Dr. Rameshwar K. Sharma, DAB No. 1431 (1993)
Department of Health and Human Services
Departmental Appeals Board
RESEARCH INTEGRITY ADJUDICATIONS PANEL
SUBJECT: Dr. Rameshwar K.
Sharma DATE: August 6, 1993
Docket
No. A-93-50 Decision No. 1431
DECISION
Dr. Rameshwar K. Sharma (Respondent) requested a hearing before
the
Research Integrity Adjudications Panel to contest two findings
of
scientific misconduct by the Office of Research Integrity (ORI) of
the
Public Health Service (PHS), as well as the administrative actions
which
PHS proposed to take against him as a result. The findings
of
scientific misconduct involve statements in two grant
applications
submitted by Respondent to PHS which ORI determined to
constitute
falsifications. In each case, ORI found that Respondent
purported to
have data which he did not in fact possess. The Respondent
admitted
that the statements were erroneous, but asserted that they were
not
intentional misstatements and did not constitute scientific
misconduct.
On the basis of its findings, ORI proposed to (1) prohibit Respondent
from
serving on PHS advisory committees, boards, or peer review groups
for three
years and (2) require any application to PHS by Respondent
during that period
to contain a certification by the applicant
institution that "the application
has been reviewed and approved by all
investigators involved in the project,"
or by "at least two qualified
scientists," if no other scientists are
involved in the project.
SUMMARY OF DECISION
After providing factual and procedural background information,
our
decision addresses the standards of conduct which ORI must prove
were
violated in order to establish scientific misconduct. Since there
were
no standards explicitly defined in applicable regulations or law
during
the time in question, ORI was obligated to show by evidence
what
standards were applicable to similarly-situated researchers. We
find
that ORI proved the existence of standards applicable during the
period
in question that would be violated, at a minimum, by
intentional,
material falsification of research methods and results in a
grant
application. We find that ORI did not prove that negligent
inclusion of
a false statement in a grant application in the circumstances
involved
in this case would so seriously deviate from accepted practice at
the
time as to constitute scientific misconduct. Thus, ORI could
establish
scientific misconduct in this case only if it proved by a
preponderance
of the evidence that Dr. Sharma intentionally falsified
material
statements in his grant applications.
ORI found scientific misconduct because it concluded that Dr.
Sharma
intentionally included erroneous statements in two grant
applications
submitted to NIH.
In regard to the first application, ORI inferred that Dr. Sharma
acted
intentionally based on its position that Dr. Sharma had
offered
inconsistent explanations of how the error occurred. ORI also
argued
that Dr. Sharma's guilty intent was shown by (1) his failure to place
a
citation after the sentence at issue, (2) a pattern of
misstatements,
(3) his failure to report the errors to NIH upon discovery,
and (4) his
general lack of credibility. We find that ORI failed to
prove by a
preponderance of the evidence that there was intentional deception
in
the first grant application.
It is important, when examining Dr. Sharma's allegedly
inconsistent
statements, to keep in mind as background the nature of the
error
involved. The sole error -- the core of this dispute which has
consumed
so much time and attention in PHS and elsewhere -- is a subscript
error
in a single sentence. Subscripts are important in distinguishing
one
protein from another in the same family. The subscript error
in
question, however, is inconspicuously located and forms no part of
any
obvious web of deceit. The application contains none of the data
or
explanations which reviewers of the applications would have expected
to
see if the erroneous statement were true. Consequently, the error
was
unlikely to mislead reviewers -- and, in fact, the evidence does
not
establish that it did. On the other hand, the record does
show,
virtually without challenge, that a typographical error could
have
occurred as a result of one wrong keystroke using
word-processing
macros. (The two subscripts which were interchanged in
the error in
question appeared about 128 times in that one
application.) The record
also shows that the same subscript
transposition by Dr. Sharma and
others occurred many times in circumstances
where it was much more
obviously an inadvertent error. All this had to
be kept in mind when
testing ORI's case, relying as it does upon collateral
actions and
statements of Dr. Sharma which ORI alleged cast the significance
of
intentional deceit upon an otherwise unremarkable error.
We have analyzed in detail the statements made by Dr. Sharma which
ORI
interpreted as inconsistent explanations for the misstatement in
the
first grant application. Although some of his statements are
ambiguous,
and at times reflect apparent communication problems, none of
his
statements, individually or collectively, persuasively demonstrates
any
intent to deceive. We therefore decline to draw the inference
from
these statements, suggested by ORI, that Dr. Sharma acted
intentionally.
We reject ORI's other arguments because--
(1) ORI did not establish that an additional citation
was
required after the sentence at issue because, but for the
error,
the reference would have been clear from the context;
(2) ORI did not prove a pattern of false statements in
this
application or other writings by Dr. Sharma;
(3) ORI did not prove that Dr. Sharma had a duty to report
to
NIH errors discovered only after the grant applications had
been
rejected for funding and an investigation was already
underway;
and
(4) ORI's attacks on Dr. Sharma's credibility were not
supported
by the record.
In regard to the second grant application, ORI relied heavily on
an
inference that intentional deception in this grant application was
part
of the pattern of misstatements about the progress of his research
as
evidenced by the first grant application. We reject this inference
for
two reasons. First, it is dependent on intentional deception in
the
first application, which ORI failed to establish. More importantly,
the
second grant application was hastily and poorly written (as Dr.
Sharma
admitted) and contained numerous statements directly contradicting
the
erroneous statement.
Therefore, we find that ORI failed to carry its burden of
proving
scientific misconduct by a preponderance of the evidence as to
either
grant application. Consequently, we conclude that ORI's findings
are
not supported and the proposed administrative actions are not
justified.
Background
Factual and Scientific Background 1/
During the time that the two applications at issue were prepared
and
submitted, Dr. Sharma was a researcher in the Department of Brain
and
Vascular Research at the Cleveland Clinic Foundation (CCF). Two of
the
major research areas in his laboratory involved --
(1) investigating the structure and function of �2
adrenergic
receptors, and in particular an �2 receptor which was
believed
to be unusual in that it coupled with guanylate cyclase
and
which was therefore assigned the name �2GC (the subject
of
Exhibit H-2, which was a grant application submitted by
Dr.
Sharma to NIH [National Institutes of Health] in February
1989,
but not funded) 2/, and
(2) investigating the role of an enzyme, identified as a 180
kD
protein, in carrying signals across cell membranes and
the
mechanisms for its regulation (the subject of Exhibit H-3,
which
was a grant application submitted by Dr. Sharma to NIH in
June
1989, but not funded).
See Transcript of Hearing, held May 13-19, 1993 (Tr.), at 869; Exs.
H-2
and H-3.
Both research projects involved study of the structure of
particular
proteins (the �2GC receptor protein or the 180 kD enzyme
protein).
Proteins are molecules which are constructed in linear chains of
amino
acids and which are vital to the structure and functioning of
living
cells. Tr. at 200, 518; ORI Scientific Terms at 1.
Receptors are large
proteins on the surface of cells which interact with
molecules in the
outside environment. Tr. at 517-9; ORI Scientific
Terms at 3. Various
kinds of receptor proteins can be defined by their
biochemical activity,
for example, adrenergic receptors bind to epinephrine
molecules. Tr. at
519; ORI Scientific Terms at 4; Exhibit H-38, at
315-8. (The main
distinguishing feature of the particular adrenergic
receptor which Dr.
Sharma was researching was that it was believed to couple
to guanylate
cyclase, rather than adenylate cyclase, which was more
common. Tr. at
520, 522-3.)
Proteins can be identified by their structure, in addition to
their
biochemical behavior. One way to research the structure of a
protein is
to seek to identify the specific sequence of amino acids which
form the
protein. Tr. at 202-3. An initial approach is to cut the
protein into
fragments, called peptides, using enzymes or chemicals which
reliably
divide the chain at predictable points. Tr. at 523.
These fragments
can be isolated and analyzed to create "peptide maps," which
show the
pattern of pieces from these breaks as a unique "fingerprint."
Tr. at
491-3, 524-5; ORI Scientific Terms at 1. A peptide map does
not
disclose the precise order of the amino acids in a protein, although
it
may point to areas of difference between similar proteins. Tr. at
493,
506-7; ORI Scientific Terms at 2. Additional work must be done
to
determine the amino acid sequence of a particular peptide, and then
to
determine the order of the sequence within the protein as a whole.
Tr.
at 527-8.
Each protein is produced by a particular gene, which is composed of
DNA
(deoxyribonucleic acid) nucleotide base sequences. Genes do
not
directly produce the protein and often contain additional material
which
is not directly translated in the creation of protein. Tr. at
541,
948-9. Rather, the DNA in a gene is translated into the shorter
form of
RNA (ribonucleic acid, also composed of nucleotides), and the RNA
in
turn translates its sequence into corresponding amino acids to
produce
the protein. Tr. at 541-2, 948. Each of the twenty common
amino acids
can be coded for by one or more sets of three nucleotides, known
as
"codons." Tr. at 200; 528-9.
Once an adequate portion of the sequence of amino acids in a protein
is
known, a possible next step is to create a probe for molecular
cloning.
A probe is a piece of cDNA ("complementary DNA") which is
synthesized
from nucleotide codons that correspond to the known amino acid
sequence.
Tr. at 206-7, 527-9. Such a probe, known as an oligomer
probe, can be
used to screen a "library," i.e., a collection of copies of all
the RNA
(reverse translated into cDNA form) in a particular cell type.
Tr. at
540, 949-50. Sometimes, more than one codon triplet can code for
a
particular amino acid, a phenomenon known as the "degeneracy" of
the
code. Tr. at 228-9, 528-30, 928. In such situations, the
scientist
constructing a probe has several alternatives. The scientist
can
construct a series of probes embodying each of the
possible
alternatives, known as "degenerate probes." Tr. at
531-2. The
scientist can select a region of the sequence to construct
the probe
which has the least degree of degeneracy. Tr. at 229-30;
530-1. The
scientist can construct a probe by guessing the most likely
combination
of codons, known as a "guessmer" probe. Tr. at 532-3,
928. In making a
guessmer probe, the choice of likely codons is
assisted by the use of
codon bias data tables which set out the tendency in
particular species
to prefer certain codon alternatives over others in coding
for
particular amino acids. Tr. at 530. The probe constructed by
the
scientist is then introduced into the library under specified
conditions
("stringency"), and the results are studied to see whether the
probe has
reacted with, or "hybridized to," any cDNA in the library.
Tr. at
542-6, 589-9. The isolated cDNA to which the probe has
hybridized is
known as a cDNA clone. Tr. at 547. The cDNA may
contain all or only a
part of the sequences necessary to produce the
protein. Tr. at 214,
550.
In the absence of data on the sequence of amino acids in a
desired
protein, scientists can also use probes based on related genes to
screen
for molecular clones of the desired protein that will hybridize to
the
probe as well. Tr. at 208, 927; see generally, Exhibit H-38,
at
104-112. This approach is feasible because hybridization can occur
with
cDNA of other, closely-related proteins. Id. In fact,
unintended
mismatches occur at times, either because the clone is not
identical to
the probe, but contains some matching sequences, or because the
wrong
codons were selected. See Tr. at 533, 598, 608, 627-30.
Related
proteins, or "families" of proteins, often have areas within their
amino
acid sequences which are identical, or "conserved," among the
family
members. Tr. at 534-5. If a probe is based on a conserved
portion of
the amino acid sequence of one family member, it would,
under
appropriate conditions, have a good chance of hybridizing to
other
members of the same family. Tr. at 537-8. Another strategy
would be to
create a probe that was based on the entire gene sequence of one
of the
family members for which cDNA had already been cloned. Tr. at
538-9.
Such a probe would be much larger than an oligomer probe (about
200-1000
nucleotides, as opposed to 15-50 nucleotides). Tr. at
539. In order to
identify the cDNA which was cloned by a probe, a
scientist would need to
(1) use the resultant clone to produce, or "express,"
the protein and
identify the protein by its chemistry and behavior, or (2)
sequence the
clone and compare it to the protein's amino acid sequence if
known. Tr.
at 548-50. This step would be necessary, even if the
probe was based on
sequence data from the desired protein, rather than a
related one,
because of the possibility of mismatches or conserved
sequences
hybridizing to something other than the target cDNA. Tr. at
955-6.
It is uncontested that Dr. Sharma did not have the amino acid
sequence
data of either of the proteins that he was studying at the time
he
submitted the grant applications at issue, although he had made
efforts
to obtain such data. In the case of �2GC, another laboratory
published
amino acid sequence data on a related member of the same family
of
proteins, i.e., �2A, derived from human platelet sources. Dr.
Sharma
used probes based on amino acid sequence data of �2A to screen a
library
from rat adrenocortical carcinoma cells in an effort to clone
�2GC. His
application sought funding to determine if the clones which
he had
obtained did, in fact, represent the unique receptor, which he had
named
�2GC. In the case of 180 kD, Dr. Sharma had peptide maps but did
not
have amino acid sequence data. In that application, he sought
funding
to continue further work on sequencing, characterizing and studying
the
functioning of the protein.
Procedural History
The initial inquiry in this case was triggered on April 20, 1990,
when
Stephen Chalberg, Ph.D., a researcher working under Dr.
Sharma,
approached Carlos M. Ferrario, Ph.D., the chairman of Dr.
Sharma's
department, with concerns that certain grant applications submitted
by
Dr. Sharma contained inaccurate statements. ORI noted that
these
allegations arose "in an atmosphere of conflict" between Dr.
Ferrario
and Dr. Sharma over various issues of personnel, job performance
and
funding. Exhibit R-10 (ORI Final Report) at 4. In addition,
Dr.
Chalberg was already anxious at that time to leave Dr.
Sharma's
laboratory. Tr. at 148. Dr. Ferrario referred the matter
to Dr.
Bernadine P. Healy, M.D., then Chair of the Research Institute at
CCF,
who convened a preliminary inquiry committee (Healy Committee),
which
found no evidence of scientific misconduct, as opposed to sloppiness,
in
the allegations before it (which did not include those relating
to
Exhibit H-2). Ex. H-4; Ex. H-5, at 5. A second inquiry
committee,
chaired by Thomas A. Hamilton, Ph.D. (Hamilton Committee), was
convened
(for reasons which are disputed) and concluded that the
allegations
against Dr. Sharma had substance. Ex. H-7, at 4.
Therefore, a formal
investigation was instituted, chaired by Andrew J.
Fishleder, M.D.
(Fishleder Committee). The Fishleder Committee
concluded that Dr.
Sharma should be "exonerated from the allegation of
scientific
misconduct" and found no "conclusive evidence" of an intent to
mislead
the study sections reviewing the grant applications to
make
recommendations to NIH about funding. Ex. H-8, at 3-4.
The matter then passed from CCF to the PHS, which began its
investigations
in November of 1990. After finding CCF's procedures
inadequate, the
Office of Scientific Integrity (OSI) undertook its own
investigation, which
was interrupted when the case was transferred to
the Office of Scientific
Integrity Review (OSIR) in October 1991. ORI
Final Report at 7.
Subsequently, the functions of OSI and OSIR were
transferred to ORI.
The ORI investigation involved interviews of
relevant witnesses, a site
visit, and consultation with scientific
advisors. Id. at 9-11. In
April 1992, OSIR issued draft reports
finding no scientific misconduct.
Exs. R-5 and R-6. After receiving
comments on the draft reports,
obtaining additional submissions, and
conducting a second interview with Dr.
Sharma, ORI issued its Final
Report and Action Notice finding misconduct in
regard to the allegations
set forth below.
Dr. Sharma appealed to the Research Adjudications Integrity Panel
on
December 21, 1992. After preliminary proceedings, a hearing was held
in
the case, May 13-19, 1993, followed by post-hearing briefing by
both
parties.
Issues
ORI found that Dr. Sharma made false statements in two grant
applications,
submitted to PHS, in order to mislead reviewers into
believing his research
to be more advanced than it was in fact. Tr. at
11-24. The
specific allegations at issue were set forth in ORI's Final
Report as
follows: 3/
[Allegation 1:] ORI finds that Dr. Sharma falsified
statements
on pages 21, 27 and 32 of Application 1 [Exhibit H-2 in
this
proceeding], and, consequently, Dr. Sharma committed
scientific
misconduct. Specifically, ORI finds that Dr. Sharma
falsely
reported the results of research conducted in his laboratory
by
stating that the probe used to screen the library and
isolate
the cDNA clones was based on the amino acid sequence data of
the
�2GC receptor when the work was done using the �2A
receptor
because Dr. Sharma did not have the amino acid sequence of
the
�2GC receptor.
* * *
[Allegation 4:] The ORI finds that the statement appearing
on
page 23, Application 3 [Exhibit H-3], was
falsified.
Specifically, ORI finds that Dr. Sharma falsely claimed
to
possess unpublished sequence data of the 180-kD protein.
ORI Final Report at 54 and 55.
ORI contended that intentionally claiming in a PHS grant application
to
have data which an applicant does not possess in order to
mislead
reviewers constituted scientific misconduct because it violated
accepted
standards of conduct in the scientific community during the
relevant
period. Dr. Sharma admitted that he did not have amino acid
sequence
data on either the �2GC receptor or the 180 kD protein at the time
these
grant applications were filed. However, he contended that
the
statements which appeared to claim such possession were
not
intentionally misleading, but were caused by errors.
Respondent
Post-Hearing Br. at 1-2, 5-6.
Thus, the key issue to be decided is whether ORI proved by a
preponderance
of the evidence on the record before us that the
misstatements in each grant
application were the result of intentional
deception.
ORI also argued in the alternative that Dr. Sharma was guilty
of
scientific misconduct even if the statements were not intentional, if
he
should have known about the false statements and was negligent
in
failing to prevent their inclusion in the grant applications.
ORI
contended that Dr. Sharma failed to follow accepted
scientific
practices, such as requesting colleagues to preview his
grant
applications, including more cites, or reporting the errors to NIH
upon
discovery. Thus, we must also decide whether ORI established
that
negligent inclusion of a false statement in a grant
application
constituted scientific misconduct under standards applicable at
the
time. We therefore turn next to defining the applicable
legal
standards.
Applicable Legal Standards
The role of the Panel is to review all the evidence before it to reach
a
de novo decision as to the existence of scientific misconduct and
the
appropriateness of the proposed actions, rather than to review
ORI's
procedures or the reasonableness of ORI's decisions on the
evidence
before ORI. Ruling on Respondent's Motion to Dismiss the
Complaint,
dated May 10, 1993 (Ruling) at 10, n.8. 4/ The Panel's
decision herein
"will be final agency action" on the proposed administrative
actions in
this matter. Guidelines on Hearings Before the Research
Integrity
Adjudications Panel (Guidelines) at 5.
The issues in this matter were bifurcated during a preliminary
conference,
held on January 19, 1993, and the parties briefed legal
issues raised by
Respondent in advance of the hearing held to resolve
factual
disputes. In a motion to dismiss, Respondent (1) challenged
the
authority of PHS to take administrative action against scientific
misconduct
committed prior to the issuance of regulations at 45 Fed.
Reg. 32,446 (August
8, 1989) (1989 Regulations) defining such
misconduct, (2) asserted that PHS
discretion did not extend to the
actions proposed here and was not supported
by a notice announcing such
actions in cases of scientific misconduct because
the notice at 56 Fed.
Reg. 27,384 (June 13, 1991) violated the Administrative
Procedure Act, 5
U.S.C. . 553, and (3) argued that PHS's authority in any
case did not
reach misrepresentations in grant applications which were never
funded.
The Panel denied Respondent's motion to dismiss, concluding that PHS
had
authority to propose administrative actions against
scientific
misconduct committed before the 1989 Regulations in order to
protect the
integrity of federal research grant funds. The Panel
rejected
Respondent's arguments concerning the Administrative Procedure
Act.
Furthermore, the Panel concluded that "[m]aterial falsifications
in
grant applications relating to the principal investigator's
research
capacity and accomplishments are clearly among the types of
conduct
which PHS may investigate and propose actions for under
its
discretionary authority." Ruling at 2. However, the Panel
also
concluded that no general policy had been established specifying
the
applicable standards of conduct or identifying particular
administrative
actions appropriate to specific instances of scientific
misconduct.
Therefore, a "case-by-case adjudication" is required to
determine: "1)
what conduct a researcher has engaged in; 2) whether
that conduct
violated applicable standards existing at the time, derived
either from
the scientific community or from federal requirements for
applying for,
conducting, or reporting federally supported scientific
research; and 3)
whether the particular administrative actions proposed are
appropriate."
Ruling at 3. The Panel further noted that, under the
Panel review
process adopted by PHS, PHS has the burden of proving
scientific
misconduct by a preponderance of the evidence, which encompasses
"both
the existence of the conduct and the standard which applies,
including
whether Respondent had whatever level of intent is required to
violate
that standard." Ruling at 3, 13; Guidelines at 6.
We found that no law or regulations established a specific definition
of
scientific misconduct against which to measure Dr. Sharma's
conduct.
However, we recognize here, as we have in other proceedings, that
the
definition adopted by PHS in 1989 acts as a limit on the scope of
these
proceedings. The 1989 Regulations define scientific misconduct as
--
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.
54 Fed. Reg. at 32,449. Thus, ORI must establish the
applicable
standards on a case-by-case basis and must exclude "honest error,"
for
example, or any conduct which does not "seriously deviate" from
accepted
practices.
ORI established at the hearing by testimony from scientists
with
experience as grant applicants and reviewers covering the relevant
field
at the time in question that intentional falsification of a
material
element of a grant application would be a serious deviation
from
accepted practices. See, e.g., Tr. at 211 (Dr. Marshak agreeing it
is
not "appropriate" in the scientific community to represent in a
grant
application that one has data which one does not yet have), 470
(Dr.
Merrick agreeing it is "an improper practice to submit a
grant
applications that includes data that you do not possess"),
678-82. Dr.
Sharma himself indicated that he thought a wrong statement
in a grant
application should be reported promptly to NIH, because his
philosophy,
for his students as well as himself, was "to have the utmost
integrity"
and not to put in data which is merely anticipated. Tr. at
847-8 (Dr.
Sharma). ORI thus could establish scientific misconduct if
it proved by
a preponderance of the evidence that Dr. Sharma intentionally
falsified
material statements in his grant applications.
In its post-hearing brief, ORI argued for the first time that
the
requisite legal standard for intent was conclusively resolved by
an
earlier debarment case, and that it included a negligence standard.
ORI
Post-Hearing Br. at 5-7, citing Robert Edward McCaa, Ph.D., DAB No.
823
(1987). On that basis, ORI asserted that, in order to "satisfy
the
requisite level of intent," ORI had only to "prove that Dr. Sharma . .
.
should have known that the false statements were in the
applications."
ORI pointed to a statement in that case that the researcher,
Dr. McCaa,
"knew or should have known" that he did not have sufficient
information
to accurately report the methods or results of experiments set
forth in
a published paper. McCaa at 33.
After reading the McCaa decision as a whole, we conclude that
ORI's
reliance on that decision is clearly misplaced, for the
following
reasons:
o The statement that Dr. McCaa "knew or
should have known" of
inaccuracies was clearly intended as a factual finding
regarding the
differing states of Dr. McCaa's knowledge of various
inaccuracies in the
published paper, rather than as a legal conclusion on
what constitutes
scientific misconduct. The discussion in McCaa makes
it clear that the
hearing officer found that, while certain of the
inaccuracies at issue
may have been merely negligent mistakes, others could
only have been
made by Dr. McCaa with the knowledge that they would mislead
the reader.
The hearing officer therefore specifically found that Dr.
McCaa
presented the paper at issue with an "intent to deceive the
reader."
McCaa at 35.
o McCaa did not frame the issues in terms
of whether scientific
misconduct had occurred (and could not have applied the
PHS definition
of scientific misconduct, which was published in 1989, after
McCaa was
issued). The issues in McCaa were whether a cause for
debarment had
been established and whether Dr. McCaa was "presently
responsible" as a
recipient of federal funds.
o The hearing officer found a cause for
debarment in a pattern of
intentional deception by Dr. McCaa, which included
fabricating data and
reporting as experimental procedures or results
inaccurate information
based solely on expectations or suppositions.
Nothing in McCaa suggests
that negligent conduct alone is a sufficient basis
for finding that a
researcher lacked integrity.
o The expert testimony in McCaa related
to the specific types of
inaccuracies at issue there, which were published in
a scientific
journal article and may have misled readers in evaluating drugs
used to
treat high blood pressure. Thus, even if the testimony in McCaa
had
established that negligent failure to prevent such inaccuracies would
be
scientific misconduct, this would not necessarily mean that
negligent
failure to prevent the inaccuracies in the grant applications at
issue
here would also constitute scientific misconduct.
The unquestionable duty of a scientist to seek accuracy, which
was
recognized generally and then applied to particular facts in McCaa,
does
not necessarily extend to a duty to achieve perfection or freedom
from
all inadvertent error. 5/ "Honest error" is expressly excluded
from the
definition of scientific misconduct adopted by PHS, so something
more
than inadvertence must be shown to establish scientific misconduct.
ORI gave virtually no notice in this case that it intended to
prove
scientific misconduct on any basis other than intentional
false
statements. Despite passing references to what Dr. Sharma should
have
known, ORI's Summary of its Case and its entire presentation at
the
hearing were directed to its claim of intentional deception. See,
e.g.,
Tr. at 12-24 (ORI opening argument) and Tr. at 961-972 (ORI
closing
argument). Therefore, Dr. Sharma could not reasonably have
been
expected to have presented any contrary evidence as to the
standards
which ORI now claims that he negligently violated.
Nevertheless, ORI contended in its post-hearing brief that it
could
establish scientific misconduct in this case by showing that Dr.
Sharma
should have known that errors existed in the grant applications.
ORI
Post-Hearing Br. at 27. ORI contended that it had established that
a
principal investigator has a duty to "ensure the accuracy" of
grant
applications, which Dr. Sharma failed to meet.
ORI's reliance, before us, for proof of negligence falling so far
below
commonly accepted standards as to constitute scientific misconduct
on
evidence of Dr. Sharma's general sloppiness in writing and
proofreading
is particularly unpersuasive. All the relevant facts were
known to ORI
from the beginning of its investigation and yet no finding of
scientific
misconduct was based on any of these items. In fact, ORI
specifically
found no scientific misconduct concerning other errors in the
grant
applications and based its result on findings that:
(1) The statement on the �2GC probe retained in the
revised
grant application "was an editing error that resulted
from
inadequate application preparation and review procedures
and
does not constitute scientific misconduct." ORI Final Report
at
54.
(2) Certain errors "resulted from poor supervisory
practices
and careless and sloppy proposal preparation.
Consequently, the
statements . . . were unintentional errors and did
not
constitute scientific misconduct." Id. at 55.
(3) A statement "resulted from uncritical integration
of
contributions from other team members, and that such
conduct
does not constitute scientific misconduct." Id.
(4) "[O]ther misstatements in the Applications . . .
were
caused by careless yet honest errors - typographical,
editing,
and supervisory - and do not constitute scientific
misconduct."
Id.
Thus, ORI explicitly took the position in this case that sloppiness,
poor
review procedures, and multiple errors, if unintentional, did not
constitute
scientific misconduct. Furthermore, ORI's scientific expert
testified
that scientists vary in the degree of care with which they
proofread their
grant applications. Tr. at 614 (Dr. Douglass). Dr.
Sharma
testified that he did proofread these applications. Tr. at 854.
The
fact that his proofreading did not eliminate the errors that have
emerged
from the close scrutiny to which these applications have been
subjected does
not suffice to demonstrate that his conduct did not fall
within the range of
practices accepted among scientists preparing grant
applications. Not
one of ORI's witnesses testified that unintentionally
submitting an
application containing errors was considered scientific
misconduct.
ORI also argued that Dr. Sharma could have prevented the error
by
providing the applications to other scientists for review
before
submitting them, and that not doing so here was "tantamount to
wilful
disregard" of their accuracy. ORI Post-Hearing Br. at
28-29. ORI
relied for its claim that such sharing was "a commonly
accepted practice
within the scientific community" on the testimony of two
scientists.
Id. at 28, n.72. Dr. Douglass testified that he personally
shares his
grants with various other researchers to get a critical review
that may
allow him to improve the grant and get a better chance of
funding. Tr.
at 583-4. Dr. Marshak testified that his practice
was to have at least
two other investigators read his grant applications and
that his
institution (Cold Spring Harbor) had a policy or at least a
suggestion
for such review, but he did not know if it applied to
senior
investigators. Tr. at 199, 230-1. Dr. Chalberg, who
testified on
behalf of ORI, stated that he did not know at the time of any
common
practice to have others review grant applications, although he
thinks
that is now the rule. Tr. at 118. ORI itself found that
CCF did not
have any clear policy requiring review of applications by other
involved
scientists, and included a recommendation for adoption of such a
policy
in its final report. ORI Final Report at 56. This evidence
is not
sufficient to establish that the failure to have a grant
application
reviewed by other scientists before submission would constitute
a
serious deviation from a commonly accepted practice. In any case,
ORI
did not disprove Dr. Sharma's assertion that he did share
the
applications with certain colleagues before submission. 6/ ORI
merely
proved that he did not share final copies of them in advance
of
submission with Dr. Chalberg, who now believes he could have caught
the
errors. See Tr. at 38, 77, 119 (Dr. Chalberg).
More rigor in proofreading and sharing the applications with peers
might
well have avoided the present controversy. 7/ However, at the
risk of
stating the obvious, we note that labeling conduct as
"scientific
misconduct" must be viewed as a significant and consequential
action:
notwithstanding the relatively minor corrective actions proposed in
a
case such as this one, the opprobrium which naturally accompanies
the
label has the potential to cause serious embarrassment and might
even
destroy a scientist's career. Thus, in the absence or law
or
regulations establishing standards, we need to take considerable care
in
assessing how substantially evidence shows a standard
distinguishing
between merely sloppy work on the one hand, and, on the other,
actions
which should produce the serious consequences that the brand
"scientific
misconduct" entails. It is against that background that we
assess ORI's
arguments concerning whether such things as lack of care in
proofing
documents rises to the status of "scientific misconduct." We
find that
no persuasive evidence was presented at the hearing or in
ORI's
submissions to support the existence of a lesser standard applicable
in
this case than one involving intentional falsification. We
therefore
limit the remainder of our analysis to a consideration of whether
ORI
proved that Dr. Sharma intentionally made false statements in his
grant
applications.
We turn next to analyzing the evidence which ORI presented to
show
intentional deception in relation to each of the grant
applications. We
first discuss the �2GC grant application (Exhibit
H-2), about which ORI
presented the bulk of its evidence, and then discuss
the 180 kD protein
grant application (Exhibit H-3).
Analysis of the Evidence on the Grant Applications
I. The First Grant Application
The charges relating to Exhibit H-2 center on a parenthetical phrase
in
one statement on page 21 of that grant application, which is
highlighted
below:
The uniqueness of the �2GC-receptor is further substantiated
by
our ongoing molecular cloning studies. Utilizing a
39-oligomer
probe (corresponding to the amino acid sequence of
�2GC-receptor
proteolytic fragment), which was synthesized using the
rat codon
bias data, three potential cDNA clones (1.4-, 2.8-, 4.5-kb)
from
2 million screened recombinants (� ZAP rat
adrenocortical
carcinoma library) have been isolated and partially
sequenced .
. . .
The essential error in this sentence is that the probe actually used
did
not correspond to �2GC sequence data but rather to sequence data of
a
related receptor protein. 8/ The experiment described here was in
fact
performed using a 39-oligomer probe which corresponded to the amino
acid
sequence of an �2A receptor fragment. Respondent Post-Hearing Br.
at 2.
The �2A sequence data was obtained from human platelet sources and
was
published by another researcher, R.J. Lefkowitz, in a paper in
Science
in 1987. Tr. at 880; Ex. R-13. 9/ We find that the
sentence was
otherwise accurate. The probe was synthesized using rat
codon bias
data, as reported. Tr. at 175-6. It was 39-oligomer in
size, as
reported. Tr. at 152. The use of the �2A probe resulted
in recovery of
three potential clones after screening of the rat
adrenocortical
carcinoma library, as reported. See, e.g., Tr. at 880
(Dr. Duda).
Therefore, the error underlying the charges relating to Exhibit
H-2 was
the substitution of �2GC for �2A in this clause. 10/
Dr. Sharma argued that this misstatement was the result of a
single
typographical error in substituting �2GC for �2A in the
underlined
portion of the sentence, thereby implying that he had amino
acid
sequence data of �2GC which was used to construct the probe used in
the
reported experiments rather than having relied on the published
sequence
data for �2A. Consequently, it is essential to examine whether
this
subscript error was most likely to have occurred as a deliberate
attempt
to mislead the grant reviewers, as ORI argued, or an unintentional
or
clerical mistake, as Dr. Sharma contended.
We examine first what the record before us establishes as to how
this
error occurred. We conclude that, in the context of the full
grant
application, this error was unlikely to and did not in fact
mislead
reviewers, and that Dr. Sharma's conduct was inconsistent
with
intentional deception. On the other hand, we conclude that
the
subscript substitution could most easily have been caused by
a
typographical error. We then turn to the arguments presented by ORI
in
support of its contention that intentional deception
nevertheless
occurred.
o The argument on which ORI relied most heavily wasthat
Dr.
Sharma offered inconsistent explanations of the error and
that,
while none of his statements constituted a
plausible
explanation, the inconsistency among them evidenced
guilty
intent.
o ORI also argued that Dr. Sharma's
guilty intent was
demonstrated by:
(1) his failure to cite the source of the
probe
immediately after the disputed statement,
(2) a pattern of misstatements that overstate
his
laboratory's achievements,
(3) his resistance to reporting the errors to NIH, and
(4) his lack of credibility.
We conclude that none of ORI's arguments persuasively support
the
allegations of intentional deception in relation to Exhibit H-2.
A. ORI's Theory of Intentional Deception Is Unlikely
ORI never fully developed a theory of its case which would explain how
Dr.
Sharma allegedly sought to mislead the reviewers by his actions in
relation
to Exhibit H-2. However, ORI alleged generally that the motive
for
intentional deception was that the reviewers would perceive the
research as
more advanced if they believed that Dr. Sharma had already
obtained amino
acid sequence data for a segment of the receptor protein
he was studying,
i.e., �2GC. ORI Post-Hearing Br. at 10-11 and record
cites
therein. There is no serious dispute that the possession of such
data
on �2GC would have been an attractive feature in the grant
application,
because a probe based on �2GC sequence instead of �2A was
at least somewhat
more likely to retrieve clones of �2GC receptor
protein 11/ and because the
data could be used later to help verify the
identity of the clones
obtained. See, e.g., Respondent's Post-Hearing
Br. at 2-3.
However, credible evidence in the record showed that an achievement
such
as obtaining amino acid sequence data on the specific receptor
protein
(i.e., �2GC) which was the subject of the research would have
been
highlighted in the grant application. Thus, one scientific expert
with
experience as a grant reviewer, Dr. Gelmann, testified that --
it would be a major accomplishment and in a grant like
this,
somewhere there would be several pages of detailed
description
about isolating that fragment, purifying it and deriving
the
sequence. And that's a major piece of work that could very
well
take more than a year. So when I read this the first time,
it's
obvious that he doesn't have this and that's got to be
a
mistake.
Tr. at 931. 12/ He also stated that the description in the
preceding
paragraph of the grant application about Dr. Sharma's "analysis of
the
putative Alpha 2GC protein" makes clear that the "analysis is far
too
preliminary to get him [Dr. Sharma] to a proteolytic fragment that
he
could sequence." Id. 13/ So the record shows that, without
giving the
data and explaining how he obtained it, Dr. Sharma was not likely
to
succeed in misleading the reviewers by the single reference to
�2GC
data, especially since other material in the grant implied that
such
data was not available. 14/
Nevertheless, ORI argued that the reviewers were, in fact, misled.
ORI
relied on the following quote from the critique prepared by the
study
section that reviewed the application:
The applicant has evidence that the receptor under
investigation
is structurally and functionally distinct from two
subtypes of
alpha-2 adrenergic receptors identified in humans . . .
.
Progress in the cloning of the gene for the alpha-2
adrenergic
receptor has been less impressive and the success of a
different
laboratory in cloning and sequencing the closely related
alpha-2
adrenergic receptor from human platelets has
obviously
diminished the appeal of the cloning studies.
ORI Post-hearing Br. at 12; Ex. R-9, at 2. Neither the quoted
language
nor its context will bear ORI's construction.
Nowhere in the report does the study section point to an achievement
of
obtaining sequence data on �2GC, even though the report
recommends
approval of the grant application "with enthusiasm" and would thus
be
expected to point to an achievement that would help justify
its
conclusion. Rather, the study section acknowledges a weakness of
the
application in that Lefkowitz' �2A research was more advanced than
Dr.
Sharma's �2GC research, since �2A had already been cloned and
sequenced.
If the study section thought that Dr. Sharma already had at
least
partial sequence data on his �2GC receptor, they would have said
that
the other laboratory had succeeded in obtaining full amino acid
sequence
data on its receptor by way of contrast. As it stands, the
sentence
implies that the study section understood that Dr. Sharma's
laboratory
had not had success in sequencing �2GC. In the portion which
was
omitted in ORI's quote, the critique refers to the "significant
strength
of the proposal" in Dr. Sharma's "demonstrated success . . .
in
purifying and biochemically characterizing membrane receptors
and
enzymes" in these cells. Ex. R-9, at 2. The study section
does not
cite as a strength any success in obtaining �2GC sequence
data. The
study section critique thus supports the conclusion that the
single
reference to �2GC sequence data in the parenthetical of the sentence
at
issue was not enough to mislead the reviewers into believing that
Dr.
Sharma had actually obtained such data.
ORI also suggested that no evidence supported the statement that the
�2GC
receptor was "structurally" distinct from other related receptors
unless the
study section believed that Dr. Sharma had amino acid
sequence data for
�2GC. ORI Post-Hearing Br. at 12. ORI cited nothing
in the record
to support this assertion. While it is obvious that
possession of the
complete amino acid sequence would be primary proof of
the structure of the
protein, ORI did not prove that less conclusive
data (such as proteolytic
cleavage results, peptide mapping, and
chemical analyses) could not be relied
on to deduce some information
about the structure of the �2GC protein and
some evidence of its
distinctness from related proteins (such as �2A).
15/ Thus, ORI did not
prove that the critique's reference to Dr.
Sharma's having evidence of
structural distinctness demonstrated that the
study section believed him
to have amino acid sequence data.
We conclude that, although a scientist focussing only on the
erroneous
statement might well assume that �2GC amino acid sequence data
was
available, a reviewer who looked at the entire application could not
be
expected to accept that reference at face value. 16/ Thus, a
single
reference in a parenthetical to making a probe using such data
risked
being viewed as an error or at least a non sequitur, or of simply
being
overlooked by the study section reviewers. ORI failed to provide
any
proof that the single reference to �2GC could plausibly have been
an
attempt at deliberate deception.
If the inclusion of the erroneous reference to �2GC was intentional
at
all, it must have been an extremely subtle deception which
was
intentionally placed in a relatively obscure place. Yet Dr.
Sharma's
conduct was inconsistent with that of someone who was attempting
to
conceal a false statement which he had knowingly inserted in
an
inconspicuous manner. For example, leaving the erroneous statement
in
the revised grant application (Exhibit H-35) (where ORI concedes that
it
was of no value to the methodology proposed), 17/ even though he
deleted
many other statements in editing the revision, is patently
inconsistent
with intentional deception. Cf. ORI Final Report at
33. If he had
consciously planted the reference in the original grant
application,
surely he would wish to remove it immediately in his revision
once it
had lost any utility and become, if anything,
counter-productive. Also,
his confused and garbled responses to the
various investigators
(discussed in detail in relation to ORI's claims of
inconsistent
statements) are not consistent with the strategic planning
required by
the intentional deception scenario. If he had been so
guileful as to
intentionally plant an inconspicuous reference in order to be
able to
deny it if its falsity were noticed, surely he would have prepared a
pat
excuse. Instead, the impression throughout is of a man baffled
and
upset by an error he cannot explain to even his own satisfaction.
18/
After observing Dr. Sharma's demeanor, we do not find it credible
that
he planned so subtle an intentional manipulation. We find it far
more
plausible that he made an honest, if careless, error.
We therefore conclude that, after looking at the context of the
statement
in the application, the reviewers' responses, and Dr. Sharma's
conduct,
intentional deception is not supported by the record as a
likely explanation
of the subscript error.
B. Typographical Error Is More Likely
A preconception existed both at CCF and at ORI that the transposition
of
�2A and �2GC could not be explained by simple mistyping because
they
required different keystrokes located far apart on a standard
keyboard.
Tr. at 119 (Dr. Chalberg), 431-2 (Dr. Ferrario), and 702 (Dr.
Bivens).
However, at the hearing, Dr. Sharma's wife explained that she
had
created macros for the laboratory computer program in which �2A and
�2GC
differed by a single keystroke. In that case, a simple
typographical
error is the most plausible possibility.
ORI responded that Dr. Sharma never told anyone about the macros
before,
and that he always said he typed the entire application.
ORI
Post-Hearing Br. at 19-20. The record cited by ORI directly
contradicts
this characterization. Dr. Sharma told ORI that his wife
helped him
whenever he needed help, that it was very difficult for him to use
the
computer to create the necessary subscripts and Greek letters, and
that
she would come in and either show him how to do it or go ahead and do
it
herself, and that she did formatting of portions of the text which
he
marked for her attention. Ex. H-31, at 220-24 (Interview of
Dr.
Sharma). 19/ Mrs. Sharma's role in helping with the typing of
grant
applications on the computer word processor was also corroborated by
a
letter from Dr. Chalberg to OSIR. Ex. H-17, at 2.
Dr. Chalberg admitted making an identical mistake in the same
grant
application by substituting �2GC for �2A in a sentence reporting
on
Lefkowitz's research and asserted that his was a typographical
error.
Tr. at 160. Obviously, he had no motivation to misrepresent the
work of
Lefkowitz as dealing with �2GC rather than �2A, and ORI did not
suggest
that this admittedly false statement constituted scientific
misconduct.
His lack of intent was apparently assumed in the absence of any
evident
benefit from the misstatement. While the lack of benefit or
motive is a
reasonable basis for finding the absence of intent, the
occurrence of an
identical error in another section of the application for
which a
benefit or motive can be assigned is not alone a sufficient basis
for
finding intent, as ORI suggested in relying on the fact that
Dr.
Sharma's error occurred in the methodology section rather than
merely
the background. ORI Post-Hearing Br. at 18. At the least,
the
admission that Dr. Chalberg made such a typographical error
corroborates
the testimony of Dr. and Mrs. Sharma that such an error was
not
difficult to make under the system of macros set up in the
laboratory's
computers. See Tr. at 801-6 (Mrs. Sharma testified that
the macros were
in a glossary to which others working on the research plans
would have
had access. Tr. at 802.). ORI itself recognized that
the occurrence of
this similar error in a context that was "clearly
typographical" lent
some support to Dr. Sharma's claim that the substitution
on page 21 was
similarly unintentional. Compare ORI Final Report at 26
with ORI
Post-Hearing Br. at 19. 20/
In fact, there have been no shortage of admissions and examples
showing
the ease with which the two adrenergic receptors can be
accidentally
transposed. See, e.g., Tr. at 618-23. For example,
ORI itself twice
asserted that "changing 2A to 2GC would not cure the false
statement" at
page 21 of Exhibit H-2, when that statement already reads 2GC
and ORI
obviously meant changing 2GC to 2A would not suffice to correct
it. ORI
Post-Hearing Br. at Table of Contents and 14.
ORI acknowledged in its Final Report that the possibility of
a
typographical error was enhanced by the frequency with which
references
to �2GC and �2A recurred in Exhibit H-2, which ORI estimated as a
total
of about 128 references. ORI Final Report at 26. ORI also
acknowledged
the Dr. Sharma's lack of expertise in computer word processing
at the
time could have played a role. Id.
We conclude that the subscript substitution most likely occurred through
a
typographical error. We next discuss the several arguments offered
by
ORI in an effort to demonstrate that the misstatements nevertheless
were
not the result of honest error.
C. ORI's Arguments On Dr. Sharma's Intent Are Not Supported
on
the Record
1. The Alleged Inconsistency of Dr.
Sharma's
Explanations
a. General considerations
Dr. Sharma admitted that he did not have �2GC amino acid sequence
data
from which to make a probe, and that he did not make a probe using
such
data, so the statement referring to such data in Exhibit H-2
is
unquestionably erroneous. See, e.g., Respondent Post-Hearing Br. at
1.
Beyond his admission of error, Dr. Sharma made a number of statements
to
Dr. Chalberg, Dr. Ferrario, the CCF inquiry committees, and
ORI
interviewers, which ORI interpreted as explanations for how this
error
occurred. Although ORI did not accept as accurate any of the
supposed
explanations, it considered them to be inconsistent with each other
and
to undermine Dr. Sharma's credibility, and therefore to be probative
of
intentional deception.
We will look at the specifics of these explanations below.
Generally,
we find that the various statements, viewed as a whole, do not
support
ORI's contention that Dr. Sharma intentionally inserted the reference
to
�2GC in order to mislead reviewers as to the status of his research.
In
many cases, the questions to which Dr. Sharma was responding
differed,
or were unclear and seemed to call for speculation, or did not
relate to
either of the grant applications at issue here. 21/ In some
cases, a
statement which ORI highlighted as inconsistent had quite a
different
meaning when read in context. At times, Dr. Sharma's
statements were
confusing and susceptible of more than one
interpretation. However,
none of the statements, alone or read
together, was consistent with
intentional deception.
In weighing Dr. Sharma's prior statements, we considered
several
factors. First, in observing Dr. Sharma's demeanor at the
hearing, we
found him to be credible in responding to the instances of
apparently
inconsistent prior statements. Second, it was evident, both
from
observing his responses at the hearing and from reviewing
the
transcripts, tapes, and reports of prior interviews with him, that
Dr.
Sharma does not communicate with facility in English (which
is
apparently not his first language), despite his general familiarity
with
the language and his proficiency in some technical areas. The
Panel
found that he did not appear to understand fully some questions to
which
he attempted to respond and that he did not always use language
with
precision. Therefore, we find it believable that some of the
prior
communications may have resulted from his misunderstandings of
the
questions or misunderstandings of his intended responses.
Furthermore, since the burden of proof in this matter rests with ORI,
the
significance of any of Dr. Sharma's ambiguous statements had to be
measured
in relation to the purposes for which ORI was offering them.
ORI did not
argue that any of the statements amounted to an admission of
what ORI
contended actually occurred. At most, ORI attempted to show
intent in a
very indirect way, by arguing that Dr. Sharma offered so
many different
explanations that the true explanation must be
intentional deception.
For this point, ORI must at least prove that the
explanations offered did
directly contradict each other and could not be
understood in a consistent
manner. Merely showing that repeated
questioning over a number of years
elicited various muddled answers does
not suffice to support ORI's claim of
intentional deception.
Overall, we find that Dr. Sharma has asserted throughout that he did
not
intentionally insert the incorrect statement in Exhibit H-2, and
has
asserted that therefore it must have been substituted by an error
either
through his typing or through his failure to catch it in
editing. The
statements which might be considered inconsistent with
this position
were references to anticipating receipt of �2GC sequence
data. ORI
considered these statements as admissions that Dr. Sharma
intentionally
wrote in �2GC in the disputed sentence in the hope that he
would get
�2GC sequence data in time. We find it unreasonable to read
these
statements as intended by Dr. Sharma to mean that he had inserted
�2GC
because he hoped to get the data in time or to remove it if
necessary
(so-called "anticipatory writing"). 22/ Anticipatory writing
makes
little sense, in light of the structure of the sentence in which
the
reference to �2GC occurs on page 21 of Exhibit H-2. Even if
the
sequence data on �2GC had arrived shortly before or after the grant
was
submitted, the sentence would be no more accurate than it is now.
The
sentence does not simply report the receipt of sequence data; it
reports
the use of that data to construct a probe, the results of using
that
probe to screen a specific library, and the particular weights
and
restriction patterns of the resulting cDNA clones. If the data
were
received, new experiments would have to be conducted and the
entire
sentence replaced with a new sentence reporting the presumably
different
results of those experiments. Dr. Sharma would have been more
aware of
this than anyone else and would also have known that this would
quickly
become obvious to any scientist who looked closely at the
sentence. He
would have had to be quite unthinking to have proffered
such an
explanation. In fact, ORI and others reviewing the case
recognized that
Dr. Sharma could not have inserted �2GC as anticipatory
writing. See,
e.g., ORI Final Report at 19, ORI Post-Hearing Br. at
22-24; Ex. H-7, at
4. Nevertheless, ORI viewed such "admissions,"
however implausible, as
evidence of some deliberate intent to deceive.
Upon close review of those statements, we find that Dr. Sharma was
making
three quite different points: 23/
-- First, that, rather than simply brush the error off as
a
"typo," he wanted to try to understand how he could have
made
such a mistake or how the investigators could think he
acted
intentionally. Thus, he speculated that his constant
concern
about trying to obtain the sequence data on �2GC might
have
caused him unconsciously either to mistype the subscript or
to
fail to notice it in proofreading, which he
called
"psychobiology." See Ex. H-31, at 272-3, 292, 320; Tr.
at
828-9. In other instances, he speculated that the
investigators
might believe he was anticipating data in order to
justify the
sentence when that was not possible. See Ex. H-31, at
298.
-- Second, that he answered various questions about whether
he
anticipated, expected or needed the data in the
affirmative,
because he did want and hope to obtain �2GC sequence
data
throughout the relevant time period. Tr. at 820, 834.
However,
he needed the data for purposes of verifying the identity of
the
clones (which he had already obtained using the �2A probe),
not
for purposes of constructing a replacement for the
probe
referred to in the relevant statement. Tr. at 821.
None of the
colloquies in prior interviews which ORI treated as
inconsistent
with this position were clear in asking Dr. Sharma whether
he
anticipated the data for purposes of constructing the probe.
-- Third, that he intended to remove the sentence from
the
revised grant application (Exhibit H-35) altogether, because
he
had changed course so that it was irrelevant to the
revised
methodology in that grant, and had missed it.
ORI was aware, as noted above, that a theory of anticipatory writing
would
not make sense, and considered these possible interpretations of
Dr. Sharma's
statements but rejected them as not credible. ORI Final
Report at
30. We reach the opposite conclusion for the reasons
discussed more
fully below. Finally, as we discuss in detail below, we
discount some
of the reports about Dr. Sharma's statements because of
the atmosphere of
conflict and mistrust which existed between Dr. Sharma
and the persons
reporting those statements, in particular Dr. Chalberg
(the original accuser
who worked in Dr. Sharma's laboratory) and Dr.
Ferrario (Dr. Sharma's former
department head).
b. Specific allegedly inconsistent statements 24/
i. Statements on "anticipatory
writing"
duringinvestigation
The Healy Committee report of its interview with Dr. Sharma described
him
as saying that at "the time he was writing the grant, he was
anticipating
that at any moment he would have had the sequence to
fashion the probe.
When the sequence data did not come, he changed
course and decided to make
the probe based on" �2A. Ex. H-5, at 3. ORI
referenced this
report as evidence that Dr. Sharma had told the Healy
Committee that he made
"an editorial error" in not removing the
reference to �2GC from the first
grant application when he did not get
the data. ORI Post-Hearing Br. at
34-35. However, ORI's brief ignored
the next sentence in the Healy
report, which states that Dr. Sharma
"pointed out that in the actual Progress
Report section of the grant, he
explained exactly what he had done, which
was: `isolated a cDNA clone
from rat brain using human platelet
alpha2-adrenergic receptor genomic
clone as a probe . . ." Ex. H-5, at
3. Since this sentence refers to a
cDNA clone rather than a 39-oligomer
probe, and to rat brain cells
rather than rat carcinoma cells, this sentence
obviously refers to the
research methodology of the later revised
application, and not to the
first application at issue here. Dr. Sharma
is reported to have said
further that "he should have taken the Page 21
statement out because he
actually used a different approach and that he
overlooked correcting
that error and it was clearly a careless mistake and
was not
intentional." Id. Evidently, the Healy Committee was not
clear about
the change in methods from the first (using an �2A 39-oligomer
probe) to
the revised version (using a genomic probe) and understood
incorrectly
that the change to which Dr. Sharma referred was from a plan to
make an
�2GC probe to the actual use of an �2A probe. 25/
ORI argued that it is immaterial that Dr. Sharma was responding
(both
before the Healy Committee and at other points in the investigation)
to
the reference to �2GC in the revised application (Exhibit H-35)
rather
than in the unfunded application at issue here (Exhibit H-2).
ORI
contended that, if Dr. Sharma included the reference in Exhibit
H-35
"because he hoped to get it [the sequence data] before it [Exhibit
H-35]
was reviewed, then he must have also purposely included it
in
Application 1 which he submitted months before." ORI Post-Hearing
Br.
at 33, n.97, and 20, n.52. This argument entirely misses the
point.
When Dr. Sharma stated (to the Healy Committee, for example) that he
had
"changed course" and "overlooked correcting the statement" when
he
revised the application, it is clear that he is saying that the
entire
statement, not just the reference to �2GC, did not belong in that
grant
application, "because he actually used a different approach,"
i.e.,
using a cDNA clone from rat brain cells. See Ex. H-5, at 3.
He thus
failed to "catch" this statement and remove it, as he had removed
all
the other disputed statements in Exhibit H-2 from Exhibit H-35. For
Dr.
Sharma to state that he meant to take the entire statement out
in
revising the grant to change its methodology does not imply that he
knew
that the statement contained the misstatement at issue, and far
less
that he intentionally included the subscript error when he first
wrote
Exhibit H-2.
Perhaps the most troubling of the statements relied on by ORI was
recorded
during the interview of Dr. Sharma by the Hamilton Committee.
26/ Dr.
Sharma stated:
Now the question comes, why in my own mind I did not -- this
is
incidentally a 48-page document. 27/ That is the only
omission
which is in 48 document [sic] that GC has not been converted
to
alpha two-A, and still a question there was in people's
mind.
Maybe Ramesh is trying to be sneaky, and is trying to pull
a
fast one because we cannot prove, we cannot get him, and
maybe
he still had a bad intent. . . . Originally, when I wrote
really
the GC -- and I am again hurting myself by saying it --
my
intention was at that time, when I had put it in, that I
might
get a sequence of GC because if I don't get a sequence of
GC,
then I will change it to alpha 2A. That takes very little
part
in the computer. Now am I making that statement correct?
Ex. H-29, at 68-69. 28/ The context of the statement was again
a
discussion of the revised grant relating to rat brain research in
which
"this statement got left" in the process of revising it to meet
the
criticisms of the study section. Id. at 67, 71-3.
Dr. Sharma explained when confronted with this statement by ORI that
he
was speculating how people might think he behaved in a "sneaky"
way,
despite the fact that only the one error occurred in the sentence
at
issue and only that one sentence was erroneously left in the
revised
grant (Ex. H-35). Ex. H-31, at 297-98. Similarly, at the
hearing, he
described this statement as "hypothesizing the situation," since
Dr.
Hamilton had told him to speculate. Tr. at 828. ORI denied
that Dr.
Sharma was told that "the norm of the day was speculation."
ORI
Post-Hearing Br. at 36. However, in fact, the following
colloquy
occurred earlier in another context in the same Hamilton
Committee
interview:
MS. HARTER: Can you think of any reason -- what
possibly
prompted you to maybe --
DR. HAMILTON: Speculate?
DR. SHARMA: That is a very good question . . . .
Ex. H-29, at 19. It was thus not unreasonable for Dr. Sharma to
believe
that he was expected to speculate about how errors might have
occurred.
Dr. Hamilton himself was not sure what Dr. Sharma meant. When
Dr.
Hamilton was asked at the hearing by ORI counsel whether there was
"any
doubt" in his mind that Dr. Sharma told his committee that "the a2GC
was
put in the February grant application, because he was
anticipating
receiving that data," he responded that he "would not put it
that way."
Tr. at 446. Instead, he said he had "no doubt that he [Dr.
Sharma] was
anticipating that data and that that had some relationship to his
having
put the term `a2GC' in there." Id. He was certain that Dr.
Sharma did
say he "anticipated having that sequence available," but
concluded: "I
can't really testify as to his intent." Tr. at 447.
29/ Dr. Hamilton's
first-hand impression about these statements is not
inconsistent with
the position that Dr. Sharma was indeed anticipating
sequence data, and
that this anticipation played some role, perhaps
unconscious, in his
error, but that Dr. Sharma did not necessarily assert
that he
consciously wrote �2GC in the hope of getting the data in time to
submit
the grant.
Dr. Hamilton also testified that Dr. Sharma pointed out first to
his
Committee that the "only error there was the inclusion of the
letters
`GC.'" Tr. at 355. He stated that Dr. Sharma said that,
if he had
referenced �2A, "then the statement would not have been in
error. And
he took us through the entire grant, pointing out that, in
fact, that
was true." Id.
In other parts of the Hamilton Committee interview, Dr. Sharma made
many
statements related to having made a typographical or computer error
in
substituting �2GC. See, e.g., Ex. H-31, at 295 ("I did not know I
put
gc in there."). Thus, Dr. Sharma said:
[A]t that time the secretarial help available to us was not
very
much -- and I am not a computer wizard . . . When I was
typing
these grants, the only misstatement, if you want to say --
and
that's not a deliberate statement -- is on page 21. . . .
I
don't want to buck the issue just by saying it's a typo and
cut
it over. No, that's not the case I'll address that
issue. It
should have been alpha two A instead of alpha 2GC.
Ex. H-29, at 52-3. It is reasonable to interpret the point of
this
statement to be that the error was caused by typing or
computer
mistakes, but that Dr. Sharma does not wish to appear to be making
too
facile an excuse. Thus, in his comments to the Hamilton
Committee,
either Dr. Sharma was indeed foolishly making opposite
statements
simultaneously to the same people or he was being
misunderstood.
Further, Dr. Sharma clearly understood in talking to the
Hamilton
Committee that anticipatory writing was not a possible explanation
for
the error in the original or revised grant. Dr. Morton, a
committee
member, pointed out that changing the subscript to 2A in Exhibit
H-2
would not make the statements about the results of the probe
correct.
Dr. Sharma responded twice that that was right, and that "in
the
original grant which I have made . . . it is very easy once you have
the
sequences to confirm the identity of the clone. And that thing
was
always at the back of my mind that ultimately we have to confirm
that
alpha 2GC is really alpha 2GC or not, and we need the sequences
for
those. But I thought I could change it." Tr. at 74.
Dr. Sharma's main point in this statement is reasonably understood to
be
that he would be able to use the sequence data to justify his
claims
that the potential clones (which he had already obtained with the
�2A
probe) were of �2GC. These claims were based largely on his
biochemical
and pharmacological studies about adrenergic receptors in the rat
cells
he was researching but on relatively little structural data. Tr.
at
952-3. The identity of the clones as �2GC could be substantiated
by
comparison to �2GC sequence data once it became available, as well as
by
expression of the protein.
In summary, we find that Dr. Sharma's statements to the Hamilton
Committee
were unclear in places. However, Dr. Hamilton was not himself
certain
whether Dr. Sharma was telling him that he wrote the reference
to �2GC
because he anticipated getting the sequence data. Overall and
in
context, we find that the statements do not significantly undermine
Dr.
Sharma's credibility or support ORI's contention that Dr. Sharma
deliberately
inserted the reference to �2GC sequence data on page 21 of
Exhibit H-2.
The Fishleder Committee report did not refer to any
anticipatory
explanations and found that the misstatement on page 21 of
Exhibit H-2
"arose because of a single typographical error." Ex. H-8,
at 3. Dr.
Sharma reiterated the assertion that the misstatement was the
result of
a typographical error numerous times. For example, in
correspondence
with OSI, Dr. Sharma repeated that the errors in the original
grant
application were "the result of a single computer-typographical error
at
a single place in a subscript on page 21: there should have been
�2A
instead of �2GC. . . . The above mentioned 39-mer probe
corresponding
to the �2A-receptor proteolytic fragment was synthesized by Dr.
Michael
Cashnell . . . ." Ex. H-20, at 2; Ex. H-21, at 2-3. In
regard to the
revised application, he stated in the same letters that the
erroneous
statement "was directly reproduced from the computer and
therefore
escaped editing." Ex. H-20, at 2; Ex. H-21, at 3; see also
Ex. R-2, at
1-3 (Comments of Dr. Sharma to OSIR); Ex. H-10, Attachment 1, at
2-3.
ii. Statements reported by Dr. Chalberg
Dr. Chalberg (the researcher in Dr. Sharma's laboratory who
initially
raised these allegations) testified that he looked at the revised
grant
application (Exhibit H-35), 30/ and noted the reference to �2GC
sequence
data as the source of a probe. He stated that he pointed this
out to
Dr. Sharma and was told that they did have the sequence data.
Tr. at
32-36. Dr. Chalberg stated that he pointed out that even if the
data
had been received, he would have known if a probe had been
constructed
based on that data and no such probe was made. Tr. at
37. According to
Dr. Chalberg, Dr. Sharma did not reply to that point,
but later showed
him a version of the grant without the disputed
statement. Tr. at 37-8.
Dr. Chalberg also testified that he was asked
by Dr. Ferrario to look at
Dr. Sharma's grants in order to identify his own
contributions as part
of his performance evaluation, and discovered in the
process that the
erroneous statement about the source of the probe appeared
in the
official copy of the revised application (Exhibit H-35). Tr. at
38-51.
He was instructed to ask Dr. Sharma about the matter again,
and
testified that Dr. Sharma told him that he [Dr. Chalberg] "still did
not
have the correct version of the grant, that the version he [Dr.
Sharma]
sent did not have that statement in it." Tr. at 71-72.
The record demonstrates that longstanding conflict existed between
Dr.
Sharma, Dr. Chalberg, and Dr. Chalberg's fiancee, a technician in
Dr.
Sharma's laboratory. See, e.g., Tr. at 101-3, 160-1, 438-9; Ex.
H-29,
at 82-84, 94-102. Dr. Chalberg was already trying to leave
the
laboratory and there is some evidence that he and his fiancee
were
exploring working under Dr. Ferrario instead of Dr. Sharma. Tr. at
148;
Ex. H-5, at 4-5 (Healy Committee Report). ORI called as a witness
Mr.
Michael Murray, a non-scientist administrator from CCF who was asked
to
sit in the meeting between Dr. Ferrario and Dr. Sharma. Mr.
Murray
reported that Dr. Chalberg's central concern was that his name was
on
the grant applications. ORI based its claim that Dr. Chalberg
acted
with disinterested motives on this assertion. Tr. at 271;
ORI
Post-Hearing Br. at 39, n.124. However, Dr. Chalberg does not
appear
among the personnel listed in Exhibits H-2 or H-35, relating
to
adrenergic receptors, and Dr. Sharma testified that Dr. Chalberg's
work
was in the area of the molecular biology of 180 kD protein. Tr. at
870.
31/ ORI presented no rebuttal testimony. Since the initial
charges Dr.
Chalberg brought to Dr. Ferrario related to the Exhibit
H-35
application, the explanation that Dr. Chalberg happened to discover
the
misstatement while reviewing the applications for his own
performance
evaluation, and acted to protect his own reputation, is
questionable and
calls his credibility into question.
However, even assuming that Dr. Chalberg was reporting the
conversations
to the best of his recollection, it is not impossible that
communication
between Dr. Sharma and Dr. Chalberg at that point may have
generated
more heat than light. It is also possible that emotion and
language
difficulty contributed to lack of complete understanding. In
any case,
questions to Dr. Sharma from Dr. Chalberg regarding statements
about an
�2GC 39-oligomer probe in the revised application would likely
have
resulted in confusion. Dr. Sharma was unlikely to know what
Dr.
Chalberg was talking about, if the statement was retained in
that
revision by unintentional error, as ORI found.
Dr. Chalberg's account is contradicted by Dr. Sharma's description of
the
conversation, which he testified occurred in the presence of Mrs.
Sharma (as
she corroborated). See Tr. at 817-8, 807-8. Dr. Sharma
testified
that Dr. Chalberg stated generally that he had a problem with
"a statement
about alpha 2GC" in one of Dr. Sharma's grant application,
but that Dr.
Chalberg did not identify a specific statement in a
particular
application. Tr. at 817-18. Dr. Sharma denied telling
Dr.
Chalberg that he had received �2GC data or that the
problematic
statement did not appear in another version of the grant
application.
Notably, Dr. Chalberg is the only witness to have testified that
Dr.
Sharma ever claimed to have received the �2GC amino acid sequence
data,
while all the others, including Dr. Ferrario, agree that Dr.
Sharma
admitted from the beginning that he did not have that data. See,
e.g.,
Exs. H-4, at 2, and H-5, at 2.
In light of their relationship at the time, Dr. Sharma may well
have
reacted defensively to an accusation by Dr. Chalberg that
something
about the 39-oligomer probe for �2GC was wrong in the
revised
application which was funded. However, it is not credible that
Dr.
Sharma would have asserted to a researcher in his own laboratory
that
they had recently received sequence data when (1) the grant
application
was submitted about six months earlier (Exhibit H-35 is dated
October
24, 1989) so recent receipt of the sequence data would be
irrelevant;
(2) the grant about which Dr. Chalberg was speaking did not
depend on
using an oligomer probe corresponding to amino acid sequence from
either
the �2A or �2GC receptors; (3) Dr. Chalberg would have ready access
to
information in the laboratory to challenge such an assertion; and (4)
it
would have been obvious to both of them, if they looked at the
specific
sentence, that receipt of �2GC sequence data would not in itself
make
the sentence true since all the results reported were those
obtained
with a �2A probe. Dr. Chalberg himself pointed out that he
would have
been well aware of it if the data had been obtained, at least if
any
probe were going to be made using it. We therefore conclude that
Dr.
Chalberg's reports of Dr. Sharma's explanations are not credible
or
accurate.
iii. Statements reported by Dr. Ferrario
Dr. Chalberg testified that he took his concerns to Dr. Ferrario as
head
of the department on April 20, 1990. Tr. at 68-71. Dr.
Ferrario
testified that Dr. Sharma came to his office later that day and was
told
about "the situation." Tr. at 402. Dr. Ferrario testified
that he did
not have expertise in molecular biology and relied on Dr.
Chalberg to
understand the significance of the charges. Tr. at 406,
437.
Dr. Ferrario testified that, at the April 20th meeting with Dr.
Bannerjee
and Mr. Murray present, Dr. Sharma told him that he wrote �2GC
in the
application they were discussing, i.e., Exhibit H-35 (see Tr. at
422-5),
because he anticipated getting the necessary data before the
grant was
reviewed. Tr. at 402-3, 425-6. 32/ Dr. Ferrario stated that
his
"recollection is that he [Dr. Sharma] initially stated that he
had
prematurely written in the grant data that was not available at
that
time, but that he expected to have it before the grant was
actually
reviewed" and that Dr. Sharma stated in regard to the receptor
sequence
data that he did not have it "at that time, but that he expected to
have
it." Tr. at 402-3. He insisted that Dr. Sharma did not
characterize
the errors in the grant application as typographical at the
April 20th
meeting, although that explanation "developed during the
following
days." Tr. at 425-33. He explained, however, that
"typographical
error" meant to him only transposing letters or misspelling
words, while
"errors" would be "saying that I will do A when I really tried
to do B.
But it takes me a few more words to say A than to say B." Tr.
at 431-2.
Therefore, he explained that, although he had earlier stated that
Dr.
Sharma had said at the meeting "that there were mistakes in retyping
the
grant and that he had not caught the error," that statement by
Dr.
Sharma would not "imply a typographical error." Tr. at 430-1.
Dr. Ferrario's interpretation is based on the preconception, noted
above,
that was shared by Dr. Lyle Bivens, who directed the ORI
investigation, that
the mistake here could not have been a classic
typographical error because
the characters "2A" and "2GC" require quite
different keystrokes in
typing. Tr. at 702. This assumption was
undercut by the
uncontradicted testimony of Mrs. Sharma, discussed
above, that she set up a
macro system for typing �2A and �2GC that
differed by only one neighboring
keystroke. Tr. at 801-6. We thus
conclude that Dr. Ferrario's
understanding that Dr. Sharma was not
talking about a typographical error on
April 20th may have resulted from
this faulty assumption. See Tr. at
433. 33/
Also, in weighing the context of Dr. Ferrario's conversations with
Dr.
Sharma, we note that the record reflects that a high level of
conflict
existed between the two. See, e.g., Ex. H-5 (report of CCF
preliminary
inquiry noting "contentious relationship . . . over the issue of
Dr.
Ferrario's hiring Dr. Sharma's molecular biology technician,
Janet
Rhine, and possible hiring of his Project Scientists Dr. Rama
Jaiswal
and Dr. Chalberg"); ORI Final Report at 44; Ex. H-31, at 246,
249,
340-1. 34/ Dr. Ferrario considered Dr. Sharma "more difficult to
talk
to or to work with than with other colleagues in the department."
Tr.
at 441. The CCF investigations dealt with Dr. Sharma's
complaints
against his treatment by and contract disputes with Dr. Ferrario,
as
well as with the allegations of scientific misconduct against
Dr.
Sharma. See, e.g., Ex. H-6; ORI Final Report at 44-45. 35/
(At times,
Dr. Sharma's statements at earlier stages of this case seem to
have
reflected his focus on his own agenda, rather than on the issues
now
before us. See, e.g., Ex. H-31, at 235-7, 252, 340-1.)
It is, of course, impossible to know exactly what was said in the
meetings
which were not recorded. We do not imply that Dr. Sharma's
complaints
necessarily had merit or that Dr. Ferrario was less than
honest in reporting
his memory of the meeting either in his memorandum
at the time (Exhibit H-4)
or in his testimony at the hearing. However,
the level of conflict, the
admitted difficulty he had in talking to Dr.
Sharma, and Dr. Ferrario's lack
of familiarity with the science involved
all make communication less reliably
accurate and misunderstanding more
likely.
Ultimately, we conclude simply that the reports from Dr. Ferrario and
Dr.
Chalberg of conversations with Dr. Sharma do not credibly support
ORI's claim
of intentional deception.
iv. Statements in letter from Dr. Sharma's counsel
Counsel for Dr. Sharma at an earlier stage of the investigation wrote
a
letter which added to the confusion by denying that Dr. Sharma had
said
he made a typographical error. Ex. H-24. The letter does so
in less
than crystal clear terms by saying that "an editing error
and
anticipatory writing are one and the same. An editing error occurs
if
one anticipates receiving the results of sequencing data and
upon
learning that those results are not available inadvertently fails
to
modify the text accordingly." Ex. H-24, at 4. On the other
hand, the
letter distinguishes between saying that �2GC was "mistyped" and
saying
that it was a "typographical error." Id. The letter argues
that Dr.
Sharma's statements to the Hamilton Committee can be read as
consistent
with an inadvertent failure to edit references after failing to
obtain
the data, and not as assertions of typographical error. Id. at
4-5.
When questioned about this letter, Dr. Sharma testified at the
hearing
that: "I don't review all legal things what people want. . .
. They do
not register. These are not the normal days for me. . .
. I probably
reviewed it, but it doesn't register in my mind what is
happening on
legal term." Tr. at 855. Shown the letter, Dr.
Sharma commented
"[w]hat I am reading, I still don't understand what the
question is and
what I am reading." Tr. at 857. Finally, he
concluded with the
following exchange:
A I don't understand the difference between the editing
error
and the typing error. So I cannot comment on this. To
me I had
very little differentiation when I use the terms editing out
a
typo. In my mind when you first write a document if you
do
something wrong that's a typo and when you proofread it,
it
becomes the editing error. So I don't differentiate because
I
think I am not a -- scholar.
Q So mistakes in proofreading are editing errors and
mistakes
in typing are typographical errors.
A. I can't comment that because I do not feel that has
anything
to do with the science.
Tr. at 859. Since ORI did not prove that Dr. Sharma understood
and
adopted the position set forth in the letter from his counsel, and
given
Dr. Sharma's manifest confusion when presented with this letter on
the
stand, we are not able to conclude that the assertion that
the
misstatement was caused by anticipating data and inadvertently
failing
to correct it can fairly be attributed to Dr. Sharma. The
most
comprehensive written statement which Dr. Sharma made about his
position
in no way suggested this analysis offered by counsel, and insisted
that
the cause of the subscript substitution was typographical error.
Ex.
R-2. We therefore do not give weight to the letter from Dr.
Sharma's
counsel as evidence of intentional deception.
c. Conclusion on inconsistent statements
Above, we have focused at length on the details of each
purportedly
inconsistent statement by Dr. Sharma, and we have found them
unavailing
to ORI's case. We want to emphasize here, however, that, in
our
attention to detail in this analysis, we have not overlooked the
larger
picture. We have considered the point of view that ORI's
contentions,
even if not all substantiated individually, might cumulatively
support a
finding that Dr. Sharma intentionally included erroneous
information in
the first application. We reiterate below some of
the factors
discussed in more depth above which underlie our conclusion that
ORI has
not shown a cumulative pattern supporting intentional deception.
As we discussed initially, the single subscript error involved here is
far
more easily explained as inadvertent. Nothing in the structure of
the
grant application, its typing or preparation, or its perception by
the grant
reviewers makes intentional deception a likely scenario.
From the beginning, when confronted with the error, Dr.
Sharma
consistently stated in every interview that he was not aware of
the
error when he submitted the application and that he believed it to
be
typographical. However, he made a variety of statements, in the
course
of the long investigation, which referred in some way to his
having
hoped to get sequence data on �2GC. None of them were in the
nature of
admissions of consciously inserting the wrong subscript.
Thus, we have
found:
o Those statements which Dr. Sharma
made about having
"meant to remove it," which ORI interpreted to mean
that he must
have known of the error in the first grant application,
were in
context responses about the revised application. It
is
uncontested that the whole sentence was left in the
revised
application inadvertently and that Dr. Sharma did mean to
take
it out because it was completely unhelpful to his
changed
methodology and because he took out all the related
sentences.
o Whenever asked about whether he
was expecting or hoping
to get sequence data on �2GC, Dr. Sharma
consistently answered
that he was, and evidence in the record supports
the accuracy of
this answer. He was hoping to obtain this data at
some point,
but in order to conduct further experiments not to repeat
the
reported experiments using another probe.
o Since both categories of
statements above can be
understood as simply accurate responses to the
questions asked,
their repetition throughout the investigation is in no
way
suspicious.
o Dr. Sharma also speculated that
he may have made the
error for the very reason that the �2GC sequence
data was so
much on his mind, which does not imply any evil intent.
o Finally, this is not a case in
which Dr Sharma claimed
to have data which he had not yet received
because he hoped to
obtain it in time to justify the assertion.
The disputed
sentence reports results of an experiment with a probe
based on
other data and receipt of the �2GC data would not have
changed
the inaccuracy of the subscript.
Therefore, we conclude that the statements attributed to Dr. Sharma
do
not, individually or collectively, constitute persuasive evidence of
an
intent to mislead.
2. None of ORI's Other Arguments Demonstrate an Intent
to
Deceive
a. Failure to provide a citation reference
At times, ORI suggested that Dr. Sharma's failure to cite the
Lefkowitz
article after the disputed statement at page 21 in Exhibit H-2 in
itself
constituted scientific misconduct. See, e.g., ORI Final Report
at
24-25. At other times, ORI referred to the omission of such a
citation
as additional evidence of an intent to deceive. We do not find
support
in the record for either interpretation.
At numerous other points in the same grant application, Dr. Sharma
plainly
credited the Lefkowitz paper as the source of amino acid
sequence data on
human platelet �2A receptor data. Thus, it is not
plausible that Dr.
Sharma was attempting to take improper credit for
Lefkowitz' work. In
retrospect, Dr. Sharma agreed that he probably
should have included a cite to
the Lefkowitz paper after the disputed
language. Tr. at 823.
However, he also explained at the hearing that
he had assumed that his
reliance on the Lefkowitz paper would be obvious
from a mention of �2A
because he had previously cited the paper in the
same section of the grant
application and had described the work of the
Lefkowitz group sequencing
�2A. Tr. at 824; Ex. H-2, at 21. Thus, he
stated that "since I
did not know that this mistake had occurred, I did
not feel that I need to
put the reference because everybody would have
identified that I could have
only get, I could have only gotten the
alpha 2A probe which referred to this
particular gene. There was no
other way." Tr. at 824.
Furthermore, ORI provided no testimony that the failure to cite
Lefkowitz
again after the statement at issue would in itself have
constituted
scientific misconduct, if the probe had been correctly
identified as
corresponding to �2A data. ORI's scientific expert
testified that he
would cite more repetitiously, "ten sentences in a
row" if appropriate, but
also stated that a scientist who was not so
careful to "overreference" would
not be less ethical. Tr. at 612-13
(Dr. Douglass). We find that
ORI did not prove that the failure to cite
to the Lefkowitz paper directly
after the disputed statement on page 21
constituted scientific
misconduct.
Nevertheless, we recognize that, had Dr. Sharma placed a cite to
the
Lefkowitz paper at the end of the disputed statement, such a
reference
would have undercut any claim that the subscript error was intended
to
mislead. This fact is demonstrated by the fact that ORI did not
find
any scientific misconduct in Dr. Chalberg's identical error on page
34
of Exhibit H-2 in a description of Lefkowitz' work which stated
that
"[r]ecently the cloning and resultant de novo expression of the
�2GC
receptor in Xenopus laevis oocytes has been reported (43)." The
number
(43) is a cite to the Lefkowitz paper and the reference to �2GC is
an
obvious error, since Lefkowitz's work was on �2A, and there was
no
motive to falsely claim otherwise. See ORI Final Report at 26; Tr.
at
619-620.
While the omission of the citation was regrettable, we find that ORI
did
not prove that it was evidence of intent to mislead or that
it
constituted a serious deviation from commonly accepted
scientific
practice.
b. The pattern of misstatements
ORI suggested that it was more likely that the errors in Exhibit H-2
were
intentional because the application contained
"repetitive
misstatements." ORI Final Report at 23. However, the
evidence before
us suggests that the other statements referenced in the
allegations
relating to Exhibit H-2 were not independently false. 36/
Rather, they
were misleading only because a reviewer would refer back to the
initial
misstatement (at Exhibit H-2 at 21) and conclude that they
were
referencing �2GC amino acid sequence data which was not in
fact
available. See, e.g., Tr. at 556-60, 588-91, 631-32 (Dr.
Douglass).
The ORI Final Report also noted that the other statements "refer
back"
to the initial statement and do not themselves "specify which
peptide
was used to construct the probe." ORI Final Report at 23 and
30.
Nothing in the record demonstrated that these statements would
be
problematic if the initial statement had correctly reported the probe
as
based on �2A sequence data obtained from the Lefkowitz
paper.
Therefore, it is unreasonable to rely on these statements
as
constituting a pattern demonstrating the intentionality of the
original
error on page 21, when the other statements would be accurate but
for
that error.
In addition to finding a pattern of misstatements in the
application
itself, ORI also offered evidence of a statement in a
memorandum
apparently prepared for a retreat held in February 1990 (over a
year
after the application was submitted) by the CCF Department of which
Dr.
Sharma was a member. Exhibit H-15. ORI contended that this
memorandum
showed another example of Dr. Sharma falsely claiming to have the
�2GC
amino acid sequence data and was therefore "instructive." ORI
Final
Report at 24. No testimony established who drafted or reviewed
specific
portions of the summary or who actually received it.
Generally, the
memorandum appears to summarize in broad strokes the staffing,
funding,
space and research directions and accomplishments of Dr.
Sharma's
laboratory for the department as a whole. ORI did not explain
what
motive Dr. Sharma would have had to attempt to mislead members of
his
own laboratory and department about the status of his research in
this
document. Members of the department not expert in this
sub-specialty of
molecular biology would be unlikely to recognize the
significance of the
specific claims; those most likely to recognize the
significance were
members of his own laboratory who would also be most likely
to catch any
inaccurate representations and many of whom were already on bad
terms
with him by that date. No evidence in the record suggested that
this
statement on his research directions formed the basis of any
benefits
which Dr. Sharma could have anticipated.
Furthermore, ORI did not prove that any statement in the summary was
in
fact false. Much of the language describing research directions
is
almost identical to unchallenged language from the abstracts in
the
corresponding grant applications. Compare Exhibit 15, at 2-3
(on
�2-adrenergic receptor) with Exhibits H-2 and H-35, at 2;
compare
Exhibit H-15, at 3 (on atrial natriuretic factor receptor) with
Exhibit
H-3, at 2. The summary also contains an assertion, apparently
the one
contested by ORI, that cDNA has been cloned for an �2GC receptor
subtype
which is "brain-specific," and that for this receptor the
nucleotide
sequence of this clone has been determined and from it the amino
acid
sequence has been inferred. Exhibit H-15, at 3. Since the
summary
indicates that this member of the �2-receptor family does not appear
in
the adrenal gland, the work referenced obviously here related to
the
research proposed in the revised application (Exhibit H-35), not
to
Exhibit H-2. In fact, the questioned statement is almost identical
to
one in Exhibit H-35 which asserts that Dr. Sharma's laboratory had
"now
cloned, sequenced, and expressed a rat brain �2-adrenergic
receptor
cDNA." Exhibit H-35, at 21. A listing of the 31 amino
acids from a
peptide which has been synthesized follows on the same
page. Id. ORI
found no scientific misconduct after its review of
Exhibit H-35. ORI
Final Report at 31-33, 54. Therefore, to the
extent that this summary
simply restates the unchallenged status of research
set forth in Exhibit
H-35, we do not see any basis in the record to conclude
that the summary
evidences a pattern of intentional misstatements.
c. The failure to report to NIH
ORI argued that Dr. Sharma's failure to report his misstatements to
NIH
evidenced "knowing deceit" and was "a deliberate attempt to
prevent
detection." 37/ ORI Post-Hearing Br. at 30. ORI's
scientific expert
testified that whether he would notify a funding agency of
an error in a
grant application would depend on the significance of the
mistake in
context and that there is "a huge spectrum with regards to errors
and
what the type of error you would notify the agency" about. Tr.
at
584-5. On the other hand, when asked if an error "of the magnitude"
of
that identified by ORI in Exhibit H-2 was "worthy of notification to
the
funding agency," he responded that he "would think so." 38/
However, it begs the question to use the failure to contact NIH before
the
allegations arose as proof of bad intent, since obviously not
reporting an
error is just as consistent with not being aware of its
existence.
Therefore, we must look at whether Dr. Sharma's actions
after learning of the
misstatements were inappropriate. The earliest
point at which anyone
has testified that Dr. Sharma's attention was
directed to misstatements in
his grant applications was in April 1990.
Within two weeks of the initial
allegations, the Healy Committee had
begun the formal investigation
process.
By that time, both grant applications at issue here had been rejected
for
funding. It is difficult to see what benefit NIH would gain from
a
notification that an error had existed in a grant application which
it
had already determined not to fund.
As to the revised, funded grant application, Dr. Sharma argued that he
did
not report the misstatement which remained because it was already
the subject
of an investigation, which he assumed would be made known to
NIH. Tr.
at 847, 852. In addition, even ORI has concluded that the
statement in
the revised application no longer was material to the
revised methodology, so
we have no basis to conclude that the error in
that grant application was so
significant that notification was clearly
demanded by the circumstances.
ORI also characterized Dr. Sharma as having "resisted informing NIH
that
his revised application contained false statements." ORI
Post-Hearing
Br. at 30. This position is based on two documents.
The first was
submitted to ORI by Dr. Sharma which stated that "[a]fter the
committee
deliberations, extraordinary pressure was put on me to admit to
being
guilty. Dr. Hamilton asked me to write to NIH, requesting
surrender of
my grant." Ex. R-2, Part II, at 3. The context
indicates that this
conversation occurred in early September 1990. The
second document was
a memorandum dated September 11, 1990 from Dr. Sharma to
Drs. Healy and
Hamilton, apparently in response, stating: "I
respectfully request your
consideration to read my response to the second
review committee. I
will then follow your instructions on the
submitting of a letter to NIH
regarding my recently funded grant." Ex.
H-10, at 1. The action
requested by Dr. Hamilton was more drastic than
informing NIH of a
misstatement. Dr. Sharma's response amounted to
agreeing to submit to
the joint decision of Drs. Healy and Hamilton as
to what letter to send
to NIH, with the one request that they read his
comments before
deciding. His attached comments again explained that
the original grant
application contained an unintentional typographical error
and then
pleaded that "[t]his seems to be a slim reed indeed upon which
to
destroy a dedicated and accomplished researcher's career." Ex.
H-10,
Attachment 1, at 1-2. Such a statement can hardly be read as a
refusal
to inform NIH of a misstatement.
In a related point, ORI argued that Dr. Sharma's persistent focus on
his
view that confidentiality had been breached in the distribution of
his
grant applications demonstrated that he was "more concerned that
the
errors had been detected and how they had been detected than the
fact
that there were errors in the applications." ORI Post-Hearing Br.
at
30-31. Undoubtedly, Dr. Sharma can be seen in many documents to
have
focussed on his concern about how Dr. Chalberg happened to have
obtained
applications for research he was not involved with, in light of
the
thick atmosphere of suspicion and conflict that appears to have
existed,
as discussed above in relation to the statements reported by
Drs.
Chalberg and Ferrario. See Ex. R-2, at 8. However, we do not
see the
connection that ORI makes from Dr. Sharma's feeling of persecution to
a
"deliberate attempt to prevent detection of his overstatements."
ORI
Post-Hearing Br. at 30. The misstatements had already come to light
at
the time that he expressed the complaints about distribution of
his
grants to which ORI referred, so he could hardly have hoped to
somehow
prevent their detection. Furthermore, Dr. Sharma's concern
about broad
distribution of his grant applications has not been proven to
be
entirely unfounded in what ORI described as the "competitive realm
of
grant applications." ORI Post-Hearing Br. at 30.
d. ORI's other attacks on Dr. Sharma's credibility
ORI questioned Dr. Sharma's overall credibility on the basis that
he
denied that he was ever called to a meeting on April 20, 1990 with
Dr.
Ferrario and Dr. Bannerjee to answer Dr. Chalberg's charges
of
scientific misconduct and that he denounced Dr. Ferrario's memorandum
of
that meeting as a "fabrication." Tr. at 22; ORI Post-Hearing Br.
at
32-24; see also Ex. H-23, at 2-3. While Dr. Sharma did say the
meeting
as reportedly described by Dr. Ferrario never occurred and
the
memorandum is a fabrication, he also said in the same ORI interview
that
he did meet with Mr. Murray and Dr. Ferrario one day between April
10th
and April 20th. He appeared to base his refusal to agree to
the
specific date largely on the fact that he found no record of a
meeting
on that date in his personal diary. See also Ex. H-23, at
2. However,
it is clear in the rest of the interview that he recalled
that a meeting
had occurred. What he most violently objected to was
the
characterization of this meeting as one where Mr. Murray called him
in
to answer Dr. Chalberg's charges. Rather, he described feeling
already
embattled in the department when he learned from a secretary that
Dr.
Chalberg was obtaining copies of his grant applications and
raising
questions about them. 39/ He then described the meeting as a
brief one
40/ in which he complained to Mr. Murray and Dr. Ferrario about why
Dr.
Chalberg was being given free access to his grants. Dr.
Sharma
acknowledged that he was informed that charges of scientific
misconduct
had been raised against him, but consistently denied that he
was
provided with the specific charges relating to the misstatements
about
�2GC before the Healy Committee (and that even then the applications
at
issue remained unclear). Dr. Sharma said that he did not recall
Dr.
Bannerjee being present at a meeting with Dr. Ferrario "where
they
discussed the alpha 2GC receptor" with him or where they
discussed
"general problems with any grants or problems in the lab."
Ex. H-31, at
363.
We find that credible testimony supports the conclusion that a
meeting
occurred on or around April 20, 1993 in which Dr. Ferrario
communicated
to Dr. Sharma that some questions about the integrity of his
grant
applications were being raised and Dr. Sharma communicated that he
was
upset about the apparent distribution of his grant
applications.
However, we do not find the inconsistencies in the various
participants'
memory of this meeting (including significant differences which
have
been noted between Dr. Bannerjee's and Dr. Ferrario's
accounts)
sufficient to demonstrate dishonesty on the part of Dr. Sharma.
ORI further challenged Dr. Sharma's credibility based on a letter he
sent
to ORI during the investigation, in which he suggested that a
number of
scientific points would have made the error in Exhibit H-2
obvious and
therefore would serve to disprove the allegation of
intentional
deception. Ex. R-2. Dr. Sharma did not press these points
before
the Panel. However, ORI alluded to these arguments as evidence
that Dr.
Sharma was "merely grasping at straws" in seeking to explain
the misstatement
in his grant application. ORI Post-Hearing Br. at 38.
The first point Dr. Sharma made was that the reference to use of rat
codon
bias data would have alerted reviewers that he was translating
from another
species and therefore supported his intent to refer to �2A
(human platelet)
data instead of �2GC (rat) data. Ex. R-2, at 2. ORI
argued to the
contrary that rat codon bias data would be consulted
regardless of the source
of sequence data for the probe. ORI
Post-Hearing Br. at 38.
Elsewhere, ORI went further and asserted that
both human and rat codon bias
data would have been referenced if Dr.
Sharma were, as he claimed, intending
to refer to translating across
species (i.e., from �2A to probe rat
cells). ORI Post-Hearing Br. at
16. The only evidence to which
ORI cited to support this assertion is
testimony by Dr. Chalberg that is
inconsistent with it. Tr. at 164.
Dr. Chalberg testified that "you
would only look at a rat bias table if
you were trying to make a rat-specific
probe, which we were trying to
do, based upon human sequence."
Id. Dr. Douglass also indicated that
in using data from one species to
construct a probe to search for
clones, whether in the same or another
species, one uses bias data for
the target species. 41/ The weight of
the scientific evidence is that
the reference to use of rat codon bias data
in construction of the probe
does not offer any conclusive information about
the intended source of
the probe. See, e.g., Tr. at 167 (Dr. Chalberg),
571-2 (Dr. Douglass).
We find that Dr. Sharma's other points do not prove that the error was
so
obvious as to demonstrate his innocent intent. For example, Dr.
Sharma
also suggested that his use of 90% stringency conditions would
have alerted
researchers that he was seeking to hybridize to a probe
based on sequence
from something other than the target protein. Ex.
R-2, at 2.
However, the scientific evidence suggests that stringency
conditions cannot
meaningfully be defined with sufficient mathematical
precision to make this
point obvious to a reviewer. Tr. at 598-9,
627-30. Similarly, Dr.
Sharma suggested that the 39-oligomer length of
the probes would have
provided reviewers a clue that he had used Dr.
Lefkowitz's �2A probes, since
they were identical in length. While the
probes were the same length,
since Dr. Sharma did, as we have found, use
the �2A probes, the evidence
established that that length was not an
uncommon one for such probes and that
reviewers would not have been
likely to make a connection between that length
and a probable reliance
on the Lefkowitz probes. See Tr. at 230,
582.
For the reasons explained above, we do not rely on these points in
our
determination that the error was not intentional. However, we also
find
that ORI did not prove that these arguments were so implausible as
to
undercut Dr. Sharma's credibility for having raised them. e. Summary
on
ORI's other arguments on intent
Overall, we find that the collateral arguments offered by ORI to
buttress
the allegation of intentional deception are largely based on
hindsight.
While the error here might have been prevented by such means
as more frequent
citations, more careful proofreading, or better review
procedures, ORI did
not show that Dr. Sharma's practices in these areas
deviated from the normal
range of practices of scientists at that time.
There is thus no basis in
these criticisms to conclude that his failure
to catch the error means that
he intentionally inserted it. Finally, we
are not persuaded that the
disagreements about the April 20, 1990
meeting or the points made by Dr.
Sharma in an effort to explain why an
inadvertent error was more consistent
with the rest of the sentence
undermine Dr. Sharma's credibility.
D. Conclusion Regarding First Grant Application
For all the reasons discussed above, we conclude that ORI has failed
to
prove by a preponderance of the evidence that Dr. Sharma included
any
misstatement in Exhibit H-2 intentionally to mislead reviewers.
II. The Second Grant Application
The charge relating to Exhibit H-3 was based on a single
clause,
highlighted below, in one sentence on page 23, which read as
follows:
[C]omparison of our unpublished sequence data of the
180-kD
protein with that of published rat brain protein
indicate
significant structural heterogeneity between
certain
CNBr-cleaved fragments of the two proteins.
Dr. Sharma admitted that he did not have unpublished amino acid
sequence
data on the 180 kD protein, but explained that he meant to
write
unpublished peptide map data from the sequencing process. Ex.
H-30, at
125; Respondent's Post-Hearing Br. at 5-6. As explained above,
amino
acid sequence data generally means the precise order of amino acids
in
either some region of or the entire length of a protein. Peptide
map
data results from an intermediate step in the process of determining
the
sequence of a protein which is based on cleaving the protein
by
chemicals which reliably divide the chain in predictable ways.
The
information available from peptide mapping was described by ORI
as
"points of the sequence." ORI Final Report at 43. ORI
acknowledged
that "a peptide map is a type of amino acid sequence
data." Id. It is
not disputed, however, that possession of full
amino acid sequence data
would indisputably represent a more advanced step in
the research
process than possession of peptide map data alone. Tr. at
493, 636.
Dr. Ravi Marala, who worked on this project with Dr. Sharma at CCF,
had,
by June of 1989 when this application was submitted, been working
toward
obtaining amino acid sequence data for "quite a while," and had
obtained
peptide map and isolated fragments which were sent to Dr.
William
Merrick for sequencing without success. Tr. at 490-2. On
this basis,
ORI concluded that Dr. Sharma was portraying his research
as
substantially more advanced than it was. ORI Post-Hearing Br. at
25.
As mentioned above, ORI placed far less weight on this allegation than
on
the charges relating to �2GC, as evidenced by the fact that only two
of the
44 pages in ORI's post-hearing brief were devoted to the 180 kD
protein
issue. In large part, ORI treated this allegation as resting on
a
continuation of its claim that Dr. Sharma was exhibiting a pattern of
falsely
claiming to be further along in sequencing proteins than he was.
See ORI
Post-Hearing Br. at 26. Since we have found ORI's basis for
charging
this pattern unsubstantiated with regard to Exhibit H-2 above,
we do not find
that it provides any foundation for the allegations with
regard to Exhibit
H-3.
ORI again attempted to demonstrate that Dr. Sharma had admitted that
he
had referred to sequence data because he anticipated obtaining the
data
in order to justify the reference in time or removing the
reference
before submitting the grant. ORI Post-Hearing Br. at 25,
n.63. The
only statement on which ORI relied for this purpose was made
by Dr.
Sharma to the Hamilton Committee:
DR. HAMILTON: . . . When you say that the use of sequence
per
se was erroneous, that you really intended or should have
said
peptide map data, when you wrote this was it written in
an
anticipatory manner --
DR. SHARMA: That's right.
DR. HAMILTON: -- that is, you expected you would have
that
sequence --
DR. SHARMA: That's right, that's right.
Ex. H-29, at 16. Dr. Sharma testified that the intention of
his
statement was to agree that he intended to write peptide map data and
to
agree that he was anticipating (was in fact actively in the process
of
seeking) sequence data on the 180 kD protein at the time of the
grant.
Tr. at 861-3. However, he testified that the statement "did not
mean
that I was getting it to put it in the grant." Tr. at 863.
As with the �2GC sequence data, so in relation to 180 kD protein
sequence
data, Dr. Sharma agreed with many questioners that he was
anticipating
getting sequence data on peptides of 180 kD, and in fact he
later got some of
that data. See, e.g., Ex. H-31, at 353-8; Tr. at 257.
However, he
consistently insisted that these responses did not imply
that he put in the
reference to sequence data intentionally in
anticipation that he would either
obtain data to justify before the
application was reviewed or would remove
the reference. Id. He
asserted throughout that he meant to refer
to peptide map data. Id.
The most telling argument that Dr. Sharma did not insert the reference
to
sequence data in Exhibit H-3 with the intent to mislead reviewers is
the fact
that the application contained a number of statements which
appeared to
contradict, more or less directly, the claim to have such
data. As a
result, the critique from the study section evaluating the
application
pointed out some of the contradictions and asked for
clarification.
Thus, the reviewers asked:
On page 23, it is stated: "...comparison of our unpublished
rat
brain protein indicate significant structural
heterogeneity
between certain CNBr-cleaved fragments of the two
proteins.",
while on page 34: "...(oligodeoxynucleotide) probes will
be
synthesized as soon as sufficient sequence data on the
guanylate
cyclase protein is available.", and finally on page 35:
...we
presently have approximately 3 nmol of purified 180-kD
for
N-terminal amino acid sequencing.". Which of the above is
true?
If the amino acid data are available, why aren't they shown?
Ex. R-8, at 3 (emphasis added). Plainly, the reviewers were not
misled
and the language of the grant was so puzzling on its face that it
was
highly unlikely to mislead. 42/ While ORI argued that the failure
to
deceive the reviewers does not "vitiate the impropriety of Dr.
Sharma's
attempt," the idea of attempting to mislead someone by telling them
two
or more contradictory, or at least apparently inconsistent, things
is
improbable.
Dr. Douglass suggested that the two statements could be reconciled to
mean
that an inadequate amount or quality of amino acid sequence data
was
available ("maybe they've only got five or seven amino acids and
that's not
enough"), so they are waiting to have sufficient amino acid
sequence
data. Tr. at 635. However, he concluded that "there just
isn't
enough information as to what they do have to make any type of
correlative
comments with regard to these two sentences." Tr. at 636.
His
suggestion would not answer the reviewers' second question, however,
i.e.,
why no data is presented if any is available.
In relation to the inaccurate description of the data which Dr.
Sharma
had, we note that (1) the term sequence data is potentially
ambiguous,
and (2) Dr. Sharma was not expert in the use of technical
molecular
biology terminology. On the first point, Dr. Marala pointed
out that
the term sequence data could be ambiguous outside of a known
context,
and that therefore one should "be more specific if . . . talking to
a
third person who is not involved in that research." Tr. at 509.
The imprecision of the term sequence data was compounded by Dr.
Sharma's
frequent use of inexact terminology, in contexts where no motive
to
deceive was suggested. See, e.g., ORI Final Report, Tab S at 1
(Letter
from Dr. Bylund to OSIR). Thus, ORI reported that its
scientific
advisors noted that Dr. Sharma's training was in medicinal
chemistry
rather than molecular biology, and that, perhaps as a result, much
of
the technical writing in his protocols is "phrased awkwardly and in
a
manner inconsistent with standard terminology." ORI Final Report at
27
(noting, as we have above, that Dr. Sharma's "conversational speech
also
is characterized by idiosyncratic phrasing").
This particular grant application received an extremely poor evaluation
by
reviewers. ORI Final Report at 41. Dr. Sharma repeatedly
expressed
during the investigation his embarrassment about the low quality
of
writing in this application and stated that he wrote it very
hurriedly.
See, e.g., Ex. H-30, at 126-8 (OSIR Interview of Dr.
Sharma). ORI
acknowledged in its final report that the "poor quality of
[Exhibit H-3]
. . . , characterized by obvious inconsistent statements,
suggests that
Dr. Sharma lacked the necessary intent to deceive or mislead
and that
many misstatements resulted from hasty preparation . . . [and] his
lack
of expertise in molecular biology." ORI Final Report at 42.
ORI
nevertheless found scientific misconduct, because it found the
statement
at issue analogous to the misstatement in Exhibit H-2 and because
it
found that Dr. Sharma was aware that peptide map data was less
advanced
than most scientists would understand by a reference to sequence
data.
Id. at 43. We find that these arguments unsupported for the
reasons
discussed above.
We find that the misstatement in Exhibit H-3 was the result of
careless
error and that ORI did not prove that Dr. Sharma intended to
mislead
reviewers about the state of his research on 180 kD protein.
Therefore,
we conclude that ORI has failed to prove by a preponderance of
the
evidence that Dr. Sharma included any misstatement in Exhibit
H-3
intentionally to mislead reviewers.
Conclusion
For the reasons explained above, we conclude that ORI did not prove by
a
preponderance of the evidence that Dr. Sharma committed
scientific
misconduct. Consequently, we conclude that ORI's findings
are not
supported and the proposed administrative actions are not
justified.
___________________________
Judith
A.
Ballard
___________________________
Norval
D. (John)
Settle
___________________________
Donald
F.
Garrett
Presiding
Panel
Member
1. The following discussion is based on the record as a whole
before
the Panel. Disputed scientific questions are discussed in the
text
where necessary. The Panel permitted the parties to submit
proposed
stipulations relating to scientific terminology. ORI submitted
a set of
definitions of scientific terms on which we have relied to the
extent
that they were not objected to or were supported by the record.
2. A revised version of this grant application (Exhibit H-35),
with a
dramatically altered research methodology, was submitted to NIH
in
October 1989. The revised application did receive funding.
The
revised, funded grant is not at issue before us, but allegations
were
raised earlier in the investigations about both Exhibits H-2 and
H-35.
At times, the two substantially different versions of the �2GC
research
grant applications created confusion for investigators and
witnesses.
3. Allegations 2 and 3, which arose during earlier stages of
the
investigation, as well as other subparts of Allegations 1 and 4,
were
determined by ORI not to constitute scientific misconduct and
are
therefore not at issue before us and are not quoted in the text.
See
ORI Final Report at 54-55. These other misstatements were found to
be
"caused by careless yet honest errors - typographical, editing,
and
supervisory." Id. at 55.
4. The Ruling as a whole is not repeated here, but is
incorporated by
reference.
5. There is no doubt that Dr. Sharma knew he had a duty to be
accurate
in his grant applications. A principal investigator must
certify in a
grant application (as Dr. Sharma did by his signature on
these
applications) that he is aware that "[w]illful provision of
false
information is a criminal offense." However, this certification
by
itself does not support a conclusion that the investigator would
be
subject to criminal or even administrative actions for unintentional
or
even negligent errors alone.
6. Dr. Sharma told ORI that he gave Exhibit H-2 to Dr. Sen and
Exhibit
H-3 to Dr. Bannerjee before submission, although it is not clear
that
either one actually did review the applications. Ex. H-30, at 129;
Ex.
H-31, at 370-3 (Dr. Sharma's OSIR Interviews). Each application
was
also certified by the Director of CCF, as well as by Dr. Sharma.
Exs.
H-2, H-3.
7. In its discussion of negligence, ORI also argued that Dr.
Sharma
could have prevented the error by citing Lefkowitz directly after
the
statement, that he had a pattern of errors demonstrating disregard
for
the accuracy of his grant applications, and that his failure to
take
action to notify NIH of the error demonstrated disregard for
accuracy.
ORI Post-Hearing Br. at 28-31. All of these points were also
cited by
ORI as arguments in support of its claim of intentional
deception. See
id. at 30. We discuss the evidence relating to
each of these areas in
more detail in relation to the analysis of intentional
deception.
However, we note here that ORI did not prove that the failure to
add an
additional cite to Lefkowitz at that point was a serious deviation
from
accepted citation practices, that the errors which were not raised
as
allegations before us formed a pattern evidencing a serious
deviation
from commonly accepted practices of grant preparation, or that
any
commonly accepted practice required notifying NIH of an
unintentional
error in a grant application which had been rejected for
funding and
which was already the subject of an investigation.
8. The other two disputed statements appeared on pages 27 and 32
of
Exhibit H-2. Each contains a reference to 39-mer probes
"corresponding
to the amino acid sequences of two internally-cleaved
peptides."
Neither statement asserts that the probes were based on �2GC
data.
However, a reviewer would assume that these statements refer back to
the
39-oligomer probe first described on page 21 of the application.
The
erroneous reference to �2GC instead of �2A probes on page 21
therefore
had the effect of making the other two statements false. See
ORI Final
Report at 23.
9. The weight of scientific testimony at the hearing was
that
scientists can use a probe based on a known protein sequence of a
member
of the same protein "family," which here was the family of �2
adrenergic
receptors, in order to look for related proteins. See, e.g.,
Tr. at
208, 215-6 (Dr. Marshak). Thus, it was not an unreasonable
scientific
strategy for Dr. Sharma to have used the published data on �2A
to
construct a probe in order to search in a different set of cells for
a
related protein, tentatively called �2GC. See Tr. at 587
(Dr.
Douglass). His argument for the existence of such a related, but
not
yet conclusively identified, protein rested on his studies of
its
biochemical and pharmacological properties, which differed in
important
ways from �2A.
10. ORI speculated in its post-hearing brief that substituting
�2A for
�2GC would not "cure" the inaccuracy in the sentence, because
a
researcher having access to published sequence data "would"
have
constructed a genomic probe rather than using the 39-oligomer
probes.
ORI Post-Hearing Br. at 14. ORI based this speculation on an
entire
textbook (Exhibit H-38) which does not directly support the point
made.
ORI cited no testimony whatsoever that Dr. Sharma's laboratory had
not
in fact followed the described procedure. Dr. Chalberg was asked at
the
hearing whether the disputed statement would "be an accurate
statement,"
with the single substitution of �2A for �2GC, and
responded: "[T]hat's
what we actually did do." Tr. at 124-25; see
also Tr. at 880-1 (Dr.
Duda, who performed the actual experiments, testifying
they got
39-oligomer probes based on �2A sequence data from Dr. Michael
Cashnell
at NIH, and used them to screen the cDNA library as described in
the
disputed sentence). ORI's scientific consultant conceded that
the
sentence in context would make sense and be accurate if the
highlighted
reference to �2GC had been replaced by a reference to �2A.
Tr. at
586-7, 631-2 (Dr. Douglass); see also Tr. at 125-7 (Dr.
Chalberg). ORI
was certainly on notice that this issue was critical and
that ORI bore
the burden of proof, yet ORI offered no testimony to support
its
speculation. For example, ORI did not offer an affidavit or
testimony
from Dr. Cashnell at NIH denying that he synthesized a 39-oligomer
probe
using the �2A data. Instead, ORI cited a comment by Dr. Sharma
that
screening with a 39-oligomer probe, instead of a cDNA probe, "would
have
been a folly," which ORI treated as an acknowledgement that Dr.
Sharma
did not use a 39-oligomer probe in the work reported in Exhibit
H-2.
Ex. R-2, at 3; ORI Post-Hearing Br. at 14, n.31. This
interpretation is
wholly unwarranted. In context, Dr. Sharma was
clearly discussing why
retaining the reference to a 39-oligomer probe in his
revised grant
application (Exhibit H-35) would have been a "folly" because
his
methodology there was different and relied on a cDNA clone as a
probe.
Scientific testimony at the hearing indicated that, while a longer
probe
might often be preferable, many factors go into the selection of a
probe
for a particular research purpose. See, e.g., Tr. at 539,
608-12.
Thus, we conclude that the statement in Exhibit H-2 was accurate but
for
the substitution of the subscript.
11. However, it is not clear that the use of an �2GC probe
would
necessarily have been more likely to succeed in hybridizing to clones
of
�2GC. The two related proteins were estimated by Dr. Sharma to be
over
90% homologous, i.e., to have more than 90% identical amino
acid
sequences. Tr. at 865; see also Tr. at 875-9 (Dr. Duda testifying
that
the two proteins were "almost identical," except for
their
distinguishing chemical behavior). To the extent that the
identical (or
"conserved") portions of the amino acid sequence were used in
designing
the probe, it would be impossible to know which protein was
represented
by a clone hybridized to the probe, regardless of whether the
probe
corresponded to �2GC or �2A, except by using the clone to produce
the
protein itself and testing the behavior of the protein ("expression")
or
by sequencing the clone and comparing it to known sequence data. Tr.
at
955-6 (Dr. Gelmann).
12. Dr. Sharma made the same point in comments he submitted to
Dr.
Lawrence J. Rhoades, Ph.D., at OSIR, in which he stated that "nowhere
in
the application is it indicated that we had the sequence of
the
�2GC-fragments. If we had that information, we would have
identified
the sequence and described it . . . ." Ex. R-2, at 2; see
also Ex.
H-29, at 55-57.
13. ORI cited to no evidence contradicting Dr. Gelmann's
assertions
about the level of detail a reviewer would have expected to see if
amino
acid sequencing data had been obtained, but argued that Dr.
Gelmann's
testimony should be "discounted substantially" for five reasons:
(1) he
"never purified a receptor membrane protein;" (2) he did not have
a
doctoral degree; (3) he "never worked with adrenergic receptors;" (4)
he
was not familiar with literature and reported research; and (5) "he
had
not reviewed the entire grant applications" at issue here.
ORI
Post-Hearing Br. at 13, n.30. We find Dr. Gelmann's testimony
credible
and decline to discount it on the bases suggested by ORI. Dr.
Gelmann
has an M.D. from Stanford University, rather than a Ph.D. Tr.
at 902;
Ex. R-15, at 1. ORI did not demonstrate that a Ph.D. was
required in
the field. Dr. Gelmann did research on tumor cell biology
at the
National Cancer Institute and was a tenured scientist at NIH.
Tr. at
902; Ex. R-15. He "has been involved in DNA cloning since
1979,"
receives NIH grants to do gene cloning, and clearly has expertise
in
molecular biology. Tr. at 903-4, 911. Furthermore, he has been
a full
member of one study section and an ad hoc member of another, as well
as
sitting on other scientific review committees. Tr. at 903; Ex. R-15,
at
3. He testified that he did not "have difficulty reviewing the
science"
in the applications, "[i]n particular as it regarded DNA cloning
and
some general aspects of protein sequencing." Tr. at 940.
Furthermore,
he testified that he did have "some familiarity" with the
biochemistry
and pharmacology of adrenergic receptors, even though he had not
himself
cloned a membrane receptor protein. Tr. at 911, 940.
Although there
was some testimony that reviewers should be familiar with the
relevant
literature, ORI did not show why such familiarity with the
literature on
a particular protein was needed to explain what reviewers would
expect
to see in a grant application announcing sequencing of a new
protein.
See ORI Post-Hearing Br. at 13, n.30; Tr. at 221, 940. Dr.
Gelmann had
not been able to review the entire applications, but testified
that he
was able to draw conclusions about the scientific questions based on
the
portions which he had reviewed. Tr. at 929, 940.
14. ORI denied that reviewers would expect to see the actual data
in
the application, but this claim is undercut, in addition to
the
testimony referenced above, by the reviewers' evaluation of Dr.
Sharma's
180 kD protein grant application, Exhibit H-3. In their
evaluation, the
reviewers ask: "If the amino acid data are available,
why aren't they
shown?" Ex. R-8, at 3. This question, though not
relating to Exhibit
H-2, strongly corroborates the testimony that reviewers
expect to see
actual amino acid sequence data in grant applications when it
is
available.
15. In fact, the definitions of scientific terms submitted by
ORI
support the conclusion that data less conclusive than amino
acid
sequence can provide substantial information on the structure and
unique
identity of a protein. Thus, biochemical analyses can
provide
information on the size, functional role, and cell location of
a
protein. ORI Scientific Terms at 1. Peptide mapping can provide
pieces
"unique enough to be used as a `fingerprint.'" Id. There
is no dispute
that Dr. Sharma had biochemical and peptide data on �2GC.
16. ORI also argued that the focus of the application on proving
the
"uniqueness" of the �2GC receptor was significant in making the
error
misleading to reviewers. ORI Post-Hearing Br. at 15.
"Uniqueness" of
the �2GC receptor was, in context, a working hypothesis that
a receptor
in rat adrenocortical carcinoma cells behaved differently
from
previously known �2 receptors and was expected to have at least
some
distinction in structure to account for this different
behavior.
Exhibit H-2; see Tr. at 864-5 (Dr. Sharma); Tr. at 875-9 (Dr.
Duda).
This hypothesis had been supported by pharmacological, biochemical
and
preliminary structural data. Id., Tr. at 944-5. Uniqueness is
in no
way contradicted, despite ORI's assertion to the contrary, by
Dr.
Sharma's expectation that the homology (i.e., shared amino
acid
sequences) between �2GC and the known �2A receptor was likely to
be
very high. Cf. ORI Post-Hearing Br. at 15, n.34, Tr. at 865.
Two
proteins can be very similar and yet differ in small but
significant
ways. Tr. at 868. In order to prove the uniqueness of
the �2GC, as
noted above, Dr. Sharma would ultimately have had to isolate
clones
which proved on expression to represent �2GC and to then obtain
full
amino acid sequence data. See, e.g., Tr. at 561 (Dr.
Douglass
testifying that proof of "uniqueness" will depend on full amino
acid
sequence data); 821, 865 (Dr. Sharma). The use of an �2GC probe
in
itself would not have demonstrated the uniqueness of �2GC in any
case.
Rather, that was a final aim of the project.
17. The revised application is not the basis of an allegation
of
scientific misconduct before us, since ORI concluded that the
sentence
containing the reference to �2GC sequence data was left in
that
application as a result of editing error. ORI Final Report at
32-33.
As noted above, the revised application was dramatically different
in
methodology. In the revised application, Dr. Sharma used an �2A
genomic
probe (rather than an �2A 39-oligomer probe) to isolate a cDNA
clone
from rat brain cells (rather than rat carcinoma). He was able
to
sequence and express this cDNA, determine that it represented an
�2
receptor, and then use it as a probe for further screening.
Exhibit
H-35; see generally ORI Final Report at Tab S at 3-5 (Letter from
Dr.
David Bylund to OSIR). In light of these changes, the
disputed
statement, which had been carried over verbatim from Exhibit H-2,
no
longer had any potential to benefit Dr. Sharma. Throughout
the
investigation, confusion persisted in interviews, when Dr.
Sharma
referred to an intent to change this sentence or to leaving
this
sentence over, about whether he meant he intended to change
the
subscript in Exhibit H-2 if he did not get anticipated data in time
to
justify it or whether he meant he intended to omit the sentence
in
Exhibit H-35 because it was not relevant there but overlooked it in
his
revision.
18. When asked at the hearing how the error got in the sentence
at
page 21 in Exhibit H-2, Dr. Sharma replied: "I do not know
that. I do
not know to this date. If I knew, it would not be
there." Tr. at 868.
19. Dr. Sharma was asked in his first OSIR interview whether he
wrote
Exhibit H-35 (the revised application) all by himself and responded
that
he did, a statement which ORI also cited in support of its assertions
in
the text. Ex. H-30, at 9. Aside from the fact that the
question
related only to the revised application not before us, having
written
something oneself plainly does not preclude receiving
secretarial
assistance in typing and formatting it. And in fact, in
relation to
Exhibit H-2 (the application at issue), Dr. Sharma told ORI that
"I
only, I typed it but I always get secondary help from my wife, you
know,
she's, because I do not, I did not know much typing at that time.
And
my wife always helps me, volunteers to help me in typing." Ex.
H-31, at
218.
20. ORI argued that Dr. Sharma would have noticed and had time
to
catch the error if it were unintentional, because he began writing
the
application in November 1988 and did submit until February 1989.
ORI
Post-Hearing Br. at 18; . However, there is no evidence that he
wrote
this section this section in advance. In fact, the experimental
results
reported in the sentence at issue were not completed until January
1989.
Tr. at 888-90 (Dr. Duda). While ORI interpreted this timing to
mean
that Dr. Sharma must have focussed on the sentence again at that
time,
it is as likely that he wrote this section for the first time at
that
late date.
21. For example, ORI noted that it was difficult to determine
what was
meant in Sharma's interview before the Hamilton Committee "because
the
questions . . . asked were not precise and Dr. Sharma often
interrupted
before the question had been asked and he had an opportunity to
reflect
on his answer." ORI Final Report at 22.
22. For one thing, claiming to have cited non-existent data but
to
have hoped to obtain it or make a correction is not exculpatory, yet
Dr.
Sharma behaved as if he thought he had offered explanations of
honest
error and expected exoneration rather than as if he had
confessed.
Second, in most cases, Dr. Sharma also said something about
mistyping or
missing the mistake during the course of the very same
interview. It
would be unreasonable for him to offer two mutually
exclusive
explanations for the same error simultaneously, so it is more
plausible
that he was trying to make different points. Third, while Dr.
Sharma
ultimately hoped to obtain �2GC sequence data, the evidence does
not
show any reasonable basis for him to have expected its receipt
during
the relevant time frame immediately before or after submission
of
Exhibit H-2.
23. ORI argued that Dr. Sharma must have said that he wrote �2GC
in
Exhibit H-2 because he anticipated getting the data, since
"[f]our
different groups of individuals" thought he had. However, those
groups
did not arrive at their understandings independently. Rather,
they had
each reviewed Dr. Ferrario's initial claim that Dr. Sharma had
offered
that "explanation," as well as interviewing Drs. Chalberg, Ferrario
and
Bannerjee. In reading the later reports and transcripts, it is
obvious
that the later reviewers were influenced by the initial
impression,
right or wrong, which had been formed of Dr. Sharma's position,
and they
framed their questions and heard his answers in that context.
24. In its oral argument and post-hearing brief, ORI numbered
the
various statements which it interpreted as multiple explanations.
For
example, ORI grouped certain statements Dr. Sharma allegedly made to
Dr.
Chalberg (that he had gotten the data or that the statement did
not
appear in the applications as submitted) as the first and
second
explanations, considered a statement from Dr. Ferrario's report of
his
meeting with Dr. Sharma (that Dr. Sharma included the statement
because
he thought he would have the data before the application was
reviewed)
the third explanation, and certain statements made to the Healy
and
Hamilton Committees and in ORI interviews (to the effect that
the
retention of �2GC was an editorial error by forgetting to remove
the
anticipatory statement) the fourth explanation, and typographical
error
the fifth explanation. We find these groupings to be misleading
and
have not used them.
25. ORI also relied in support of the Healy Committee's
interpretation
of Dr. Sharma's explanation on an anonymous committee member
who
allegedly told ORI that Dr. Sharma said that "he `fully expected'
to
have the sequence data and `that is why he wrote it in'
the
application." ORI Post-Hearing Br. at 35, n.102. We give no
credence
to this comment, since ORI presented the inconsistency of Dr.
Sharma's
statements as central to its case and yet failed to produce
this
witness. ORI cited only to its own final report, which failed even
to
identify the committee member. ORI Final Report at 15.
26. The transcript of the Hamilton Committee interview must
be
discounted to some extent in light of several problems. First,
Dr.
Hamilton testified that there were gaps in the taping of some
interviews
and so some statements might not have been recorded. Tr. at
377-8.
Second, Dr. Hamilton testified that portions of the statements
which
were recorded were difficult or impossible to transcribe, although
"the
transcript is as good a representation of the tape as one could
get."
Tr. at 387-8. The tape itself was provided for the record and
upon
review, it is evident that there were inaudible portions although
the
quoted sections appeared to be transcribed accurately. Exs. 29 and
29A.
It is therefore impossible to be certain that the statements by
Dr.
Sharma represented a full picture of his explanations to the
Hamilton
Committee. Third, there is uncontradicted evidence in the
record that
Dr. Sharma's request to have counsel with him in the interview
was
denied and that he was not permitted to review the transcript to
"make
any clarifications, corrections or comments." Ex. R-2, Part II,
at 2-3;
Ex. H-31, at 312-5.
27. The page length reference is more consistent with the
revised
grant application, Exhibit H-35, which was 47 pages. The
original
application was 52 pages. Ex. H-2.
28. ORI was particularly swayed in its assessment of Dr.
Sharma's
credibility by its review of Dr. Sharma's interview by the
Hamilton
Committee. Tr. at 689-90 (Dr. Lyle Bivens of ORI); see also
ORI Final
Report at 49-50. ORI viewed the "crux" of that "presentation"
as the
claim by Dr. Sharma to have "had a reasonable basis for anticipating
the
�2GC amino acid sequence data," while ORI contended he could not
have
expected that data because Dr. Marshak of Cold Spring Harbor had
already
told him that no further work could be done on it. ORI Final
Report at
30. Dr. Sharma presented documentation about his
collaboration with Dr.
Marshak, but later clarified that he was "aggressively
pursuing
obtaining" �2 sequence (from Dr. Marshak as well as at least two
other
laboratories with which he documented earlier collaborations)
"before
the other laboratory [Lefkowitz] reported cloning of this
receptor."
Ex. H-23, at 2 (Letter from Dr. Sharma to OSIR). However, he
stated
that "[a]fter this receptor [�2A] was cloned our enthusiasm
for
sequencing �2GC subsided. We were then only interested in obtaining
its
sequence sometime in the future for the sole purpose of identifying
one
of our isolated clones as the �2GC." Id. This position is
consistent
with the weight of evidence at the hearing that comparison of
potential
clones obtained with the �2A probe with �2GC sequence data
once
available was a reasonable research strategy. See, e.g., Tr. at
821,
954-5. Dr. Sharma could not have expected imminent receipt of
sequence
data from Dr. Marshak during the time frame when the application
was
prepared and submitted, because Dr. Marshak had informed Dr. Sharma
or
his staff some time in 1988 that the samples of �2GC had not
yielded
useful data, and no new samples had been sent. Tr. at
187-90. However,
ORI did not prove that Dr. Marshak made clear to Dr.
Sharma before 1990
that Dr. Marshak would do no further work on the project,
although Dr.
Marshak did apparently communicate on several occasions that
his
participation was becoming more "difficult." Tr. at 191. Only
in May
of 1990 did Dr. Marshak return the samples and end the
collaboration.
Ex. H-11, at 1. This chronology further supports Dr.
Sharma's position
that he was not expecting the data for this application but
continued to
anticipate that further efforts might yield sequence data for
future
comparison with the clones he had obtained. Dr. Sharma testified
that
the reason he brought the Cold Harbor correspondence to the
committee
was that he had gotten the "impression that there was some doubt
that I
had not started the work on the sequence . . . ." Tr. at
822. Some of
his inexplicable comments to the Hamilton Committee may
also have
reflected this additional layer of confusion about whether he was
being
asked to prove that he really had made some independent efforts to
get
�2GC before deciding to use Lefkowitz' probes after the �2A data
was
published.
29. ORI argued that Dr. Hamilton's opinion that Dr. Sharma did
offer
an anticipatory writing explanation was based on a review of "all
the
tapes of the [Hamilton] . . . Committee, not just the transcribed
one."
ORI Post-Hearing Br. at 36. We cannot give additional weight to
his
statements on that account, since ORI did not submit the
additional
tapes into evidence or offer any explanation for failing to do
so. In
any case, despite ORI's characterization of Dr. Hamilton's
testimony at
the hearing as having "clearly remembered Dr. Sharma's
conflicting
explanations," as quoted in the text, Dr. Hamilton still appeared
to be
uncertain even at the hearing whether or not Dr. Sharma told
his
Committee that he did intend to insert �2GC in the hope of
obtaining
data in time to justify it. See ORI Post-Hearing Br. at
36.
30. See Tr. at 41 and 44, identifying the application which
Dr.
Chalberg saw first as Exhibit H-35.
31. Although Dr. Chalberg wrote basic protocols of the
molecular
biology methodologies in the laboratory, which were in the
computer
database to be inserted into grant applications or writings by
Dr.
Sharma, Dr. Chalberg repudiated any claim to be an author of any
of
these grants. Ex. H-17, at 1.
32. Dr. Bannerjee's recollection of whether Dr. Sharma stated at
the
April 20th meeting that he wrote �2GC in the disputed sentence
because
he hoped to get the data in time to justify it was considerably
less
certain than Dr. Ferrario's. At the hearing, Dr. Bannerjee
testified
that he "think[s] what happened" was that he was called in to
Dr.
Ferrario's office to hear Dr. Sharma's explanation. Tr. at
642. He
reported that Dr. Sharma said that the "real thrust of the
research" in
Exhibit H-35 was "something else" and that Dr. Sharma said he
"did not
know what this problem is all about and he has to look into this
matter
more." Id. All Dr. Bannerjee remembered of the discussion
about the
�2GC receptor was that Dr. Sharma said he did not have the sequence
but
that in any case in the revised application he had switched to using
the
cDNA clone in rat brain research, and "something was left over I
guess
in the background section." Id. at 643. When Dr. Bannerjee
was asked
if he had "any doubt in [his] mind sitting there today that the
Alpha
2GC was discussed with Dr. Sharma" in the April 20th meeting, all
he
responded was that he "think[s] it was discussed in that meeting."
Id.
at 644. Dr. Bannerjee made absolutely no reference to the
anticipation
explanation which Dr. Ferrario understood Dr. Sharma to have
been
offering at that meeting. Even more striking is a question by
Dr.
Douglass to Dr. Sharma during the latter's second OSIR interview,
in
which Dr. Douglass quotes at length from Dr. Bannerjee's OSIR
interview
(which was not submitted for the record). There, Dr.
Bannerjee was
directly asked if Dr. Sharma said he submitted the application
hoping to
get the data before the review. Dr. Bannerjee was quoted as
responding
that "he did not say anything about that in our first meeting
because
that meeting did not last more than ten minutes, you know, in
Ferrario's
room." Ex. H-31, at 361. Thus, Dr. Bannerjee does not
corroborate Dr.
Ferrario's account.
33. Mr. Murray (the administrator who attended the meeting)
added
little to the question of what explanation Dr. Sharma may have
offered
then, if indeed he, as a non-scientist, clearly understood the
precise
charges. Mr. Murray stated only that Dr. Sharma admitted he did
not
have the sequence data, though he understood that Dr. Sharma had
hoped
to. Tr. at 257. Mr. Murray's contemporaneous memorandum had
no
reference to anticipation of data, but simply said that "Dr.
Sharma
readily admitted that Dr. Chalberg's claims were accurate." Ex.
H-9.
While he thereby agrees with Dr. Ferrario that a meeting occurred
in
which Dr. Sharma was told of charges of scientific misconduct
relating
to an �2GC grant and admitted that any claim to have �2GC sequence
data
was erroneous, he does not corroborate Dr. Ferrario's perception
that
Dr. Sharma said he wrote the sentence because he thought would have
the
data before the grant was reviewed. Cf. Ex. H-4, at 2 (Dr.
Ferrario's
memorandum).
34. An additional point which must be noted is that, according to
the
Healy Committee report, Dr. Healy, then the head of the
Research
Institute, had asked Dr. Ferrario about a week before these charges
were
raised by Dr. Chalberg whether "there was any evidence of
poor
performance or scientific misconduct" by Dr. Sharma to explain
the
"recent discontent in his section." Ex. H-5, at 1. Dr.
Ferrario said
there was not, and mentioned that Drs. Chalberg and Jaiswal had
not
brought any such complaints to him. Id. at 1-2. A little over
a week
thereafter, Dr. Ferrario gave copies of Dr. Sharma's applications to
Dr.
Chalberg to review, and allegations of misconduct resulted. In
light of
such coincidences, and the clear evidence of conflict within
the
laboratory and the department, we cannot accept as proven ORI's
claims
that Drs. Ferrario and Chalberg acted reluctantly and against their
own
interests in attacking Dr. Sharma at the time these charges arose.
Cf.
ORI Post-Hearing Br. at 39-40.
35. Further, while ORI stated that Dr. Sharma's complaints
against Dr.
Ferrario were found to be groundless by the Hamilton Committee,
ORI
cited nothing in the record to that effect. ORI Post-Hearing Br. at
40.
The Hamilton Committee was instructed to review the complaints
relating
to Dr. Ferrario, but did not include any response in its
report. Exs.
H-6, H-7. The Healy Committee report stated that "it
was unacceptable
practice" for the department chairman to hire staff from a
senior
investigator's laboratory without his consent to get "special
technology
that that senior investigator offers." Ex. H-5, at 5.
This conclusion
suggests that Dr. Sharma's suspicions concerning the motives
of his
accusers may have had some basis in reality. Cf. id. at 4;
ORI
Post-Hearing Br. at 40.
36. The other statements, with the problematic clauses
highlighted,
were as follows:
Two oligonucleotide-39-mer probes, based on rat codon
usage
(98), corresponding to the amino acid sequences of
two
internally cleaved peptides, were synthesized and used to
screen
the unamplified � ZAP (Statagene Cloning Systems)
rat
adrenocortical carcinoma cDNA expression library of two
million
phage.
Two oligonucleotide-39-mer probes, based on rat codon
usage
(98), corresponding to the amino acid sequences of
two
internally-cleaved peptides, were used to screen the
phage
libraries.
Exhibit H-2, at 27 and 32 (emphasis added).
37. ORI also relied on Dr. Sharma's failure to notify NIH in
relation
to the claim that such negligent conduct showed "disregard for
ensuring
the accuracy" of grant applications and constituted
scientific
misconduct. ORI Post-Hearing Br. at 30. This claim is
addressed above.
38. This statement is considerably less forceful than the
paraphrase
of it by ORI to read such an error "warranted immediate
notification to
NIH." ORI Post-Hearing Br. at 30, n.80 (citing Tr. at
584-5). In fact,
the actual statement by Dr. Douglass does not clearly
set out an
accepted standard for when to notify NIH, but rather indicates
that
researchers use discretion in evaluating whether an error
is
significant. However, Dr. Sharma himself agreed that he would have
a
duty to inform NIH if a significant error existed in an
application
which was before NIH for possible funding. Tr. at
847-8.
39. Both Mr. Murray and Dr. Ferrario indicated at the hearing
that Dr.
Sharma was not summoned by Mr. Murray, but rather was called by
Dr.
Ferrario's secretary. Tr. at 297; Tr. at 417-8.
40. Dr. Bannerjee's interview with ORI supported the description
of
Dr. Sharma's participation in the meeting as brief, five or ten
minutes.
Ex. H-31, at 361. Mr. Murray stated that Dr. Sharma's
participation
lasted not more than 30 minutes. Tr. at 296. Dr.
Ferrario had no idea
how long the meeting lasted. Tr. at 421.
41. "If you were trying to use rat to go to human, you'd have to
look
up a human." Tr. at 571. Thus, Dr. Sharma would have had to
"look up"
rat data to use human sequence for a probe "to go to" rat
cells.
42. ORI argued that Dr. Sharma intended to mislead and was
prevented
only because Dr. Chalberg wrote a portion of the application (on
page 35
of Exhibit H-3) which stated that probes would be synthesized "as
soon
as sufficient sequence data" became available. ORI Post-Hearing
Br. at
26. This argument is without merit, since Dr. Chalberg made no
claim to
have written the numerous other contradictory statements in
the
application, including those cited by the reviewers.
Ex.