCI and the University of
Pittsburgh School of Medicine in 1992. Dr. Olszowy is currently a Post
Doctoral Fellow at Washington University in St. Louis in the Department
of Pathology.
-- Roderich Schwarz, M.D. Dr. Schwarz received his M.D. degree in
1984. In 1987, Dr. Schwarz began working in Respondent's laboratory at
PCI on a post-doctoral research fellowship. Experiments performed by Dr.
Schwarz in Respondent's laboratory included growing human infector cells
(NK cells) and testing their cell killing activity. These experiments
also included the effect of various antibodies on the cell killing
activities of NK cells. Other of Dr. Schwarz's experiments for
Respondent included studying the activity of NK cells by labeling them
with radioactive substances and then measuring the amount of radiation
they released over time as an expression of how many cells were killed
by the NK cells. Dr. Schwarz also performed a total of four cell
sorting experiments for Respondent, using a process known as flow
cytometry. Dr. Schwarz is currently a resident in the Department of
Surgery in the University of Pittsburgh.
-- William H. Chambers, Ph.D. Dr. Chambers came to the University of
Pittsburgh as a post-doctoral researcher in 1986 and worked in
Respondent's laboratory. Dr. Chambers is currently employed by PCI and
is an assistant professor in the Department of Pathology in the
University of Pittsburgh Medical School.
The allegations of scientific misconduct in this case relate to two
applications to NIH for research funding which Respondent wrote and
which the University of Pittsburgh submitted to NIH in February and
October 1989. The general objective of these applications was to
receive funds for continuation of the research begun with the 1987
research grant.
On February 28, 1989, the University of Pittsburgh filed an application
(February application) with NIH for research funding of $961,904 (RO1
CA43764-04) entitled, "Role of Laminin/Laminin Receptors in NK
Function." G. Ex. 1. Respondent wrote the February application and
signed it as Principal Investigator/Program Director. The stated
purpose of the February application was to perform studies on human
cells similar to those which had been performed previously by Respondent
on rat cells, to isolate and purify p48, to clone and sequence p48, to
establish that p48 is a novel protein, and to discern its relationship
to laminin. This application included a number of figures and tables.
NIH reviewed the application and, while finding the application to have
merit, did not approve it for funding. One area of concern expressed by
the NIH reviewers was the apparent cross- reactivity between rabbit
anti-laminin and other substances besides p48. They expressed
skepticism that the allegedly unique substance (rabbit anti-laminin)
identified by Respondent could nevertheless react with several different
proteins.
On October 31, 1989, the University of Pittsburgh filed an amended
application (October application) with NIH (RO1 CA43765- 04A1) entitled,
"Role of Laminin/Laminin Receptors in NK Function." G. Ex. 4. The
application requested funding from NIH totaling $1,024,112. Respondent
wrote the October application and signed the application as Principal
Investigator/Program Director. The October application was in many
respects identical to the February application. The October application
contained the same statements, figures, and tables as were contained in
the February application purporting to prove the existence and function
of p48. The October application also contained an additional figure
(Figure 7) depicting the results of a nucleotide sequence, and text
purporting to explain the cross- reactivity between anti-laminin and
other substances. The additional discussion and experimental results in
the October application were aimed specifically at responding to the
concerns raised by NIH in its evaluation of the February application
which resulted in its decision not to fund the proposed grant.
Attempts by researchers in Respondent's laboratory to identify p48 and
the research techniques they used
Researchers in Respondent's laboratory attempted to identify p48 using a
process known as immunoprecipitation of proteins. The purposes of
immunoprecipitation include establishing the presence of proteins in
cells or on the surface of cells and determining the molecular weights
of proteins that have been identified. A protein's molecular weight is
of critical importance in identifying that protein, inasmuch as each
unique protein has a specific molecular weight which is different from
that of other proteins.
In performing immunoprecipitation, proteins which have been labeled with
a radioactive substance are added to lanes in a gel. A gel consists of
glass plates between which is contained a compound, acrylimide. Using a
technique involving the use of an electrical current (electrophoresis),
proteins that are added to a gel migrate different distances in the gel
according to their molecular weights. Electrophoresis in a gel operates
like a strainer which segregates proteins within the gel according to
their molecular weights. The heavier the protein, the higher it will
appear in the gel. In order to establish points of reference in a gel
to determine the molecular weights of proteins that are precipitated,
proteins of predetermined molecular weight are precipitated in
designated lanes of the gel (marker lanes).
After radioactively-labeled proteins are precipitated in a gel, a
photographic film is exposed to the gel to produce an autoradiogram, or
photographic record of the proteins precipitated in the gel, which will
include marker proteins in specified lanes, and proteins which have been
precipitated as a consequence of immunoprecipitation. 2/ The
radioactive substances, which include the immunoprecipitated proteins
and the marker proteins, will then create images on the photographic
film which correspond to their positions in the gel. The molecular
weight of the immunoprecipitated proteins represented by the images
produced in an autoradiogram can be determined by comparing them with
the predetermined marker bands which are also present in the
autoradiogram. The weight of a protein that appears between two marker
bands in an autoradiogram can be determined by measuring its linear
relationship to those bands. If the molecular weight of a protein
immunoprecipitated in a gel is, for example, 48 kilodaltons, then the
image of that protein produced by an autoradiogram of the gel should
correspond to a point in the marker lane which is between the 43 and 68
kilodalton marker bands, and which is relatively close to the 43
kilodalton marker band.
The radioactive substances used in Respondent's laboratory to label
proteins through immunoprecipitation included S-35 methionine and I-125
(radioactive iodine). S-35 methionine is methionine, an amino acid,
which contains a radioactive sulfur molecule (S-35). The
immunoprecipitation process using S-35 methionine is also known as
metabolic labeling and will label all proteins located inside a cell.
If an NK cell which has been exposed to S-35 methionine manufactures
p48, the p48 manufactured by that cell will contain S-35 methionine.
A necessary step in immunoprecipitation of p48 involving S-35 methionine
is to solubilize (break down) the cells being studied so that their
proteins will be released into a solution. The proteins are then
exposed to anti-laminin antibody so that p48 (assuming it exists) will
bond to the antibody. Using a variety of techniques, the antibody
(which now may be attached to p48) is removed from the solution. If
material containing an antibody which has bonded to a protein that has
been labeled with S-35 methionine is immunoprecipitated in a gel, then,
presumably, an autoradiogram of that gel will produce an image of the
labeled protein and will enable the researcher to determine that
protein's molecular weight. If, in fact, a protein having a molecular
weight of 48 kilodaltons has been isolated using S-35 methionine
labeling, then an image should appear on the autoradiogram corresponding
to a molecular weight of 48 kilodaltons.
There is the possibility, however, that an experiment with S-35
methionine might produce inconclusive results. Because the process
necessarily causes cells to rupture, there is no way to determine if any
protein identified by S-35 methionine labeling comes from the surface of
a cell or from inside it. It was important for Respondent to ascertain
whether any protein he had identified as reacting to anti-laminin
antibody was from the surface of a NK cell, inasmuch as he had theorized
that p48 is present on NK cells' surfaces. One method to clarify the
ambiguous results which might occur with S-35 methionine labeling is to
use another labeling technique known as radio-iodination, which uses
I-125 labeling.
Immunoprecipitation following I-125 labeling does not rupture the cell,
thus enabling the researcher to determine the molecular weight of
proteins found on the surface of the cell. I-125 labeling involves
replacing tyrosine, an amino acid which is a component of proteins on
the surface of cells, with radioactive iodine molecules. Proteins which
have been labeled with I-125 are then immunoprecipitated and an
autoradiogram is made to determine the molecular weights of these
proteins. If a protein on the surface of NK cells having a molecular
weight of 48 kilodaltons has been isolated using I-125 labeling, then an
image should appear on the autoradiogram corresponding to a molecular
weight of 48 kilodaltons.
Events leading up to the allegations that Respondent committed
scientific misconduct 3/
Beginning as early as 1987, Dr. Olszowy became concerned that the
experimental results which he and Respondent had interpreted as
establishing the presence of p48 on NK cells might be artifacts. In
science, an "artifact" is an experimental result which misleads a
researcher into making an incorrect observation. Dr. Olszowy conducted
numerous experiments in 1988 to resolve the issue of whether findings of
p48 were based on artifactual data. The results of these experiments,
which Dr. Olszowy communicated to Respondent, served only to strengthen
Dr. Olszowy's conviction that findings of p48 were artifactual.
Dr. Olszowy first became concerned that the protein which he and
Respondent had identified as p48 from experiments using S-35 methionine
labeling might in fact be actin, a common protein present in cells.
Actin has a molecular weight of 43 kilodaltons, and is therefore easily
confused with other proteins having similar molecular weights.
Beginning in December 1988, Dr. Olszowy attempted to resolve his concern
that what had been identified as p48 in experiments using S-35 labeling
was in fact actin, by using I-125 labeling techniques. Actin is not
present on the surface of cells and, therefore, experiments using I-125
labeling should rule out the presence of actin. However, the
experiments Dr. Olszowy performed using I-125 labeling did not satisfy
him that a unique protein having a molecular weight of 48 kilodaltons
had been identified. Dr. Olszowy was unable to identify clearly a
protein having a molecular weight of 48 kilodaltons, using I-125
labeling. Rather, his experiments produced evidence of a common
protein, albumin, which is present in the fluid surrounding cells.
Dr. Olszowy began telling Respondent, at least one year prior to
Respondent preparing and submitting the February application to NIH,
that the protein identified as p48 might be based on artifactual data.
Dr. Olszowy and Respondent had several discussions concerning whether
what had been previously identified as p48 was an artifact, with
Respondent pointing out that experiments continued to show the blocking
of lysis of tumor cells by anti-laminin. Respondent directed Dr.
Olszowy to perform experiments to explain this apparent contradiction.
Prior to February 1989, Dr. Olszowy conducted experiments to resolve the
contradiction identified by Respondent by injecting purified laminin
manufactured from tumors in mice into rabbits in order to obtain
anti-laminin antibodies. The laminin which was used in these
experiments was 95-99% pure, leaving open the possibility that
impurities in the laminin injected into the rabbits might produce
antibodies to the impurities along with antibodies to the laminin. Dr.
Olszowy hypothesized that the rabbits were producing antibodies to mouse
immunoglobulin (IgG) along with antibodies to laminin. Dr. Olszowy
concluded that antibodies to IgG were being manufactured along with
anti-laminin antibodies, and, therefore, the anti-laminin that was being
used to test the blocking of the ability of NK cells to destroy tumor
cells was contaminated with antibodies to IgG. Dr. Olszowy further
concluded that the blocking of the ability to destroy tumor cells in the
experiments he had earlier performed was not due to the action of an
antibody to p48, but rather was due to the blocking effect of an immune
complex which included antibodies to IgG.
One reason that Dr. Olszowy repeatedly raised with Respondent the issue
of p48 being explained by an artifact was that the possibility affected
Dr. Olszowy's Ph.D. thesis. Dr. Olszowy's Ph.D. thesis was premised on
the existence of p48. On several occasions, Dr. Olszowy asked
Respondent to convene a meeting of his thesis committee so that the
committee could be apprised of the results of Dr. Olszowy's research.
Respondent did not agree to convene a meeting of the thesis committee,
but told Dr. Olszowy that he should focus on doing other experiments on
other subjects.
In October 1989, Dr. Olszowy asked Respondent how he could justify
pursuing renewal of a research grant to study p48 when experimental
results raised so strongly the possibility that p48 might be explained
as artifactual. Tr. at 219. Respondent told Dr. Olszowy that if p48
turned out to be explained by an artifact, he would use any research
money he obtained to study p48 for some other purpose. Tr. at 220.
Respondent told Dr. Olszowy that this is basically what everyone did.
Id.
Respondent prepared both the February and October applications without
showing them to Dr. Olszowy. In neither the February nor October
application did Respondent mention that p48 might be explained by an
artifact, nor did Respondent mention any of Dr. Olszowy's experimental
results which called into question whether p48 was a unique protein, as
Respondent contended in the applications.
Dr. Olszowy discussed his concerns that p48 might be explained by an
artifact with Dr. Chambers no later than 1988. Dr. Olszowy expressed
concern to Dr. Chambers that Respondent's reluctance to convene a
meeting of Dr. Olszowy's thesis committee jeopardized Dr. Olszowy's
thesis, and ultimately, his progress towards obtaining a Ph.D. Dr.
Olszowy and Dr. Chambers discussed how Dr. Olszowy could ethically
reveal his concerns about p48 in a way which would apprise members of
Dr. Olszowy's thesis committee of those concerns. Dr. Olszowy and Dr.
Chambers agreed that it would be appropriate for Dr. Olszowy, after
advising Respondent of his intentions, to raise these concerns at a
meeting of the PCI Journal Club, a periodic gathering of investigators,
graduate students, and post-doctoral fellows to discuss current
scientific literature. Dr. Olszowy presented his findings concerning
p48 to the Journal Club in November 1989. In attendance at the Journal
Club was Dr. Carol Dahl, a faculty member on Dr. Olszowy's thesis
committee.
Dr. Dahl and other faculty members who attended the Journal Club brought
to Dr. Herberman's attention the findings that Dr. Olszowy had
presented. Dr. Herberman was familiar with the contents of the October
application and became concerned that Dr. Olszowy's findings appeared
to contradict some of the central points of the October application.
Dr. Herberman met with Dr. Olszowy on December 7, 1989, at which time
Dr. Olszowy explained why he thought p48 might be explained by an
artifact. Dr. Herberman then advised Dr. Olszowy that these findings
appeared to conflict with the statements Respondent had made in the
October application. Dr. Olszowy advised Dr. Herberman that he had
never seen either the February or October applications.
Shortly after the December 7 meeting, Dr. Herberman provided Dr.
Olszowy with a copy of the October application. On or about December
15, 1989, Dr. Herberman met again with Dr. Olszowy. Dr. Olszowy told
Dr. Herberman that he recognized Figures 1 and 2 in the October
application as being photographs of autoradiograms of experiments that
Dr. Olszowy had performed. Dr. Olszowy then showed Dr. Herberman the
actual autoradiograms on which Figures 1 and 2 were based. Dr. Olszowy
told Dr. Herberman that the legends in Figures 1 and 2 in the October
application did not report accurately either the methodology or the
conclusions of his experiments. After this meeting Dr. Herberman
compared the legend for Figure 1 of the October application against the
autoradiogram produced by Dr. Olszowy for the experiment depicted in
Figure 1, and concluded that the legend in the application
misrepresented the molecular weight of the protein in Figure 1.
On December 20 or 21, 1989, Dr. Herberman met with Respondent. Also
present at the meeting were: Dr. George Bernier, Dean of the University
of Pittsburgh School of Medicine; Dr. Sheldon Adler, Associate Dean for
Faculty Affairs of the University of Pittsburgh School of Medicine; and
Dr. Thomas Gill, Chairman of the Department of Pathology at the
University of Pittsburgh School of Medicine and Respondent's academic
supervisor. Dr. Herberman told Respondent that Dr. Olszowy had raised
questions about Figures 1 and 2 in the October application and asked
Respondent to explain these figures. Dr. Bernier asked Respondent to
provide either himself or Dr. Herberman with primary experimental data
to explain Figures 1 and 2.
Respondent told the other participants at the meeting that he believed
that the October application described accurately the results which were
depicted in Figures 1 and 2. When Dr. Herberman showed Respondent the
autoradiograms that Dr. Olszowy had provided him for Figures 1 and 2,
Respondent stated that he was not sure that the autoradiograms presented
by Dr. Olszowy were the autoradiograms from which Figures 1 and 2 were
derived. Respondent stated that he would have no problem in obtaining
primary experimental data that would refute or explain Dr. Olszowy's
contention that there were discrepancies between the legends for Figures
1 and 2 in the October application and the results depicted in the
autoradiograms from which Figures 1 and 2 were derived. Respondent
further stated that he intended to produce documentation to show that
Figures 1 and 2 were derived from experimental results other than the
autoradiograms which Dr. Olszowy had provided to Dr. Herberman.
On or about January 7, 1990, Respondent met with Dr. Herberman and
provided him with a blue notebook, the cover of which was labeled
"Hiserodt #3." G. Ex. 15. Respondent told Dr. Herberman that the
Hiserodt #3 notebook contained experimental data which he had obtained
from experiments which he had performed personally, which were different
from those experiments performed by Dr. Olszowy. At that meeting
Respondent told Dr. Herberman that he prepared the Hiserodt #3 notebook
contemporaneously with the experiments he had performed. Respondent
directed Dr. Herberman's attention to pages 33 and 34 of the Hiserodt
#3 notebook and told him the entries on those pages represented the
results of the experiment that was described in Figure 2 of the February
and October applications. Respondent told Dr. Herberman that the
photograph on page 34 of the Hiserodt #3 notebook was made from an
autoradiogram which recorded the results of the experiment described in
Figure 2 of the applications.
Also at the January 7 meeting, Respondent admitted to Dr. Herberman
that he might have stated incorrectly the molecular weight of the
protein in Figure 1 of the February and October applications.
Respondent told Dr. Herberman that Dr. Olszowy had told Respondent at
first that the molecular weight of the protein represented in Figure 1
was 48 kilodaltons; later Dr. Olszowy had told Respondent that the
molecular weight of the protein was actually 73 kilodaltons. Respondent
explained to Dr. Herberman that he had elected to accept Dr. Olszowy's
first statement of the molecular weight of the protein.
On or about January 8, 1990, Dr. Herberman met with Drs. Bernier and
Gill to discuss the January 7th meeting and the Hiserodt #3 notebook.
At this meeting Dr. Bernier expressed skepticism about the veracity of
the Hiserodt #3 notebook and about Respondent's representations
concerning how he had prepared it. Drs. Herberman, Bernier, and Gill
concluded that the University of Pittsburgh should withdraw the October
application from NIH consideration, pending resolution of questions
concerning how Respondent prepared the application and the Hiserodt #3
notebook. On January 9, 1990, the University of Pittsburgh wrote to NIH
requesting that the October application be withdrawn from NIH
consideration. G. Ex. 17-A. This request was signed by Respondent, Dr.
Herberman, and two other officials of the University of Pittsburgh.
Drs. Herberman and Bernier again met with Respondent on January 18,
1990. At this meeting, Respondent at first reiterated to Drs. Herberman
and Bernier that the Hiserodt #3 notebook recorded contemporaneously
generated primary experimental data. Respondent asserted once more that
the experiment which was the basis for Figure 2 was recorded in the
notebook. Respondent also stated again that the autoradiogram which Dr.
Olszowy had provided to Dr. Herberman, and which Dr. Olszowy contended
was the autoradiogram from which the photograph in Figure 2 had been
made, was not in fact the autoradiogram from which the photograph in
Figure 2 had been made. Respondent told Drs. Herberman and Bernier that
the autoradiogram provided to them by Dr. Olszowy bore a superficial
resemblance to the autoradiogram from which the photograph in Figure 2
had been made.
Dr. Bernier then advised Respondent that he would have the ink in the
Hiserodt #3 notebook dated, in order to determine whether the notebook
contained contemporaneously recorded experimental data or was a
fabrication. Respondent then admitted that he had prepared the Hiserodt
#3 notebook within two or three weeks prior to the January 7 meeting.
Respondent then further admitted that the figures in the applications
did not describe accurately the results of experiments.
On or about January 23, 1990, Respondent signed minutes of the January
18 meeting, in which Respondent admitted that:
-- Figure 1 in the October application consisted of an
autoradiogram in which the lane markers had been deleted, and a
listing of apparent molecular marker weights had been
substituted;
-- Figure 1 incorrectly designated the molecular weight of the
protein depicted in that figure as 48 kilodaltons, when in fact
the protein had an actual molecular weight of 73 kilodaltons;
-- Respondent knew that there was a question about the actual
molecular weight of the protein in Figure 1 prior to submitting
the application, but elected to submit the application (and
Figure 1) with an incorrect designation of the protein's
molecular weight;
-- no experiment corresponding to the depiction of Figure 2 in
the October application had been performed on the date stated
in Respondent's notebook;
-- the experiment described in the legend to Figure 2 had not
been performed;
-- the experiment depicted in Figure 2 was an experiment
involving rat lymphocytes, rather than subpopulations of human
lymphocytes as stated in the description of Figure 2; and
-- the Hiserodt #3 notebook was a fabrication that Respondent
had prepared after Drs. Herberman and Bernier began to question
the veracity of the October application.
G. Ex. 17.
On January 22, 1990, Dr. Bernier wrote to the Office of Scientific
Integrity of the Department of Health and Human Services (the
predecessor of ORI) to inform it of allegations of misconduct by
Respondent in connection with the October application. G. Ex. 19. This
letter led to ORI's investigation and the allegations and proposals
which form the basis of this case.
ORI issued a report of its investigative findings. G. Ex. 93. The
conclusions contained in that report constitute ORI's determination of
scientific misconduct and the basis for ORI's proposed administrative
actions. They were also relied upon by the Deputy Assistant Secretary
as the basis for the proposal to debar Respondent. The overall
conclusion of the report is that Respondent deliberately falsified
portions of the February and October applications. ORI based this
conclusion on findings that:
-- Figure 1 in the February and October applications
misrepresented the correct molecular weight determinations of
the substance depicted in that figure.
-- Figure 2 in the February and October applications
was represented as the results of an experiment using
subpopulations of human lymphocytes when in fact, the
experiment depicted in the figure involved rat lymphocytes.
-- A laboratory notebook which Respondent submitted to Dr.
Herberman as proof of the correctness of Figures 1 and 2 was
fabricated.
-- Other figures and tables in the February and October
applications were falsified, fabricated, or misrepresented.
ORI also concluded that Respondent committed scientific misconduct by
failing to maintain primary research data which supported certain
figures and tables in the February and October applications, and by
providing ORI with only summary information supporting these figures and
tables, in response to ORI's request for supporting primary data.
Respondent's Arguments
Respondent advances both procedural and substantive defenses against
ORI's charges of scientific misconduct. Respondent contends that ORI
has no authority to investigate alleged misconduct involving any
application that either did not receive funding from NIH or was not
pending before NIH as of the date that allegations of misconduct were
made to ORI or its predecessor agency. He argues that ORI has no
authority to investigate Respondent's conduct or to make determinations
that Respondent engaged in scientific misconduct, inasmuch as the
University of Pittsburgh withdrew the October application before
notifying ORI's predecessor of possible misconduct by Respondent.
Respondent asserts, therefore, that the allegations of his misconduct
involve only matters which are of concern to the University of
Pittsburgh.
Using similar reasoning, Respondent contends that ORI lacks authority to
investigate the allegations of scientific misconduct concerning the
Hiserodt #3 notebook or to make determinations of misconduct concerning
the notebook and Respondent's presentation of it to University of
Pittsburgh officials. Respondent asserts that, inasmuch as he created
the Hiserodt #3 notebook several months after submission of the October
application, in response to an inquiry from officials at the University
of Pittsburgh, any questions about the notebook should be resolved by
the University of Pittsburgh.
Respondent concludes his argument concerning authority to investigate
and make determinations of misconduct by asserting that, inasmuch as ORI
has no authority to investigate the allegations of his misconduct, this
Panel has no authority to hear such allegations, to make findings of
fact and conclusions of law as to misconduct, to impose administrative
actions, or to make recommended conclusions concerning the proposal to
debar him.
Respondent also denies that he committed scientific misconduct.
Respondent asserts that figures and tables in the February and October
applications, contrary to ORI's determinations, are true and correct.
Respondent further avers that there were no standards in effect either
at the University of Pittsburgh or within PHS, governing his obligation
to maintain research data. Therefore, according to Respondent, his
failure to provide ORI with data which satisfied ORI's demand for
primary data to support certain tables and figures in the applications
cannot be deemed to be misconduct. Respondent maintains, furthermore,
that his laboratory notebooks contain the information necessary to
support any questioned figures and tables.
Respondent asserts that, at bottom, the charges of scientific misconduct
emanate from a conspiracy among his former colleagues at the University
of Pittsburgh which is fueled by both personal and professional
jealousy. Respondent contends that Dr. Olszowy was motivated to accuse
him falsely of misconduct by jealousy over Respondent's personal
relationship with Dr. Olszowy's former wife. Respondent alleges that
the actions of Dr. Herberman and others at PCI and University of
Pittsburgh Medical School were the product of their jealousy over his
scientific discoveries in the field of NK cells.
Applicable Legal Standards
Scientific misconduct
The definition of scientific misconduct contained in the 1989
regulations states:
Misconduct or Misconduct in Science means fabrication,
falsification, plagiarism or other practices that seriously
deviate from those that are commonly accepted within the
scientific community for proposing, conducting, or reporting
research. It does not include honest error or honest
differences in interpretations or judgments of data.
42 C.F.R. 50.102 (effective November 8, 1989, 45 Fed. Reg. 32,446
(August 8, 1989)). The regulation's definition of scientific misconduct
plainly encompasses the deliberate making of material false or
fabricated statements in proposing and reporting research in grant
applications.
ORI's allegations of scientific misconduct by Respondent, however,
address conduct which both predates and is subsequent to the adoption of
regulations defining scientific misconduct that became effective
November 8, 1989. The principal allegations of misconduct occurring
prior to November 8, 1989 -- that Respondent willfully falsified and
fabricated experimental findings in applications for research funding --
involve allegations which, if proven, would establish violations of
standards of conduct which predated the adoption of the 1989 regulations
that define scientific misconduct. 4/ Indeed, Respondent has never
argued that if ORI's allegations of falsifications and fabrications were
proven true, the falsified and fabricated statements would not be
considered to be scientific misconduct under the standards in the
scientific community prior to the promulgation of the 1989 regulations.
The misconduct which Respondent is alleged to have committed after
November 8, 1989 -- consisting of engaging in efforts to conceal his
previous misconduct by fabricating a notebook -- would, if proven, be
scientific misconduct under the 1989 regulation's definition of
misconduct as including "fabrication." Thus, the misconduct which
Respondent is alleged to have committed would be scientific misconduct
under the standards in effect prior to November 8, 1989, or under the
1989 regulations.
Indeed, the standards of scientific conduct which are involved in this
case have not changed with the adoption of the 1989 regulations. Thus,
the willful falsification and fabrication of scientific data which
Respondent is alleged to have engaged in would constitute scientific
misconduct under either the standards predating the 1989 regulations or
the 1989 regulations. Both prior and subsequent to the adoption of the
1989 regulations, applicants for research funds have had a duty to
honestly and truthfully report the experimental results on which they
premise their applications. Willful falsification of experimental
results, or deliberate inclusion of materially misleading or inaccurate
statements as to those experimental results in applications, was
scientific misconduct prior to adoption of the 1989 regulations and
continues to be scientific misconduct.
In cases involving allegations of misconduct that predate the effective
date of the 1989 regulations, ORI's burden is to establish the standards
of conduct that were applicable to similarly-situated researchers, and
to prove further that the respondents in those cases violated such
standards. Dr. Rameshwar K. Sharma, DAB No. 1431, at 1-2 (1993). In
Sharma, we concluded that ORI established that those standards included,
at a minimum, prohibitions against intentional, material falsification
of research results in a grant application. Sharma at 2. The Sharma
decision further concluded that ORI had not demonstrated that such
standards included negligent inclusion of a false statement in a grant
application. 5/ Id.
On the issue of standards prevailing prior to November 8, 1989, ORI
presented the testimony of Helen Kim Bottomly, Ph.D. Dr. Bottomly is
an expert in the field of cellular immunology and is knowledgeable in
the standards commonly accepted in the scientific community for a
principal investigator on an NIH grant. Dr. Bottomly's experience
includes having served as a grant reviewer for NIH. Her testimony as to
standards prevailing in the scientific community was neither challenged
nor contradicted by Respondent. We find her testimony to be persuasive.
ORI proved through Dr. Bottomly's testimony that the prevailing
standards of conduct for scientists in effect prior to November 8, 1989
included requirements that researchers honestly and truthfully report
experimental results and make good faith efforts to verify the results
of experiments reported by others and relied on in applications. Tr. at
615. Thus, we find here, as was found in Sharma, that prior to November
8, 1989, a person responsible for presenting an application for research
funding had a duty to be honest and truthful about his or her research.
The making of statements which are deliberately false or materially
misleading about experimental results constitutes scientific misconduct
under that standard. Negligent inclusion of a false statement, as
opposed to dishonesty, has not been demonstrated by ORI to constitute
scientific misconduct under the pre-1989 standards of conduct.
The hearing which we conducted in this case was a de novo hearing.
Although the ORI report containing allegations of misconduct defines the
issues which we decide here, it is not proof that Respondent committed
scientific misconduct. ORI's burden of proof on all issues of
scientific misconduct is to establish by a preponderance of the evidence
that facts exist which meet the legal test for misconduct. Our decision
as to whether Respondent engaged in scientific misconduct is based on
the evidence offered by the parties and rests, ultimately, on our
conclusions as to whether ORI proved scientific misconduct by a
preponderance of the evidence. Likewise, ORI must prove the
reasonableness of the proposed administrative actions under the
circumstances of this case.
Debarment
Administrative debarment from grants and contracts is provided for by
regulation. See 45 C.F.R. Part 76; 48 C.F.R. Subpart 9.4; and 48 C.F.R.
Subpart 309.4. By means of an administrative debarment, individuals or
entities are excluded from eligibility for grant and contract awards
from the federal government for a specified period of time.
Administrative debarments are discretionary actions taken to protect the
interests of the public and the government and are not punitive.
Gonzalez v. Freeman, 334 F.2d 570 (D.C. Cir. 1964); 45 C.F.R. 76.115
and 48 C.F.R. 9.402(a) and (b). The regulations provide that the
causes for debarment include:
Any other cause of so serious or compelling a nature that it
affects the present responsibility . . . .
45 C.F.R. 76.305(d), 48 C.F.R. 9.406-2(c).
Federal policy requires the award of grants and contracts only to
responsible parties. Debarment is not mandatory upon a determination
that a cause for debarment exists. A determination to debar is made
after consideration of "the seriousness of the . . . acts or omissions
and any mitigating factors." 45 C.F.R. 76.300 and 48 C.F.R.
9.406-4(a). In any debarment action, the cause for debarment must be
established by a preponderance of the evidence, with the burden falling
on the agency proposing debarment. 45 C.F.R. 76.314(c)(1), (2), and
48 C.F.R. 9.406- 3(d)(3).
The standard for debarment does not mention scientific misconduct
specifically as a cause for debarment. However, the "other cause"
language of 45 C.F.R. 76.305(d) and 48 C.F.R. 9.406- 2(c) would
encompass scientific misconduct, where the misconduct is of so serious
or compelling a nature that it affects the present responsibility of a
person. Scientific misconduct of the types alleged in this case has
been found to be an "other cause" justifying debarment in Dr. David
C.
Bridges, DAB No. 1232 (1991), and in Robert Edward McCaa, Ph.D., DAB No.
823 (1987). See also Dr. Paul F. Langlois, DAB No. 1409 (1993).
Regulations governing debarment provide that the period of debarment
shall be commensurate with the seriousness of the cause. 45 C.F.R.
76.320(a), 48 C.F.R. 9.406-4(a). The regulations provide that
generally, the debarment period should not exceed three years. However,
a longer period of debarment will be justified in cases where
circumstances warrant. 45 C.F.R. 76.320(a)(1), 48 C.F.R.
9.406-4(b).
This case was referred to us by the Debarring Official to make findings
of fact and proposed conclusions of law. Regulations provide that, in
cases of proposed debarment where additional proceedings (including an
evidentiary hearing) are necessary, the Debarring Official may refer the
matter to another official for findings of fact. 45 C.F.R.
76.314(b)(2), 48 C.F.R. 9.406- 3(d)(2)(ii). The regulations provide
further that the Debarring Official may reject any such findings, in
whole or in part, only after specifically determining them to be
arbitrary and capricious or clearly erroneous. Id. The findings of
fact that we make below address both the issues of scientific misconduct
and cause for debarment.
The Panel's Authority to Hear this Case, to Review
Administrative Actions, to Make Findings of Fact and
Proposed Conclusions of Law as to Debarment
Respondent asserts that this Panel is without authority to find that
Respondent committed misconduct or engaged in conduct which justifies
debarment. 6/ Respondent asserts that ORI or its predecessor have
authority only to investigate misconduct involving an application
actually pending within the Department of Health and Human Services at
the time that the investigation is opened. He argues that because the
October application was withdrawn before an investigation into
Respondent's conduct was commenced, ORI is without "jurisdiction"
to
make findings of misconduct and we are without authority to review those
findings and, presumably, to make recommended conclusions of law about
Respondent's possible debarment.
Respondent did not articulate a basis, either in enabling legislation or
in regulations, for his argument that ORI had no authority to
investigate allegations of misconduct, and that we have no authority to
adjudicate the issues. The gravamen of his argument is that, inasmuch
as the October application was withdrawn prior to an investigation being
commenced by ORI's predecessor, there was literally nothing pending
before DHHS to investigate. Respondent argues further that it would be
inequitable to Respondent to investigate and decide allegations that he
engaged in misconduct, because to do so would penalize him for his
efforts to correct errors that he had detected in the applications.
These arguments are close to those which the respondent made in Sharma.
In Sharma, the respondent contended that the Public Health Act (Act), 42
U.S.C. 289b(b), authorized PHS to investigate allegations of
misconduct only in cases where funding had been granted. The Presiding
Panel Member there ruled that the authority to consider allegations of
misconduct extends to applications for funds whether or not applications
are funded. Dr. Rameshwar Sharma, DAB Docket No. A-93-50, Ruling on
Respondent's Motion to Dismiss the Complaint (May 10, 1993) (Ruling).
The Ruling in Sharma found that the Act could not be read reasonably in
so narrow a way as the respondent advocated. The language in the Act
authorizing investigations into misconduct "in connection with projects
for which funds have been made available" means that the alleged
misconduct must only be connected with projects for which PHS funding
has been made available. That would include proposals for funding that
are not funded as well as those proposals that are funded. The Act
neither states nor suggests that misconduct may be found only in cases
where funding has been approved:
Surely, misrepresenting one's research accomplishments or
capacities in an effort to obtain funding is connected with the
research project being proposed. Furthermore, projects "for
which funds have been made available" is broader than "funded
projects." It can reasonably be interpreted to subsume
projects proposed for funding under one of PHS's grant
programs.
Ruling at 15.
We affirm the analysis contained in the Ruling. The authority to
investigate scientific misconduct extends beyond applications for grants
that are funded. The authority applies to misconduct made in the
process of applying for grants, whether or not grants ultimately are
funded.
Here, Respondent is contending that the applications at issue were not
only unfunded, but were withdrawn prior to the commencement of an
investigation by ORI's predecessor. We do not find this to be an
impediment, either to the conduct of an investigation into possible
misconduct, or the adjudication of determinations made by ORI.
Withdrawal of an application does not strip DHHS of the authority to
investigate misconduct that may have occurred in connection with the
application process. 7/ The broad purpose of the Act plainly is to
oblige DHHS to take action with respect to scientific misconduct which
is committed in the process of applying for research funding. The event
that triggers the authority to investigate and take action concerning
misconduct is the filing of an application for research funds. The
legitimate concern of DHHS in such cases, which is recognized implicitly
in the Act, is to deal with attempts to deceive DHHS into approving
funds.
The fact the applications in question were withdrawn prior to the
commencement of this investigation does not affect DHHS's authority to
impose debarment. The debarment regulations for procurement and
non-procurement transactions respectively cover the debarment of a
"contractor," defined in part as any individual who "reasonably
may be
expected to submit offers for" government contracts and of persons "who
have participated, are currently participating or may reasonably be
expected to participate in transactions under Federal non-procurement
programs." Thus, Respondent, who was a prinicpal investigator under
prior grants and who submitted these withdrawn applications seeking
continued funding, is clearly covered by the debarment regulations as
one who has had federal funding and who may reasonably be expected to
seek federal grants or contracts in the future. 45 C.F.R. 76.110(a)
and 48 C.F.R. 9.403. The issue in a debarment case is whether a party
has engaged in conduct from which lack of present responsibility can be
inferred. 45 C.F.R. 76.313 and 48 C.F.R. 9.406-1. In this case,
what is at issue is whether Respondent attempted to deceive NIH into
approving an application for research funds. The alleged deception is
relevant to Respondent's present responsibility to handle federal funds
because it relates directly to Respondent's honesty. The fact that in a
given case an application might be withdrawn before a final funding
decision may be made, while it may in some instances say something about
a party's integrity, does not prevent the Debarring Official from taking
action based on the representations made by the party who presented the
application. Furthermore, Respondent signed the October application as
the principal investigator, agreeing to accept responsibility for the
scientific conduct of the project detailed in the application. G. Ex.
4, at 1.
Respondent also contends that ORI is without authority to investigate
Respondent's presentation of the Hiserodt #3 notebook to University of
Pittsburgh officials and that this Panel is without authority to hear
allegations concerning the notebook, because he produced the notebook in
the course of an internal investigation at the University of Pittsburgh.
He argues that the notebook played no part in the University's
submission of grant applications to NIH.
The premise of Respondent's argument is unsound. The notebook was an
integral component of Respondent's attempt to convince NIH to fund a
grant application. Although Respondent did not present the notebook to
NIH, he prepared it in order to convince the University of Pittsburgh to
offer continued support for the October application. To the extent that
the notebook involves dishonesty by Respondent, it is part and parcel of
the alleged attempt by Respondent to deceive NIH into funding a grant
application through misconduct. The notebook and circumstances
surrounding the notebook's creation and presentation are legitimate
matters for ORI to investigate as an element of an alleged attempt to
deceive NIH. Furthermore, the circumstances surrounding the notebook
are relevant to the question of Respondent's possible debarment as they
bear on the issue of whether Respondent is presently responsible to
receive federal funds. We therefore have authority to consider the
issues raised concerning the Hiserodt #3 notebook.
The grant applicant for the October application was the University of
Pittsburgh. The October application was pending with NIH in December
1989, when Drs. Herberman and Bernier first met with Respondent to
question him about allegations of false statements in the applications.
These officials had the authority and responsibility on behalf of the
University of Pittsburgh to ensure that applications filed by the
University were prepared honestly. Had these officials known at their
first meeting with Respondent that the February and October applications
were falsified, they doubtless would have acted immediately to inform
NIH of that, and to withdraw from consideration the October application.
In fact, they waited until early January 1990 to direct that the
application be withdrawn. They waited until then because Respondent had
assured them that he could produce primary experimental data to verify
the experimental results described in the October application.
The Hiserodt #3 notebook which Respondent presented to Drs. Herberman
and Bernier in January 1990 was represented by Respondent to constitute
the primary experimental data that the two officials requested. These
officials withdrew the application in January 1990, because they were
not persuaded by Respondent's efforts. Had Respondent succeeded in
convincing them that the October application was based on accurate
experimental data, presumably the application would not have been
withdrawn. Thus, the notebook was prepared by Respondent to at least
influence indirectly NIH's consideration of the October application, and
its preparation and presentation are a legitimate subject for ORI to
investigate and for us to hear as an aspect of this case.
Discussion of Our Findings of Fact
ORI argued that the February and October applications contained numerous
statements and figures which are false, which misrepresent the status of
the research conducted in Respondent's laboratory, or for which
Respondent has not produced primary supporting data. These statements
include Figures 1 and 2 in the February and October applications, Figure
7 in the October application, Table 1 in the February and October
applications, and Figure 4 in the February application, which is
presented also as Figure 3 in the October application. ORI further
alleged that Respondent fabricated the Hiserodt #3 notebook to conceal
his falsification of Figures 1 and 2 in the October application (and in
the February application as well, inasmuch as Figures 1 and 2 are
essentially identical in the two applications).
We will discuss each of these figures and tables and the Hiserodt #3
notebook in turn. At the outset, we note that the preponderance of the
evidence in this case establishes that Respondent falsified deliberately
Figures 1 and 2 in the February and October applications, Figure 7 in
the October application, Table 1 in the February and October
applications, and Figure 4 in the February application, which is
presented also as Figure 3 in the October application. The
preponderance of the evidence establishes also that Respondent
fabricated the Hiserodt #3 notebook in an effort to cover up his
falsification of figures 1 and 2 in the October application (and in the
February application as well).
Alleged statements for which Respondent has not produced primary
supporting data include: Figure 5 in the February application, which is
presented also as Figure 4 in the October application; Figure 7 in the
February application, which is presented also as Figure 6 in the October
application; and Table 2 in both the February and October applications.
These statements are discussed later in this decision, beginning at page
50.
Figure 1 in the February and October applications
Figure 1 in the February and October applications is a photograph of an
autoradiogram purporting to show the existence of a protein with a
molecular weight of 48 kilodaltons. The identical photograph is in
Figure 1 in both the February and October applications. The photograph
shows five lanes in which molecules appear to have been
immunoprecipitated. Alongside the left-hand margin of the photograph,
Respondent added a legend showing the location of molecular weight
markers, reading from the top down, of 200 kilodaltons, 97 kilodaltons,
68 kilodaltons, 44 kilodaltons, 27 kilodaltons, and 18 kilodaltons.
In both the February and October applications, Respondent represented in
Figure 1 that immunoprecipitation of human A-LAK cells labeled with
I-125 using anti-laminin antibodies produced evidence of a protein with
a molecular weight of 48 kilodaltons. The photograph in Figure 1
contains images of proteins in lanes 2 and 4, which Respondent labeled
"P 48." Respondent's intent in including Figure 1 in the applications
was to convince NIH that he had experimental results which established
the presence of p48 on human A-LAK cells by immunoprecipitation, using
human A-LAK cells labeled with I-125 and anti-laminin (anti-p48)
antibodies.
The captions to Figure 1 in both applications are identical except for
the following: the caption in the February application states that lane
3 consists of "IgG Isotype control," whereas the caption in the October
application states that lane 3 in the photograph consists of "IgG
control"; and the caption in the February application states that lane
4
consists of "Anti-p48 MoAb (4.1.5)," whereas the caption in the October
application states that lane 4 consists of "Anti-laminin (cross-reactive
with kappa light chain)."
Dr. Olszowy testified credibly and without contradiction that the
photograph in Figure 1 was made from an autoradiogram which he produced
to record the results of an experiment that he had conducted in December
1988. Tr. at 226, 228, 244. Dr. Olszowy was able to identify the
photograph in Figure 1 as coming from an autoradiogram that he developed
from an experiment because of the presence of a pattern of spots on the
photograph that matched the pattern of spots on the autoradiogram he
developed. Tr. at 227- 28. He testified that exposure of photographic
film to radiation to create an autoradiogram will result in incidental
spotting on the developed negative. Tr. at 175. Thus, each
autoradiogram produces its own unique pattern of extraneous dots or
spots that can be viewed as the autoradiogram's "fingerprint." A
researcher can identify an autoradiogram from its unique "fingerprint."
The autoradiogram identified by Dr. Olszowy as being the source for the
photograph in Figure 1 actually depicted seven lanes rather than the
five lanes depicted in the photograph in Figure 1. G. Ex. 98. The two
lanes that were not represented in the photograph in Figure 1 were the
two lanes on the extreme left and right side of the autoradiogram.
These two outside lanes were the marker lanes that contained the
proteins of predetermined molecular weight. The autoradiogram used to
produce the photograph in Figure 1 had marker lanes marked with proteins
with molecular weights of 200, 97, 68, 43, 24, and 14 kilodaltons. The
immunoprecipitation process kits used in Respondent's laboratory always
produced these same standardized molecular weights in the marker lanes.
Tr. at 172.
On this autoradiogram the I-125 labeling produced bands in the third and
fifth lanes with a molecular weight of approximately 68-73 kilodaltons.
Dr. Olszowy theorized that these bands denoted the presence of another
artifact, the common protein albumin, rather than p48. Tr. at 226,
238-39.
But when Respondent used the photograph from this autoradiogram in
Figure 1, Respondent did not include the whole photograph; rather, he
deleted the outside marker lanes from the photograph, so that the bands
in the third and fifth lanes in the autoradiogram now appeared in the
second and fourth lanes of Figure 1. Instead of the marker lanes,
Respondent typed a legend of molecular weights along the left side of
the photograph. In doing so, Respondent moved the whole legend of
molecular weights upwards, so that the bands appearing in the second and
fourth lanes were depicted by Respondent as having a molecular weight of
48 kilodaltons rather than the actual molecular weight of 68-73
kilodaltons depicted on the autoradiogram. Thus the legend which
Respondent included on the left side margin of the photograph in Figure
1 purporting to show molecular weight markers did not correspond with
the actual molecular weight markers contained in the autoradiogram from
which the photograph was made.
Respondent asserted that he cut off the marker lanes from the photograph
because there was no need to include that information in the
application. Tr. at 1137-39. Respondent testified that he "knew" that
experiments had shown the existence of p48. Tr. at 1138-40, 1146.
Respondent testified that in a rush to submit the February application
he retrieved a photograph from his files and assumed that the protein
depicted on that photograph showed the existence of p48. Tr. at
1135-36. Respondent explained that he made the starting point of the
legend that appeared to the left of the photograph in Figure 1 the bands
showing what he assumed was a protein at 48 kilodaltons and then labeled
the other points on the legend, upward and downward, from there. Tr.
at 1141, 1149.
We make the following findings in regard to Figure 1:
o The legend showing molecular weights which Respondent
included on the left side of the photograph in Figure 1 is
false.
o The molecular weight of the protein depicted in the
photograph in Figure 1, which Respondent stated to be 48
kilodaltons, is actually 68-73 kilodaltons.
o Respondent's statement in Figure 1 that the protein depicted
in the photograph in Figure 1 has a molecular weight of 48
kilodaltons is false.
o Respondent's representation in the caption to Figure 1 that
it depicts experimental results establishing the presence of
p48 in human A-LAK cells by immunoprecipitation, using A-LAK
cells labeled with I-125 and anti-laminin (anti-p48)
antibodies, is false.
We further find that Respondent deliberately falsified Figure 1. We base
this finding on the following:
o The highly self-serving nature of these false statements
about Figure 1 makes it far more likely that they are
deliberate rather than inadvertent. The false statements
contained in Figure 1 are the heart of Respondent's
contentions about the p48 protein. Respondent knew that he
needed to satisfy NIH that he had identified p48 on the
surface of NK cells in order to obtain funding of the
applications.
o Respondent had a motive to falsely represent experimental
data rather than report accurately the state of research in
his laboratory. Respondent knew that NIH would not likely
fund a grant if it was aware that the premise of the
application was based on artifactual data. Respondent knew
when he created Figure 1 that the meaning of the
experimental data generated in his laboratory was in doubt.
Respondent knew at the very least that any photograph of the
autoradiogram that he used in the two applications might be
argued by Dr. Olszowy to show that p48 did not exist. Yet,
Respondent did not disclose in either of the applications
that there was even the possibility of some conflicting data
to his theory in his laboratory.
o Respondent has not explained persuasively his
contention that he constructed Figure 1 based on an
essentially unlabeled photograph and his memory of what it
depicted. Respondent easily could have ascertained
what the photograph he used for Figure 1 actually
represented. Respondent knew that the original
experimental data for experiments conducted in his
laboratory, including the autoradiogram from
which the photograph in Figure 1 was made, were
maintained in an organized form by Dr. Olszowy and
by other researchers. Respondent had access to this
data at the time the applications were prepared, and, in
fact, referred to it at times.
o The way which Respondent altered the photograph
contained in Figure 1 is consistent with a deliberate
falsification. In order to represent that the molecular
weight of the protein depicted in the figure was 48
kilodaltons, Respondent had to delete marker bands from both
sides of the photograph which, when read accurately, showed
plainly that the protein depicted in the autoradiogram had a
different molecular weight than is shown in the figure. The
marker bands which Respondent deleted represented
standardized molecular weights with which Respondent was
familiar. The molecular weight markers which Respondent
typed on the altered photograph do not correspond to the
marker bands which Respondent deleted. Nor do these
molecular weight markers correspond to the standardized
molecular marker bands utilized by Respondent's laboratory
and PCI to calibrate autoradiograms.
o Respondent's contention that he misread the molecular weight
of the protein depicted in Figure 1 is not plausible in
light of the fact that Dr. Olszowy had specifically
brought to his attention the fact that the molecular
weight of the protein was 68-73 kilodaltons, rather
than the 48 kilodaltons which Respondent represented the
molecular weight of the protein to be.
o Respondent's contention that the misstatements in Figure
1 were the product of simple human error is belied by his
failure to discover and correct his "error" in the
February application in the several months between his
submitting the February and October applications. In
fact, Respondent not only repeated this "error" but also
made highly specific revisions to his caption to Figure 1
in the October application which suggest that he had to
evaluate the implications of Figure 1 before including it
again in the October application.
Respondent's contention that his labeling of the
protein in Figure 1 was an oversight is belied by the fact
that he knew, from discussions with Dr. Olszowy, that there
was at the very least a question about the molecular weight
of the protein depicted in the photograph. In fact,
Respondent admitted to Drs. Herberman and Bernier and,
ultimately, signed a statement admitting that he had elected
to disregard Dr. Olszowy's statement to him that the protein
depicted in the photograph had a molecular weight of 68-73
kilodaltons.
We therefore find that the preponderance of the evidence establishes
that Respondent deliberately misrepresented the molecular weight of the
protein depicted in the photograph in Figure 1 as 48 kilodaltons in
order to convince NIH that he had proof of p48 on the surface of NK
cells.
Figure 2 in the February and October applications
Both the caption to Figure 2 and the photograph in Figure 2 are
identical in the February and October applications. In both
applications, Respondent represents in Figure 2 that the
immunoprecipitation of purified human cells labeled with I-125 using
anti-laminin antibody produced p48. Figure 2 contains a photograph of
an autoradiogram which has experimental results that Respondent purports
to explain in the caption to the photograph.
The photograph in Figure 2 has three lanes. On the right side of the
photograph, Respondent wrote "P48" at a point corresponding to molecular
weight bands in the second and third lanes. On the left side of the
photograph, Respondent added a legend listing molecular weights of 200,
97, 68, 44, and 27 kilodaltons. The molecular weight bands in the
second and third lanes are just above the legend's mark of 44
kilodaltons. Respondent's intent in submitting Figure 2 to NIH was to
prove that he had established the presence of p48 on the surface of
purified (sorted) human cells labeled with I-125 using anti-laminin
antibody.
Dr. Olszowy testified that the photograph in Figure 2 was made from an
autoradiogram which he made to record the results of an experiment he
had conducted in June 1988. Tr. at 250. Dr. Olszowy testified that
this autoradiogram had two separate gels on it and that the photograph
in Figure 2 came from the right half of the bottom gel on the
autoradiogram. Tr. at 252. Dr. Olszowy testified that he was able to
identify the photograph in Figure 2 as coming from that part of the
autoradiogram because the photograph, although cropped, shows a dark
smear or blot that occurs at the bottom of the second lane that
corresponds to a stain of excess radiation that appears at the bottom of
the second lane in the lower right half of the autoradiogram. Tr. at
253.
Dr. Olszowy testified that the experiment depicted on the lower right
half of the autoradiogram from which the photograph in Figure 2 was
developed involved labeling rat cells with S-35 methionine. Tr. at 254,
256. Dr. Olszowy testified that on the autoradiogram beneath the
experiment he wrote the words "35 S rat x-tract." Tr. at 251-52. Dr.
Olszowy testified that it was his practice to put ink markings on
autoradiograms as soon as he received the autoradiograms. Tr. at 256.
Dr. Olszowy further testified that the original photograph made from
this autoradiogram also had the words "35 S rat x-tract" underneath
that
portion of the gel that Respondent used in Figure 2. Tr. at 253-54.
In comparing the autoradiogram to Figure 2, Dr. Olszowy thus identified
as untrue three statements in the caption to Figure 2: that purified or
sorted cells were used in the experiment, that these cells were human
cells, and that the experiment used the I- 125 immunoprecipitation
process. Tr. at 255-58.
Each of these misstatements is significant. First, purified or sorted
cells are cells which have been run through a flow cytometer, producing
95-100% pure cells. The greater the purity of the cells, the less
likely is the possibility of contaminants in the cells that would reduce
the reliability of experiments made with these cells. Thus, results
from an experiment using purified cells would be considered by a
reviewer to be more accurate and reliable than an experiment using
unsorted cells.
Second, the issue of whether human cells or rat cells were used in an
experiment is important. Dr. Bottomly testified that the use of human
cells rather than rat cells in an experiment was significant because the
ultimate purpose of NK cell research is the killing of human tumors.
Tr. at 634. Therefore an experiment involving human cells would be more
likely to persuade a reviewer of the worthiness of the research than one
employing rat cells.
Finally, the use of I-125 rather than S-35 methionine in an experiment
trying to establish the existence of p48 on the surfaces of NK cells is
extremely significant because I-125 labels only proteins found on the
surfaces of cells. The S-35 methionine method, on the other hand, does
not discriminate between proteins which are contained in the cell's
interior and proteins expressed on the cell's surface (because the
cell's walls are destroyed). Thus, if the purpose of one's research is
to establish the existence of a particular protein on the surface of a
NK cell, evidence of that protein derived from an experiment using I-125
labeling would be more significant to a reviewer than would be evidence
derived from an experiment using S-35 methionine labeling. Furthermore,
use of I-125 labeling eliminates the possibility of the artifact actin
being mislabeled as p48.
Respondent denied the existence of any false statements in Figure 2.
Respondent asserted alternatively that if Figure 2 did contain errors,
they were either unintentional or insignificant. Respondent contended
that he created Figure 2 from a photograph dated June 28, 1988 that he
retrieved from his files. Respondent testified that this photograph
pictured an autoradiogram without any labeling whatsoever; there were no
molecular weight markers or descriptive words under any lanes. Tr. at
1166. Respondent testified that he understood the photograph to
represent several different experiments in which human NK cells, rat
cells, and tumor cells were analyzed by immunoprecipitation with anti-
laminin antibodies. Tr. at 1167. Respondent testified that he took
this unmarked photograph which depicted both human and rat experiments,
removed the part that he thought was the experiment with human cells,
assumed that it was from an experiment using sorted cells with I-125,
and used that part of the photograph in Figure 2. 8/
Respondent averred that the experiment depicted in Figure 2 was
initiated based on discussions between Respondent and Dr. Schwarz. Tr.
at 1167-68. He asserted that Dr. Schwarz performed the experiment
depicted in Figure 2 in June 1988 using sorted human cells, and that Dr.
Schwarz gave him the photograph he used to make Figure 2. Tr. at 1168.
Respondent further maintained that as both experiments in the lower half
of the photograph, one using human cells, the other rat cells, depicted
the presence of p48, it was inconsequential that he might have
mistakenly used that portion depicting an experiment with rat cells in
Figure 2 and claimed it as an experiment using human cells. Tr. at
1170- 71.
It is apparent from the evidence that Dr. Olszowy's account of the
relationship between Figure 2 and the experiment that Dr. Olszowy
conducted is accurate. We conclude that Figure 2 was made from a
photograph of an autoradiogram generated from an experiment conducted by
Dr. Olszowy. Dr. Olszowy's testimony is corroborated by an original
autoradiogram which is in evidence and which plainly is the
autoradiogram from which the photograph in Figure 2 was made. G. Ex.
99. Furthermore, that autoradiogram bears the handwritten legend
attested to by Dr. Olszowy. There is nothing in the record that
supports Respondent's assertion that the experiment depicted in Figure 2
was performed by Dr. Schwarz.
We make the following findings in regard to Figure 2:
o The experiment on which Respondent based Figure 2 did not
involve human cells, as is stated by Respondent in the
February and October applications, but involved rat cells.
o Respondent's statement in Figure 2 that the experiment
depicted in that figure involved human cells is false.
o The experiment on which Respondent based Figure 2 did not
utilize purified or sorted cells, as is stated by Respondent
in the February and October applications, but utilized
unsorted cells.
o Respondent's statement in Figure 2 that the experiment
depicted in the figure involved purified cells is false.
o The experiment on which Respondent based Figure 2 did not
involve labeling with I-125, as is stated by Respondent, but
involved labeling with S-35 methionine.
o Respondent's statement in Figure 2 that the experiment
depicted in the figure involved labeling with I-125 is
false.
We further find that Respondent deliberately falsified Figure 2. We base
this finding on the following:
o As with the statements in Figure 1, the highly self- serving
nature of the false statements in Figure 2 makes it far more
likely that they are deliberate rather than inadvertent.
The false statements contained in Figure 2, along with the
false statements contained in Figure 1, constitute the
central "proof" in the February and October applications
that Respondent had isolated p48 on the surface of human
cells. Respondent knew that he needed to satisfy NIH that
he had identified p48 on the surface of NK cells in order to
obtain funding of the applications.
o Also as with Figure 1, Respondent had a motive to fabricate
experimental data rather than report accurately the state of
research in his laboratory. Respondent knew that NIH would
not likely fund a grant it if it was aware that the premise
of the application might be explained by an artifact.
o While the presence of any one of three significant false
statements in Figure 2 might be explained conceivably by
inadvertent error, the presence of all three false
statements is evidence of a deliberate falsification by
Respondent. The cumulative effect of the three false
statements was to persuade a reviewer that the experiment
depicted in Figure 2 had more merit and significance than it
actually did.
o Respondent has not explained persuasively his contention
that he constructed Figure 2 based on an unlabeled
photograph and his memory of what it depicted. Respondent
easily could have ascertained what the photograph he used
for Figure 2 actually represented. Respondent knew that the
original experimental data for experiments conducted in his
laboratory, including the autoradiogram from which the
photograph in Figure 2 was made, were maintained by his
researchers. Respondent had access to this data at the time
the applications were prepared.
Respondent provided no plausible explanation for his
asserted recollection that the experiment from which Figure
2 was ostensibly derived took place in June 1988.
Respondent's contention that Figure 2 was based on an
experiment performed by Dr. Schwarz and on a photograph
supplied to him by Dr. Schwarz of an experiment performed on
June 28, 1988, is unsupported and is rebutted by the
autoradiogram which is the basis for Figure 2.
o Respondent's assertion that it was insignificant whether the
experiment showing the alleged presence of p48 used human
cells or rat cells is contradicted by the expert testimony
of Dr. Bottomly that the use of human cells adds weight to
the value of an experiment to a reviewer.
o Had the false statement in Figure 2 been the product of
inadvertence or simple human error, Respondent simply could
have acknowledged that, instead of fabricating experimental
results to cover up his misstatements. However, when Dr.
Herberman raised questions about the accuracy of Figure 2,
Respondent tried to cover up his false statements by
fabricating experimental results and representing that the
fabricated results constituted primary experimental data
supporting Figure 2. See our discussion of the Hiserodt #3
notebook beginning at page 42.
We therefore find that the preponderance of the evidence establishes
that Respondent deliberately falsified the results of the experiment
depicted in Figure 2 of the February and October applications in order
to deceive NIH into concluding that Respondent had established the
presence of p48 on the surface of purified human cells using the I-125
process.
Figure 7 in the October application
The persons who reviewed the February application on behalf of NIH noted
that, based on that application, polyclonal rabbit anti-laminin appeared
to manifest unusual properties, including its ability to
immunoprecipitate monoclonal kappa light chain of the IgG class antibody
besides p48. In other words, anti-laminin appeared to react with
several substances in addition to p48. The reviewers expressed
skepticism that a specific antiserum (rabbit anti-laminin) could react
with so many diverse molecules. Dr. Herberman discussed the NIH review
of the February application with Respondent and suggested to Respondent
that, in an amended application, he might allay the concerns expressed
by the NIH reviewers by matching the DNA sequence of p48 with the DNA
sequence of the kappa light chain of IgG. A high degree of homology
(similar molecular sequences) between the DNA sequence of p48 (or
anti-laminin) and that of the kappa light chain of IgG might explain the
cross-reactivity between the molecules, and would resolve the skepticism
about such cross-reactivity expressed by NIH reviewers.
In the October application Respondent added a figure (Figure 7) to those
which he had included in the February application. In the caption to
Figure 7, Respondent describes the figure as representing the nucleotide
sequence homology of the B2 subunit of laminin and a variable region
sequence of kappa light chain. Respondent asserts that in areas of the
figure marked with asterisks and delineated with boxes, there are
sequence homologies of 60 to 70 percent. It is clear that Respondent's
purpose in including Figure 7 in the October application was to provide
an explanation for the cross-reactivity between anti- laminin and
various molecules and thus to allay the concerns expressed by the NIH
reviewers in their review of the February application.
Dr. Olszowy, at Respondent's direction, did the computer sequence
comparison that produced Figure 7. Dr. Olszowy testified that the
comparison showed that the portion of laminin B2 which Respondent
reproduced as Figure 7 is in a portion of DNA which is never translated
into protein. Tr. at 273. As for providing an explanation for the
cross-reactivity between anti-laminin and other molecules, Dr. Olszowy
termed the result of the comparison, "a complete washout." Id. Dr.
Olszowy explained that if the comparison is from an untranslated
sequence of DNA, it is nonsense to assume that the comparison is in any
way an indication that laminin B2 and the kappa light chain of IgG have
similar protein sequences. Tr. at 276-77. Dr. Olszowy testified that
he told Respondent that the sequence depicted in Figure 7 was from an
untranslated portion of DNA. Tr. at 277.
Respondent testified that he put Figure 7 in the October application
"almost as an afterthought." Tr. at 1195. Respondent explained that
he
supplied Figure 7 to NIH as a potential explanation for the
cross-reaction between p48 and the kappa light chain of IgG. Id.
Respondent testified that he used the word "speculative" in the
application to describe Figure 7 because he had no information that the
portion of the sequence could not be translated in the NK cell. Tr. at
1196.
Respondent, however, did not tell NIH that the homologies depicted in
Figure 7 were from portions of DNA that are untranslated -- that is to
say, do not play a meaningful role in the reproduction of proteins --
and that, therefore, Figure 7 does not provide a significant explanation
of the cross reactivities between the anti-laminin antibody and other
substances. Figure 7 is thus misleading, and suggests a finding which
the underlying research did not in fact establish.
There is nothing in the text of the October application that advises a
reader that Figure 7 represents untranslated portions of DNA molecules.
Respondent discusses Figure 7 at page 24 of the text of the October
application. After describing Figure 7, Respondent states:
Although speculative, these data suggest that the NK-associated
48 kDa protein may be related to classical B cell antigen
recognition receptors and may, therefore, represent a novel
recognition receptor expressed on NK cells. These speculations
remain valid if the p48 protein is indeed, translated from B2
chain messenger RNA or a highly related mRNA.
G. Ex. 4, at 4. The use of the word "speculative" does not signal
that
Figure 7 is derived from untranslated portions of DNA. Rather, it
suggests that the similarities depicted in Figure 7 are a possible,
albeit speculative, explanation for the cross-reactivity between the
antibody and other substances. A reviewer reading this language might
infer reasonably that Respondent was representing that the homologies
depicted in Figure 7 are from the translated portion of DNA, inasmuch as
there would be no possible explanation for cross-reactivity in
homologies contained in the untranslated portion.
We make the following findings in regard to Figure 7:
o The homologies depicted by Respondent are from untranslated
portions of DNA.
o Homologies in untranslated portions of DNA of different
molecules do not explain possible cross- reactivity of those
molecules, because the untranslated portions of DNA are not
responsible for the manufacture of proteins.
o Respondent did not state, either in the legend to Figure 7
or elsewhere in the October application, that the homologies
depicted in Figure 7 were from untranslated portions of DNA.
o A reviewer would not be able to determine from reading
Figure 7 that the homologies depicted in that figure are
from untranslated portions of DNA.
o Respondent's inclusion of the term "speculative" in the
portion of the text of the October application which
describes the DNA sequence homologies between anti-laminin
and other molecules does not suggest to the reader that the
homologies depicted in Figure 7 are from untranslated
portions of DNA.
o Figure 7 in the October application is misleading because it
suggests to a reviewer that the homologies depicted in the
figure explain the cross-reactivity between anti-laminin and
various molecules, when in fact, the homologies depicted in
the figure do not explain such cross-reactivity.
We further find that Respondent deliberately failed to include in Figure
7 the relevant information that the homologies depicted therein are from
untranslated portions of DNA. We base this finding on the following:
o It was very much in Respondent's self-interest to provide an
incomplete and misleading description of Figure 7 in the
October application. Respondent knew that he had to explain
the cross-reactivity of anti- laminin and other molecules in
order to obtain grant funding from NIH because of the
concerns expressed by the reviewers of the February
application. Had Respondent told NIH that the sequences he
depicted in Figure 7 were from untranslated portions of DNA,
he would have made it clear that he was not offering
meaningful evidence to respond to the concerns expressed by
NIH.
o Respondent knew that the homologies that he depicted in
Figure 7 were from untranslated portions of DNA. Dr. Olszowy
did the research which produced the computer-generated DNA
sequence on which Figure 7 was based, and told Respondent
that the similarities which had been discovered were from
the untranslated portions of the molecule.
o Respondent knew that homologies between untranslated
portions of DNA would not explain the cross- reactivity
between anti-laminin and other molecules, including IgG.
o Respondent has not offered a persuasive explanation for his
failure to apprise NIH that the DNA sequence depicted in
Figure 7 is from the untranslated portions of the molecule.
Respondent's assertion that he included Figure 7 in the
October application as an afterthought, suggesting that he
attached little significance to the figure and that it was
not intended to mislead anyone, is not credible. In fact,
we find that Respondent offered Figure 7 as critical
evidence intended to persuade NIH to fund the application.
We therefore find that the preponderance of the evidence establishes
that Respondent included Figure 7 in the October application in order to
mislead deliberately NIH reviewers into concluding that DNA sequence
homologies accounted for the cross- reactivity between anti-laminin and
other molecules.
Table 1 in the February and October applications
In both the February and October applications, Respondent included a
Table 1, which was a representation of laminin (p48) on various human
lymphoid subsets. The caption to Table 1 is identical in the February
and October applications. In the caption to Table 1, Respondent
represented that the laminin expression on the sorted cells depicted in
the table was determined by a process known as three-color flow
cytometry "using Texas Red labeled anti-laminin." Flow cytometry is
a
method for sorting and separating cells.
Dr. Schwarz performed the cell sorting experiments employing flow
cytometry for Respondent's laboratory. Dr. Schwarz testified that, upon
examining the data in Table 1, he did not know the source of that data.
Tr. at 559. Dr. Schwarz testified that he performed only one experiment
using three-color flow cytometry with Texas Red labeling and that
experiment was a failure. Tr. at 558-59. Dr. Schwarz testified that
three-color flow cytometry is a more accurate and sophisticated
mechanism for cell sorting than is two-color flow cytometry. Tr. at
578. Dr. Schwarz explained that two-color flow cytometry is less
precise than three-color flow cytometry and will not produce as reliable
results as are produced by three-color flow cytometry. Tr. at 593-94.
Thus, by asserting that three-color flow cytometry had been utilized in
the experiment that produced the data represented in Table 1, Respondent
claimed greater accuracy and precision for the experimental results
depicted in Table 1 than was justified.
Respondent testified that he did not perform the experiment which
produced the data used in Table 1, but that he received that information
from Dr. Schwarz. Tr. at 1175. Respondent contended that he stated in
the application that the results were determined by three-color
cytometry using Texas Red labeled anti- laminin because he erroneously
interpreted how Dr. Schwarz performed the experiment which produced the
data used in Table 1. Tr. at 1175-76. Respondent explained that he had
asked Dr. Schwarz to a do a three-color analysis of the anti-laminin
antibody Respondent had personally prepared. Tr. at 1176. When he
received the results from Dr. Schwarz, Respondent testified that he
erroneously assumed that Dr. Schwarz had used three-color cytometry,
when Dr. Schwarz had actually employed a two-color process. Id.
Respondent contended that the only mistake he made in Table 1 was
describing it as using three-color flow cytometry when it actually used
two-color flow cytometry and that the results depicted in Table 1, while
representing a modified two- color flow cytometry experiment, would be
close to the results received from a three-color flow cytometry
experiment. Tr. at 1177-78. Respondent stated that he had no reason to
question the numbers in Table 1 because those results were similar to
numbers obtained from other experiments using two-color flow cytometry.
Tr. at 1178-79.
We make the following findings in regard to Table 1:
o Respondent's assertion that Dr. Schwarz performed the
cell-sorting experiments from which Respondent derived Table
1 is false. Dr. Schwarz's uncontradicted testimony is that
he did not know the source of the data produced in Table 1
and that he never performed successfully a sorting
experiment involving three-color flow cytometry.
o During the period between January 1987 and the spring of
1989, Dr. Schwarz attempted to perform only one experiment
for Respondent involving three-color flow cytometry, and
that experiment was a failure.
o The data in Table 1 could not have been derived from the
three-color flow cytometry experiment performed by Dr.
Schwarz.
o Respondent's representation in Table 1 of the February and
October applications that cells were sorted by three-color
analysis using Texas Red labeled anti-laminin is false.
There is no evidence to show that Respondent or others
working with him ever performed successfully such
experiments.
We further find that Respondent deliberately falsified Table 1. We base
this finding on the following:
o It was in Respondent's self-interest to represent in Table 1
that cells had been sorted using three-color flow cytometry,
because three-color flow cytometry is a more accurate and
precise method of cell sorting than is two-color flow
cytometry.
o Respondent's contention that Table 1 represents an actual
modified two-color flow cytometry experiment is
unsubstantiated. Respondent produced no evidence to prove
that he or others working with him had actually performed
even a modified two-color flow cytometry experiment. Dr.
Schwarz did not perform either a two-color or a three-color
cell sorting experiment which produced data corresponding to
that which is represented in Table 1.
o There is no evidence that Dr. Schwarz or anyone else told
Respondent anything that would cause Respondent to believe
reasonably that sorting experiments had been carried out
successfully using three-color flow cytometry. Respondent's
assertion that he erroneously concluded that Dr. Schwarz had
performed three-color flow cytometry, when in fact Dr.
Schwarz had performed two-color cytometry, is not credible
in light of Dr. Schwarz's credible testimony that he never
told Respondent that he had successfully sorted cells using
three-color flow cytometry. Furthermore, in view of the
difference between three- and two- color flow cytometry,
Respondent's contention that he interpreted erroneously the
results of Dr. Schwarz's experiments is not plausible.
Respondent is an experienced scientist who knows the
difference between three- and two-color flow cytometry.
We therefore find that the preponderance of the evidence establishes
that Respondent deliberately stated falsely in the February and October
applications that experiments described in Table 1 had been performed
with cells sorted by three-color analysis using Texas Red labeled
anti-laminin.
Figure 4 in the February application and Figure 3 in the October
application
Figure 4 in the February application is identical to Figure 3 in the
October application. 9/ The figures depict two graphs which demonstrate
the inhibition to killing of target cells caused by the presence of the
antibody to p48. In the captions to the figures, Respondent stated the
figure depicted experimental results showing anti-laminin inhibition of
target cell killing by IL-2 activated Leu 19+/CD3- NK cells and Leu
19+/CD3+ T cells. Respondent stated further that the experiment used
sorted cells of more than 97% purity which were tested for killing
against three different target cells in the presence or absence of anti-
laminin antibodies.
Respondent contended that Dr. Schwarz performed the experiments which
supported these two graphs. Tr. at 1180.
Dr. Schwarz denied performing these experiments. He testified that
whenever he performed a cell sorting experiment, he kept records of the
experiment in his laboratory notebook. Tr. at 556. Dr. Schwarz
testified that, while he performed three cell sorting experiments for
Respondent of the type depicted in the figures, he did not draw the
graphs depicted in those figures. Tr. at 557. Dr. Schwarz testified
that the results of the sorting experiments he performed were not
depicted in the graphs, and his laboratory notebook did not contain any
of the data depicted in the graphs. Id.
Respondent offered no evidence to prove that he, Dr. Schwarz, or someone
other than Dr. Schwarz performed these experiments. The graphs which
Respondent offered as Figure 4 in the February application and Figure 3
in the October application were therefore offered by Respondent without
any substantive proof that they were based on actual experiments.
We make the following findings in regard to Figure 4 in the February
application and Figure 3 in the October application:
o Respondent's assertion that Dr. Schwarz performed the cell
sorting experiments from which Respondent derived the data
depicted in Figure 4 in the February application and Figure
in the October application is false.
o Dr. Schwarz performed a total of three cell sorting
experiments for Respondent of the type described in the
figures.
o None of the experiments which Dr. Schwarz performed for
Respondent yielded results which match the data depicted in
the figures.
o Respondent's representations in Figure 4 in the February
application and Figure 3 of the October application that
experiments had been performed by or for him using sorted
cells and yielding the results depicted in the figures are
false.
We further find that Respondent deliberately falsified Figure 4 in the
February application and Figure 3 in the October application. We base
this finding on the following:
o It was in Respondent's self-interest to represent that the
experiments in the figures, showing that the purported
anti-laminin blocked the killing effect of NK cells, had
been performed as depicted.
o Respondent's contention that the experimental data which is
the basis for the graphs depicted in the figures were
supplied to him by Dr. Schwarz is refuted by Dr. Schwarz's
testimony that he never performed the experiments depicted
in the figures.
o Respondent has not produced any records or other documents
which support his contention that he relied upon data
supplied to him by Dr. Schwarz.
We therefore find that the preponderance of the evidence establishes
that Respondent deliberately stated falsely in Figure 4 of the February
application and Figure 3 of the October application that experiments
using sorted cells had been performed by or for him yielding the results
depicted in the figures.
The Hiserodt #3 notebook
ORI determined that Respondent fabricated the Hiserodt #3 notebook
deliberately in an attempt to deceive Drs. Herberman and Bernier into
believing that figures in the October application were accurate and
truthful. Three individuals had first-hand knowledge of the
circumstances surrounding the Hiserodt #3 notebook: Dr. Bernier, Dr.
Herberman, and Respondent. Each testified about the notebook at the
hearing.
Dr. Herberman testified that, at the first meeting with Respondent on
December 20, 1989 to discuss the October application, he and Dr. Bernier
asked Respondent for primary data concerning Figures 1 and 2. Tr. at
951. Dr. Herberman testified that Respondent responded that there would
be no problem in providing the primary data for Figures 1 and 2. Tr. at
956.
Dr. Herberman testified further that on January 7, 1990 Respondent came
to Dr. Herberman's office and gave him the Hiserodt #3 notebook.
According to Dr. Herberman, Respondent explained to him that the
notebook contained primary experimental data for experiments that he had
performed himself over the previous one and a half years. Id. Dr.
Herberman testified that Respondent stated that, while Dr. Olszowy
performed the majority of experiments in the laboratory, Respondent
himself carried out several experiments and recorded these in his own
laboratory notebook. Id. Dr. Herberman averred that Respondent then
opened the notebook to pages 33 and 34 and stated that the pages
contained the primary data for the experiment described in Figure 2 of
the October application. Tr. at 956-58. Dr. Herberman further
testified that Respondent told him that he had made the entries in the
notebook contemporaneously with his receipt of experimental results.
Tr. at 957.
Dr. Herberman recounted that at his January 8, 1990 meeting with Dr.
Bernier he showed Dr. Bernier the notebook and that Dr. Bernier
expressed doubts about the notebook being a laboratory notebook that had
been used for a year and a half because of the notebook's pristine
condition. Tr. at 965. Dr. Herberman then testified about events at
the January 18 meeting. Dr. Herberman testified that when Dr. Bernier
asked Respondent whether the notebook was a contemporaneously-generated
primary notebook or a notebook that had been just recently prepared,
Respondent replied that it was a contemporaneously-generated primary
notebook. Tr. at 969. Dr. Herberman testified that when Dr. Bernier
then raised the possibility of having the Federal Bureau of
Investigation date the ink in the notebook, Respondent broke down and
admitted that he had prepared the notebook during the two or three weeks
prior to the January 7 meeting with Dr. Herberman. Tr. at 969-70.
In his testimony, Dr. Bernier confirmed that at the December 20, 1989
meeting he asked Respondent if he had primary data for Figures 1 and 2,
and that Respondent had answered that he did. Tr. at 435. Dr. Bernier
testified that in early January 1990, Dr. Herberman showed him the
notebook that Respondent had presented to Dr. Herberman, and that Dr.
Herberman stated that Respondent had told him that the entries in the
notebook were made at the time the experiments were performed. Tr. at
437, 464. Dr. Bernier testified that, upon examining the notebook, he
thought the notebook was in too pristine a condition to have been a
laboratory notebook assembled over a period of years. Tr. at 437. Dr.
Bernier testified that at the January 18, 1990 meeting, in response to
his questions, Respondent indicated that the information in the notebook
was entered at the time the experiments were performed. Tr. at 440.
Dr. Bernier testified that when he suggested that the entries in the
notebook could be dated by some type of ink analysis, Respondent
suddenly became very remorseful and admitted that the figures in the
grant application were incorrect and that he had constructed the
notebook over the Christmas 1989 vacation. Tr. at 440-41.
At the hearing Respondent testified that after leaving Dr. Herberman's
office on December 20, 1989, he returned to his laboratory. Respondent
testified that he looked for the autoradiograms and photographs for
Figures 1 and 2 in the applications, but that he could not find them.
Respondent testified that, in his desire to prove to Dr. Herberman that
his laboratory had detected p48 in a number of experiments, he went to
his files on the evening of December 20 and assembled data which
supported the concepts that laminin-like molecules were expressed on NK
cells and that the blocking function that had been seen was not an
artifact. Tr. at 1113. Respondent testified that he took the only
notebook he could find and put the data from his files into the
notebook, recalling to the best of his knowledge when those experiments
were done and what they showed. Id. Respondent testified that he
worked until 10:00 or 11:00 the night of December 20 completing the
notebook from beginning to end. Tr. at 1114-15. Respondent testified
that the notebook represented that p48, and not any artifact, had been
seen in a number of experiments. Tr. at 1116.
Respondent averred that he attempted to deliver the notebook to Dr.
Herberman at his office the next day, but that Dr. Herberman was not
there. Tr. at 1117-18. Respondent then went on his planned Christmas
trip to California. Respondent testified that when he returned, he made
an appointment to see Dr. Herberman in his office on January 7, 1990.
Tr. at 1119. He recalled that he brought the notebook along with a
binder and loose paper and gave them to Dr. Herberman. Id. Respondent
asserted that Dr. Herberman never asked him if the notebook was his
original primary data notebook. Tr. at 1120. Respondent testified that
he told Dr. Herberman that he could not find the primary data for
Figures 1 and 2, but that he brought other experiments supporting the
presence of p48 in human and rat cells. Id.
According to Respondent, at the January 18, 1990 meeting with Drs.
Herberman and Bernier, Dr. Bernier asked Respondent if the experiments
in the notebook were his experiments. Tr. at 1125. Respondent admitted
replying that they were. Id. However, he contended that he meant by
this statement that the experimental results were present in his files,
and not that he himself had personally performed the experiments. Id.
Respondent then asserted that Drs. Herberman and Bernier asked him if a
particular experiment indicated in the notebook as being performed in
December 1988 had been performed, with Dr. Herberman stating that he had
checked the records of the flow cytometer which indicated that no such
experiment had been performed at that time. Tr. at 1126. Respondent
testified that he could not understand that because he knew that
particular experiment had been done at least twice by Dr. Schwarz. Tr.
at 1126-27.
Respondent testified that the January 18 meeting ended with him telling
Drs. Herberman and Bernier that he was sorry for the mistakes he had
made in the notebook and in the grant application. Tr. at 1127.
On January 23, 1990, Respondent signed minutes of the January 18
meeting, which included the admission that the Hiserodt #3 notebook was
a fabrication prepared after an investigation of the applications had
begun. G. Ex. 17.
The appearance and contents of the Hiserodt #3 notebook support strongly
an inference that Respondent deliberately created the notebook to
deceive Drs. Herberman and Bernier into believing it was a
contemporaneous recording of experiments performed by Respondent. The
notebook's contents do not support Respondent's contention that the
notebook constituted a summary of experimental results addressing the
issue of whether p48 could be explained by an artifact. The very title
of the notebook, "Hiserodt #3," suggests that Respondent intended
Drs.
Herberman and Bernier to regard the notebook as the third in a series of
his laboratory notebooks. The entries in the notebook are not summary
statements at all; rather, they look like contemporaneous observations
of experimental results. The appearance of a contemporaneously
generated record is reinforced by the fact that the notebook reports
experimental results in a chronological sequence. Thus, the notebook's
structure would appear to have no purpose other than to convince Drs.
Herberman and Bernier that the results were recorded contemporaneously.
Furthermore, the notebook contains many experimental results that are
irrelevant to the issue of p48. The inclusion of irrelevant data
suggests that Respondent was trying to convince Drs. Herberman and
Bernier that the results proving the existence of p48 were generated in
the course of other laboratory activities and were recorded
contemporaneously. Finally, the use of different color inks at various
points in the notebook plainly appears intended to make a casual reader
think that results were recorded at different times.
We conclude that, on balance, Dr. Herberman's and Dr. Bernier's accounts
of Respondent's statements concerning the Hiserodt #3 notebook are
credible. Respondent's version is not. Respondent's version is belied
by his written admission that he fabricated the notebook. It is belied
by the appearance and contents of the notebook. Finally, it is belied
by the changing and inconsistent accounts that Respondent has given of
the circumstances under which he created the notebook. See our
discussion of Respondent's credibility, beginning at page 47.
We make the following findings in regard to the Hiserodt #3 notebook:
o Respondent told Dr. Herberman when he presented him with the
Hiserodt #3 notebook at the January 8 meeting that the
notebook contained contemporaneously-generated primary data,
including the experiment on which Figure 2 in the February
and October applications is based.
o Respondent told Drs. Herberman and Bernier at the January 18
meeting that the Hiserodt #3 notebook contained
contemporaneously-generated primary data.
o The format and content of the Hiserodt #3 notebook were
designed by Respondent to suggest that the notebook is a
record of experimental results generated contemporaneously
with the outcome of experiments performed by Respondent.
The Hiserodt #3 notebook does not contain
contemporaneously-generated experimental results from
experiments performed by Respondent.
o Respondent admitted that the Hiserodt #3 notebook is a
fabrication he created after officials at the University of
Pittsburgh began to inquire about the veracity of the
October application.
We also conclude that Respondent fabricated the laboratory notebook
which he presented to Dr. Herberman in January 1990 as a deliberate
cover up of false statements in the February and October applications,
based on the following:
o The only purpose Respondent could have had in presenting the
notebook to Dr. Herberman was to satisfy the request of Drs.
Herberman and Bernier for contemporaneously-generated
experimental data to substantiate Figures 1 and 2 in the
February and October applications. Had Respondent told Dr.
Herberman that the notebook contained reconstructed data, as
he now asserts, he would have in effect admitted that he was
unable to substantiate Figures 1 and 2 in the applications.
o The format and contents of the notebook were designed by
Respondent to deceive Drs. Herberman and Bernier into
believing that it was a contemporaneous record of
experimental results.
o Respondent told Dr. Herberman when he presented him with the
notebook in early January 1990 that it contained
contemporaneously-generated primary experimental data which
substantiated elements of the February and October
applications, when Respondent knew that the notebook was, at
best, a reconstruction of experiments. Indeed, when
Respondent presented the notebook to Dr. Herberman, he
directed Dr. Herberman's attention to specific pages in the
notebook and contended that they contained the primary
experimental data supporting Figure 2 in the February and
October applications.
o At the January 18, 1990 meeting, Respondent again contended
at first that the notebook contained
contemporaneously-generated primary data supporting the
February and October applications when he knew that this
contention was untrue.
o At the January 18, 1990 meeting, after Dr. Bernier mentioned
the possibility of having the F.B.I. date the ink in the
notebook, Respondent then admitted that the notebook did not
contain contemporaneously- generated primary data.
Subsequently, Respondent signed a statement in which he
acknowledged that the laboratory notebook was a fabrication
which he prepared after PCI and University of Pittsburgh
officials had raised questions concerning the veracity of
the February and October applications.
We therefore find that the preponderance of the evidence establishes
that Respondent fabricated the Hiserodt #3 notebook in order to deceive
others into believing that he had primary experimental data to support
the statements he made in the February and October applications
concerning Figures 1 and 2, to cover up the false and misleading
statements in those applications, and to persuade officials at PCI to
continue to support the applications.
Respondent's credibility
We make findings about Respondent's credibility because they affect our
conclusion as to his intent in writing the February and October
applications. We also make such findings because our conclusion as to
Respondent's credibility bears directly on our findings concerning his
present responsibility to deal with federal monies, and our debarment
recommendation. The regulations pertaining to debarment provide that
the causes for debarment include "any other cause" that affects "the
present responsibility" of an individual. 45 C.F.R. 76.305(d); 48
C.F.R. 9.406-2(c). Certainly, the credibility and general honesty of
a person is key to the present responsibility of that person to receive
federal grant funds. Whether Respondent can be trusted with future
federal grant funds depends on Respondent's ability to comport himself
with complete truthfulness.
We have discussed the deliberate falsehoods Respondent made in the
figures and tables of the February and October applications to make his
research appear more favorable for grant purposes. We have found
Respondent's explanations for the misrepresentations in the applications
not to be credible. We have found that Respondent deliberately
falsified experimental results and omitted available information that
might indicate his thesis about the existence of p48 was incorrect.
Respondent augmented the falsehoods in the February application with
additional falsehoods in the October application. Thus, when the
February application, with its falsified figures and tables, did not
receive funding because of concerns expressed by NIH reviewers,
Respondent concocted another figure, Figure 7, to address those
concerns. When Respondent was confronted about the falsified figures in
the applications by Drs. Herberman and Bernier, Respondent attempted to
cover up the falsehoods with a fabricated notebook.
We find that Respondent's dishonest behavior was not limited to an
isolated incident; rather, he engaged in an unremitting pattern of
behavior evidencing indifference to the truth. What emerges from this
pattern of falsehoods and deceptions is the conclusion that, at least in
his dealings with NIH and the University of Pittsburgh, Respondent has
acted in a manifestly dishonest way.
Furthermore, Respondent's pattern of dishonesty did not end when the
October application was withdrawn and the University of Pittsburgh
reported Respondent's misconduct to ORI's predecessor. Throughout ORI's
investigation of Respondent and the proceedings before this Panel,
Respondent has demonstrated that he is still not a trustworthy
individual.
We find that Respondent continues to be less than truthful, in light of
his conflicting and inconsistent testimony concerning his discussions
with Drs. Herberman and Bernier and his preparation of the Hiserodt #3
notebook, as well as the fact that his testimony is contradicted in key
respects by the credible testimony of other witnesses and by exhibits in
evidence. Examples include the following:
o When interviewed by ORI on November 14, 1990, Respondent
stated that he prepared the Hiserodt #3 notebook on January
5, 1990, after returning from his vacation in California.
G. Ex. 84, at 133. At a deposition taken on April 24, 1992,
in a civil lawsuit brought by Respondent against the
University of Pittsburgh, Respondent again testified that he
prepared the notebook on January 5, 1990, after his return
from California. G. Ex. 85, at 159.
o However, in his testimony at the hearing for this case on
September 3, 1993, Respondent testified that he prepared the
Hiserodt #3 notebook on the evening of December 20, 1989,
before he left for his vacation in California. Tr. at
1113-15.
o When interviewed by ORI on November 14, 1990, Respondent
stated that he was aware at the December 20 meeting with
Drs. Herberman and Bernier that they had the autoradiograms
and laboratory notebooks created by Dr. Olszowy. G. Ex. 84,
at 76.
o However, in his testimony at the hearing for this case on
September 3, 1993, Respondent testified that he went back to
his laboratory after the December 20 meeting and searched
for Dr. Olszowy's autoradiograms and notes but was unable to
find them. Tr. at 1112, 1117.
o When interviewed by ORI on November 14, 1990, Respondent
stated that he had the autoradiogram in his office for
Figure 2 of the February and October application. G. Ex.
84, at 150-51. At the deposition in the civil lawsuit which
Respondent gave on April 24, 1992, Respondent testified that
on December 20, 1989, after the December 20 meeting with
Drs. Herberman and Bernier, he went back to his office and
found the photographs he had used to construct Figures 1 and
2 in the February and October applications. G. Ex. 85, at
148.
o However, in his testimony at the hearing for this case on
September 3, 1993, Respondent testified that, on December
20, 1989, after the December 20 meeting, he went back to his
office and searched his files, but was unable to find the
photographs he had used to construct Figures 1 and 2 of the
February and October applications. Tr. at 1112.
o In his testimony at the hearing for this case on September
3, 1993, Respondent testified that he did not represent to
Dr. Herberman or to Dr. Bernier that the Hiserodt #3
notebook contained contemporaneously- generated primary
experimental data. Tr. at 1120. This testimony is
contradicted by the credible testimony of Drs. Herberman and
Bernier. It is also contradicted by the Hiserodt #3
notebook which was made by Respondent to look like
contemporaneously- generated primary experimental data
through such artifices as the use of different colored inks
and the inclusion of extraneous data. It is further
contradicted by Respondent's admission that the Hiserodt #3
notebook is a fabrication. G. Ex. 17.
o Respondent's testimony that Dr. Schwarz did the cell sorting
experiments which are the basis for Table 1 in the February
and October applications and for Figure 4 in the February
application and Figure 3 in the October application is
contradicted by the credible testimony of Dr. Schwarz that
he did not perform the experiments.
Additionally, in the course of the hearing Dr. Olszowy testified that,
after his discovery that the existence of p48 could be explained by an
artifact, when he asked Respondent how Respondent could continue to
pursue grant funds for a project that was no longer viable, Respondent
replied that he would use the grant funds for something else because
that is what everybody else does. Tr. at 219-20. It is difficult to
imagine Respondent uttering a more self-damaging indictment of himself.
Despite having ample opportunity to cross-examine Dr. Olszowy,
Respondent never questioned Dr. Olszowy about this statement. During
his own testimony, Respondent never even denied making the statement
attributed to him by Dr. Olszowy.
Respondent has attempted to attribute the allegations of his dishonesty
to conspiracy against him by former colleagues and University of
Pittsburgh officials. Respondent offered no evidence that would suggest
to a reasonable fact finder that he is the victim of a conspiracy; to
the contrary, the credible testimony of the other witnesses in this case
refutes Respondent's contention. For example, we find no support for
Respondent's assertion that Dr. Olszowy's statements and testimony were
fueled by personal animus resulting from a brief relationship between
Respondent and Dr. Olszowy's former wife, which took place well after
Dr. Olszowy's divorce.
Our Conclusions as to Scientific Misconduct
Applying our above analysis and the legal standards to the facts we have
found, we conclude that:
o The deliberate changing of data and results to support
Respondent's reported conclusions and including such false
and deceptive statements in the February and October
applications violate a prevailing and recognized standard in
the scientific community that researchers report their
findings honestly.
o The deliberate changing of data and results to support
Respondent's reported conclusions and including such false
and deceptive statements in the February and October
applications is falsification within the definition of
scientific misconduct contained in 42 C.F.R. 50.102.
o The deliberate making up of data, as evidenced by the
Hiserodt #3 notebook, to support statements made by
Respondent in the applications is "fabrication" and falls
within the definition of scientific misconduct contained in
42 C.F.R. 50.102.
We conclude, moreover, that it is unnecessary for us to make findings
that Respondent failed to provide adequate primary data to ORI, or to
maintain such data, for Figure 5 in the February application, which is
presented also as Figure 4 in the October application, Figure 7 in the
February application, which is presented also as Figure 6 in the October
application, and Table 2 in both the February and October applications.
We reach this conclusion for two reasons. First, given our findings
that Respondent falsified deliberately experimental results and
fabricated the only purported primary data he presented in order to
obtain grant funding, it is unnecessary to separately consider
Respondent's failure to maintain data. The willful falsification of
experimental results and fabrication of data which we find Respondent to
have committed is so egregious in this case that there is no need for us
to look beyond that in order to find misconduct of a very high order of
magnitude.
Second, ORI's proof as to the issue of Respondent's failure to maintain
primary data concerning Figure 7 in the February application, which is
presented also as Figure 6 in the October application, and Table 2 in
both the February and October applications, is not nearly so persuasive
as its proof as to Respondent's willful falsification of certain other
experimental results. Indeed, ORI did not offer independent expert
testimony as to the meaning of "primary data" and as to the standards
prevailing in the scientific community for maintenance of primary data.
Discussion of 1) Our Recommendations and Proposed
Conclusions of Law Concerning Debarment, and 2) Administrative
Actions
The misconduct engaged in by Respondent is egregious. Respondent
deliberately falsified critical sections of two applications for NIH
research funding and attempted to cover up his actions by fabricating a
notebook. Respondent has continued to deny engaging in misconduct
notwithstanding overwhelming and essentially unrebutted evidence to the
contrary. Respondent has not presented us with evidence of any
circumstances which would justify or explain his misconduct.
Our responsibilities in this case include recommending whether
Respondent should be debarred and, if so, recommending a term of
debarment. It also includes deciding on the propriety of administrative
actions proposed by ORI. For the reasons discussed below, we recommend
that Respondent be debarred and that a term of debarment of five years
be imposed. For the reasons discussed below, we also uphold the
proposed administrative actions determined by ORI, subject to ORI's
modification of its position regarding the correction of an article
which appeared in Journal of Immunology.
Debarment
The cause for debarment here is "any other cause of so serious or
compelling a nature that it affects the present responsibility" of
Respondent. 45 C.F.R. 76.305(d) and 48 C.F.R. 9.406-2(c). A
preponderance of the evidence in this case establishes that Respondent
is not presently responsible to serve as a recipient of federal funds.
Thus, we have concluded that a cause for debarment has been established.
The existence of a cause for debarment, however, does not mandate that a
debarment be imposed. The regulations provide that a determination to
debar is made after consideration of the "seriousness of the . . . acts
or omissions and any mitigating factors." 45 C.F.R. 76.300 and 48
C.F.R. 9.406(1)(a). The record here contains evidence of no
mitigating factors supporting a decision not to debar. Moreover,
considering the seriousness of Respondent's violations of certain
fundamental standards of conduct, we find no reason to refrain from
debarment.
Respondent violated fundamental standards of conduct. In light of the
high degree of trust inherent in research grants of the type Respondent
sought, under which performance cannot be readily verified or
qualitatively monitored, there is no lesser sanction that would
adequately protect the public interest. The government has an
obligation to award its limited federal research monies only to those it
determines will use those funds responsibly.
ORI proposed that Respondent be debarred for five years, and we so
recommend that a term of debarment of five years be imposed. This is a
case where circumstances warrant a term of debarment longer than the
three-year term which is the benchmark debarment period provided for by
regulations. 45 C.F.R. 76.320. The longer term is, in our opinion,
merited by the egregious circumstances of this case and by Respondent's
failure to offer any mitigating circumstances for his misconduct.
The conduct engaged in by Respondent establishes that he is not
presently responsible to act as a recipient of federal funds. Grant
awards for scientific research depend "heavily upon the trust which the
government places in the principal investigator to direct and oversee
the research conducted with the support of grant funds." McCaa at 58;
Bridges at 88; Langlois at 11. Respondent flagrantly breached that trust
by attempting to deceive NIH into funding grant applications premised on
falsified experimental data. Respondent further demonstrated his lack
of responsibility by attempting to cover up his deception, and in so
doing, to further deceive NIH.
We base our recommendation that a five-year term of debarment be imposed
on both the egregious nature of Respondent's misconduct and Respondent's
failure to offer any mitigating evidence to justify imposition of a
shorter term of debarment than five years. Respondent engaged in a
pattern of false statements and deception extending over a period of
several years. He deliberately falsified not one, but two applications
for research funding. When he was unsuccessful in his first attempt to
deceive NIH into approving funding for his research, he engaged in
additional falsehoods and deceptions intended to deceive NIH further.
He concealed from NIH and from officials at the University of Pittsburgh
the fact that the premise of his research and of the grant applications
had been called into serious doubt. He attempted to cover up his
falsehoods and deceptions when they were on the verge of being
discovered.
The misconduct engaged in by Respondent involves the central premise of
the research for which he sought NIH funds. Had Respondent succeeded in
deceiving NIH, he would have obtained dishonestly more than $1,000,000
of public funds and deprived honest scientists of scarce research
dollars.
Respondent has offered no justification for his misconduct. He
continues to deny engaging in dishonesty, despite overwhelming evidence
to the contrary. He has offered less than honest explanations for his
actions and his motivations. He has provided no convincing explanation
for his attempt to deceive NIH or University of Pittsburgh officials.
Perhaps most important, Respondent has not demonstrated any awareness of
his ethical responsibility as a scientist. There is nothing in the
record of this case to show that Respondent can be trusted to serve as a
recipient of public funds, either now, or in the foreseeable future.
For all of these reasons, we conclude that circumstances warrant a
debarment of more than three years, and we recommend a five-year term.
Respondent contends that it would be inequitable to debar him now.
Respondent asserts that he was stigmatized by ORI and its predecessor's
investigation into his misconduct. During the pendency of the
investigation, according to Respondent, he was unable to obtain either
academic or private employment in his chosen field. Therefore,
according to Respondent, debarment at this time would constitute an
additional and unreasonable punishment for his conduct.
Respondent misperceives the reasons for debarment. Debarment is not a
punishment. It is a remedy which is designed to protect federally
funded programs from individuals who have shown by their conduct that
they are not trustworthy to deal with program funds. We recommend
debarment here because Respondent has established by his dishonesty that
he is untrustworthy and that he is likely to continue to be
untrustworthy. We recommend debarment not to punish Respondent, but to
protect program funds. Therefore, any impediments to Respondent's past
employment that may have resulted from the investigation conducted by
ORI and its predecessor are irrelevant to our recommendation.
We make the following proposed conclusions of law regarding our
recommendation that Respondent be debarred.
Respondent's dishonest and deceptive conduct with
respect to the February and October applications, his
attempts to cover up that dishonest and deceptive conduct
from University of Pittsburgh officials, and his continuing
lack of honesty with respect to his misconduct, establish
that he is not presently responsible to participate in
transactions under federal non-procurement programs. 45
C.F.R. 76.110(a) and 76.305(d); 48 C.F.R. 9.406-1(a).
The egregious nature of Respondent's dishonesty, his
pattern of dishonest conduct, and his continuing denial of
dishonesty along with the absence of any mitigating
circumstances in this case, are circumstances warranting
that Respondent be debarred for more than three years. 45
C.F.R. 76.320(a)(1).
The circumstances of this case warrant that Respondent
be debarred for a term of five years. 45 C.F.R.
76.320(a)(1).
Administrative actions
ORI proposed three administrative actions be taken with respect to
Respondent: (1) Respondent be prohibited from serving on PHS advisory
committees, boards, or peer review groups for seven years; (2)
Respondent's PHS-sponsored research be monitored for its accuracy by the
awardee institution for seven years; and (3) an article which appeared
in the Journal of Immunology be corrected.
Respondent needs to demonstrate that he has become a truthful
individual, committed to the integrity of his scientific research.
Currently, he has not shown, for the myriad of reasons discussed above,
that he is fit to offer advice on scientific matters or to evaluate the
work of other scientists. Requiring that Respondent be prohibited from
serving on PHS advisory committees, boards, or peer review groups for a
period of seven years is reasonable under the circumstances of this
case.
Similarly, he has not shown that he can perform research without
supervision. Requiring that an institution employing Respondent monitor
him for the accuracy of any PHS-sponsored research for a period of seven
years is also reasonable under the circumstances of this case. 10/
ORI also proposed that corrections be made to the article, "The
Expression and Functional Involvement of Laminin-like Molecules in
Non-MHC Restricted Cytotoxicity by Human Leu-19+/CD3- Natural Killer
Lymphocytes," which appeared in Journal of Immunology, Vol. 141,
3318-23, 1988. Figure 2 in that article is a reproduction of Figure 4
in the February application and Figure 3 in the October application,
which we have found to have been falsified deliberately by Respondent.
ORI proposed that the article be corrected to reflect that Figure 2 may
not be relied upon.
In response to our inquiry seeking the authority for such an action, ORI
acknowledged that it does not have the authority to compel a non-PHS
scientific journal to accept proposed corrections or retractions to a
previously-published article. ORI explained that scientific journals
generally require that the author of a published article agree to a
correction or a retraction before it will be published. ORI argued,
however, that as a condition for receipt of future federal funding,
Respondent can be compelled to request that the Journal of Immunology
article be corrected, because the article involves the reporting of
research developed with PHS funds. Respondent has not disputed this
contention. We conclude that it is appropriate to order that, as a
condition for receiving federal funds in the future (independent from
any debarment that may be imposed), Respondent be required to request
that the Journal of Immunology article be corrected so as to advise
readers that Figure 2 in the article may not be relied upon.
Conclusion
For the reasons discussed above, we conclude that ORI proved by the
preponderance of the evidence that Respondent committed scientific
misconduct. We conclude that the proposed administrative actions are
justified (with one minor modification). We further recommend to the
Debarring Official that Respondent be debarred for a period of five
years.
___________________________ Donald
F. Garrett
___________________________ M.
Terry Johnson
___________________________ Steven
T. Kessel Presiding Panel Member
1. The hearing was held in Pittsburgh, Pennsylvania at the request of
the parties. Only the Presiding Panel Member of the Panel was present
at the hearing, but the other Panel members were provided the transcript
of the hearing and all the exhibits admitted at the hearing. Although
given the opportunity, neither party requested that a scientist be a
member of the Panel.
At the hearing Respondent was represented by counsel as he was
throughout all proceedings in this matter before this Panel. While ORI
called 10 witnesses, Respondent called no witnesses other than himself
at the hearing to refute the allegations of scientific misconduct.
Exhibits offered by ORI which were received into evidence are referred
to in this decision as "G. Ex. (number), (page)." Exhibits offered
by
Respondent which were received into evidence are referred to in this
decision as "R. Ex. (number), (page)." References to the transcript
of
the hearing are made as "Tr. at (page)."
2. All of the autoradiograms which are in evidence in this case had
standardized marker bands generated by a kit which is manufactured for
the purpose of producing standard marker bands. These standardized
marker bands were 200 kilodaltons, 97 kilodaltons, 68 kilodaltons, 43
kilodaltons, 24 kilodaltons, and 14 kilodaltons.
3. The background information in this section was derived from the
testimony given at the hearing held in this appeal. To the extent there
was a controversy over any particular event described in this section,
we have evaluated the testimony of Respondent and that of Drs. Olszowy,
Herberman, Bernier, and Schwarz and have included the version of events
that we found credible. We discuss the reasons for our findings on the
credibility of these individuals below.
4. Respondent has not contended that the prevailing standards in
effect prior to November 1989 imposed a less stringent obligation of
honesty and truthfulness on applicants for funding than is imposed by
the regulations. Respondent has argued only that, under the standards
contained in the 1989 regulations, he cannot be found to have committed
scientific misconduct because all the questioned statements are not
false. See Brief on Behalf of John C. Hiserodt, M.D., Ph.D.
5. In actions relating to activities that occurred before the adoption
of the 1989 regulations, we have never imposed our own definition of
scientific misconduct. Rather, we have required ORI to demonstrate the
prevailing definition within the scientific community at the time in
question for a similarly situated scientist, including the level of
intent required. Thus, we did not in Sharma hold that negligence in
making erroneous statements was not scientific misconduct. We held in
Sharma that ORI, after full opportunity to do so, failed to demonstrate
based on evidence from the scientific community that negligence in
making erroneous statements of the type that occurred in that case was
scientific misconduct. We also recognized that the definition of
scientific misconduct adopted by PHS in 1989 acted as a limit on the
scope of any proceedings and that the definition excluded "honest error"
or any conduct which does not "seriously deviate" from accepted
practices.
6. In 1992, the Research Integrity Adjudications Panel, under the
direction of the Departmental Appeals Board in the Office of the
Secretary of the Department of Health and Human Services, was given
responsibility for hearing appeals from the findings of scientific
misconduct made by ORI. See 57 Fed. Reg. 53,125 (November 6, 1992).
This Panel's authority to hear this matter is based on ORI's having
found (whether correctly or not) that scientific misconduct occurred and
Respondent's having appealed that finding. Id.; "Guidelines: Hearings
Before the Research Integrity Adjudications Panel" (September 30, 1992).
7. The October application was withdrawn by PCI in January 1990.
Respondent's contention that he telephoned NIH in late December 1989 to
withdraw the October application is without substantiation and
contradicted by the credible testimony of Dr. Herberman. Tr. at 966.
In fact, PCI had begun to investigate allegations of misconduct by
Respondent before it withdrew the October application. Therefore, we do
not accept Respondent's assertion that he withdrew the October
application in order to correct "errors" in that application.
8. At the hearing Respondent proffered two exhibits that were rejected
by the Presiding Panel Member. One, R. Ex. 7, was a photograph of an
autoradiogram showing two gels, with the right- hand portion of the
lower gel cut out. Respondent maintained that this was the photograph
from which he cut out the segment used in Figure 2. The other exhibit,
R. Ex. 11, was, according to Respondent, the original page depicting
Figure 2 from the applications; on this page, Respondent asserted, was
the section of the photograph he cut out from R. Ex. 7.
Respondent produced these exhibits for the first time on the last day of
the hearing held in this case. The Presiding Panel Member denied
admission of these exhibits because of Respondent's failure, in direct
contravention of repeated instructions by the Presiding Panel Member, to
submit copies of proposed exhibits to ORI in a timely fashion.
Respondent offered no explanation for his untimely presentation of the
exhibits. The Presiding Panel Member ruled that ORI would be prejudiced
by the introduction of the exhibits at such a late time in the
proceedings.
9. This figure is also reported as Figure 2 in an article co- authored
by Respondent and Dr. Schwarz entitled, "The Expression and Functional
Involvement of Laminin-like Molecules in Non-MHC Restricted Cytotoxicity
by Human Leu-19+/CD3- Natural Killer Lymphocytes," in the Journal of
Immunology, Vol. 141, 3318-23, 1988.
10. Obviously, if the Debarring Official determines to debar
Respondent, no federal funds will be available to Respondent for the
period of debarment. This administrative action is meaningful only for
time not encompassed by any debarment