Department of Health and Human Services
DEPARTMENTAL APPEALS BOARD
SUBJECT: Docket No. 89-207 DATE: March 7, 1991
Decision No. 1232
FINDINGS OF FACT, PROPOSED CONCLUSIONS OF LAW, AND RECOMMENDED
DECISION FOR THE PROPOSED DEBARMENT OF DR. C. DAVID BRIDGES
The Deputy Assistant Secretary for Management and Acquisition of the
Department of Health and Human Services issued a proposal to debar Dr.
C. David Bridges from contracting or subcontracting with the Federal
Government and from eligibility or involvement in nonprocurement
transactions (grants) with the Federal Government for a period of five
years. The proposal to debar was based on a finding that Dr. Bridges
improperly used information from a draft scientific manuscript sent to
him for peer review. More specifically, the proposal stated that Dr.
Bridges had published, as his own work, experimental methods and
procedures taken from the draft manuscript. The proposal relied
generally on the findings and conclusions in a report prepared for the
National Institutes of Health by a panel of scientific experts. The
alleged scientific misconduct concerned research conducted by Dr.
Bridges with the support of grant funds awarded by the National Eye
Institute, one of the National Institutes of Health. Thus, the
Debarring Official determined that a cause for debarment of a serious or
compelling nature existed and that this cause affected Dr. Bridges'
responsibility as a recipient of federal funds.
At the Debarring Official's request, I conducted a fact-finding
proceeding under 45 C.F.R. 76.314(b) and 48 C.F.R. 9.406-3(d) and
prepared findings of fact, proposed conclusions of law, and a
recommended decision on the proposed debarment based on the full record
of that proceeding.
Below, I first state my recommended decision that Dr. C. David Bridges
be debarred for three years on the basis of the cause proposed. The
sections that follow are:
o a discussion of the applicable regulatory provisions;
o a general procedural history of this proceeding;
o an explanation of the area of scientific research involved in
o a discussion of the administrative record and the weight and
significance accorded some of the evidence;
o the findings of fact and analyses of the basis for those
o the proposed conclusions of law and analyses of why I propose
those conclusions to the Debarring Official.
I. RECOMMENDED DEBARMENT DECISION
Dr. Bridges, the Respondent in this case, was a professor of
ophthalmology and biochemistry at Baylor College of Medicine in Houston,
Texas. His specialty is vision research.
Among the disputed material facts central to this proceeding, the most
critical concern whether Dr. Bridges began experiments on a series of
protocols during May of 1986, or during August of 1986 just after he
read the draft manuscript allegedly plagiarized.
The Department of Health and Human Services (DHHS) bears the burden of
proof to establish the proposed cause for debarment by a preponderance
of the evidence. Below, I make detailed findings concerning facts
material to determining whether the cause for debarment exists. Where
material facts were disputed, the facts as found met the preponderance
of the evidence standard. I am basing my recommended decision on these
facts and on the proposed conclusions of law concerning violations of
standards of conduct for scientific research which I found to affect the
Respondent's current responsibility.
I find that DHHS proved by a preponderance of the evidence that Dr.
Bridges' experimental work began during August of 1986 and that the
protocols and the published conclusions from Dr. Bridges' experiments
were derived from information reported in the draft manuscript. My
recommended decision to the Debarring Official that Dr. Bridges be
debarred for three years is based primarily upon my findings and
conclusions that Dr. Bridges:
o plagiarized privileged information from a draft manuscript sent
to him in confidence for peer review;
o failed to promptly decline to act as a peer reviewer, with the
possible effect of delaying the manuscript's publication;
o failed to make available to the grantee institution and to the
grantor agency adequate primary data related to the scientific research
o violated accepted standards of conduct for scientific research;
o violated standards of conduct applicable to principal
investigators on federally supported projects; and
o disregarded standards of conduct with which he was well familiar
in order to deceive others about the conduct of his experiments.
The extreme seriousness of the misconduct found here must be noted. The
peer review process places before individuals unknown to the scientist
whose work is under review his/her most important possession -- the
methods, results, and conclusions concerning unpublished scientific
research. Preserving the confidentiality of material in the peer review
process is critical to the continued viability of the process of
scientific advancement. There is no question that the misuse that I
find occurred here is a classic and feared example of the abuse of the
peer review process.
In determining to recommend to the Debarring Official that the
Respondent be debarred, I considered the strong public interest in
protecting the integrity of the scientific research process, and in
preventing the potential for abuses of federal funds. The record
indicated that Dr. Bridges' disregard for accepted standards of conduct
affected his actions throughout 1986, when the research in question was
conducted, and continued to affect Dr. Bridges with regard to his
failure to maintain and make available adequate primary data related to
the research he conducted. I further conclude that there are no factors
that would mitigate against a conclusion that debarment is warranted.
The Respondent's disregard for accepted standards of conduct and his
efforts to deceive others about the conduct of his experiments reflects
an overall lack of integrity, care, and judgment.
Thus, for the reasons discussed more fully below, I recommend to the
Debarring Official that the interests of the public and of the Federal
Government require that Dr. C. David Bridges be debarred for a
three-year term beginning January 1, 1991. 1/ I am recommending a term
of debarment which is less than the five-year term proposed by the
Debarring Official. Notwithstanding the serious nature of the
misconduct found, three years is the standard term for an administrative
debarment and I find no justification on this record for a longer term.
II. REGULATORY AUTHORITY AND STANDARDS
This proceeding was held under the authority of the regulations
governing administrative debarments from grants and contracts. See 45
C.F.R. Part 76 and 48 C.F.R. Parts 9.4 and 309. By means of an
administrative debarment, individuals or entities are excluded from
eligibility for non-procurement (grant) and procurement (contract)
awards from the Federal Government for a specified period of time.
Administrative debarments are discretionary actions taken to protect the
interests of the public and the government and are not punitive.
Gonzalez v. Freeman, 334 F.2d 570 (D.C. Cir. 1964); 45 C.F.R. 76.115 and
48 C.F.R. 9.402(a) and (b).
The causes for debarment are enumerated in the regulations at 45 C.F.R.
76.305(c) and 48 C.F.R. 9.406-2. The cause upon which the Debarring
Official based this contested proposal to debar is:
Any other cause of so serious or compelling a nature that it
affects the present responsibility . . . .
DHHS bears the burden to establish the alleged cause for debarment by a
preponderance of the evidence. 45 C.F.R. 76.314(c) and 48 C.F.R.
Federal policy requires the award of contracts and grants only to
responsible parties. Debarment is not mandatory upon a determination
that the cause for debarment exists. A determination to debar is made
after consideration of "the seriousness of the . . . acts or omissions
and any mitigating factors." 45 C.F.R. 76.300 and 48 C.F.R.
9.406(1)(a). The term of a debarment is for "a period commensurate with
the seriousness of the cause," but generally does not exceed three
years. 2/ 45 C.F.R. 76.320(a) and 48 C.F.R. 9.406-4(a).
The regulations provide the steps that DHHS and the Debarring Official
are to follow. 45 C.F.R. 76.310 through 314 and 48 C.F.R. 9.406-3. The
regulations provide that debarment procedures are to be as informal as
possible consistent with principles of fundamental fairness. 48 C.F.R.
9.406-3(b). The regulations further provide for additional proceedings
where a submission made in response to a proposal to debar raises a
genuine dispute over material facts. The Debarring Official may refer
the matter to another official to prepare findings of fact and may
reject those findings only if the Debarring Official determines them to
be arbitrary and capricious or clearly erroneous. The Debarring
Official's decision on the proposed debarment is made after the
conclusion of the fact-finding proceedings and is based on the
administrative record. See 45 C.F.R. 76.314(b) and 48 C.F.R.
III. PROCEDURAL HISTORY
On September 30, 1988, the National Institutes of Health (NIH) appointed
a panel 3/ (NIH Panel) of scientists expert in vision research and
related areas "to review allegations that privileged information may
have been inappropriately used [by Dr. C. David Bridges] in the
preparation of a published article." Agency Exhibit (A.Ex.) 79. 4/ The
article in question is "The Visual Cycle Operates via an Isomerase
Acting on All-trans Retinol in the Pigment Epithelium," which was
published in Science Magazine in June of 1987 with Dr. Bridges as the
The controversy concerned whether Dr. Bridges made inappropriate use of
information in a draft manuscript provided to him in confidence for peer
review. That draft manuscript had been subsequently revised and
published as "Isomerization of all-trans-retinoids to 11-cis-retinoids
in vitro" in the April 1987 Proceedings of the National Academy of
Sciences (PNAS). Drs. Paul S. Bernstein, Wing C. Law, and Robert R.
Rando were the authors of the PNAS paper.
In the fall of 1987, allegations of impropriety with regard to the PNAS
draft manuscript came formally to the attention of Baylor College of
Medicine. Dr. Bridges had been at Baylor since 1977 and had resigned
during August of 1987, effective on October 15, 1987, to accept a
faculty appointment with another university. In September of 1987, an
ad hoc Baylor faculty committee (Baylor Committee) began an internal
investigation of the allegations. The Baylor Committee issued its
report on May 24, 1988. The Baylor Committee concluded that Dr. Bridges
had acted improperly, primarily with regard to attempting to gain
priority for his own work. See A.Ex. 94 (Item 1).
Dr. Bridges informed NIH that he did not accept the Baylor Committee's
findings. A.Ex. 81. Since Dr. Bridges was a recipient of federal
research grant funds and because of the serious nature of the alleged
misconduct, NIH decided to appoint an investigatory panel. A NIH Panel
was formally appointed on September 30, 1988 and was assisted by various
DHHS personnel. The final report of the NIH Panel was issued on May 12,
1989. 5/ The Panel had received comments from Dr. Bridges on a draft of
the full report and from Dr. Rando and Baylor officials on relevant
excerpts. Dr. Bridges also submitted further comments to the Panel
after the final report had been submitted to NIH. The Panel made no
substantive revisions to its report in light of Dr. Bridges' further
comments. There were a number of conclusions reached by the NIH Panel;
most critical here is the conclusion that Dr. Bridges had plagiarized
the PNAS manuscript. See Ex. 4, p. 13. The Panel recommended to NIH
that it take action commensurate with the seriousness of its findings.
See Ex. 4, p. 1.A committee of senior NIH staff reviewed the Panel
report. The senior staff committee findings were presented in a June 2,
1989 memorandum to the Director of NIH. This committee accepted the NIH
Panel's report, concluding Dr. Bridges had "misused the privileged
information available to him in formulating the experiments he allegedly
conducted and he failed to acknowledge properly the source of that
information." Ex. 3, p. 11. Among other actions, the committee
recommended that the Director request that debarment proceedings be
initiated. Ex. 3, p. 13. By memorandum dated June 23, 1989 the
Director of NIH, with the concurrence of the Assistant Secretary of
Health, forwarded a debarment recommendation within DHHS. Ex. 2.
On August 14, 1989, the Debarring Official notified Dr. Bridges that
DHHS was proposing a five year debarment based on the findings of the
NIH Panel. Ex. 6. The proposed debarment from contracting and
subcontracting would bar any federal agency from accepting or soliciting
bids and proposals and awarding or renewing contracts or subcontracts
with Dr. Bridges, absent a compelling reason to do so in accordance with
48 C.F.R. 9.405(a). The proposed debarment from nonprocurement
transactions would bar eligibility to receive or participate in
nonprocurement transactions, such as grants and cooperative agreements,
unless an exception was granted in accordance with 45 C.F.R. 76.215. In
addition, if debarred, Dr. Bridges would be included on the "List of
Parties Excluded from Federal Procurement and Nonprocurement Programs"
maintained by the General Services Administration.
Dr. Bridges timely submitted to the Debarring Official written argument
and information in opposition to the proposed debarment. See 45 C.F.R.
76.313(a) and 48 C.F.R. 9.406-3(c)(4). Dr. Bridges' response stated the
belief that there were genuine issues of material fact with regard to
the proposed debarment and that considerations of fairness and due
process required a trial type hearing. Ex. 8. The Debarring Official
then determined that there were "questions concerning the material facts
of the case" and referred this matter to the Departmental Appeals Board
(DAB) to conduct the necessary proceedings and prepare the written
findings of fact. Ex. 1. The Debarring Official later extended his
request to encompass the preparation of a recommended decision on the
debarment, following procedures determined appropriate by the DAB.
December 22, 1989 Request to the DAB.
The Chair of the Departmental Appeals Board designated me as the hearing
officer. Dr. Bridges was represented by counsel during the proceeding
before me. Both Dr. Bridges, by counsel, and DHHS submitted numerous
documents into the administrative record. Also, I presided over a
hearing lasting more than four weeks during which both parties presented
witnesses and had the opportunity to cross-examine opposing witnesses.
The record contains in excess of 300 documentary exhibits, many of which
are long and complex, as well as visual exhibits presented at the
hearing. I set post-hearing proceedings requiring both parties to
submit proposed factual and legal conclusions and to brief other issues
I identified for them. Hearing Transcript (Tr.) 5604-5609. I then
concluded the proceedings by holding an oral argument.
IV. EXPLANATION OF THE SCIENTIFIC RESEARCH
Because the issues of fact include scientific matters, below is a brief
and general explanation of the area of scientific research which the
PNAS and Science articles concern. This explanation was developed from
the record in the debarment proceedings and is not intended to be
The visual pigments of the eye contain a photosensitive system in the
retina which, like film when exposed to light, change and transmit a
signal which eventually ends up as vision. Tr. 164-167 (Dr. Rando); see
A.Ex. 161 (Items 1 and 7); A.Exs. 183 and 184; and Ex. 8 (Item 2).
However, unlike film which can be exposed only once, the eye
continuously renews this pigment. George Wald in the 1940's discovered
that the photosensitive visual pigment, rhodopsin, was made up of a
protein called opsin combined with a derivative of Vitamin A called
11-cis retinal (an isomer). The 11-cis retinal exists only in the
visual system of sighted animals. The absorption of light by the eye
results in changing the 11-cis retinal to all-trans retinal. This
change is called isomerization (in this case, photoisomerization).
Isomerization refers to the process by which a molecule of identical
empirical formula, but different physical properties, is created. When
the 11-cis to all-trans photoisomerization occurs, the pigment rhodopsin
bleaches. Therefore, for vision to proceed, the bleached material,
which has changed and is now composed of all-trans retinal, must be
reconverted to the 11-cis form. This regeneration process must occur in
the dark and it is not photochemically induced. For an explanation of
the vision cycle, see Tr. 2506-2513 (Dr. Bridges); and CDB V. Exs. J and
K.The two scientific articles at the center of this controversy
explained how that rhodopsin regeneration, elusive to vision scientists
for so many years, takes place. Ex. 8 (Item 2); A.Ex. 161 (Item 1).
This experimentation solved the puzzle of how the eye adapts from light
to darkness because of the presence of a substance that converts Vitamin
A to a form necessary for the photoreceptor cells of the retina to
adjust to darkness. It was the reverse process of converting all-trans
back to 11-cis that was discovered here. That process is referred to as
isomerization of all-trans retinoids to 11-cis retinoids (the term
retinoid refers to all forms of Vitamin A). Tr. 164-167 (Dr. Rando);
see A.Exs. 161 (Items 1 and 7); 183, and 184; and Ex. 8 (Item 2). It is
this reverse process that generates 11-cis retinal for rhodopsin
regeneration thus allowing vision to proceed.
This experimentation for the first time showed the visual cycle
operating outside the living animal; these experiments successfully
confirmed a system that can produce 11-cis retinoids in vitro (studies
conducted in tissue culture as opposed to studies conducted in intact
living animals or organisms). Tr. 167 (Dr. Rando).
The PNAS paper reported that there was an isomerizing activity that
transforms all-trans retinoids into 11-cis retinoids and the site of
this synthesis is the pigment epithelium. A.Ex. 161 (Item 1). The
paper concluded that it was, however, still an open question as to which
type of retinoid -- retinol, retinal, or retinyl palmitate -- is the
actual substrate and resulting product for the trans to cis
isomerization. Substrate is what the enzyme converts into product.
This paper states that while all-trans retinol is the most likely
substrate for isomerization, it is not unambiguously proven. A.Ex. 161
(Item 1); A.Ex. 31 (Item 8c).
The Science paper concluded that there was an eye-specific,
membrane-bound enzyme (retinol isomerase) that converts all-trans to
11-cis retinol in the dark. Ex. 8 (Item 2). The paper concluded
further that the retinol isomerase (i.e., enzyme) is concentrated in the
pigment epithelium, determining that the Vitamin A compound that is
isomerized is retinol rather than retinal or a retinyl ester. Ex. 8
(Item 2). Unlike the PNAS paper, the Science paper, therefore,
concluded that all-trans retinol was the substrate for an isomerase
enzyme (retinol isomerase) which is converted into 11-cis retinol (the
V. DECISION PROCESS
The findings of fact, proposed conclusions of law, and recommended
debarment decision set forth here are based upon the entire documentary
record as well as the hearing testimony presented by the parties. This
includes consideration of information developed by the Baylor Committee
and the NIH Panel in connection with each of their inquiries. Using
these sources along with the parties' submissions of documents,
testimony, and arguments, I have made independent findings with respect
to the contested facts.
DHHS had the burden of proof in this proceeding to prove the existence
of the alleged cause for debarment by a preponderance of the evidence.
That standard required DHHS to prove by information that when compared
to the opposing information "leads to the conclusion" that the disputed
material facts upon which it relied were "more probably true than not."
45 C.F.R. 76.105 and 48 C.F.R. 9.403. I assigned no presumptive weight
to the conclusions of the prior investigatory bodies. I found the NIH
Panel report and the testimony of the expert scientists on that Panel to
be a reliable source of expert opinion on the generally accepted
standards of scientific conduct and on the significance of the alleged
misconduct to the scientific community. In addition, there were
scientists other than the NIH Panel who testified and in general their
testimony corroborated that of the Panel on these matters.
Also, while I did not regard the conclusions stated in the NIH Panel
report alone to establish the proposed cause for debarment, I found
highly significant their conclusions and later testimony that (1) there
was no logical, scientific progression in Dr. Bridges' work leading up
to the development of the protocols at issue, and (2) that without the
benefit of the information in the PNAS manuscript, the results and
conclusions as stated in the Science article could not have been derived
from data Dr. Bridges presented in support of the Science article. I
accorded great weight to these expert opinions.
However, I did not find that there were inadequate supplies of
radioactive Vitamin A to conduct the experiments at the time Dr. Bridges
asserted they were conducted, which was the opinion testimony of one
Panel member. I was unable from the record before me to verify
independently the factual assumptions (about how much of this material
was available at any given time) upon which the expert opinion was
based. Also, the NIH Panel report concluded that the Science paper was
seriously flawed scientifically for a number of reasons. There was also
some testimony on this aspect of the report by the Panel members, one of
whom thought, in retrospect, that the Panel had not needed to develop
that conclusion. I make no finding as to the scientific soundness of
the Science article in these respects. The Science article was a peer
reviewed publication. The alleged scientific flaws concern complex
scientific matters which I conclude are tangential, not material, to
determining whether the cause for debarment is established. Thus, I do
not address this further in the context of the debarment proceeding.
This was a lengthy proceeding with a complex and detailed documentary
record. In this regard, there were other matters developed in the
administrative record which I also conclude are immaterial to the
ultimate issue presented. Thus, I have not developed findings of fact
and conclusions of law relating to matters such as, all aspects of
priority of observation and appropriate recognition of others' work,
circumstances leading up to the Baylor investigation (such as the
telephone calls to Dr. Rando by some Baylor personnel), and the merits
of the scientific debate between Dr. Bridges and Dr. Rando reflected in
correspondence to Science magazine after publication of the Science
In reviewing the record and evidence before me, I considered the direct
evidence. I considered the circumstantial evidence and the inferences
which could reasonably be drawn from that evidence. I considered
opinion testimony from the qualified experts, including Dr. Bridges, and
whether that opinion testimony should be accepted or rejected.
In weighing the evidence before me, it was necessary for me to assess
the credibility of the witnesses present at the hearing. My assessments
are stated below, when relevant to my evaluation of the evidence
presented. I was impressed by the Panel members' care and objectivity
in assessing the matters before them. I was persuaded that they were
not biased against Dr. Bridges in any way despite efforts by Dr.
Bridges' counsel to establish such bias. In general, Dr. Bridges was
less credible than other witnesses because of the pattern of
inconsistent statements and/or admitted falsehoods concerning the
research in question, the handling of the peer reviewed article, and the
disposition of the original primary data. On balance, Dr. Bridges'
testimony consisted of a largely hypothetical and speculative rationale
for his account of the conduct of the experiments in question. In
addition, Dr. Bridges' lengthy and confusing testimony concerning the
scientific progression of the work in question was in marked contrast to
testimony of Drs. Rando and Bernstein who concisely and logically
articulated an explanation of the work in their laboratory leading up to
the experiments reported in their PNAS paper.
I used the general requirements for debarment proceedings as a guide.
However, I gave special consideration to ensuring the fairness of this
proceeding because Dr. Bridges is an individual who depends on federal
research grant funds for his livelihood. Dr. Bridges raised a number of
procedural objections to the Debarring Official regarding the adequacy
of the prior inquiries. Ex. 7.
In this regard, I find that Dr. Bridges has now had a full opportunity
to rebut the matters concerning the proposed debarment. I held a full,
evidentiary hearing which was transcribed. Dr. Bridges had the
opportunity to submit extensive documentary exhibits, present his own
witnesses, cross-examine opposing witnesses, submit written briefing,
and present oral argument. I have considered the full record developed
in the proceeding before me in reaching my determinations.
VI. FINDINGS OF FACT
1. THE RESPONDENT, DR. C. DAVID BRIDGES, WHILE EMPLOYED AS A PROFESSOR
AT BAYLOR COLLEGE OF MEDICINE, HOUSTON, TEXAS, WAS PRINCIPAL
INVESTIGATOR ON GRANT NO. RO1 EY02489, AWARDED TO BAYLOR BY THE NATIONAL
EYE INSTITUTE, PART OF THE NATIONAL INSTITUTES OF HEALTH.
2. DR. BRIDGES RECEIVED FEDERAL FUNDING IN EXCESS OF $2 MILLION FOR
RESEARCH ACTIVITIES UNDER THIS GRANT FROM SEPTEMBER 1, 1977 UNTIL JUNE
3. DR. BRIDGES WAS A PROFESSOR AT BAYLOR IN THE DEPARTMENTS OF
OPHTHALMOLOGY (FROM 1977) AND BIOCHEMISTRY (FROM 1980) UNTIL HE RESIGNED
EFFECTIVE OCTOBER 15, 1987 TO ACCEPT AN APPOINTMENT AT PURDUE
4. DR. BRIDGES HAD SERVED AS A MEMBER OF AN NIH STUDY SECTION THAT
REVIEWS GRANT APPLICATIONS AND HAD BEEN DISTRIBUTING EDITOR FOR THE
JOURNAL VISION RESEARCH. DR. BRIDGES HAD SERVED AS A PEER REVIEWER FOR
NUMEROUS OTHER JOURNALS.
5. DR. BRIDGES IS A VISION RESEARCHER WHOSE INTEREST IS THE
BIOCHEMISTRY OF THE VISUAL PROCESS, SPECIFICALLY THE INTERSTITIAL
RETINOL BINDING PROTEIN (IRBP) AND THE ISOMERASE ACTIVITY THAT IS
ESSENTIAL TO RHODOPSIN REGENERATION IN THE EYE.
6. THE PROPOSAL TO DEBAR DR. BRIDGES FROM RECEIPT OF FEDERAL CONTRACT
AND GRANT FUNDS FOR A PERIOD OF FIVE YEARS IS BASED ON THE FINDING THAT
DR. BRIDGES ENGAGED IN SCIENTIFIC MISCONDUCT IN CONNECTION WITH AN
ARTICLE PUBLISHED IN SCIENCE, VOLUME 236 (JUNE 27, 1987), AT P. 1678,
ENTITLED, "THE VISUAL CYCLE OPERATES VIA AN ISOMERASE ACTING ON
ALL-TRANS RETINOL IN THE PIGMENT EPITHELIUM" (THE SCIENCE PAPER).
7. DR. BRIDGES AND RICHARD ALVAREZ, A RESEARCH TECHNICIAN IN HIS
LABORATORY, AUTHORED THE SCIENCE PAPER.
8. THE ALLEGATIONS OF SCIENTIFIC MISCONDUCT CONCERN A MANUSCRIPT
RECEIVED BY DR. BRIDGES FOR PEER REVIEW WHICH WAS SUBSEQUENTLY REVISED
AND PUBLISHED IN THE PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES,
VOLUME 84 (APRIL 1987) AT P. 1849 (THE PNAS PAPER).
9. MR. ALVAREZ NEVER SAW OR KNEW OF THE PNAS MANUSCRIPT DURING 1986
WHEN HE WAS WORKING ON THE FROG SERIES PROTOCOLS AND THE RATONE PROTOCOL
(THE FROG SERIES) THAT WERE THE BASIS FOR THE SCIENCE PAPER. THEREFORE,
THE ALLEGED MISCONDUCT IS ATTRIBUTED TO DR. BRIDGES ALONE. 6/
10. IN SEPTEMBER 1987, A BAYLOR COLLEGE OF MEDICINE AD HOC COMMITTEE
BEGAN AN INTERNAL INVESTIGATION OF ALLEGED IMPROPRIETIES BY DR. BRIDGES
WITH REGARD TO THE PNAS MANUSCRIPT.
11. THE BAYLOR COMMITTEE CONCLUDED THAT DR. BRIDGES HAD IMPROPERLY
ATTEMPTED TO GAIN PRIORITY FOR HIS WORK, HAD ALTERED RECORDS TO FALSELY
SUGGEST THAT THE FROG SERIES OF EXPERIMENTS BEGAN PRIOR TO RECEIPT OF
THE PNAS MANUSCRIPT, AND THAT DR. BRIDGES HAD THE OPPORTUNITY TO USE THE
METHODOLOGY IN THE PNAS ARTICLE IN HIS WORK REPORTED IN THE SCIENCE
12. IN MAY OF 1988, THE BAYLOR COMMITTEE REPORT WAS TRANSMITTED TO NIH.
13. IN LIGHT OF THE SERIOUS NATURE OF THE BAYLOR COMMITTEE FINDINGS AND
DR. BRIDGES' CHALLENGE TO THOSE FINDINGS, NIH CONVENED A PANEL OF
SCIENTISTS EXPERT IN THE VISION RESEARCH FIELD AND/OR RELATED AREAS.
14. NIH CHARGED THE PANEL TO DETERMINE WHETHER PRIVILEGED INFORMATION
AVAILABLE TO DR. BRIDGES WAS USED AND ACKNOWLEDGED APPROPRIATELY, TO
REVIEW RESEARCH DATA SUPPORTING THE SCIENCE ARTICLE, AND TO DESCRIBE THE
NATURE AND EXTENT OF ANY INACCURACIES FOUND.
15. THE NIH PANEL CONCLUDED IN RELEVANT PART--
THE COMPLETE ABSENCE OF CONVINCING DOCUMENTATION AND EYEWITNESS
ACCOUNTS, OTHER THAN DR. BRIDGES AND MR. ALVAREZ, MADE
IMPOSSIBLE ANY CERTIFICATION THAT THE EXPERIMENTS REPORTED IN
SCIENCE WERE PERFORMED AS DESCRIBED;
THE OVERWHELMING WEIGHT OF THE EVIDENCE SUGGESTED THAT DR.
BRIDGES PLANNED AND CONDUCTED THE FROG SERIES EXPERIMENTS
REPORTED IN THE SCIENCE ARTICLE AFTER READING THE PNAS
THE EXPERIMENTS AND CONCLUSIONS IN THE SCIENCE PAPER ARE BASED
ON THE PROTOCOLS AND CONCLUSIONS IN THE PNAS ARTICLE, EVEN
THOUGH THE EXPERIMENTATION REFLECTED IN THE SCIENCE ARTICLE DOES
NOT SUPPORT THE CONCLUSIONS REACHED THEREIN AND SEEMED TO BE
INCOMPLETELY PERFORMED AND INACCURATELY REPORTED.
16. BASED ON THE CONCLUSIONS OF THE NIH PANEL, NIH REQUESTED THAT THE
DEBARRING OFFICIAL BEGIN DEBARMENT PROCEEDINGS AGAINST DR. BRIDGES.
DISCUSSION OF GENERAL BACKGROUND
The findings of fact relevant to an understanding of the general
background of this dispute are uncontested. These findings are derived
from and supported by the documentary record and the testimony before
me. See A.Exs. 210, 208, 94 (the Baylor Committee Report), 104, and 161
(Item 1) (the PNAS paper); and Exs. 4 (the NIH Panel Report) and 8 (Item
2) (the Science paper);
PEER REVIEW OF THE PNAS PAPER
17. ON JUNE 21, 1986, DR. BRIDGES LEFT BAYLOR FOR AN EXTENDED TRIP TO
BOSTON AND SCOTLAND.
18. ON JULY 7, 1986, DR. JOHN DOWLING FROM HARVARD UNIVERSITY SENT A
MANUSCRIPT AUTHORED BY DRS. PAUL S. BERNSTEIN, WING C. LAW, AND ROBERT
R. RANDO TO DR. BRIDGES FOR PEER REVIEW.
19. DR. BRIDGES RETURNED TO HOUSTON ON JULY 22 AND TO HIS LABORATORY ON
JULY 28, 1986.
20. THE MANUSCRIPT OF THE PNAS PAPER HAD ARRIVED IN DR. BRIDGES'
LABORATORY SOME TIME BEFORE HIS RETURN ON JULY 22, 1986.
21. DR. BRIDGES READ THE MANUSCRIPT OF THE PNAS PAPER DURING THE FIRST
WEEK IN AUGUST 1986.
22. IN A HANDWRITTEN LETTER DATED SEPTEMBER 2, 1986, DR. BRIDGES
DECLINED TO ACT AS A REVIEWER ON THE PNAS MANUSCRIPT STATING THAT IT WAS
"INAPPROPRIATE TO PASS MORE THAN A BRIEF COMMENT ON THE [MANUSCRIPT]."
23. DR. BRIDGES' SEPTEMBER 2, 1986 LETTER WAS CRITICAL OF THE
BERNSTEIN/LAW/RANDO MANUSCRIPT, STATING THAT IT WAS NOT SUITABLE FOR
PUBLICATION IN ITS CURRENT FORM IN THAT IT WAS "MESSILY WRITTEN" WITH A
"TOTAL LACK OF PRIMARY DATA."
24. DR. BRIDGES' SEPTEMBER 2, 1986 LETTER FALSELY STATED THAT HE HAD
JUST RETURNED FROM SCOTLAND WHEN HE HAD ACTUALLY RETURNED SIX WEEKS
25. DR. BRIDGES' SEPTEMBER 2, 1986 LETTER FALSELY STATED THAT HE HAD
BEEN INVOLVED IN SIMILAR RESEARCH SINCE BEFORE THE MEETING OF THE
ASSOCIATION FOR RESEARCH IN VISION AND OPHTHALMOLOGY (ARVO) IN MAY 1986.
26. DR. BRIDGES' LETTER FALSELY STATED THAT HE HAD DISCUSSED "OUR
PRELIMINARY BUT ENCOURAGING FINDINGS WITH BERNSTEIN IN SARASOTA (ARVO
27. THE OTHER REVIEWER ON THE BERNSTEIN/LAW/RANDO MANUSCRIPT RETURNED
HIS COMMENTS IN LATE AUGUST 1986.
28. BECAUSE DR. BRIDGES DECLINED REVIEW, A THIRD REVIEWER HAD TO BE
OBTAINED FOR THE BERNSTEIN/LAW/RANDO MANUSCRIPT.
29. DR. DOWLING COMMUNICATED THE ACCEPTED MANUSCRIPT TO THE NATIONAL
ACADEMY OF SCIENCES ON DECEMBER 1, 1986 AND IT WAS PUBLISHED IN APRIL
30. DR. BRIDGES' FAILURE TO DECLINE REVIEW PROMPTLY AFTER READING THE
PNAS MANUSCRIPT HAD THE POTENTIAL TO DELAY ITS PUBLICATION.
DISCUSSION OF PEER REVIEW OF THE PNAS PAPER
The facts regarding Dr. Bridges' peer review of the manuscript authored
by Drs. Bernstein, Law, and Rando for PNAS are largely uncontested. Dr.
Bridges left the country on June 21, 1986, returning to Houston on July
22, 1986 and to his lab at Baylor on July 28, 1986. On July 7, 1986,
Dr. Dowling sent the PNAS manuscript to Dr. Bridges for peer review.
Tr. 3078 (Dr. Dowling). He read the PNAS manuscript sometime during the
first week in August. Tr. 3101 (Dr. Bridges). It is also undisputed
that Dr. Bridges did not decline to review the manuscript until
September 2, 1986. A.Ex. 161 (Item 9); Tr. 3078 (Dr. Dowling). Of
critical importance here are the contents of Dr. Bridges' September 2,
1986 letter to Dr. Dowling. A.Ex. 161 (Item 9). The letter contains
several false statements; its contents immediately call into question
the honesty, veracity, credibility, and motivation of Dr. Bridges.
The testimony and documentary exhibits show that certain statements made
in Dr. Bridges' September 2 letter were false. The letter states, "I
have just returned from Scotland and found the Bernstein and Rando paper
in the mail." A.Ex. 161 (Item 9). Dr. Bridges admitted that at the
time he wrote the letter he had not just returned from Scotland, but had
in fact returned six weeks earlier. Tr. 3568 (Dr. Bridges). Dr.
Dowling indicated that usual time to review a PNAS paper is short (one
to two weeks), although sometimes in summer review time might be longer.
Tr. 3103 (Dr. Dowling). Dr. Bridges indicated that the reason he had
stated that he had "just returned" was that he had kept the paper for
four weeks. Tr. 3568 and 5080 (Dr. Bridges). In fact, Dr. Bridges
admitted that he misled Dr. Dowling as to the date of his return from
Scotland. Tr. 5079 (Dr. Bridges). Dr. Dowling testified that when he
first received Dr. Bridges' letter he had no reason to doubt the
veracity of that statement, but he subsequently learned that Dr. Bridges
had in fact returned from Scotland in late July 1986. Tr. 3102 (Dr.
Dowling). Dr. Dowling indicated that Dr. Bridges had not been truthful
to him at all times. Dr. Dowling testified that based on his long
association with Dr. Bridges, he understood Dr. Bridges' use of the word
"just" to imply that Dr. Bridges had returned within a week or less from
Scotland. Tr. 3113 and 3119-3121 (Dr. Dowling). The effect of Dr.
Bridges' language was to purposefully mislead Dr. Dowling into believing
that Dr. Bridges had not held this paper for as long as he did.
Dr. Bridges' letter states next:
It [finding the Bernstein/Rando paper in the mail] has put me in
something of a predicament because we were doing rather similar
experiments just before ARVO and I remember discussing our
preliminary findings with Bernstein in Sarasota. . . The work in
my lab. was that of a graduate student and Rick Alvarez - we are
much further advanced now, but delays during the summer (plus
IRBP, which has been eating us up over the past 4 years) has
meant that we are still not ready for publication.
A.Ex. 161 (Item 9). The documentary record and the testimony show that
neither of these two statements is true. The record indicates that the
only experimentation even purportedly related to the experiments
reported in the Bridges/Alvarez Science paper was conducted in November
1985 on bovine eyes, not frogs as in the Science paper. The bovine
experiment did not use the same experimental methods later used by Dr.
Bridges in the Science paper. See below, Development of Research
Methods Reported in the Science and PNAS papers. For example, Dr.
Bridges employed Bovine Serum Albumin (BSA) differently in the Science
paper than he did in the November 1985 bovine experiment. As is
discussed below, in the opinion of several expert witnesses, the
November 1985 bovine experiments, which Dr. Bridges claimed were the
precursor experimentation, were different from the experiments reported
in the Science paper. There is no basis in fact, therefore, for Dr.
Bridges' statement that he was doing similar experiments just before the
May 1986 ARVO meeting.
Furthermore, in arguing the ultimate issue in dispute here, Dr. Bridges
has contended that his work on the frog series experiments reported in
the Science paper did not begin until after the May 1986 ARVO meeting.
Consequently, his statement in this letter that he was performing
"rather similar experiments just before ARVO" could not possibly
reference the critical frog series experiments. Emphasis added. Dr.
Dowling testified that he now believes Dr. Bridges' implication in the
September 2, 1986 letter that he and Mr. Alvarez were carrying out these
experiments in the spring of 1986 was not true. Tr. 3113-3114 (Dr.
Dr. Bridges also repeatedly contended that he first began to discuss the
possibility of conducting the frog isomerase experiments with his
graduate student, Dr. Lin, in January 1986 as one of two possible thesis
projects for her. Ex. 8, p. 34; see generally Tr. 3212-3221 (Dr.
Bridges). Dr. Lin testified that during the time that Dr. Bridges
discussed the possibility of doing her thesis on the isomerase, he gave
her reprints of the theoretical background for the isomerase project but
he had never shown her any preliminary results he might have had on the
frog isomerase or results from the November 1985 bovine experiments.
Tr. 2089 (Dr. Lin). Dr. Lin also testified that in the Spring of 1986
she made a decision between the two thesis projects suggested by Dr.
Bridges and decided to pursue a project other than the isomerase. She
then began her thesis project on May 20, 1986. Dr. Lin indicated that
she had never worked on the isomerase, nor had any other graduate
student worked on the isomerase experiment during the time she worked in
the Bridges' lab (Summer of 1985 to August 1987). Tr. 2090 and 2101
(Dr. Lin). Consequently, I find that Dr. Bridges' statement in the
letter that the work in his lab was that of a graduate student was
false. A.Ex. 161 (Item 9).
Dr. Bridges also wrote to Dr. Dowling that he had discussed his findings
with Dr. Bernstein at the May 1986 ARVO meeting, yet Dr. Bernstein
denied that Dr. Bridges spoke directly to him or that he responded to
Dr. Bridges. A.Ex. 158; Tr. 451-452 (Dr. Bernstein); Tr. 3225-3226 (Dr.
Bridges). Rather, Dr. Bridges asked a question of one of the authors
presenting a paper during that meeting, which question was addressed to
the whole group and not to Dr. Bernstein individually. Dr. Fong had a
recollection similar to Dr. Bernstein's. Tr. 2137-2139 (Dr. Fong).
Taken together, the false statements made in Dr. Bridges' September 2,
1986 letter to Dr. Dowling show a pattern of conduct of intentional
deception which permeates the entire record. This pattern of
inconsistent statements and obvious deceptions caused me to question Dr.
Bridges' overall credibility.
Furthermore, the circumstances surrounding Dr. Bridges' receipt, review,
and return of the PNAS manuscript potentially delayed publication of the
Bernstein, Law and Rando paper. While Dr. Dowling testified that Dr.
Bridges' handling of the manuscript did not delay publication "in any
significant way," this is a judgment in hindsight. Tr. 3117 (Dr.
Dowling). PNAS requires two "formal reviewers." Tr. 3081 (Dr.
Dowling). When Dr. Bridges did not review the paper it was then
necessary to obtain a third reviewer. Tr. 3081-82 (Dr. Dowling). The
PNAS manuscript was not referred to a third reviewer until October 9,
1986, after completion of the revisions made as a result of the first
reviewer's comments (he returned his comments in late August, 1986).
Tr. 3081-3082, and 3100 (Dr. Dowling). If Dr. Bridges had returned the
manuscript declining to act as a reviewer within twenty-four hours of
reading it, as Dr. Dowling testified was customary (Tr. 3123), an
additional reviewer could have been obtained in August.
PNAS is published bi-monthly. Dr. Bridges stated that in his experience
PNAS usually publishes "very rapidly" and he thought the PNAS article
would have been in print before the end of the year. Tr. 4360 (Dr.
Bridges). As a result, Dr. Bridges stated that his "goal was to . . .
get my paper submitted before his [Rando's] paper came out." Tr. 4374
(Dr. Bridges). Therefore, he submitted his paper to Nature in November
1986 in an attempt to try to publish his results before the PNAS
manuscript appeared in print. Tr. 4374 (Dr. Bridges). Thus, it is
reasonable to conclude that if Dr. Bridges had returned the manuscript
immediately, the paper would have been communicated to PNAS some time
before December 1986 and published before April 1987.
Most important, however, is the undeniable fact that Dr. Bridges read
the PNAS paper carefully. Tr. 3101 (Dr. Dowling). He had commented
that he was "concerned at the total lack of primary data," that such
data are a "sine qua non" and "should be presented with cleaner results
from a better defined system," and that "the paper was messily written."
A.Ex. 161 (Item 9). From Dr. Dowling's testimony, I find that he
regarded these comments as consistent with the first reviewer's, who had
stated that the manuscript was "not yet suitable for publication" and
"not as clearly written as it might have been." Tr. 3100-3101 and 3122
(Dr. Dowling). These comments are significant because they demonstrate
how familiar Dr. Bridges was with the manuscript's contents. While at
the time Dr. Dowling did not regard Dr. Bridges' comments on the
manuscript to be inappropriate, this opinion was formed in the context
of Dr. Dowling's initial belief that Dr. Bridges had "just returned."
Tr. 3122-3124 (Dr. Dowling).
THE SCIENCE PAPER
31. THE SCIENCE PAPER REPORTS SOME DATA AND RESULTS FROM DR. BRIDGES'
FROG SERIES OF EXPERIMENTS. THE FROG SERIES AT ISSUE HERE INCLUDED
FIFTEEN FROG PROTOCOLS AND THE RATONE PROTOCOL.
32. ON NOVEMBER 5, 1986, DR. BRIDGES SUBMITTED A MANUSCRIPT OF AN
EARLIER VERSION OF THE SCIENCE PAPER TO THE JOURNAL NATURE WHICH
REJECTED THE MANUSCRIPT ON JANUARY 12, 1987.
33. A REVISED MANUSCRIPT WAS SUBMITTED TO SCIENCE ON JANUARY 27, 1987,
ACCEPTED ON APRIL 22, 1987, AND PUBLISHED JUNE 26, 1987.
34. DR. BRIDGES SENT A PREPRINT OF THE ACCEPTED SCIENCE MANUSCRIPT TO
DR. DOWLING PRIOR TO THE MAY 1987 ARVO MEETING.
35. DR. DOWLING TOLD DR. BRIDGES THAT THE SCIENCE ARTICLE DID NOT
PROPERLY CREDIT THE PNAS ARTICLE, WHICH DR. BRIDGES HAD ACCESS TO THE
36. ARVO ABSTRACTS FOR THE 1987 MEETING INCLUDED ABSTRACTS OF THE
RESEARCH REPORTED IN THE SCIENCE AND THE PNAS ARTICLES.
37. AFTER PUBLICATION OF THE 1987 ARVO ABSTRACTS, DR. BERNSTEIN BROUGHT
TO DR. RANDO'S ATTENTION THE SIMILARITIES IN THE ABSTRACTS OF THE
SCIENCE AND PNAS PAPERS.
38. IN RESPONSE TO QUESTIONS FROM DR. RANDO, DR. DOWLING IDENTIFIED DR.
BRIDGES AS ONE OF THE REVIEWERS FOR THE PNAS MANUSCRIPT.
39. AT A MEETING SUGGESTED BY DR. DOWLING WHICH OCCURRED DURING THE MAY
1987 ARVO MEETING, DRS. BERNSTEIN, RANDO, AND BRIDGES AGREED TO CHANGES
TO THE SCIENCE MANUSCRIPT, PRIMARILY TO THE ABSTRACT, THE INTRODUCTION,
AND THE FOOTNOTE REFERENCE TO THE PNAS ARTICLE.
40. THE CHANGES ULTIMATELY MADE TO THE SCIENCE PAPER WERE NOT THOSE
AGREED TO BY DRS. RANDO AND BERNSTEIN.
41. IT IS THE POLICY OF SCIENCE MAGAZINE THAT THE EDITORS DO NOT MAKE
ANY CHANGES WHICH THE AUTHORS HAVE NOT APPROVED AT THE PROOF STAGE, THE
STAGE AT WHICH THE AGREED UPON CHANGES WERE TO BE MADE.
42. DR. BRIDGES FALSELY ATTRIBUTED ALTERATIONS TO THE AGREED UPON
CHANGES SOLELY TO THE EDITORS OF SCIENCE MAGAZINE.
43. DR. BRIDGES DID NOT MAKE THE CHANGES AGREED TO BY DRS. RANDO AND
BERNSTEIN BECAUSE HE WAS IRRITATED BY DR. RANDO.
44. DR. BRIDGES LATER ADMITTED RESPONSIBILITY FOR THE ACTUAL CHANGES
MADE TO THE SCIENCE ARTICLE.
45. THE ACTUAL CHANGES MADE TO THE SCIENCE ARTICLE FAILED TO
ACKNOWLEDGE PRIORITY OF OBSERVATION BY DRS. BERNSTEIN, LAW, AND RANDO
AND FALSELY SUGGESTED THAT DR. BRIDGES' SCIENCE PAPER WAS SUBMITTED
BEFORE HE SAW A VERSION OF THE PNAS MANUSCRIPT.
46. THE ACTUAL CHANGES TO THE FOOTNOTE REFERENCE TO THE PNAS ARTICLE
FALSELY SUGGESTED THAT MR. ALVAREZ SAW A COPY OF THE PNAS MANUSCRIPT AND
WERE AMBIGUOUS WITH REGARD TO ACCORDING PRIORITY OF OBSERVATION TO THE
47. DR. BRIDGES SOUGHT PUBLICITY FOR THE SCIENCE ARTICLE,
CHARACTERIZING IT AS MAKING A MAJOR DISCOVERY WHICH HAD ELUDED
RESEARCHERS FOR 30 YEARS.
DISCUSSION OF THE SCIENCE PAPER
Findings 31 through 44 are established on the record. Ex. 4, p. 18;
A.Exs. 31 (Item 8A), 161 (Item 2); Tr. 48-49 (Dr. Knight), 200 and 355
(Dr. Rando), 453-454 (Dr. Bernstein), 3083-3088, 3105-3107, 3116 (Dr.
Dowling), and 4280-4290 (Dr. Bridges). In addition, Agency proposed
findings of fact 18 through 22, as well as the Baylor and NIH reports
state these matters in some detail. See A.Ex. 94 at 7-17 and Ex. 4 at
3-4. No proposed findings of fact contrary to these were proposed by
Findings 45 and 46 pertain to the effect of the changes that were agreed
to by Drs. Bernstein and Rando as compared to the changes actually in
the Science article as published. Finding 47 concerns publicity for the
Science article. I discuss the basis for these findings below.
Findings 42 through 46 are material factors affecting my evaluation of
the overall credibility and persuasiveness of the presentation made on
Dr. Bridges' behalf, including Dr. Bridges' testimony. Finding 47 is of
interest but is tangential to the central question of plagiarism.
The Science manuscript in press in May 1987 stated in the abstract as
Thirty years have elapsed since Wald and his colleagues showed
that 11-cis retinal was isomerized to all-trans when rhodopsin
was bleached, yet nothing is understood about the reverse
process that generates 11-cis retinal for rhodopsin
regeneration. It is not known whether the isomerization is
enzyme mediated . . . . These questions have now been resolved
in the present report; radiolabeled all-trans retinol and high
performance liquid chromatography have been used to demonstrate
the existence of an eye-specific . . . .
According to Dr. Rando, after meeting with Dr. Bridges at ARVO 1987, Dr.
Bridges agreed to make the following changes (pertinent language
indicated below in capital letters) to his manuscript:
Thirty years have elapsed since Wald and his colleagues showed that
11-cis retinal was isomerized to all-trans when rhodopsin was
bleached, YET LITTLE HAS BEEN UNDERSTOOD about the reverse process
that generates 11-cis retinal for rhodopsin regeneration. UNTIL
RECENTLY, IT WAS not known whether the isomerization is enzyme
mediated . . . . IN THE PRESENT REPORT, radiolabeled all-trans
retinol and high performance liquid chromatography have been used
to demonstrate the existence of an eye-specific . . . .
The version of the abstract as it was actually published in Science is
Thirty years have elapsed since Wald and his colleagues showed
that 11-cis retinal was isomerized to all-trans when rhodopsin
was bleached, YET LITTLE HAS BEEN UNDERSTOOD about the reverse
process that generates 11-cis retinal for rhodopsin
regeneration. IT IS NOT KNOWN WHETHER the isomerization is
enzyme-mediated . . . Radiolabeled all-trans retinol and high
performance liquid chromatography have NOW been used to
demonstrate the existence of an eye-specific, membrane-bound
enzyme . . . .
Ex. 8 (Item 2).
The introductory paragraphs of the original manuscript of the Science
paper read as follows:
The isomerization of all-trans retinoids to the 11-cis
configuration is essential for visual pigment regeneration in the
eye (1), but it has been suggested recently that the isomerization
may not be enzyme-mediated (2). A "retinal isomerase" originally
reported by Hubbard (3) apparently acted by photoisomerization of
an artifactually generated protonated Schiff base composed of
all-trans retinal and phosphatidylethanolamine (6). Furthermore,
this observation probably lacks physiological significance, because
exposure to potentially isomerizing light does not influence the
course of dark-adaptation in vertebrates (5). Here we have studied
frogs and rats . . . .
The changes agreed to by Dr. Rando, Dr. Bernstein, and Dr. Bridges were
The isomerization of all-trans retinoids to the 11-cis
configuration is essential for visual pigment regeneration in
the eye (1). (Deletion). A "retinal isomerase" originally
reported by Hubbard (3) apparently acted by photoisomerization
of an artifactually generated protonated Schiff base composed of
all-trans retinal and phosphatidylethanolamine (6).
Furthermore, this observation probably lacks physiological
significance, because exposure to potentially isomerizing light
does not influence the course of dark adaptation in vertebrates
(5). ALTHOUGH IT HAD BEEN SUGGESTED THAT THE ISOMERIZATION MAY
NOT BE ENZYME-MEDIATED (2) RECENT DATA FROM THESE AUTHORS HAS
DEMONSTRATED THE EXISTENCE OF RETINOL-SPECIFIC ISOMERASE IN
PIGMENT EPITHELIUM. HERE . . .
The Science paper as published actually read in pertinent part as
Although it had been suggested that the isomerization may not be
enzyme-mediated, recent data by the same authors THAT APPEARED
SINCE THE PRESENT WORK WAS SUBMITTED demonstrated a
retinol-specific isomerase in pigment epithelium.
Ex. 8 (Item 2).
After the ARVO 1987 meeting between Drs. Bridges, Bernstein, and Rando,
footnote reference 2 in Dr. Bridges' article was to read as follows:
P. S. Bernstein, J. R. Lichtman, R. R. Rando, Biochemistry 24,
487 (1985). More recently, however, Bernstein et al., Proc.
Nat. Acad. Sci. (1987) have demonstrated that the isomerizing
reaction is enzymatic, and have obtained results similar to
those reported here. A version of their manuscript was made
available to the present authors by J. E. Dowling.
A.Ex. 94. 8/
The Science paper, as published, changed reference 2 to reference 5 and
was worded, as follows:
P. S. Bernstein, J. R. Lichtman, R. R. Rando, Biochemistry 24,
487 (1985); P. S. Bernstein. W. C. Law, R. R. Rando, Proc. Natl.
Sci. U. S. A. 84, 1849 (1987). A version of the latter
manuscript was shown to the present authors by J. E. Dowling.
See Tr. 210-218 (Dr. Rando) and Tr. 497-502 (Mr. Alvarez); Ex. 94 (Item
The Science manuscript initially made no mention of the research and
results of the Bernstein, Law, Rando group. Indeed, since the PNAS
manuscript contents were a privileged communication, there is some
question whether it would have been appropriate to do so without
coordination with the authors. See Tr. 4282 (Dr. Bridges); and A.Ex. 31
(Item 8A). In any event, it was Dr. Dowling who initially raised with
Dr. Bridges some obligation to acknowledge the work reflected in the
PNAS manuscript which Dr. Bridges had seen during the summer of 1986.
Tr. 3087 (Dr. Dowling).
Although it appears that Dr. Rando believed upon review of the Science
manuscript that improper use had been made of the privileged material in
the PNAS draft manuscript (A.Ex. 156), the meeting and the changes
discussed were not intended to address this possibility. Dr. Rando
testified that his initial concern was Dr. Bridges' review of the PNAS
manuscript while apparently conducting similar work. Tr. 203 (Dr.
Rando). Drs. Bernstein and Rando were concerned that they were not
properly referenced since the text of the Science article stated that
there was "nothing" known about the isomerase reaction. Tr. 454 (Dr.
Bernstein). Dr. Bernstein testified that while it was a little
premature to expect Dr. Bridges to cite their article, the basis for
their concern was that Dr. Bridges knew of their work. Tr. 455 (Dr.
Bernstein). Also, generally, literal priority in publication would be
established simply based on the publication dates. Tr. 3095 (Dr.
Dowling). As a practical matter it would be difficult to determine the
priority in observation here without the type of references which Dr.
Rando sought to add because both articles were published in the same
year. The Baylor Committee found that Dr. Bridges had acted in "an
unprofessional manner" by failing to assure the agreed upon changes were
actually part of the published article. A.Ex. 94, p. 4.
One factor which apparently influenced Dr. Bridges with regard to the
changes actually made was that Dr. Rando wrote directly to Science
magazine to report these changes. A.Ex. 187. Dr. Bridges stated that
he was not "given the opportunity to make the changes before he [Dr.
Rando] did so." Tr. 4301 (Dr. Bridges). Dr. Dowling stated that Dr.
Bridges was irked at Dr. Rando and that this had influenced Dr. Bridges
with regard to the changes actually made. Tr. 4290 (Dr. Bridges); and
Tr. 3105-3107 (Dr. Dowling).
From Dr. Rando's perspective, the agreed upon changes were necessary to
reflect the chronology of events of the review of the PNAS manuscript
and preparation of the Science article. Tr. 355 (Dr. Rando). The
object of the changes was for Dr. Bridges to acknowledge that he had
seen the PNAS paper prior to submission of the Science paper and to
revise the introduction to the Science paper so as to not undercut the
contribution to the field of the PNAS paper. Tr. 207-210 (Dr. Rando).
This was apparently a cordial meeting where the changes were discussed
in the context of giving proper priority to the PNAS paper. Tr. 219
(Dr. Rando). The statements in the Science article as published
diminish the priority in observation accorded the PNAS paper (1) by not
acknowledging in the abstract that the PNAS paper reported that the
reaction in question is enzyme mediated, and (2) by distancing the
Science article from the PNAS article in the introduction by referring
to the article as having "appeared since the present work was
submitted." Given the changed text, the shorter statement in the
footnote, that the Science authors saw a version of the PNAS manuscript,
becomes ambiguous in context. The changes made to the language agreed
to by Dr. Rando, while subtle, alter the Science article to no longer
clearly accord priority of observation.
There is documentary and testimonial evidence concerning publicity for
the Science article. Tr. 4290-4302 (Dr. Bridges); A.Exs. 161 (Item 7),
166, 183, and 189. While Dr. Bridges at one time disclaimed any
responsibility (A.Ex. 156), Dr. Bridges ultimately did not deny that he
had sought out this publicity. On April 27, 1987, Dr. Bridges had
referred the approved Science manuscript to the Baylor Assistant
Director of Publications and Internal Communications stating that the
work was a "major breakthrough." A.Ex. 189. Dr. Bridges was
responsible for a June 1987 news release by Baylor which was published
in the Texas Medical Center News and reported as a "science/technology
concentrate" by Chemical and Engineering News. A.Exs. 183, 161 (Item
7), 166. The news release Dr. Bridges approved in June 1987 explicitly
stated that the Science article "comes 30 years after the last major
finding." A.Ex. 183. No sooner was the piece published (June 29, 1987)
in Chemical and Engineering News than two letters in response commented
respectively on the "similar results" and "experimental conditions" of
the earlier PNAS article. A.Ex. 166. For Dr. Bridges to agree to and
seek out publicity for the Science article claiming, in essence, sole
credit for this breakthrough at a time when he knew this to be untrue
calls into question his integrity and honesty in this matter in general.
CONDUCT OF THE FROG SERIES OF EXPERIMENTS
48. DR. BRIDGES DID NOT DO LABORATORY BENCH WORK ON A REGULAR BASIS.
49. DR. BRIDGES CONDUCTED ONLY LIMITED LABORATORY BENCH WORK ON THE
FROG SERIES PROTOCOLS WHICH WERE THE BASIS FOR THE SCIENCE ARTICLE.
50. DR. BRIDGES DESIGNED EACH OF THE FROG SERIES PROTOCOLS.
51. MR. ALVAREZ MAINTAINED THE RECORDS FOR THE FROG SERIES OF
52. THE FROG SERIES EXPERIMENTAL RECORDS CONSISTED OF DATA MAINTAINED
ON A COMPUTER HARD DISK AND BACK-UP FLOPPY DISKS AS WELL AS LABORATORY
NOTEBOOKS AND EXPERIMENTAL DATA.
53. FOR THE FROG SERIES EXPERIMENTS MR. ALVAREZ MAINTAINED NOTEBOOKS
AND EXPERIMENTAL DATA IN FILES IN A CABINET NEAR HIS DESK.
54. MR. ALVAREZ'S NOTEBOOKS AND EXPERIMENTAL DATA FILES INCLUDED:
DATED EXPERIMENTAL PROTOCOLS; TABULATED SCINTILLATION COUNTER DATA;
NOTES, TABLES, AND GRAPHS CONCERNING THE IDENTIFICATION OF 11-CIS,
13-CIS, 9-CIS, AND ALL-TRANS RETINOL; SOME DATED RAW DATA FROM THE
SCINTILLATION COUNTER; AND SOME BATCH INFORMATION FROM AMERSHAM
CORPORATION ON TRITIATED RETINOL.
55. COMPUTER RECORDS MAINTAINED BY MR. ALVAREZ CONSISTED OF A STATEMENT
OF EACH PROTOCOL AND EXPERIMENTAL DATA MAINTAINED ON A SPREADSHEET
PROGRAM CALLED LOTUS 1-2-3. A.EX. 104, ITEMS 10 AND 11. THE PROTOCOLS
WERE DATED ON OR ABOUT THE TIME THE EXPERIMENTS WERE ACTUALLY PERFORMED.
56. MR. ALVAREZ MAINTAINED BACK-UP FLOPPY DISKS ON A PROGRAM CALLED "DS
BACK-UP" FOR ALL OF THE INFORMATION MAINTAINED ON THE COMPUTER HARD
57. THE FROG SERIES DATA WAS INITIALLY KEPT ON AN IBM XT COMPUTER.
58. SOME TIME AFTER MARCH 1987, DATA ON THE FROG SERIES PROTOCOLS WAS
TRANSFERRED ONTO THE COMPUTER HARD DISK OF A PANASONIC COMPUTER ACQUIRED
DURING THE SPRING OF 1987. THIS DATA WAS SHIFTED TO THE PANASONIC
BECAUSE THE IBM XT HAD EXPERIENCED SEVERAL HARD DISK CRASHES.
DISCUSSION OF CONDUCT OF THE FROG SERIES OF EXPERIMENTS
After hearing the testimony and reviewing the documents submitted, I
determine that Dr. Bridges did not do laboratory bench work on a regular
basis and conducted only limited bench work on the frog series of
experiments. On balance, I do not find Dr. Bridges' testimony that he
was greatly involved in the actual lab work persuasive. See, Tr.
3406-3852 (Dr. Bridges' description of the frog series experiments).
Rather, the preponderance of the evidence showed that Dr. Bridges
usually did not perform laboratory bench work. His two laboratory
technicians testified that Dr. Bridges did not perform experiments at
the bench on a regular basis. Tr. 725, 760, and 957 (Mr. Alvarez).
This is consistent with the testimony of one of Dr. Bridges' character
witnesses, Dr. Ostroy. Dr. Ostroy stated that as a scientist, Dr.
Bridges' style "is not of a hands-on laboratory individual," but,
rather, his style is "to administer the lab." Tr. 5169 (Dr. Ostroy).
The testimony was that Dr. Bridges' bench work was generally limited to
performing (or watching that the performance was correct) of some
"tricky" dissections. Tr. 957, 5314-5316 (Mr. Alvarez).
Furthermore, the overall recollection of those who worked in Dr.
Bridges' lab was that Dr. Bridges' participation in the actual
experimentation on the frog series was limited. During the period of
time that Dr. Bridges claimed the frog series was performed, only Dr.
Bridges recalls that he had such extensive involvement in the actual
bench experimentation. Tr. 725, 957, and 5169 (Mr. Alvarez). While Dr.
Lin thought she saw Dr. Bridges and Mr. Alvarez conducting experiments
in the laboratory on perhaps two occasions, she could not remember an
exact date or month, nor could she verify what actual research was being
conducted. Tr. 1950, 2090-2093, 2094, and 2122 (Dr. Lin).
Furthermore, if the frog series research had begun in May 1986 and
continued through to October 1986 and if Dr. Bridges had conducted the
majority of the frog series of experiments as he testified, it is highly
unlikely given the size and layout of Dr. Bridges' laboratory that Dr.
Lin, who was allegedly performing her work in the same part of the lab
at around the same time, would have had only two occasions to observe
Dr. Bridges and Mr. Alvarez working together. Tr. 2079-2080, 2104 (Dr.
Lin); Tr. 3419-3458, 3473, 3481, 3525, 3559, 3593, 3595, and 3597-3598
(Dr. Bridges); and CDB V. Ex. F. None of the other members of Dr.
Bridges' laboratory testified that they saw Dr. Bridges and Mr. Alvarez
working together on the experiments. 10/ Also, while Dr. Bridges
testified that he also performed some of the frog series dissections,
Dr. Lin had no recollection of this, and Mr. Alvarez flatly denied that
Dr. Bridges performed any of the frog series dissections. Tr. 1950,
2090-2094 (Dr. Lin), and 5317 (Mr. Alvarez). Mr. Alvarez testified that
Dr. Bridges' assistance in the frog series of experiments was limited to
helping with the fraction collection during the performance of the frog
one experiment only. Tr. 726, 760, and 5314 (Mr. Alvarez). I also find
Dr. Bridges' testimony of his intense involvement in the frog series of
experiments less persuasive because of the lack of familiarity Dr.
Bridges exhibited with the frog series experiments during his testimony
when he attempted to relate data and results reported in sections of the
Science article to particular frog series protocols. Tr. 3406-3852 (Dr.
While Dr. Bridges designed each of the frog series protocols after
consulting with Mr. Alvarez, Mr. Alvarez was responsible for reporting
these protocols and the experimental results. Tr. 514-522, 5398-5399
(Mr. Alvarez). Dr. Bridges testified that since 1982 he had not kept
laboratory notebooks or notes on research being conducted. Tr.
4259-4260 (Dr. Bridges). Rather, it was his practice to have the lab
staffer carrying out the research keep the laboratory records of the
experimentation. Tr. 4260 (Dr. Bridges). Dr. Bridges indicated that
the only records he kept were a personal diary in which he made notes
regarding the overall operation of his laboratory as well any ideas that
might come up. Tr. 3204 (Dr. Bridges).
Dr. Bridges did not dispute Mr. Alvarez's testimony about the types of
records maintained by Mr. Alvarez for the frog series. A.Exs. 19, 58,
and 104 (Items 10 and 11); Tr. 2157 (Dr. Fong); Tr. 5346, 5397-5399 and
5497 (Mr. Alvarez). Although Dr. Bridges was subsequently critical of
the way Mr. Alvarez maintained the laboratory records for the frog
experiments, this criticism is disingenuous. There is no indication
that Dr. Bridges, as Mr. Alvarez's employer and the principal
investigator of the grant project, instructed Mr. Alvarez to do
otherwise. A.Ex. 128 at 2. Furthermore, there was testimony by other
researchers indicating that it was not possible to keep the printouts
from machines such as scintillation counters and high pressure liquid
chromatographs in bound lab notebooks. Tr. 471 (Dr. Bernstein).
Consequently, some researchers use loose leaf notebooks or files to keep
all this data. Tr. 471 (Dr. Bernstein); and Tr. 5172-5173 (Dr. Ostroy).
Moreover, there is no evidence that Dr. Bridges discouraged Mr. Alvarez
from using the computer to enter the results of the experiments. Thus,
there is no indication that Mr. Alvarez's method of keeping records was
out of the ordinary in Dr. Bridges' lab. Also, there is no basis in
this record for finding other than that Mr. Alvarez's record keeping
practices were acceptable under current scientific standards. Tr.
5172-5173 (Dr. Ostroy).
EXPERIMENTAL DATA FOR THE SCIENCE ARTICLE
59. DESPITE REPEATED REQUESTS TO PROVIDE THE PRIMARY EXPERIMENTAL DATA
PERTAINING TO THE SCIENCE ARTICLE, DR. BRIDGES HAS PROVIDED ONLY
INCOMPLETE AND SEEMINGLY INACCURATE DATA.
60. DR. BRIDGES LED THE BAYLOR COMMITTEE TO BELIEVE THAT HE HAD
DISCARDED HIS PRIMARY DATA FROM THE FROG SERIES EXPERIMENTS.
61. WHILE DR. BRIDGES ASSERTED THAT THE PRIMARY DATA MAINTAINED BY MR.
ALVAREZ HAD BEEN LOST OR STOLEN DURING AUGUST 1987, THIS WAS NOT
REPORTED TO BAYLOR AUTHORITIES AT THAT TIME.
62. DR. BRIDGES HAS NEVER SATISFACTORILY ACCOUNTED FOR WHY THE PRIMARY
DATA MAINTAINED BY MR. ALVAREZ WAS NOT MADE AVAILABLE.
63. DURING AUGUST 1987, DR. BRIDGES REMOVED FROM MR. ALVAREZ'S FILING
CABINET THE NON-COMPUTERIZED EXPERIMENTAL DATA FOR THE FROG AND RAT
PROTOCOLS MAINTAINED BY MR. ALVAREZ.
64. DR. BRIDGES ALSO TOOK RESEARCH DATA MAINTAINED BY ANOTHER RESEARCH
TECHNICIAN IN HIS LABORATORY, MR. ROBERT LANDERS.
65. DR. BRIDGES PROVIDED BATCH ANALYSIS SHEETS OF A TYPE MAINTAINED BY
MR. ALVAREZ IN HIS RECORDS.
66. DR. BRIDGES HAS NEVER SATISFACTORILY ACCOUNTED FOR WHY THE BACK-UP
FLOPPY DISKS MADE BY MR. ALVAREZ WERE NOT MADE AVAILABLE.
67. DR. BRIDGES PROVIDED ONLY 66 PAGES OF COMPUTER GENERATED DATA AND
OTHER FRAGMENTARY PIECES OF DATA TO SUPPORT HIS CONTENTION THAT THE FROG
SERIES EXPERIMENTS BEGAN IN MAY 1986.
68. ON OCTOBER 7, 1987, MR. ALVAREZ PROVIDED TO THE BAYLOR COMMITTEE
COPIES OF FROGONE AND FROGTWO PROTOCOLS DATED AUGUST 6, 1986 AND AUGUST
69. ON OR ABOUT JANUARY 5, 1988, THE 66 PAGES WAS RETRIEVED FROM THE
PANASONIC WHEN A PURDUE COMPUTER TECHNICIAN LOCATED THE FILES ON A
SUBDIRECTORY OF THE PANASONIC COMPUTER. THE FILES HAD NOT BEEN DELETED
FROM THE HARD DISK.
70. MANY PERSONNEL INCLUDING DR. BRIDGES HAD ACCESS AND SOME
FAMILIARITY WITH THE COMPUTERS AND THEIR OPERATION.
71. THE PANASONIC COMPUTER WAS SEALED AND PACKED FOR SHIPMENT TO PURDUE
IN SEPTEMBER 1987.
72. DR. BRIDGES HAS NEVER SATISFACTORILY ACCOUNTED FOR WHY HE WAITED
UNTIL JANUARY 1988 TO PROVIDE ANY COMPUTERIZED DATA (THE 66 PAGES) FROM
THE RECORDS ON THE PANASONIC COMPUTER.
DISCUSSION OF EXPERIMENTAL DATA FOR THE SCIENCE ARTICLE
The record shows that Dr. Bridges was not forthcoming in providing
primary experimental data pertaining to the Science paper despite the
serious nature of the allegations against him. 11/ Within this context,
it is important to note that a principal investigator must keep complete
and accurate records in support of any scientific research conducted.
In this instance, the supporting experimental documentation would have
conclusively shown whether any misconduct occurred. 12/ Thus, taken as
a whole, Dr. Bridges' actions confused and obscured the investigatory
proceedings both at Baylor and at NIH. Tr. 1548-1549, 1843-1849 (Dr.
Bradshaw); Ex. 4, pp. 25-27; and A.Ex. 94, pp. 21-22. As we detail
below, we can draw a negative inference in part from the circumstances
surrounding Dr. Bridges' failure to produce original primary data.
1. What the Baylor Committee first understood from Dr. Bridges with
regard to the disposition of the experimental data.
From the initiation of the Baylor investigation in September 1987, the
Baylor Committee understood Dr. Bridges to say that he had discarded
some of the experimental data related to the Science paper in
preparation for his move to Purdue University. Ex. 8 (Item 34); and
A.Ex. 25. Furthermore, while Dr. Bridges claimed he called Dr. Knight,
the Committee Chair, to correct this perception expressed in Dr.
Knight's September 30, 1987 letter, the only inaccuracy noted by Dr.
Knight on his copy of the letter is as follows:
10/1 3.10 - phone call- D. Bridges- not in agreement with dates
of Para. 3. Says initiated work in May.
Ex. 8 (Item 34). Dr. Bridges' copy of the same letter, however, has a
notation in Dr. Bridges' handwriting that he called Dr. Knight and
clarified two points--(1) that the successful experiments were in May
not August, and (2) that the discarded material was "mainly stuff from
London and Miami" (material dating up to 1965). Ex. 8 (Items 34 and
35). However, while Dr. Bridges maintained that he told the Committee
that he had only discarded very old material, both the Baylor
Committee's response to the NIH Preliminary Report and Dr. Knight's
testimony stated that both Dr. Knight and the rest of the Baylor
Committee understood Dr. Bridges to tell them that some of the
experimental records on the frog series was discarded in packing up for
Dr. Bridges' move to Purdue. A.Exs. 25, 26, and 38 (Item 1); and Tr. 42
(Dr. Knight). In fact, when the Baylor Committee requested that Dr.
Bridges supply them with a copy of the complete experimental protocols,
Dr. Bridges stated again on December 15, 1987 that "the laboratory was
in the process of a major move, materials were being discarded and
packed up." A.Exs. 129, and 31 (Item 8N). Consequently, Dr. Bridges'
handwritten notation on his copy of the letter conflicts with his
earlier and later statements. There is no indication that Dr. Bridges
sent Baylor his copy of the September 30, 1987 letter. In weighing this
handwritten notation against Dr. Bridges' other statements and the
understanding of the Baylor Committee, I find that Dr. Bridges led the
Committee to believe that he was unable to provide copies of the
experimental protocols because these materials had been discarded. 13/
2. What Dr. Bridges later informed the Baylor Committee about the
disposition of the experimental data.
Next the record shows that by a November 12, 1987 letter, sent
approximately three months after the Baylor Committee investigation
began, Dr. Bridges told the Baylor Committee for the first time that he
was unable to provide the Baylor Committee with copies of the
experimental protocols or other primary data. 14/ He stated:
It appears that much of the data from these early experiments
was taken from our files at the time when Liou took the
recombinant DNA clone notebooks and other documents from my
laboratory. I trust that Alvarez will confirm that files and
documents were missing from his filing cabinet on the morning of
August 17, 1987.
A.Ex. 31 (Item 8L).
The record does not support a finding that the retinol isomerase
experimental data had been "taken." There is no indication from the
record that the alleged theft of certain materials from Dr. Bridges'
laboratory in August 1987 was related to the frog series experiments,
that any information from the frog series experiments was taken, or that
Dr. Bridges ever claimed that frog series experimental materials were
also stolen at the time of the alleged theft by Dr. Liou of certain
material related to Dr. Liou's work. Rather, the record shows that the
August 1987 controversy with Dr. Liou provided an opportunity for Dr.
Bridges to cover up the lack of experimental data to support the
At the time of the alleged theft of materials from Dr. Bridges' lab in
August 1987, all the correspondence and communications from Dr. Bridges
to Baylor University indicate that the materials allegedly taken
involved experimental materials, experimental records, and notebooks of
methods, all relating to his joint research with Dr. Liou, rather than
the frog isomerase series experiments. A.Exs. 25, 31 (Items 8H, I, and
J), and 180. In fact, pursuant to an agreement reached between Dr.
Bridges and Dr. Liou, Dr. Bridges submitted to Baylor a detailed list of
materials and documents that were allegedly taken and necessary for his
research which were to be returned by Dr. Liou. A.Ex. 31 (Item 8E).
While this list is very particularized, it does not mention any
materials or documents related to the conduct of the isomerase
experiments. If Dr. Bridges went to the trouble to submit a detailed
report of missing materials, it is highly unlikely that he would fail to
include on that list missing records and materials for the isomerase
experiments, arguably one of the most important vision discoveries in 30
Moreover, a memorandum from the Chair of Dr. Bridges' department at
Baylor states that Dr. Bridges assured him on September 24, 1987 that
all matters regarding the restitution of the materials and documents
allegedly taken from his laboratory had been concluded to Dr. Bridges'
satisfaction. A.Exs. 25 and 31 (Item 8D); see also A.Ex. 31 (Item 8F)
(in which the Department Chair on September 16, 1987 requested that Dr.
Bridges inform him whether there were still any items from Dr. Bridges'
detailed list that Dr. Bridges required); and Ex. 8 (Item 32) (in which
Dr. Bridges informed the Department Chair on September 18, 1987 that
certain materials had not yet been received). Dr. Bridges admitted that
he had never informed Baylor about any alleged disappearance of Mr.
Alvarez's materials until well after the Baylor inquiry had begun. Tr.
4224 and 4228-4229 (Dr. Bridges). Dr. Bridges conceded that he did not
include Mr. Alvarez's materials on the inventory list. Dr. Bridges,
however, failed to explain why, if these materials had been taken, he
did not reference them even generally on this list. Dr. Bridges stated
that while many things were missing, he felt that given the
circumstances it was better to let the whole thing "slide." Tr. 4234
(Dr. Bridges). Thus, he had made no formal report of the missing
isomerase documents. Tr. 4235 (Dr. Bridges). I find incredible Dr.
Bridges' argument that he wanted to let the theft of the isomerase
materials "slide," considering that at the time of the alleged theft of
these materials there was a controversy brewing regarding the frog
series experiments reported in Science. Taking all these factors
together, I find that at the time of the alleged August 1987 theft of
materials from Dr. Bridges' laboratory, no materials or documents
related to the isomerase experiments were taken.
3. The circumstances supporting the conclusion that Dr. Bridges
removed the isomerase experimental data from Mr. Alvarez's filing
Furthermore, with the foregoing background established, the record
supports the finding that shortly after the alleged theft of materials
from Dr. Bridges' laboratory, Dr. Bridges removed from Mr. Alvarez's
filing cabinet the non-computerized experimental data for the frog
series protocols maintained by Mr. Alvarez. Both Mr. Landers and Mr.
Alvarez testified that on August 17, 1987 they discovered that their
experimental documentation was missing from their filing cabinets. Tr.
653-655 (Mr. Alvarez); Tr. 962 (Mr. Landers); see also Tr. 1060-1064
(Dr. Liou) (testimony from Dr. Liou that certain of his laboratory
notebooks and experimental materials were removed from his office space
in Dr. Bridges' lab on or about August 15, 1987). Mr. Alvarez testified
that Dr. Bridges said that he had removed Mr. Alvarez's materials for
safekeeping in light of the recent alleged theft of materials from his
laboratory. Tr. 653-655 (Mr. Alvarez); and A.Exs. 19 and 31 (Item 8M).
Mr. Alvarez also testified that Dr. Bridges assured him that he would
have continued access to the materials if needed. Tr. 654-655 (Mr.
While Dr. Bridges disputed this recollection, it is consistent with the
overall events occurring at that time. Tr. 4217-4224 (Dr. Bridges);
A.Ex. 36. Dr. Fong, the most senior member of Dr. Bridges' laboratory,
assisted with the detailed inventory list of the items missing from the
lab after the alleged theft by Dr. Liou. At the time of the alleged
theft, Dr. Fong did not notice that either Mr. Alvarez's or Mr. Landers'
notebooks and materials were missing. Dr. Fong testified that he first
learned that Mr. Alvarez's notebooks and materials were missing on
August 17, 1987 when Dr. Bridges told him that Mr. Alvarez had taken
them. Tr. 5269 (Dr. Fong); and Tr. 4216-4217 (Dr. Bridges). Even
though Dr. Fong and Dr. Bridges claim they became aware that Mr.
Alvarez's materials were missing on August 17, 1987 after the alleged
theft, as noted earlier, these items were not included on the very
detailed inventory prepared by Dr. Bridges with the help of Dr. Fong on
August 24, 1987. A.Ex. 31 (Item 8E). Moreover, Dr. Bridges never filed
a report specifying that these materials were taken. A.Ex. 25; and Tr.
4224 (Dr. Bridges).
The record also indicates that Dr. Bridges later used certain data that
would have been in Mr. Alvarez's missing files. A.Ex. 95. Dr. Bridges
disputed that he used data from the missing files in preparing his
abstract for ARVO 1988. A.Ex. 36. Dr. Bridges argued that the data for
this abstract was available to him in full and complete summaries,
including graphs and tables, that he kept in working files in his home.
Tr. 4251-4253 (Dr. Bridges). Earlier, at the NIH Panel's request, Dr.
Bridges submitted brief research records asserted to be the material he
used in the preparation of the 1988 ARVO abstract. The NIH Panel
commented that "Dr. Bridges' statements that he had complete records at
home are contrary to anything said or given to the Panel earlier." Ex.
4, Final Report, p. 42; see also Tr. 1842-1849 (Dr. Bradshaw).
The record also shows that after the NIH Panel submitted its Final
Report on May 11, 1989 to NIH, Dr. Bridges submitted a supplemental
response to the Panel's Preliminary Report with some attached
documentation. A.Ex. 30. Among these documents were Batch Analysis
Sheets for tritiated retinol sent from the Amersham Corporation on which
appear handwritten notations allegedly in Mr. Alvarez's writing. Ex. 8
(Items 5, 6, 7, and 22); and A.Exs. 25 and 30. Dr. Bridges testified
that he only would keep summaries of data, including graphs and tables,
in the files he kept at his home. Dr. Bridges' testimony also
corroborates Mr. Alvarez's testimony that these Batch Analysis Sheets
instead were typically kept in Mr. Alvarez's files. Tr. 3879 (Dr.
Bridges); and A.Ex. 19. Furthermore, Dr. Bridges provided no reasonable
explanation why he waited almost two and one half years after the Baylor
inquiry began to submit this documentation. I find, as the NIH Panel
did at one point, that the presentation of new data in response to the
preliminary report of the NIH Panel raises concerns not only about Dr.
Bridges' candor but about what experimental documentation he actually
had in his possession. A.Exs. 16 and 26; and Tr. 1851 (Dr. Bradshaw).
Dr. Bridges contended that he would have had no motivation for taking
Mr. Alvarez's materials for safekeeping in August 1987 since the Baylor
inquiry did not start until more than a month later. A.Ex. 36. While
it is true that the Baylor inquiry did not start until September 1987,
Dr. Bridges had notice as early as May 1987 when he received a call from
Dr. Dowling about his Science paper that a controversy was brewing.
Moreover, Dr. Bridges met with Drs. Rando and Bernstein at ARVO later in
May 1987 and knew of their concerns. Given the allegations that had
surfaced as of May 1987, it is simply not credible that Dr. Bridges
would have made no effort to safeguard the very documentation that would
prove that the frog series experiments began before he received the
privileged information. By the time Mr. Alvarez's materials were
removed in August 1987, the Science paper had been published without the
changes agreed to by Dr. Bridges and Dr. Rando. Consequently, there was
sufficient motivation for Dr. Bridges to have removed Mr. Alvarez's
4. The circumstances surrounding Dr. Bridges' belated production to
the Baylor Committee of certain fragmentary pieces of data and the 66
pages of the computer printouts.
The record also reflects that both the Baylor Committee and, later, the
NIH Panel made repeated requests to Dr. Bridges to present all relevant
documents in support of the isomerase research. A.Exs. 31 (Item 8K),
66, 115, 129, and 135; Tr. 1635-36 (Dr. Litman), Tr. 1845, 1848-52,
1874-76; and Tr. 5151-5153 (Dr. Adler). Even after these repeated
requests, Dr. Bridges presented only fragmentary pieces of data to the
Baylor Committee. A.Exs. 31 (Item 8L), 128, 130 and 132; and Tr.
1548-49 and 1843-1849 (Dr. Bradshaw). Despite the seriousness of the
allegations against him, Dr. Bridges did not provide Baylor with any
information until November 12, 1987 that appeared to be directly related
to the conduct of the isomerase research and the antecedent
experimentation. A.Ex. 31 (Item 8L). This documentation, however, was
far from complete. It did not contain any of the experimental protocols
for the frog series experiments. There was nothing presented in Dr.
Bridges' submissions to Baylor from the time the investigation began in
September 1987 until January 1988 that could support a conclusion that
Dr. Bridges even developed and performed the protocols reported in the
Science paper. A.Exs. 31 (Items 8 and 8L), 130, and 128. By letter
dated January 13, 1988 Dr. Bridges finally submitted to Baylor "data
found stored on the hard disk of one of our computers while it was being
set up by our Department's computer technician" consisting of "66 pages
of protocols, data and graphs spanning 5 months from May 14, 1986 to
October 14, 1986." A.Ex. 121. Dr. Bridges stated that this information
confirmed the timetable and the progression of his isomerase studies.
Dr. Bridges never satisfactorily accounted for why he waited until
January 1988 to provide the 66 pages of computerized data. The record
shows that Mr. Alvarez began in late 1985 to keep his experimental
records on the computer with the consent of Dr. Bridges. Mr. Alvarez
testified that initially these records were kept on the hard disk of the
laboratory's IBM PC XT computer with floppy disks backing up all of the
experimental records. A.Ex. 31 (Item 8M); Tr. 510 (Mr. Alvarez). The
record shows that after there was a hard disk crash of this computer in
the spring of 1987, the information on the hard disk of this computer
was transferred to a Panasonic computer (compatible with the IBM PC XT)
some time after that computer was acquired in March 1987. A.Ex. 31
(Item 8M); Tr. 1890, 1907-11 (Mr. Ohlant); and Tr. 2158 (Dr. Fong). The
Panasonic computer was sealed and packed for shipment to Purdue sometime
in September 1987 and was delivered to Purdue with Dr. Bridges' other
equipment and boxes sometime in October 1987. Tr. 2369 and 2451 (Ms.
Burch); and Tr. 2154, 5277 (Dr. Fong). While Dr. Fong indicated that he
suggested to Dr. Bridges shortly after their arrival at Purdue that Dr.
Bridges should look on the hard disk of the Panasonic computer to see if
any of the isomerase material was there, Dr. Bridges claimed he did not
consider this suggestion until some time in January 1988 when a computer
technician happened to be helping his secretary set up some other
computer equipment in the lab. Tr. 5277-79 (Dr. Fong); and Tr. 4237-38
(Dr. Bridges). While Dr. Fong and Ms. Burch clearly remembered that Mr.
Alvarez kept his experimental records on first the IBM PC XT and then
the Panasonic clone, they could not remember where the Panasonic
computer was kept at Purdue from their arrival in October 1987 until the
computer technician found the experimental records listed on a
subdirectory of the hard disk on January 5, 1988. Tr. 2160 (Dr. Fong);
Tr. 2417 (Ms. Burch); Tr. 4862 (Mr. Thomas); and Ex. 4, p. 42.
Conversely, there is no proof that Dr. Bridges did not have access to
the Panasonic computer before January 1988. Tr. 4872 (Mr. Thomas).
The computer technician testified that this information (the 66 pages)
was on the computer hard disk and had never been deleted. Tr. 4873 and
4875 (Mr. Thomas). 15/ He further testified that accessing the
subdirectories was not difficult. Tr. 4862 (Mr. Thomas). Furthermore,
there was testimony that Dr. Bridges had some understanding of
computers. Tr. 2212 (Dr. Fong). Clearly, given Dr. Bridges' knowledge
that Mr. Alvarez had kept the experimental records on the computer and
given the serious allegations of misconduct against Dr. Bridges, there
is no reasonable explanation why he did not look at the Panasonic
computer as soon as he arrived at Purdue.
Dr. Bridges has never accounted for why the back-up floppy disks for the
frog series of experiments were not made available. Mr. Alvarez
testified that all the frog series of experiments entered on the
computer hard disk were backed up on floppy disk. Tr. 510 (Mr.
Alvarez). Mr. Alvarez stated that these floppy disks were kept next to
the computer. A.Ex. 31 (Item 8m). Dr. Fong testified that it was Mr.
Alvarez's customary practice to back up on a floppy disk all data he
entered onto the computer. Tr. (Dr. Fong). Mr. Alvarez also indicated
that at the time his other materials were removed from his filing
cabinet, the back-up floppy disks were not removed. A.Ex. 31 (Item 8M).
Mr. Alvarez presumed that the floppy disks were moved to Purdue with Dr.
Bridges. A.Ex 31 (Item 8M). The floppy disks were not mentioned as
missing on the list submitted to Baylor. A.Ex 31 (Item 8E). In fact,
Dr. Bridges has never mentioned the existence or whereabouts of the
5. Mr. Alvarez's production to the Baylor Committee of dated
protocols for FROGONE and FROGTWO.
Furthermore, there are conflicting experimental records for the frog
series experiments. On October 7, 1987, Mr. Alvarez provided to the
Baylor Committee copies of protocols for FROGONE and FROGTWO. A.Ex. 104
(Items 12 and 13). These protocols were dated August 6, 1986 and August
19, 1986. Mr. Alvarez explained that he had obtained these protocols
from the computer in "late June of 1987" after he first read the Science
paper in order to refresh his memory about the experiments and that
these copies were not kept with the other frog series materials in his
filing cabinet. A.Exs. 59 and 104 (Item 11); and Tr. 5504-5508 (Mr.
The protocols submitted by Mr. Alvarez are different in certain respects
from the protocols for FROGONE and FROGTWO included in the 66 pages of
computer printouts submitted by Dr. Bridges on January 13, 1988. The
FROGONE protocol in the 66 pages includes the following purpose
PURPOSE OF EXPERIMENT WAS TO USE HOMOGENIZED FROG RPE-CH-IPM-RET
AS ENZYME SOURCE FOR ISOMERIZATION FROM AT TO 11-CIS. BSA IN
RPMI WILL BE USED AS RETINOID DONOR AS IN BOV RPE4 AND RET4
(11.13.85) USING MIN VOL ETOH BUT NO PREPURIFICATION ON
SEPHADEX. USE ALPHA-VT E AS ANTOXIDANT. SCALE FROM 3ML TO 1ML
INCUBATION MEDIUM (NOTES 3/20/86). THIS TIME SUBJECT THE CRUDE
HOMOGENATE TO A 700G SPIN TO REMOVE NUCLEI AND DEBRIS.
A.Ex 104 (Item 16A). Mr. Alvarez testified that he did not recall
including a purpose statement when he included this protocol on the
computer. A.Ex. 116. Also, the records provided by Mr. Alvarez show a
600 g spin, while the 66 pages show a 700 g spin for centrifugation.
A.Ex. 104 (Items 12 and 13), compared with A.Ex. 104 (Item 16A), p. 1;
and Tr. 5320-5321 (Mr. Alvarez). Mr. Alvarez also indicated that the
copies of the two protocols he submitted to the Baylor Committee with
the August 1986 dates also indicated the use of 2 ul of ethanol, which
is consistent with the volume of ethanol reported in the Science paper,
whereas the 66 pages presented by Dr. Bridges indicated volumes of
ethanol ranging from 3 ul to 8 ul. Tr. 5320-5321 (Mr. Alvarez); A.Ex.
104 (Items 12 and 13), compared with A.Ex. 104 (Item 16A).
I find the dates included in the 66 pages are of no evidentiary value in
determining when the experiments were actually performed. In making my
finding I considered the fact that the 66 pages of data were only
provided at the conclusion of the Baylor Committee inquiry and were
derived from a computer which was at all times in Dr. Bridges' custody
and control. I also considered significant the absence of a credible
explanation by Dr. Bridges of (1) why the computer data was not provided
earlier to the Baylor Committee; (2) what happened to the floppy back-up
disks; and (3) why no original primary data was provided. The 66 pages
are not rendered more persuasive evidence than the two pages supplied by
Mr. Alvarez simply by the quantity of the material.
In sum, I find that Dr. Bridges was responsible for whatever disposition
was made of the original primary data. Moreover, there is ample
evidence in the record to support a negative inference that the original
primary data, if provided, would not support Dr. Bridges' account of the
frog series experiments.
RESEARCH METHODS REPORTED IN THE SCIENCE AND PNAS ARTICLES
73. THE DEMONSTRATION OF THE ISOMERASE ENZYME REPORTED IN THE SCIENCE
AND PNAS ARTICLES WAS EXTREMELY IMPORTANT AND HAD ELUDED VISION
RESEARCHERS FOR ABOUT 30 YEARS.
74. THE RESEARCH METHODS USED FOR THE SCIENCE AND PNAS ARTICLES WERE
THE SAME WITH RESPECT TO SEVERAL CRITICAL VARIABLES: THE LOW VOLUME OF
ETHANOL; THE TYPE AND CONCENTRATION OF THE CARRIER PROTEIN (BSA); AND
THE LOW SPEED CENTRIFUGATION TO REMOVE MEMBRANE ORGANELLES.
75. THE SCIENCE AND PNAS ARTICLES BOTH REPORTED THE USE OF TRITIATED
RETINOL IN 2 UL ETHANOL.
76. THE SCIENCE AND PNAS ARTICLES BOTH REPORTED A LOW VOLUME OF ETHANOL
.2 PERCENT FOR THE SCIENCE ARTICLE AND .4 PERCENT FOR THE PNAS ARTICLE.
77. THE SCIENCE AND PNAS ARTICLES BOTH REPORTED A 2.5 MG/500 UL LEVEL
78. THE PROTOCOLS REPORTED IN BOTH THE SCIENCE AND PNAS ARTICLES USED
HOMOGENIZED FROG TISSUE AND LOW SPEED CENTRIFUGATION.
DISCUSSION OF RESEARCH METHODS FOR THE SCIENCE AND PNAS ARTICLES
There is no question that the demonstration of the isomerase enzyme
reported in the Science and PNAS articles was an important scientific
discovery. 16/ Recognizing this, Dr. Bridges stated in the abstract
section of his article:
Thirty years have elapsed since Wald and his colleagues showed that
11-cis retinal was isomerized to all-trans when rhodopsin was
bleached, yet little has been understood about the reverse process
that generates 11-cis retinal for rhodopsin regeneration . . .
Radiolabeled all-trans retinol and high performance liquid
chromatography have now been used to demonstrate the existence of
an eye-specific, membrane bound enzyme (retinol isomerase) that
converts all-trans to 11-cis retinol in the dark.
Ex. 8 (Item 2) (emphasis added). Moreover, a press release prepared by
Baylor with the assistance of Dr. Bridges also indicated the major
significance of this discovery:
Part of the puzzle of how the eye adapts from light to darkness has
been put together by a Baylor College of Medicine researcher. . . .
Bridges said his report comes 30 years after the last major finding
concerning how the visual cycle operates at the molecular level.
A.Exs. 161 (Item 7) and 183.
Despite the fact that this discovery had eluded vision scientists for so
long, the PNAS and Science articles reported the same discovery and were
published just months apart. A review of the descriptions of the
research methods reported in these two articles shows that they were the
same with respect to certain variables:
o the low volume of ethanol; o the type and
concentration of the carrier protein (BSA); and o the low
speed centrifugation to remove membrane organelles.
Both articles reported the use of tritiated retinol in 2 ul of ethanol,
resulting in a low volume of ethanol, .2 percent for the Science paper,
and .4 percent for the PNAS paper. Tr. 1570-1573 (Dr. Litman); Ex. 4,
pp. 10 and 24. Both articles also report the use of BSA as a carrier
protein at the same level of 2.5 mg/ 500 ul. Tr. 1570 and 1581-1583
(Dr. Litman); Ex. 4, pp. 10 and 24. Both articles report low speed
centrifugation of retinal pigment epithelium homogenate, the Science
article using a 700 g spin for 20 minutes and the PNAS article using a
600 g spin for 10 minutes. Ex. 4, p. 24. As expert testimony showed,
these variables were critical to the success of the experiments. Tr.
4894-4895, 4913-4922 (Dr. Adler); and Tr. 1576-1585 (Dr. Litman). This
is not to say that the actual variables were identical as reported, but
the difference was of negligible scientific significance (i.e., the
difference between a 600 g spin and a 700 g spin). Tr. 5136-5137 (Dr.
Moreover, as noted above, the striking similarities elicited immediate
comment from two readers of the science concentrate, in Chemical and
Engineering News (June 29, 1987), crediting Dr. Bridges and Mr. Alvarez
with the discovery of an eye specific membrane-bound enzyme that
converts all-trans to 11-cis retinol in the absence of light. Dean Bok,
a vision scientist from the University of California, wrote in the
September 14, 1987 letters to the editors:
A recent science concentrate . . . takes note of a recently
published paper by Bridges and Alvarez . . . These authors
report the discovery of an eye-specific membrane-bound enzyme
that converts all-trans to 11-cis retinol in the absence of
light. This is indeed an important result since this enzyme has
eluded vision scientists for about 30 years.
In the interest of fairness however, I wish to direct your
attention to a paper by Bernstein, Law, and Rando [Proc. Natl.
Acad. Sci., 84, 1849 (1987)], which appeared two months
earlier. Since Bridges and Alvarez acknowledge that they had
access to the manuscript of Bernstein et al., and in light of
the fact that the experimental conditions were similar, it seems
reasonable to give appropriate coverage of the latter
A.Ex. 166 (emphasis added); Ex. 8 (Item 29) (Abstract from Dean Bok from
ARVO meeting). In the September 21, 1987 letters to the editors, L.
Birladeanu of Harvard University also commented:
I read with great interest the science concentrate, "Enzyme
completes visual cycle" (C&EN, June 29, 1987, page 22).
However, I wonder whether you are aware that very similar
results were published a few months earlier in an article by P.
S. Bernstein, W. C. Law, and R. R. Rando in Proceedings of the
National Academy of Sciences, page 1849.
When abstracts were published in the 1987 ARVO Meeting Abstract Issue
from both the Rando laboratory and the Bridges laboratory on the
experiments subsequently reported in the PNAS and Science articles, the
striking similarity in the abstracts moved Dr. Rando, in Spain on
sabbatical, to call Dr. Dowling to ask whether Dr. Bridges had served as
a referee of the Bernstein, Law, and Rando PNAS manuscript. Tr. 198-201
(Dr. Rando); Tr. 3084 (Dr. Dowling); see Findings of Fact Nos. 37 and 38
above. Dr. Dowling indicated that Dr. Bridges had acted as a reviewer
of the PNAS paper. Tr. 203 (Dr. Rando); Tr. 3085 (Dr. Dowling). Dr.
Rando testified that he met with Dr. Dowling at the end of April 1987
about Dr. Bridges' having reviewed his paper. Tr. 205 (Dr. Rando). At
that time, Dr. Dowling had just received a preprint copy from Dr.
Bridges of the accepted Science paper and the two of them looked over
the paper. Tr. 204. Dr. Rando testified that there was a strong
similarity between the techniques used in the two papers --
We [Rando and Dowling] also noticed that the paper's experimentally
. . . in their important . . . issues were, I thought, very
similar, . . . as did my coworkers, as did Dr. Dowling. That is
the experimental techniques appeared similar in terms of which
fraction of membranes they were looking at, the centrifugation, the
use of ethanol, the use of carrier proteins, the other issues which
were absolutely critical to the outcome of the experiments.
Tr. 205 (Dr. Rando); Tr. 3083 (Dr. Dowling).
Moreover, Dr. Bridges testified that having read the PNAS manuscript
"once carefully," he found "it was embarrassingly close. . . . It was
remarkably close." Tr. 4359 (Dr. Bridges). Thus, the documentary
evidence and the testimony before me showed that research methods
reported in the two papers were similar on their face.
DEVELOPMENT OF RESEARCH METHODS REPORTED IN THE SCIENCE AND PNAS
79. THE DEVELOPMENT OF THE SUCCESSFUL PROTOCOL ULTIMATELY REPORTED IN
THE PNAS ARTICLE TOOK DRS. BERNSTEIN, RANDO, AND LAW ABOUT SIX MONTHS OF
80. DRS. BERNSTEIN AND RANDO PROVIDED A LOGICAL AND CONCISE RATIONALE
FOR THE DEVELOPMENT OF THE SUCCESSFUL PROTOCOL FOR THE EXPERIMENTS
REPORTED IN THE PNAS ARTICLE.
81. DR. BRIDGES' NOVEMBER 1985 BOVINE EXPERIMENT WAS DESIGNED TO
EXAMINE THE USE OF RETINOL BY RETINA PIGMENT EPITHELIAL CELLS (RPE) NOT
TO DEMONSTRATE THE ISOMERASE REACTION. THIS EXPERIMENT CANNOT BE
REGARDED AS THE EXPERIMENTAL ANTECEDENT OF THE FROG SERIES BECAUSE OF
ITS DIFFERENT OBJECT AND THE DIFFERENT TECHNIQUES USED.
82. DR. BRIDGES DID NOT PROVIDE A LOGICAL AND CONCISE RATIONALE FOR THE
DEVELOPMENT OF THE FROG SERIES PROTOCOLS; THESE PROTOCOLS REPRESENTED A
STEP BACKWARD IN CERTAIN ASPECTS OF TECHNIQUE AND WERE DEVELOPED WITHOUT
83. THE LOW ETHANOL VOLUMES WERE IN CONTRAST TO PREVIOUS WORK IN THIS
AREA WHERE LARGE VOLUMES OF ALCOHOL WERE TYPICALLY USED.
84. ALTHOUGH UNKNOWN WHEN THE PNAS AND SCIENCE ARTICLES WERE PUBLISHED,
AN EXTREMELY LOW ETHANOL LEVEL WAS A CRITICAL VARIABLE IN DEMONSTRATING
THE ISOMERASE REACTION SINCE ETHANOL ACTS TO INHIBIT THE ENZYME
85. A USE OF .25 PERCENT ETHANOL PREVIOUSLY REPORTED BY DR. BRIDGES WAS
NOT AN EXPERIMENTAL ANTECEDENT IN THE DEVELOPMENT OF THE FROG SERIES
86. WITHOUT EXPERIMENTAL TRIAL, DR. BRIDGES INCREASED THE LEVEL OF
RADIOACTIVITY BUT LOWERED THE VOLUME OF THE CARRIER PROTEIN WHEN THE
FROG PROTOCOLS ARE COMPARED TO THE 1985 BOVINE EXPERIMENT.
87. DR. BRIDGES DEVELOPED A SUCCESSFUL PROTOCOL FOR IDENTIFYING THE
ISOMERASE REACTION IN FROGONE WITHOUT ANY ANTECEDENT EXPERIMENTATION.
DISCUSSION OF DEVELOPMENT OF RESEARCH METHODS REPORTED IN THE SCIENCE
AND PNAS ARTICLES
It was hotly contested whether the frog series experiments had their
antecedent in prior work in Dr. Bridges' laboratory. Dr. Bridges
testified at length concerning the historical progression of his work as
represented by his many published papers (Tr. 2450-2750, 3146-3156);
with reference to his own and others' work, he also testified concerning
the particular variables included in the frog series experiments that
were critical to the successful demonstration of the isomerase reaction
(Tr. 2755-2799, 3406-3852). As discussed below, Dr. Alice Adler and Dr.
Bernard Litman testified that in their opinion Dr. Bridges had not
established the expected experimental development for the frog series
protocols in work in his laboratory and that his prior published papers
did not establish an experimental antecedent for the frog series
As compared with the convoluted and lengthy (over two weeks) case
presented by Dr. Bridges, Drs. Rando and Bernstein provided a logical
and concise rationale for the development of the methods used in the
Dr. Rando testified that development of the methods which successfully
identified the isomerase and which were reported in the PNAS article
took approximately six months of experimental trial, from late 1985
until the membrane experiments began in March 1986. Tr. 401 (Dr.
Rando); see also Tr. 4897 (Dr. Adler).
Dr. Bernstein described the progression in his work from 1982 until the
work reported in the PNAS article. Tr. 420-429 (Dr. Bernstein). Dr.
Bernstein had been working to identify the isomerase from 1982 on.
Their first experiments were "double label" experiments designed to
determine whether there was an isomerase. Tr. 420 (Dr. Bernstein). Dr.
Bernstein testified that this work took about one year and did not yield
the results they had hoped. He further testified that their results
were consistent with the possibility that there was no isomerase enzyme,
but that this possibility was "still a very strong focus of our work for
future use." Tr. 422 (Dr. Bernstein). In the summer of 1983, Dr.
Bernstein testified that he began to take a "much more pharmacological
approach" to the isomerase work and that for two years his work involved
the biochemical pathways of the eye and resulted in identifying "a
number of interesting compounds" but was not "definitive" on the
existence of an isomerase. Tr. 423 (Dr. Bernstein). He testified that
in the late summer of 1985 he and Dr. Rando had "hit upon a new approach
to looking at whether or not an isomerase existed." Tr. 423 (Dr.
Bernstein). These were in vivo (living animal) experiments which were
"quite definitive that the aldehydes could not be a substrate" for the
reaction. 18/ Tr. 424 (Dr. Bernstein). Dr. Bernstein testified that
they were "excited" about these results and after he met with his thesis
committee in November 1985 his plan was to "start with whole animals and
move to eventually, if things continued well, to move on to the ultimate
goal, which would be in tissue homogenates, to look for an isomerase
enzyme." Tr. 425-426 (Dr. Bernstein). Dr. Bernstein testified that
other laboratories, including Dr. Bridges', had had "uniformly negative
results . . . at least reproductively" when looking for the isomerase.
Tr. 426 (Dr. Bernstein). He then described the experiments he
subsequently did using whole animals, an eye cup preparation (experiment
done on living cells by removing the front part of the eye), and
ultimately homogenized material. Tr. 427-429 (Dr. Bernstein).
Dr. Bernstein described these homogenate experiments as involving taking
the "retina and the pigment epithelium only . . . leaving behind the
sclera and the choroid," using a culture medium, and then sonicating the
tissue to break up the intact cells to preclude metabolic reactions.
Tr. 429-432 (Dr. Bernstein). Dr. Bernstein described the use of the low
speed spin of 600 g to get a "very cloudy pink supernatant" above the
pellet, a low speed membrane preparation. Tr. 431-432 (Dr. Bernstein).
Dr. Rando described the purpose of the low speed spin as removing heavy
membrane fragments. Tr. 337 (Dr. Rando). Dr. Bernstein testified that
their "first successful experiment . . . was probably in late March or
early April . . . 198." Tr. 432 (Dr. Bernstein).
Dr. Bernstein attributed the success of the experiment to its being a
"radioactive tracer experiment" (decided upon in consultation with Dr.
Rando) (Tr. 433), using high specific activity tritiated retinol, using
BSA as a carrier to solubilize the Vitamin A (Tr. 434 and 337 (Dr.
Rando)), and using a low volume of ethanol, which did not destroy the
enzyme (Tr. 434-435). Dr. Bernstein described the series of experiments
done to confirm the results and to "just examine the system." Tr.
435-443 (Dr. Bernstein). The experiments for the PNAS paper were
completed by mid-June 1986 and then written up for submission.
Both Dr. Rando and Dr. Bernstein discussed the development in Dr.
Rando's laboratory of the experimental methods overall and in particular
those variables that they regarded as critical to the success of these
experiments. Ex. 167; and Tr. 333-341 (Dr. Rando) and 477-485 (Dr.
Bernstein). Dr. Bernstein testified that "[t]he 600 g supernatant was
never used in any studies of isomerase activity before" (Tr. 483); that
the "large amount of radioactivity (2 uCi) was important to the
identification of "small amounts on the HPLC" (Tr. 479); that 2 ul
ethanol was important because higher concentrations would destroy the
enzyme activity (Tr. 479). Dr. Bernstein testified that in light of the
existing literature a number of approaches "could have been done." Tr.
485 (Dr. Bernstein). Dr. Rando testified that "the low ethanol
concentration was simply a by-product of recognizing that we had to . .
. do a tracer experiment." Tr. 336 (Dr. Rando).
Dr. Rando testified that the "critical aspects of the experimental
approach" were the 600 g supernatant, the 2 uCi all-trans retinol
(Amersham 60 Ci/mmol) in 2 ul of ethanol, and the .5% BSA, in that with
these variables another researcher could get the same results. Tr. 398
(Dr. Rando). Dr. Rando testified that his interest was in defining
whether an enzyme was involved, where it was, and how it was controlled.
Tr. 188 (Dr. Rando). Dr. Rando stated theirs was the first study of the
isomerase to combine these variables. Tr. 399 (Dr. Rando). Dr. Rando
Oh, I think you could probably find all of them individually used
in different kinds of experiments. I think as an ensemble,
together, all together, no one had used it in isomerase work, in an
investigation of this particular system.
Tr. 399 (Dr. Rando). Dr. Rando also testified that at the time of the
PNAS article "we did not have the evidence that would have allowed us to
stipulate which substrate was the isomerase, that's why we called it a
generic, a retinoid isomerase." Tr. 371 (Dr. Rando).
Drs. Rando and Bernstein impressed me with their concise, clear
explanation of the development of the methods reported in the PNAS
article. There was both a developmental progression in Dr. Bernstein's
work in the years preceding the experiments reported in PNAS and a
cogent explanation of the progression from whole animals to the eye cup
preparation to the homogenate from November 1985 on. Their explanation
of the experimental methods for the PNAS article was convincing,
especially with regard to the variables considered critical and how
those variable were selected. In this regard Dr. Adler testified that
Dr. Rando's explanation to the Panel--
seemed to be a reasonable development of the methodology in terms
of the way most of us would go about setting up the experiment.
Tr. 4895 (Dr. Adler); see Tr. 4919-4920 (Dr. Adler).
Dr. Bridges' explanation of the development of the research protocol for
the Science article was in marked contrast to the explanation provided
by Drs. Rando and Bernstein. Notwithstanding Dr. Bridges' lengthy
testimony detailing many published articles, his testimony was not
adequate to establish the type of progressive work in the isomerase area
that was readily apparent from Drs. Rando and Bernstein's testimony. I
did not find credible Dr. Bridges' linking the particular methods at
issue here with the entire history of his work on Vitamin A in the
visual cycle. I also did not find credible Dr. Bridges' efforts to show
the rational development of these methods for the frog series
experiments by the isolated use of a particular variable by others or by
Dr. Bridges himself. I note, once again, that the quantity of the
evidence presented does not determine its weight. While it was
undisputed that Dr. Bridges is a knowledgeable and extremely productive
scientist who had a long-standing interest in the isomerase, his last
published work in this particular area had been in 1983. His subsequent
concentration was in other aspects of the vision cycle, particularly the
IRBP. Both Drs. Litman and Adler testified that they could find no
experimental progression, as they would have expected, for the frog
series experiments. Tr. 1596-1598, 1634, 1640 (Dr. Litman); and Tr.
4924-4925, 4958 (Dr. Adler).
The NIH Panel examined an experiment conducted in November 1985 asserted
to be the experimental antecedent of the isomerase work reported in the
Science article. 19/ The record includes copies of five pages of
material on this experiment: a handwritten protocol page, and four
pages containing scintillation counter data and HPLC profiles. The HPLC
profile graphs show peaks labeled with the numeral eleven and a question
mark. Ex. 8 (Item 31); Tr. 2779-2791 (Dr. Bridges). However, this
bovine experiment used BSA which was pre-loaded with tritiated retinol
and purified through a gel filtration column to remove any ethanol. Dr.
Adler testified that this was a different experiment from the frog
series reported in the Science article. Tr. 4898-4899 and 4927 (Dr.
Adler). She testified that the 1985 bovine experiment was designed to
see how retinol is delivered to the retina pigment epithelium and
whether IRBP has a role in this process, not for the "primary reason" of
demonstrating the isomerase. Tr. 4899 (Dr. Adler).
Dr. Adler testified that certain of Dr. Bridges' prior papers were
precursors for the isomerase work in the sense of looking for the site
of the isomerase reaction but that in no way was the prior work a
precursor in terms of the experimental methods used. Tr. 5139 and
5143-5144 (Dr. Adler). It was apparent from Dr. Adler's testimony that
she was familiar with Dr. Bridges' work and had on hand in her
laboratory a number of his papers (Dr. Adler had testified by telephone
from her laboratory). Tr. 4890, 4899-4901, 4907-4911, 4927, and 4942
(Dr. Adler). She said that there seemed to be no preliminary
experimentation for the frog series. Tr. 4899 (Dr. Adler). She
testified that all experimental conditions were in place the first time
Dr. Bridges' laboratory tried to find the isomerase reaction. Tr. 4900
Dr. Adler testified that it was highly unlikely that established
experimental methods such as those in the 1985 bovine experiment would
be changed all at once without some trial and error development. Tr.
4924 (Dr. Adler). She described FROGONE as the perfect method and
testified that it represented a sudden change in technique. Tr. 4925
(Dr. Adler). Dr. Litman testified that the critical variables in the
frog series methods did not derive logically from prior experimental
work. Tr. 1634 (Dr. Litman).
Drs. Adler and Litman testified that large volumes of ethanol were
typically used in experiments such as this. Tr. 1573 (Dr. Adler) and
4923 (Dr. Litman). Dr. Litman testified that the low volume (.2% --
Science article and .4% -- PNAS article) of ethanol in these isomerase
experiments was an "innovation required to see the isomerase." Tr. 1597
(Dr. Litman). Dr. Litman testified that Dr. Bridges had "little
rationale" for the ethanol volume used for the frog series experiments
in light of the 2% and 4% ethanol levels reported in two of Dr. Bridges'
1983 articles (Ex. 8 (Item 27) and CDB Ex. 69). Tr. 1581-1582 (Dr.
Litman); and see also 4902-3, 4923 (Dr. Adler). In addition, the use of
a low volume, .25% ethanol, was not an antecedent when used in
experiments reported in one of Dr. Bridges' 1986 papers. Dr. Adler
testified that this was a "different type of experiment" requiring "just
. . . tiny amounts" and that "we've all done that." Tr. 4910-11 (Dr.
Adler). Moreover, I do not find credible Dr. Bridges' explanation that
the low volume of ethanol in the frog series was designed to avoid the
harmful effect of colloidal dispersions of free Vitamin A. 20/ Tr.
2755-2766, 2794, and 5567-5568 (Dr. Bridges). In any event, I rely on
Dr. Adler's expert opinion that such dispersions were not a problem and
were irrelevant. Thus, I find Dr. Bridges' explanation inadequate as a
rationale for the volume of ethanol used. Tr. 4930, 4965, 5139-5142,
and 5145-47 (Dr. Adler) and 5567 (Dr. Bridges).
The frog series methods used the same level of BSA (2.5 mg/500ul) as the
PNAS methods. Tr. 1570 and 1581-1583 (Dr. Litman). Although Dr.
Bridges cited to earlier references in the literature to BSA and to his
use of BSA in the 1985 bovine experiments, these do not establish a
rationale for the level selected for the frog series. Tr. 2768-2772,
2780, and 3053-3143 (Dr. Bridges). The publications relied on by Dr.
Bridges were not referenced in the Science article. Moreover, BSA had
not been generally used as a substrate carrier protein. Tr. 4940 (Dr.
Adler). As pointed out above, Dr. Adler had testified that the use of
BSA in the 1985 bovine work was very different. Tr. 4927 (Dr. Adler).
Also, Dr. Litman stated that when compared to the 1985 bovine work, the
frog series methods illogically reduced the concentration of BSA, the
carrier protein, while raising the concentration of the retinol to be
carried. Tr. 1582 (Dr. Litman); see also Tr. 4927-4928 (Dr. Adler).
Dr. Litman testified that the frog series methods inexplicably increased
the level of radioactivity relative to that used in the 1985 bovine work
at a time when the carrier protein was reduced. Tr. 1595 (Dr. Litman).
The 1985 bovine experiment used a suspension of bovine retina pigment
epithelium cells; the frog series methods used homogenized frog tissue
with a low speed spin, as did the PNAS paper. Dr. Adler testified that
the low speed spin was not customary and that no one had done that
before in isomerase work. Tr. 4919 and 4921 (Dr. Adler). Dr. Bridges
did not directly contradict this testimony.
Dr. Litman testified that there was an absence of transition
experimentation between the 1985 bovine experiment and the frog series
protocols because four to six parameters had been changed at the same
time in a presumably successful assay. He testified that standard
practice would be to change a variable at a time unless there is a
predictable consequence from a particular change. He testified that he
had personally not seen the circumstance where a scientist determines
the correct set of variables without trial and error experimentation.
Tr. 1644-1647 and 1638-1640 (Dr. Litman). Dr. Litman testified in
detail about the significance of the differences between the 1985 bovine
experiment and the frog series protocols. Tr. 1576-1585 (Dr. Litman).
Dr. Litman testified that the lack of transition experimentation coupled
with the methodological shift made in the frog series to conditions the
same or close to those used in the PNAS paper led to the Panel's
conclusion that Dr. Bridges did not independently develop the methods
for the frog series experiments. Tr. 1596-1597 (Dr. Litman); see also
Tr. 4932 (Dr. Adler).
Dr. Litman testified that the Panel had asked Dr. Bridges for all data
that would support Dr. Bridges' account of the conduct of the frog
series experiments. Tr. 1635-1636 (Dr. Litman). Dr. Adler testified
that the Panel had asked Dr. Bridges and Dr. Rando the same questions
concerning how their experimental protocols were developed. She
testified that the Panel would have examined any information presented
by Dr. Bridges. Tr. 4899, 4964 and 5151-5154 (Dr. Adler). Dr. Litman
testified that at the Panel's November 1988 meeting Dr. Bridges had
provided no "real explanation" for the low level of ethanol and the
centrifugation. Tr. 1598 (Dr. Litman).
During this proceeding, Dr. Bridges referenced a number of publications
as establishing a logical basis in the scientific literature for the
methods used in the frog series protocols. Tr. 5128-5133 (Dr. Adler).
Dr. Adler testified that such material was not relevant since--
You can find any method you want in the literature, but if they are
not in use in your lab, and you can't show that you were planning
to use them, I really don't think they are relevant.
Tr. 5151 (Dr. Adler).
Based on Dr. Adler's and Dr. Litman's testimony, I find that, even if
there were a presumed 11-CIS retinol peak in HPLC profile graphs of the
data resulting from the 1985 bovine work, the methods reported in the
Science article were not derived from that work. Moreover, I am
persuaded that the methods reported in the Science article were an
abrupt change in Dr. Bridges' methods without antecedent
experimentation. Tr. 4923-4925 (Dr. Adler); Tr. 1597, 1634 (Dr.
Litman). I find that the methods in the frog series represented a step
backwards in the sense that the gel-filtration technique used in the
1985 bovine work was a "better" technique which avoided ethanol
altogether. Tr. 4923-4924 (Dr. Adler); Ex. 4 at 11. I was also
unpersuaded by references to the appearance of isolated variables in
prior work or by Dr. Bridges' explanations of the bases for the
experimental design. See Dr. Bridges' reply to the final NIH Panel
report at 26-38.
Accordingly, I find that Dr. Bridges did not provide a logical and
concise rationale for the development of the experimental methods in the
frogs series protocols. Since Dr. Bridges' methods were adopted without
any antecedent experimentation and were an abrupt methodological shift
to methods either identical or close to those reported in the PNAS
manuscript, the logical inference is that he derived the methods from
reviewing the PNAS article.
88. AS IS THE STANDARD PRACTICE IN SCIENTIFIC RESEARCH, THE SPECIFIC
ACTIVITY FOR TRITIATED RETINOL SHOWN IN SOME OF THE PROTOCOLS INCLUDED
IN THE 66 PAGES WAS TAKEN BY MR. ALVAREZ FROM EITHER THE AMERSHAM BATCH
ANALYSIS SHEETS OR FROM THE VIAL OF TRITIATED RETINOL.
89. THE METHODS SECTION OF THE SCIENCE ARTICLE REPORTS USE OF TRITIATED
RETINOL WITH A SPECIFIC ACTIVITY OF 53 CURIES PER MILLIMOLE (CI/MMOL).
90. THE 66 PAGES REFLECT A DATE OF MAY 28, 1986 FOR FROGTHREE.
91. FROGTHREE IS THE FIRST PROTOCOL IN THE 66 PAGES TO REPORT A
SPECIFIC ACTIVITY FOR TRITIATED RETINOL; THE SPECIFIC ACTIVITY REPORTED
WAS 53 CI/MMOL.
92. TRITIATED RETINOL WITH A SPECIFIC ACTIVITY OF 53 WAS USED FOR
93. DURING 1986, TRITIATED RETINOL WITH A SPECIFIC ACTIVITY OF 53
CI/MMOL FIRST WAS SHIPPED TO BAYLOR IN AUGUST.
94. FROGTHREE WAS CONDUCTED IN AUGUST 1986, NOT MAY 1986.
95. NOT EVERY PROTOCOL NOTED A SPECIFIC ACTIVITY FOR THE TRITIATED
RETINOL USED. WHERE A SPECIFIC ACTIVITY WAS NOTED IN THE 66 PAGES, THIS
IS CONSISTENT WITH THE USE OF TRITIATED RETINOL DELIVERED DURING AND
AFTER AUGUST 1986 FOR THE FROG SERIES EXPERIMENTS FROM FROGTHREE ON.
96. 126 FROGS WERE USED FOR THE FIFTEEN FROG PROTOCOLS.
97. 96 FROGS WERE USED BY DR. LIN FOR HER THESIS WORK BETWEEN MAY 20,
AND AUGUST 26, 1986.
98. FROGS WOULD HAVE BEEN AVAILABLE IN AN ADEQUATE NUMBER TO CONDUCT
THE FIFTEEN FROG PROTOCOLS WHETHER THE EXPERIMENTS WERE BEGUN IN MAY OR
IN AUGUST 1986.
DISCUSSION OF AVAILABLE MATERIALS
A. Tritiated Retinol
Tritiated retinol was an essential reagent for the frog series of
experiments. Whether supplies of tritiated retinol were adequate for
the conduct of the frog series experiments in the time sequence alleged
by Dr. Bridges was contested. As I discuss below, I make no finding as
to whether there was an adequate supply of tritiated retinol available
in Dr. Bridges' laboratory to have permitted the conduct of the frog
series experiments beginning in May 1986. The record does, however,
conclusively place the conduct of FROGTHREE in August 1986, contrary to
Dr. Bridges' purported timing for that experiment of May 28, 1986. My
finding here that FROGTHREE was conducted in August 1986 is but one of
the bases for my finding that the frog series experiments began after
review of the PNAS manuscript.
The Amersham tritiated retinol used in the frog series experiments is
all-trans retinol (Vitamin A) which carries a radiolabel (tritium)
marker at the 11, 12 position. See CDB V. Ex. P. It is this radiolabel
which makes it possible to identify the proportions of the various forms
of Vitamin A in experiments such as those at issue here. See Tr. 2814
(Dr. Chytil). The specific activity of this compound is "the amount of
radiation expressed either by milligram of the compound or millimol of
the compound. In this case it was . . . between 40 and 60 curies per
millimol." Tr. 2820 (Dr. Chytil). High performance liquid
chromatography can be used to purify tritiated retinol before it is
used. Tr. 2826 (Dr. Chytil); Tr. 4663 (Mr. Riis, an Amersham technical
representative). The radiochemical purity and specific activity are
different. Tr. 4632 (Mr. Riis). Specific activity relates to the decay
of the tritium atom and indicates how highly radioactive the Vitamin A
is. Tr. 4634 and 4671 (Mr. Riis). The manufacturer, Amersham, only
determines the specific activity once -- during the original analysis.
After that the concern is radiochemical purity -- how much of the
compound remains as tritiated all-trans retinol. Tr. 4637 (Mr. Riis).
Mr. Riis testified that Amersham would advise that tritiated retinol not
be held more that one month before use. Tr. 4643 (Mr. Riis).
Notwithstanding this, however, Mr. Riis also testified that
radiochemical purity was affected by the specific activity of the
compound and by its concentration, storage, and handling -- he agreed,
therefore, that diluting and aliquoting the tritiated retinol for
storage could slow its radiochemical breakdown. Tr. 4643 (Mr. Riis).
He testified that it was conceivable that this product could be used
even after a considerable period of time, but the company would not
recommend this. Tr. 4662 (Mr. Riis). Mr. Riis also testified that the
specific activity would change slightly over time but that even after
two years the initial specific activity assigned by the manufacturer
would still be used. Tr. 4651 (Mr. Riis). High specific activity
tritiated retinol falls within the range 40 -- 60 Ci/mmol. So long as
high specific activity retinol was used, it did not matter to the
success of the experiments at issue here where in that range the
tritiated retinol fell. Tr. 433 (Dr. Bernstein); and Tr. 711-712 (Mr.
The record contains Amersham Batch Analysis Sheets for tritiated
retinol. The Batch Analysis Sheets identify each batch by number and
give its specific activity, molecular weight, radioactive concentration,
and radiochemical purity. As shown by the Amersham copies (A.Ex. 17) of
the batch sheets, each batch remained available for sale until upon
reanalysis its radiochemical purity fell below Amersham's
specifications. 21/ The dates in 1985 and 1986 that orders were placed
from Dr. Bridges' laboratory with Amersham for tritiated retinol and the
batch of product which likely filled each order were essentially
undisputed. See A. V. Ex. F; and Tr. 4030 (Dr. Bridges) (Dr. Chytil);
CDB V. Ex. AA-13. These orders were placed on a "RUSH" or "ASAP" basis
and were generally received overnight or at least in a few days. A.Ex
65; and Tr. 713 (Mr. Alvarez).
The order dates, batch numbers, and specific activities are as follows.
July 22, 1985 Batch 24 56 Ci/mmol August 14, 1985
Batch 25 56 Ci/mmol October 16, 1985 Batch 26 56
Ci/mmol January 9, 1986 Batch 27 60 Ci/mmol August 18, 1986
Batch 29 53 Ci/mmol September 12, 1986 Batch 30 53
Ci/mmol October 31, 1986 Batch 31 53 Ci/mmol December
9, 1986 Batch 32 60 Ci/mmol
The 66 pages (A.Ex. 104 (Item 16A)) show the following dates for the
frog series protocols:
FROGONE -- 5/14/86 FROGTWO -- 5/21/86 FROGTHREE -- 5/28/86
FROGFOUR -- 6/3/86 FROGFIVE -- 6/5/86 FROGSIX -- 6/18/86
FROGSEVEN -- 8/06/86 FROGEIGHT -- 8/19/86 FROGNINE -- 8/26/86
FROGTEN -- 9/5/86 FROG 11 -- 9/10/86 FROG 12 -- 9/16/86 FROG 13
-- 9/23/86 FROG 14 -- 9/30/86 FROG 15 -- 10/8/86 RAT 1 --
In contrast, the protocols provided by Mr. Alvarez to Baylor during
October 1987 show 8/6/86 for FROGONE and 8/19/86 for FROGTWO. A.Ex. 104
(Items 12 and 13).
The methods section (footnote reference 21) of the Science article
states that to each incubation was added:
. . . 2 ul of an ethanol solution containing 22 pmol of all-trans
(11,12-3H) retinol (Amersham; 53 Ci/mmol . . . the all-trans
retinol had been freshly purified by HPLC . . .
The protocol for FROGTHREE is the first of the protocols to report a
specific activity for tritiated retinol; the specific activity reported
was 53 Ci/mmol. A.Ex. 104 (Item 16A), p. 12. This protocol states in
5 ul 11,12-3H-ALL-TRANS RETINOL (53 Ci/mmol . . . )
Not all the protocols report a specific activity for the tritiated
retinol. The protocols reporting a specific activity and the specific
activity stated are as follows: FROGTEN -- 53 Ci/mmol; FROG 11 -- 53
Ci/mmol; FROG 12 -- 53 Ci/MMOL; FROG 13 -- 53 Ci/mmol; FROG 15 -- 60
Ci/mmol; RATONE -- 53 Ci/mmol.
Amersham Batches 29 and 30, respectively, filled the August and
September 1986 orders. It is clear then that given the higher specific
activities of the earlier batches within the time period relevant here,
tritiated retinol with a specific activity of 53 Ci/mmol was not
available from Amersham before the August 1986 shipment.
The NIH Panel examined the available supplies of tritiated retinol in
attempting to determine whether there were adequate supplies to
corroborate Dr. Bridges' purported May 1986 date for beginning the Frog
series experiments. The NIH Panel report stated that "[t]he rate of
deterioration makes unlikely the use of any preparation older than that
represented by the January 14, 1986, shipment for FROGONE through
FROGEIGHT." Ex. 4. The Panel report went on to state that "[a]s
indicated by the specific activities of the tritiated retinol used,
whatever experimentation was done appears to have been started in August
1986, as maintained by Mr. Alvarez, rather that in May 1986, as
maintained by Dr. Bridges." Ex. 4, p. 9.
Dr. Chytil testified that the Panel had examined the number of
experiments that Dr. Bridges claimed were done against the supply of
retinol. Dr. Chytil testified that the Panel had "concluded that the
experiment could not have been done [at the times asserted by Dr.
Bridges] because there was not enough radioactive retinol available then
in Dr. Bridges' laboratory." Tr. 2816 (Dr. Chytil). Based on his
analysis of the amount of tritiated retinol required for each protocol
and the number of incubations for each protocol, Dr. Chytil testified
that 320 uCi of purified all-trans retinol would have been required for
the frog series experiments. See A. V. Ex. G.; and Tr. 2840-2847.
This finding concerning the amount of tritiated retinol required
conflicts with the analysis presented by Dr. Bridges. In the May 16,
1989 reply to the NIH Panel's "Preliminary Report," in the response to
the proposal to debar, and again at the fact finding hearing held for
the debarment proceeding, Dr. Bridges presented a contrary analysis
based on the Panel's assumption that no shipment before the January 1986
shipment would have been available for the isomerase experiments. A.Ex.
30, pp. 23-33; and Ex. 8, pp. 15-23; CDB V. Ex. AA-1- AA-13. Dr.
Bridges testified that the isomerase experiments required 164.7 uCi of
purified retinol (Tr. 3862 (Dr. Bridges)) and provided charts to show
that (even assuming that the January and August 1986 Amersham shipments
were the only available retinol), supplies were adequate. Dr. Bridges
asserted that, even allowing for radiochemical decay and purification
losses, there were 36 uCi remaining from the January 1986 shipment after
FROGEIGHT and 51 uCi remaining from the August shipment after FROG 15
and RATONE. Ex. 8, pp. 19-20.
To support a finding that the frog series experiments began in May 1986,
Dr. Bridges relied on handwritten entries on some of the Batch analysis
sheets that state a purported receipt date for the shipment as well as
indicate its use for the isomerase work. Batch sheets for Batches 27,
29, and 24 were purportedly marked in this way by Mr. Alvarez. The
batch sheet for Batch 30 shows a receipt date of "9/15/86" but no use
for the isomerase work. See Ex. 8 (Items 5, 6, 7, and 22). These
handwritten entries appear on only unverified copies of these documents.
Moreover, even if these batches were used for the isomerase work, this
is not indicative of the timing. On balance, I was not persuaded to
accord any weight to the annotated batch sheets as evidence of the
timing of the frog series experiments.
Dr. Bridges questioned the Panel's reliance on Mr. Alvarez's statement
that approximately 60 uCi were purified to provide adequate tritiated
retinol for each experiment. Ex. 8, p. 21. Dr. Bridges also asserted
that the Panel failed to take into account supplies of tritiated retinol
on hand in his laboratory. Dr. Bridges asserted that there were
possible sources other than the Amersham deliveries for January and
August 1986. A.Ex. 30, pp. 31-32; and Ex. 8, pp. 20-21. Dr. Bridges
testified that Batches 24, 26, 27, 29 and 30 provided an available
supply of 1,139 uCi of tritiated retinol. Tr. 3882 (Dr. Bridges); and
CDB V. Ex. AA-13. Dr. Bridges testified that the January shipment
(Batch 27 -- 60 uCi/mmol) would have been diluted and aliquoted for
storage. Tr. 3887 (Dr. Bridges).
After consideration of the analyses of whether there were sufficient
supplies of tritiated retinol in fact available to conduct the frog
series experiments beginning in May 1986, I conclude that I can make no
finding on this issue. The Panel's assumption that it was unlikely that
supplies prior to the January 1986 shipment were used cannot be
verified. Mr. Riis' testimony corroborates Dr. Bridges' testimony, at
least in concept, that under certain conditions tritiated retinol could
be used after storage if purified. Thus, the Panel's assumption is
undercut. While Dr. Bridges has detailed the supplies he asserted were
available, this cannot be verified either since there is no question
that there were other experiments requiring tritiated retinol ongoing in
his laboratory. See Tr. 3257-3261 (Dr. Bridges). Mr. Landers and Dr.
Liou used tritiated retinol in their work during this period. Tr.
983-996 (Mr. Landers); Tr. 1048-1050 (Dr. Liou); and CDB Exs. 61 and 64.
It is simply not plausible that shipments of a product which is regarded
by the manufacturer as unstable would be ordered without a current need
and simply stored. Moreover, even if there were stored supplies of this
product, this provides no evidence for the source of the product used
for the frog series experiments. See CDB Exs. 86, 87, 88, and 88A. In
the absence of contemporaneous documentation for tritiated retinol
recording each source, when received, the quantity, and its use, it is
impossible to find conclusively what supplies were available and what
use was made of these available supplies. It is reasonable to conclude,
however, that due to the nature of the product, fresh material would be
used if available.
Moreover, Dr. Chytil's testimony about the amount of tritiated retinol
used was based on the number of incubations in each of the frog series
protocols. The number of incubations found by Dr. Chytil is much higher
than the number testified to by Dr. Bridges, Mr. Alvarez, and Dr. Adler.
23/ Consequently, I cannot verify the amount of retinol Dr. Chytil
testified was required.
The findings which I have made are narrow and are clearly established by
I do find, however, that the record supports the finding that FROGTHREE
was conducted in August 1986. Mr. Alvarez testified that the specific
activity shown in the frog series protocols was taken either from the
Amersham batch analysis sheets or from the vial of tritiated retinol.
Tr. 5324 (Mr. Alvarez). Mr. Riis' and Dr. Adler's testimony provide
strong support for a finding that the practice testified to by Mr.
Alvarez is the standard practice in scientific research. Tr. 4930 and
5155-5157 (Dr. Adler). Mr. Alvarez testified that he used tritiated
retinol on hand in the laboratory for the initial experiments, that he
kept no records as to daily use, and that it was his practice to purify
the tritiated retinol for the isomerase experiments to obtain pure
all-trans retinol. Tr. 715-716 and 5341 (Mr. Alvarez). Mr. Alvarez
also testified that there was not a lot of tritiated retinol on hand
when the frog series experiments were started. Tr. 722 (Mr. Alvarez).
Dr. Bridges provided several, ultimately unpersuasive, rationales to
explain the 53 uCi entry in FROGTHREE. First, Dr. Bridges implied that
this entry was a mistake by speculating that this entry may have been
based on information Mr. Alvarez had obtained from Amersham that would
have reflected the specific activity for tritiated retinol shipped at
some later point, not what was actually used for FROGTHREE. A.Ex. 36,
p. 8. At the hearing, however, Dr. Bridges testified that Batch 24
provided the tritiated retinol for FROGTHREE and quite possibly for
FROGONE and FROGTWO. He testified further that at least two batches,
Batch 24 and Batch 29, and possibly a third batch, Batch 30 shipped in
September 1986, would have provided tritiated retinol with a specific
activity of 53 uCi for the frog series experiments. Tr. 3882-3887 (Dr.
Bridges). Dr. Bridges testified that as of May 1986, Batch 24 with an
initial specific activity from the Amersham Batch Analysis sheet of 56
uCi would have had an actual specific activity of 53 uCi. See CDB V.
Exs. W-1 -- W-5 and AA 13. Dr. Bridges also testified that the specific
activity of 60 uCi for FROG 15 in the 66 pages was an error. Tr. 3885
(Dr. Bridges). When asked if he had any idea where the 60 uCi/mmol was
from, Dr. Bridges testified that --
No, unless he just used the 60 curies that was the original value
for the January shipment without making any correction for decay of
the tritium. . . . It would have been a little careless.
Tr. 3886 (Dr. Bridges).
In his testimony, Dr. Bridges did not dispute that tritiated retinol
with a specific activity of 53 uCi was used for FROGTHREE. Moreover,
while there are a number of other instances where the accuracy of
entries on the 66 pages was questioned, in light of the published
methods in the Science article which reference the specific activity of
53 uCi, the overwhelming weight of the evidence is that the 53 uCi
reported in the protocol was accurate. The question then becomes what
was the source of that product.
I have concluded that Dr. Bridges' testimony concerning the use of Batch
24 for FROGTHREE lacks even a patina of credibility. Dr. Bridges'
testimony was inconsistent with his earlier explanation that the 53 uCi
entry was a mistake. Moreover, it was a notable omission that Dr.
Bridges did not testify that the 53 uCi reported in FROGTHREE was in
fact a recalculation of the specific activity for Batch 24 which was
done at the time the experiment was conducted. There is no support in
the record for a standard practice requiring the recalculation of the
specific activity. Indeed, the evidence shows that this would not have
been done. The use of high specific activity tritiated retinol would be
reported using the manufacturer's initial calculation, as Mr. Alvarez
testified was done. Dr. Adler testified that the specific activity of
the tritiated retinol would not change over time due to the long
half-life of the tritium. Tr. 4931 (Dr. Adler). She also testified
that it is the conventional practice to report the original specific
activity for tritiated retinol. Tr. 5154-5157 (Dr. Adler).
Consequently, I accorded substantial weight to Mr. Alvarez's testimony
since he was responsible for maintaining the records for the frog series
experiments and his testimony as to his practice for entering the
specific activity was corroborated as the standard practice by Dr. Adler
and Mr. Riis. I reject Dr. Bridges' testimony that Batch 24 from July
1985 was used for FROGTHREE. Thus, I find that FROGTHREE was conducted
in August 1986 after the receipt of Amersham Batch 29 and that the
specific activity reported in that protocol shows that Batch 29 was used
Since a specific activity of 53 uCi was recorded for five subsequent
protocols, FROGTEN, FROG 11, FROG 12, FROG 13, and RATONE, the
unavailability of tritiated retinol with a specific activity of 53 uCi
prior to the August and September 1986 deliveries is consistent with a
finding that FROGTHREE was conducted August 1986 followed by the other
frog series experiments. Furthermore, although FROG 15 reports use of a
specific activity of 60 uCi, this does not undercut my finding.
Tritiated retinol with a specific activity of 60 assigned by the
manufacturer was available in the laboratory from the January and
December 1986 shipments. Furthermore, while RATONE was reported in the
Nature manuscript, that manuscript did not report results from all the
frog series experiments so there is no reason to assume that RATONE was
necessarily conducted after FROG 15. Tr. 3406-3852 (Dr. Bridges).
With regard to the significance of the available supply of frogs as
evidence of the chronology of the frog series experiments, the NIH Panel
report stated --
The records on frog purchases were like most of the documentation
provided to the Baylor Committee and the NIH Panel: inadequate for
any conclusion regarding the chronology of events. . . . The frog
facility was shared by several laboratories within the Department
of Ophthalmology; therefore, specific attribution of use and/or
purchase was not feasible. . . .
Ex. 4, p. 38. In response to the proposal to debar, however, Dr.
Bridges asserted that the May 12, 1986 order for 200 frogs to be
delivered on May 20, 1986 could be directly linked to the frog series
experiments in light of the timing of the order and the fact that the
requisition was attributed to "RA/C.D.Bridges" and charged to Dr.
Bridges' grant, No. 02489. Ex. 8 (Item 26) (purchase requisition).
Mr. Alvarez testified that he used frogs on hand when he began the frog
series experiments. He testified that it was the practice to use frogs
on hand when needed even if they belonged to other investigators. 24/
Tr. 717-718 (Mr. Alvarez). He did not recall, but did not dispute
making the May 12, 1986 order. He also testified that the May 12, 1986
order was not linked to any experiment he was conducting. Tr. 718-720
It is uncontroverted that Dr. Lin used 96 frogs between May 20, 1986 and
August 26, 1986 for her thesis work. Tr. 2110 (Dr. Lin); and Tr. 3853
(Dr. Bridges). It is also uncontroverted that 126 frogs were used for
the frog series experiments. Tr. 3853 (Dr. Bridges). Dr. Bridges
further testified that the frog series experiments had required 90 frogs
by the end of August 1986.
Dr. Bridges testified to further orders for 200 frogs which were placed
on August 6, 1986 and September 4, 1986. See A.Ex. 65 (Items 1 and 4),
which detail these and other frog orders. The record contains charges
assessed to Dr. Bridges for the frog vivarium. These charges are by
"bin" of frogs without any indication of the number of frogs per bin.
We have no contemporaneous record showing the use for any particular
shipment of frogs.
The record here does not support linking any particular delivery of
frogs to the frog series experiments. It can be noted that the
deliveries in August and September 1986 are consistent with the
purported August 1986 start date but consistency alone is not adequate
for a finding on chronology. Given the orders in May, August, and
September 1986 and the informal practice of using frogs on hand, even if
the frogs belonged to other investigators, I find that frogs were
available for either a May or August 1986 start date.
EXPERIMENTAL DATA DO NOT CORROBORATE THE SCIENCE ARTICLE
99. THE 2 UL ETHANOL REPORTED IN THE SCIENCE ARTICLE DIFFERED FROM WHAT
WAS REPORTED IN THE 66 PAGES. NO PROTOCOL REPORTS THE USE OF 2 UL
ETHANOL; REPORTED LEVELS VARY FROM 3 UL IN FROGONE AND FROGTWO, TO 4 UL,
AND 5 UL, IN SOME LATER PROTOCOLS AND 8 UL IN THE RAT PROTOCOL.
100. THE AVAILABLE EXPERIMENTAL DATA DOES NOT PROVIDE A BASIS FOR THE
CONCLUSION REACHED IN THE SCIENCE ARTICLE THAT THE PIGMENT EPITHELIUM IS
THE SITE OF THE ISOMERASE REACTION SINCE THE DATA FOR FROGSIX WERE
DISCARDED WITHOUT A VALID SCIENTIFIC BASIS TO REJECT DATA FROM THAT
PROTOCOL WHILE ACCEPTING DATA FROM FROGEIGHT.
101. THE SCIENCE ARTICLE REPORTED THAT EXPOSURE OF THE ENZYME TO
TRYPSIN CONFIRMED THE FORMATION OF 11-CIS RETINOL. NO PROTOCOL OR DATA
WAS PRESENTED BY DR. BRIDGES FOR PERFORMANCE OF THIS EXPERIMENTATION AS
102. THE SCIENCE ARTICLE REPORTED THAT THE ENZYME WAS SEDIMENTED BY
CENTRIFUGATION AT ONE HUNDRED THOUSAND TIMES G FOR ONE HOUR. WHILE THE
PROTOCOL FOR FROG 10 INDICATES SUCH AN EXPERIMENT, THERE WAS NO DATA IN
EITHER THE 66 PAGES OR OTHER PRESENTED DOCUMENTATION TO SHOW THIS
EXPERIMENT WAS PERFORMED.
103. NO EXPERIMENTAL DATA ARE AVAILABLE FOR ANY PROTOCOLS WRITTEN AFTER
DISCUSSION OF EXPERIMENTAL DATA DO NOT CORROBORATE THE SCIENCE ARTICLE
In certain respects, the experimental data offered by Dr. Bridges as
support for the Science paper does not corroborate what is reported in
the Science article. 25/ Dr. Litman testified that what the Panel found
"striking was the lack of correspondence that occurred between what was
listed in the Science protocol and in the frog series protocols." Tr.
1570-1571 (Dr. Litman).
The Science paper reported in the methods section (footnote reference
21) that to each incubation was added:
. . . 2 ul of an ethanol solution containing 22 pmol of all-trans
[11, 12 -3H] retinol (Amersham; 53 Ci/mmol). . . .
Ex. 8 (Item 2). The experimental data supplied by Dr. Bridges (the 66
pages and other data) failed to show any use of 2 ul of ethanol; rather,
the 66 pages indicated varying levels from 3 ul in FROGONE and FROGTWO,
to 4 ul and 5 ul in later protocols and 8 ul in the RATONE protocol. 26/
Ex. 8 (Item 2) compared with A.Ex. 104 (Item 16A); A.Ex. 55; and Tr.
4542 (Dr. Bridges). Dr. Bridges explained that the use of 2 ul in the
Science article was possibly a typographical error in the paper. Ex. 8,
p. 11 and A.Ex. 36. Yet, Dr. Bridges failed to offer a reasonable
explanation as to how this "minor" error slipped by all the various
stages of submissions for this article, from the submission to Nature to
the submission to Science and the attendant revisions before
publication. Ex. 8, p. 11. 27/ Moreover, while the 66 pages failed to
indicate the use of 2 ul of ethanol, this reported use was consistent
with the protocols of FROGONE and FROGTWO dated August 6, 1986 and
August 19, 1986, respectively, submitted by Mr. Alvarez. A.Ex. 104
(Items 12 and 13). Furthermore, the testimony presented indicated that
Mr. Alvarez prepared a methods statement for Dr. Bridges which Dr.
Bridges used in writing the isomerase article. Tr. 3892-3893 and 4312
(Dr. Bridges). The use of 2 ul in the methods section is entirely
consistent therefore with the protocols Mr. Alvarez presented with the
August 1986 dates. A.Ex. 36. 28/.
Expert witness testimony also indicated that the conclusion in the
Science paper that the isomerization occurred in the retinal pigmented
epithelium was not supported by any data submitted in support of the
research. Tr. 1386, 1388-89, 1402, and 1413 (Dr. Goldberg); Tr.
1602-1605 (Dr. Litman). Dr. Litman testified that only two experiments,
FROGSIX and FROGEIGHT, were relative to the localization of isomerase
activity. These results were reported in Figure 3 of the Science paper.
Tr. 1602 (Dr. Litman). The experts concurred that a comparison of the
data in the 66 pages with what is actually reported in the Science paper
indicated an arbitrary use of the data without a scientific basis for
using it in that way. Dr. Litman explained that customary scientific
practice is that you exclude data from reported research only if there
is an absolutely sound scientific basis for the exclusion and there is a
documented problem with the data. Otherwise, all data must be included
in the publication. Tr. 1603-1606 (Dr. Litman). Dr. Litman indicated
that a review of the Science paper with the data for FROGSIX included in
the 66 pages indicated that Dr. Bridges discarded the data for FROGSIX
related to isomerase activity in the retina, noting only that the retina
preparation was dirty, when it appeared that FROGSIX yielded results
that were inconsistent with the results of FROGEIGHT. Tr. 1602-1605
(Dr. Litman); Tr. 1386 (testimony of Dr. Goldberg corroborating Dr.
Litman); Tr. 3538-3541 (Dr. Bridges); and compare Ex. 8 (Item 2), Figure
3, and A.Ex. 104 (Item 16A) (the results on the graph at p. 47 for
retina with the notation of "some RPE contamination" with the graph at
bottom of p. 53 marked "clean retina.") 29/ There was no documentation
other than the handwritten entry that the retina preparation was dirty
to explain why the data was discarded. The record supports the finding
that the available data from FROGEIGHT does not support the conclusion
reached in the Science paper since there was no further experimentation
to document that the results reached in FROGSIX were due to a dirty
There is also no protocol or experimental data in the 66 pages of
computer print-outs or the other documentation presented to support the
Science paper statement:
Confirmation that an enzyme was involved in the formation of
11-cis retinol was provided by the observation that its
formation was inhibited by phenylmthylsulfonyl fluoride (1 mM)
and destroyed by prior incubation at 37 degree C with trypsin
Ex. 8 (Item 2), p. 1679; A.Ex. 104 (Item 16A); Tr. 1416-1417 (Dr.
Goldberg); and Tr. 5589 (Dr. Bridges). Dr. Bridges did not dispute that
there was no protocol or data in the supporting documentation to support
this conclusion. He offered no explanation why such data was missing.
As a result, there is no experimental data to support the result
reported in the Science paper.
Similarly, the Science paper reported that the enzyme was sedimented by
centrifugation at one hundred thousand g for one hour. Ex. 8 (Item 2),
p. 1679. While the 66 pages sets forth a protocol at FROGTEN for this
experiment, there is no data in the 66 pages or the other documentation
presented (A.Ex. 31 (Item 8L, Att. K-R)) to show that this experiment
was actually performed. Tr. 1430-31 (Dr. Goldberg); and Tr. 4346-4347
(Dr. Bridges). Dr. Bridges contended that the experiment was performed
and stated he was sure he helped with the experiment for FROGTEN. Tr.
4346 (Dr. Bridges). In the absence of any experimental data, however,
there is no support for Dr. Bridges' statement that the experiment was
performed. Moreover, without the documentation, there is no support for
the result reported in the Science paper.
The record also shows that there is no experimental documentation
available for any of the protocols written after FROGTEN (except that no
data would have been generated for FROG 14). Tr. 3828-3850 (Dr.
Bridges); A.Ex. 104 (Item 16A). Dr. Bridges testified that while he
thought it might be possible that part of FROG 11 was reported in the
Science paper, none of the other frog experiments after FROGTEN were
reported in Science. 30/ Tr. 3828-3850 (Dr. Bridges). Dr. Bridges
contended that RATONE for which no supporting experimental data could be
found, was also reported in Science. Tr. 3852 (Dr. Bridges). Without
the documentation to support the experimentation, there is no
verification that the experiments were performed as contended.
THE EXPERIMENTAL PROTOCOLS AND CONCLUSIONS FOR THE SCIENCE ARTICLE WERE
DERIVED FROM THE PROTOCOLS REPORTED IN THE PNAS MANUSCRIPT
104. DR. BRIDGES DEVELOPED THE FROG SERIES PROTOCOLS AFTER READING THE
MANUSCRIPT FOR THE PNAS ARTICLE.
105. THE CONCLUSIONS REACHED IN THE SCIENCE ARTICLE ARE NOT LOGICALLY
BASED ON THE UNDERLYING EXPERIMENTAL DATA AND COULD BE DERIVED FROM THE
DATA FOUND IN THE 66 PAGES ONLY WITH THE BENEFIT OF THE CONCLUSIONS
REACHED IN THE PNAS MANUSCRIPT.
DISCUSSION OF THE EXPERIMENTAL PROTOCOLS FOR THE SCIENCE ARTICLE WERE
DERIVED FROM THE PROTOCOLS IN THE PNAS MANUSCRIPT
These findings are based on certain more narrow findings stated above.
Here, I find that the preponderance of the evidence shows that Dr.
Bridges developed the frog series protocols after reading the manuscript
for the PNAS article and that the conclusions stated in the Science
article were developed with the benefit of the data and results reported
in the PNAS manuscript.
Dr. Bridges was the only person in his laboratory to read the PNAS
manuscript; he designed the protocols for the frog series experiments.
I find above that the circumstances concerning the receipt and review of
the PNAS manuscript were misrepresented in many respects. Dr. Bridges'
misrepresentations concerning (1) the conduct of the frog series of
experiments and (2) responsibility for the text of changes to the
Science article, substantially undercut Dr. Bridges' testimony
concerning the May 1986 conduct of the frog series experiments. Thus, I
find that I can accord that testimony very little weight. There was a
striking lack of direct testimony from others in the laboratory for Dr.
Bridges' asserted May start date. While I did not find Drs. Lin and
Fong to be untruthful, they had very little direct knowledge of the
isomerase work to report and I found they were motivated by their
personal regard for Dr. Bridges to accept his account for when these
experiments were done. Their testimony therefore was in the context of
having accepted the May starting time rather than providing independent
evidence supporting this.
I found above that, contrary to the May 1986 date asserted by Dr.
Bridges, FROGTHREE was conducted in August 1986, after receipt of the
tritiated retinol in Batch 29 (specific activity 53). The method used
in FROGONE to demonstrate the isomerase reaction was not obvious on the
face of the scientific literature or 30 years would not have elapsed
without this discovery. Having placed FROGTHREE in August 1986 based on
the uncontroverted use of tritiated retinol with a specific activity of
53, I then find no basis to accept the May 1986 dates for FROGONE or
Mr. Alvarez's testimony was consistent with what the documentary record
shows he told both Baylor and the NIH Panel. To the best of his
recollection, the frog series experiments started in August 1986. He
testified that due to his concern about the footnote reference to the
"authors" having seen a draft of the PNAS manuscript, he had printed out
protocols of FROGONE and FROGTWO which were not filed with the rest of
his data for these experiments. Mr. Alvarez's testimony impressed me as
straightforward, and I was not persuaded that he was biased against Dr.
Bridges. Although Mr. Alvarez had been very displeased when Dr. Bridges
did not inform him of Dr. Bridges' plans to leave Baylor so that Mr.
Alvarez could look for other work, this was not sufficient to establish
a motive for purposely falsifying the start date of the frog series
work. Since Mr. Alvarez was co-author on the Science article, he would
have no discernible interest in falsifying the data. In many respects
the May date was more favorable to both Mr. Alvarez and Dr. Bridges
since it would establish the independent significance of the frog series
work. The 66 pages are not rendered more persuasive evidence than the
two protocol pages for FROGONE and FROGTWO provided by Mr. Alvarez
simply by the quantity of material. Moreover, a notable difference
between the protocols is the purpose statement for FROGONE included with
the 66 pages. Mr. Alvarez did not recall such a statement in the
protocol he had prepared, and the fact that it refers to the minimal
volume of ethanol suggests that Dr. Bridges added it later.
Dr. Bridges' failure to provide to Baylor and to the NIH Panel primary
data adequate for those investigations is significant. I found above
that Dr. Bridges did not account for this failure. Moreover, I found
that Dr. Bridges was the party having control and custody of the primary
data maintained by Mr. Alvarez and of the various computerized records
(both the back-up floppy disks and the computer hard disk records).
These inquiries, before Baylor, NIH, and now the Debarring Official, are
undisputedly serious; the failure to promptly provide primary data to
address the questions that arose concerning improper use of the contents
of the PNAS manuscript supports a negative inference that this data if
provided would not have supported Dr. Bridges' account of the conduct of
the frog series experiments. That such an inference is reasonable is
supported by representations even as late as the debarment hearing that
other files for the Science article may exist (Tr. 5593 (Dr. Bridges))
and by Dr. Bridges' failure to address at all the status of the back-up
Based on the above, I find that the frog series experiments were
conducted beginning in August 1986. This finding, when combined with
the findings concerning Dr. Bridges' failure to provide the primary data
for the frog series experiments and the development of the frog series
protocols without antecedent experimentation (including the absence of a
credible explanation for the selection of the critical variables)
supports the finding that the frog series protocols were developed by
Dr. Bridges after he read the PNAS manuscript. I further find that the
critical variables used in the frog series experimental protocols were
derived from the methods stated in the PNAS article.
Furthermore, I find that Dr. Bridges reached the conclusions stated in
the Science article with the benefit of the data and results presented
in the PNAS article. Dr. Litman testified that the Science article did
not accurately report the data in the 66 pages and that the results were
not consistent with the experimental data in that data was discarded or
selected in a way that was not accepted practice in scientific research.
Tr. 1602-1608 (Dr. Litman). I found above that in some respects, the
data in the 66 pages was not accurately reported in the Science article.
Significant here is the misrepresentation of the volume of ethanol used
as being 2 ul when the 66 pages report volumes ranging from 4 ul to 8
ul. Given Dr. Litman's opinion that certain data was disregarded
without scientific basis from FROGSIX, I find that the data were
selected to support the result Dr. Bridges wished to report. It thus
becomes obvious that Dr. Bridges reached the conclusion concerning the
retinol isomerase which is stated so definitively in the Science article
with the benefit of the results reported in the PNAS manuscript.
VII. PROPOSED CONCLUSIONS OF LAW
After considering the findings of fact and the record as a whole for
this proceeding, I propose these conclusions of law to the debarring
official for use in reaching a decision on the proposal to debar Dr. C.
ACCEPTED STANDARDS OF CONDUCT FOR SCIENTIFIC RESEARCH
1. DR. BRIDGES DID NOT ADHERE TO CERTAIN ACCEPTED STANDARDS OF CONDUCT
FOR SCIENTIFIC RESEARCH FOR HANDLING OF A MANUSCRIPT RECEIVED FOR PEER
REVIEW. THESE STANDARDS ARE:
TO ACT PROMPTLY WHEN DECLINING TO REVIEW A MANUSCRIPT ON THE BASIS
THAT THE PROPOSED REVIEWER'S CURRENT RESEARCH IS CLOSELY RELATED TO
THAT REPORTED IN THE MANUSCRIPT;
TO TREAT INFORMATION CONTAINED IN A MANUSCRIPT RECEIVED FOR PEER
REVIEW AS CONFIDENTIAL AND PRIVILEGED; AND
TO TAKE NO ACTION THAT MIGHT DELAY PUBLICATION OF A COMPETITIVE
MANUSCRIPT.2. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE
WAITED UNTIL SEPTEMBER 2, 1986 TO INFORM DR. DOWLING THAT HE
COULD NOT SERVE AS A REVIEWER FOR THE PNAS MANUSCRIPT. DR.
BRIDGES FAILED PROMPTLY TO DECLINE TO REVIEW THE MANUSCRIPT.
3. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE DEVELOPED THE
METHODS AND CONCLUSIONS FOR THE FROG SERIES EXPERIMENTS WITH KNOWLEDGE
OF THE CONTENTS OF THE PNAS MANUSCRIPT. THE METHODS AND CONCLUSIONS FOR
THE FROG SERIES EXPERIMENTS AND FOR THE SCIENCE ARTICLE WERE DERIVED
FROM THE PNAS MANUSCRIPT. DR. BRIDGES THUS PLAGIARIZED THE PNAS
MANUSCRIPT; HE THEREBY FAILED TO TREAT THIS INFORMATION AS PRIVILEGED OR
4. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE TOOK ACTIONS WHICH
COULD HAVE DELAYED PUBLICATION OF A COMPETITIVE MANUSCRIPT.
5. DR. BRIDGES DID NOT ADHERE TO CERTAIN ACCEPTED STANDARDS OF CONDUCT
FOR REPORTING SCIENTIFIC RESEARCH. THESE STANDARDS ARE:
TO REPORT EXPERIMENTAL PROCEDURES ACCURATELY;
TO REPORT EXPERIMENTAL RESULTS ACCURATELY; AND
TO REPORT CONCLUSIONS WHICH TAKE INTO ACCOUNT ALL EXPERIMENTAL
DATA AVAILABLE UNLESS THERE IS A SCIENTIFICALLY SOUND RATIONALE
FOR DISREGARDING DATA.
6. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE FAILED TO REPORT
ACCURATELY THE EXPERIMENTAL METHODS FOR THE FROG SERIES EXPERIMENTS IN
THE SCIENCE ARTICLE.
7. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE SELECTIVELY REPORTED
DATA FROM THE FROG SERIES EXPERIMENTS. DR. BRIDGES FAILED TO REPORT
8. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE REPORTED CONCLUSIONS
WHICH WERE BASED ON SELECTED DATA AND DERIVED FROM PRIVILEGED
INFORMATION FROM ANOTHER'S MANUSCRIPT. DR. BRIDGES DID NOT HAVE A
SCIENTIFICALLY SOUND RATIONALE FOR DISREGARDING DATA.
9. DR. BRIDGES' DEVIATIONS FROM ACCEPTED STANDARDS OF CONDUCT FOR
SCIENTIFIC RESEARCH SHOW A FLAGRANT DISREGARD FOR ACCEPTED RESEARCH
DISCUSSION OF ACCEPTED STANDARDS OF CONDUCT FOR SCIENTIFIC RESEARCH
The record includes two documents which contain information about
accepted standards of conduct for scientific research. "On Being A
Scientist" is a booklet published by the National Academy of Sciences in
1989 which is directed toward "students beginning to do scientific
research." A.Ex. 205. "Honor in Science" is a booklet published by
Sigma Xi, The Scientific Research Society, in 1986 which is "intended as
practical advice to those entering careers in scientific research."
A.Ex. 206. These booklets describe expected ethical standards for
scientific research and contain entries that pertain to the standards
which I have concluded apply and were violated here. For example, these
booklets discuss plagiarism, treatment of research data, and use of
privileged data. These materials are cited further below. It was
undisputed that these materials would be generally accepted as authority
by the scientific research community and that they reflect standards of
conduct that would have been accepted in 1986, the time at issue here.
In reaching my conclusions about the accepted standards of conduct
relevant to this case, I also relied on the testimony of the scientists
appearing as witnesses in this case. I further relied on the standards
of conduct stated as conclusions of law in a prior debarment decision,
Decision and Findings of Fact for the Proposed Debarments of Robert
Edward McCaa, Ph.d., DAB No. 823 (1987). As I noted in that prior case,
standards of conduct for scientific research are continually evolving
and there may be some areas of regional variation or personal
discretion. I have been able to discern, however, certain fundamental
principles common to the scientific community as a whole. The standards
for handling peer reviewed manuscripts and for reporting scientific
research that are stated in these conclusions reflect these fundamental
principles. I have evaluated my findings concerning Dr. Bridges'
conduct against these standards and concluded that Dr. Bridges violated
these standards of conduct as described below.
Standards for handling a peer reviewed manuscript
Dr. Ralph Bradshaw, chairman of the NIH Panel, testified concerning his
experience with the peer review of scientific papers. Tr. 1530-1531
(Dr. Bradshaw). He also testified concerning review practices common to
scientific journals. Tr. 1531-1544 (Dr. Bradshaw). He stated that
manuscripts in the peer review process are privileged documents and
remain so until either rejected or accepted and actually published. He
was emphatic that it is common practice for a scientist to disqualify
him/herself on the grounds of conflict of interest from reviewing a
manuscript that "closely resembles or closely deals with [what] that
individual scientist is working on." Tr. 1535 (Dr. Bradshaw). He
testified that it usually took him about "five minutes" to return a
manuscript where he had determined not to act as a reviewer on conflict
of interest grounds. He testified that it was ordinarily possible to
determine from the title or the abstract whether a conflict existed. He
stated that this was not a "difficult" decision and that--
. . . the title is already . . . something that's a warning light,
you can read about as far as the abstract and you know immediately
that this is . . . too close to what you're doing, and you would
never have to read beyond that. Tr. 1537-1538 (Dr. Bradshaw).
With regard to the time within which scientists typically decline review
of manuscripts where there is a conflict, Dr. Bradshaw testified that --
I would say within a few days to a week, and the variation would
be -- appear to be more likely related to the time when they
finally got the manuscript and looked at it and said, oh, my
goodness, this is a conflict, I can't do this and then send it
. . . anything longer would be extraordinary. I have never
experienced it in my years on the editorial board . . .
Tr. 1562 (Dr. Bradshaw). Dr. Bradshaw testified that he would regard
even "a limited review" of a manuscript where there was a conflict of
interest as "an unethical practice." Tr. 1563 (Dr. Bradshaw). Dr.
Bradshaw also testified that upon receipt of a manuscript presenting a
conflict he would --
. . . return the . . . manuscript without review. But then I
personally would contact the editor . . . [or] the author
directly . . . .
. . . I would take certain measures to protect myself and my
laboratory personnel, because although the other laboratory
might be ahead, we would certainly want to publish our results .
. . .
Tr. 1864-1865; see also Tr. 1867-1870 (Dr. Bradshaw).
The other scientists' testimony was consistent with Dr. Bradshaw's
concerning the handling of peer reviewed material and the speedy action
taken to decline to review where there is a conflict. There was,
however, recognition that a scientist might actually "peek inside and
see what the guy found . . . but . . . just send the thing right back."
Tr. 1451 (Dr. Goldberg). Dr. Goldberg stated that a conflicting
manuscript should be returned within twenty-four hours so that peer
review would not be delayed and to avoid a conflict of interest. Tr.
1451-1452 (Dr. Goldberg). Dr. Adler confirmed that no use whatsoever
could be made of any data or experimental methods contained in a
manuscript received for peer review. Tr. 5147-5148 (Dr. Adler).
The National Academy of Sciences booklet states --
Special care must be taken when dealing with unpublished
materials belonging to others, especially . . . papers seen or
heard prior to publication or public disclosure. Such
privileged material must not be exploited . . . Scientists also
must be extremely careful not to delay publication or deny
support to work that they find to be competitive . . .
Scrupulous honesty is essential in such matters.
A.Ex. 205 at 9071.
The Sigma Xi publication states --
You are entitled to expect that research data you have collected
will be used by you alone unless you have agreed [otherwise] . .
. in which cases you are entitled to appropriate credit.
A.Ex. 206 at 20.
While there was some disagreement among the scientific experts about
whether it was appropriate even to continue to read a manuscript once it
was identified as closely related to the reviewer's own work, the
experts agreed with the booklets' statements on standards of conduct
that any information obtained from the manuscript must be treated as
confidential and privileged, that is, that it would be unethical to
appropriate research methods as one's own.
I have concluded that Dr. Bridges violated the standards of conduct as
Conclusion of Law No. 2. Dr. Bridges deviated from the standards of
conduct when he waited until September 2, 1986 to inform Dr. Dowling
that he could not serve as a reviewer for the PNAS manuscript. Dr.
Bridges failed promptly to decline to review the manuscript. It was
uncontested that Dr. Bridges read the PNAS manuscript some time during
the first week of August 1986. By letter dated September 2, 1986, Dr.
Bridges declined to review the PNAS manuscript on grounds it was close
to research he was currently conducting. The length of time that passed
here was "extraordinary" (Tr. 1562 (Dr. Bradshaw)) and a clear
violation of the standard's requirement that declining to review be
prompt. See Findings of Fact Nos. 17-30.
Conclusion of Law No. 3. Dr. Bridges deviated from the standards of
conduct when he developed the methods and conclusions for the frog
series experiments with knowledge of the contents of the PNAS
manuscript. The methods and conclusions for the frog series experiments
and for the Science article were derived from the PNAS manuscript. Dr.
Bridges thus plagiarized the PNAS manuscript; he thereby failed to treat
this information as privileged and confidential.
The standard requires absolute confidentiality be accorded to another's
privileged data unless it has been agreed otherwise. In discussing what
constitutes plagiarism the National Academy of Sciences states --
Plagiarism is the most blatant form of misappropriation of credit.
A broad spectrum of misconduct falls into this category . . . a
person's work will inevitably incorporate and overlay with that of
others. However, occasional overlap is one thing; systematic,
unacknowledged use of the techniques, data, words or ideas of
others is another . . . .
The intentional use of another's intellectual property without
giving credit may seem more blameworthy than the actions of a
person who claims to have plagiarized because of inattention or
sloppiness. But, as in the case of fraud, the harm to the
victim is the same regardless of intention. Furthermore, given
the difficulty of judging intentions, the censure imposed by the
scientific community is likely to be equally great.
A.Ex. 205 at 9071.
The Sigma Xi publication states --
The spectrum of plagiarism in science is even broader . . . . It
includes the use of knowledge picked up . . . when acting as a
journal referee . . . .
. . . Stealing words is more obvious than stealing someone's
ideas. Unfortunately, it is usually also less important.
A.Ex. 206 at 16.
The findings of fact that the frog series experiments were conducted
beginning in August 1986, after Dr. Bridges had read the PNAS
manuscript, and that he derived the methods and conclusions for those
experiments from that manuscript result in the conclusion that Dr.
Bridges plagiarized the PNAS manuscript. See Findings of Fact Nos. 104
and 105. I have concluded that no specific finding as to his intent to
plagiarize is necessary.
While Dr. Bridges argued that he did not violate any applicable standard
since the PNAS manuscript was accorded no protection under federal
copyright law and thus was in the public domain, this argument does not
take into account the accepted standards for the conduct of scientific
research. Whether he violated federal copyright law is simply not
germane to the question presented here. Federal copyright law is
irrelevant to a determination of whether there is scientific misconduct;
research scientists are not precluded from agreeing that their field
requires different or higher standards of conduct. Moreover, the
question ultimately presented concerns eligibility to receive limited
federal research dollars, a question not addressed by copyright
principles. There is a valid public interest in denying scarce research
funds to an individual who has been found to engage in scientific
misconduct. Dr. Bridges' use of privileged information in developing
his own research protocols -- results from which he then attempted to
publish as rapidly as possible -- violated accepted standards of conduct
Conclusion of Law No. 4. Dr. Bridges deviated from the accepted
standard of conduct when he failed promptly to inform Dr. Dowling that
he could not review the PNAS manuscript. See Finding of Fact No. 30.
Dr. Bridges thus failed to avoid actions which could adversely affect
the publication of a competitive manuscript.
Standards for reporting scientific research
The standards of conduct for accurate reporting of experimental
procedures and results were stated in DAB No. 823 at 48. The standards
found to apply in that case also apply here. From the testimony in this
proceeding, I derived an additional standard which applies here. That
standard states the obligation of a research scientist to report
conclusions which take all available experimental data into account
unless there is a scientifically sound rationale for disregarding the
Dr. Litman testified that data from a series of experiments could not be
selected arbitrarily for publication. He testified that unless there
was a scientifically sound rationale for disregarding data it must be
reflected in the reported results. Tr. 1603-1608 (Dr. Litman). Dr.
Goldberg also testified that sound scientific practices required that
data not be selected to fit with the results reported. He stated "if
you've run three reactions and each one is showing a different
proportionality, you don't just choose the one that -- fits what you
want to show." Tr. 1377 (Dr. Goldberg).
In this regard, the National Academy of Sciences publication states --
General rules for distinguishing a priori "good" data from "bad"
cannot be formulated with much clarity. Nevertheless, good
scientists have methods that they can apply in judging the
reliability of data . . . they impose constraints on how those
observations can be interpreted. A researcher is not free to
select only the data that fit his or her prior expectations. If
certain data are excluded, a researcher must have justifiable
reasons for doing so.
A.Ex. 205 at 9061.
I have concluded that Dr. Bridges violated these standards of conduct as
Conclusion of Law No. 6. Dr. Bridges deviated from the standards of
conduct when he failed to report accurately the experimental methods for
the frog series experiments in the Science article. The methods
reported in the Science article include only the use of 2 ul of ethanol
while the 66 pages submitted by Dr. Bridges' report varying levels of
ethanol. Finding of Fact No. 99.
Conclusion of Law No. 7. Dr. Bridges deviated from this standard when
he selectively reported data from the frog series experiments. Dr.
Bridges failed to report results accurately. Dr. Bridges failed to
report results from an experiment where there was no scientific basis to
disregard those results. Dr. Bridges disregarded the data for FROGSIX
without a valid scientific rationale. Finding of Fact No. 100.
Conclusion of Law No. 8. Dr. Bridges deviated from the standards of
conduct when he reported conclusions which were based on selected data
and derived from privileged information from another's manuscript. Dr.
Bridges reported conclusions that were not warranted based on all
experimental data available because he did not have a scientifically
sound rationale for disregarding the data from FROGSIX. Findings of
Fact Nos. 100 and 105.
I found that the data reported in the Science article were selected in
order to support the conclusions that Dr. Bridges had derived from the
information contained in the PNAS manuscript. The seriousness of this
factual finding cannot be over-emphasized. The accurate reporting of
scientific data and results as well as the conclusions derived by the
scientist from those data and results is the heart of scientific
research. Replication of another's work and progress in the resolution
of scientific questions depend on this honesty in reporting. From the
Sigma Xi publication's discussion of the importance of honesty in
research and reporting I conclude that this is regarded by scientists as
integral to progress in science. A.Ex. 206 at 2-6.
Dr. Bridges' deviations from accepted standards of conduct for
scientific research show a flagrant disregard for accepted research
From the evidence presented in this case, I found certain standards that
I concluded were basis tenets of scientific research. These standards
were reflected in documents intended to guide students just beginning as
research scientists. There is no basis for concluding that Dr. Bridges
was unaware of these standards. Dr. Bridges was an experienced research
scientist who had published many peer reviewed articles. He had also
acted as an editor for a professional journal. It was undisputed that
he was knowledgeable about peer review practices as an author, reviewer,
and editor. It was also undisputed that he knew of the fundamental
standards I have determined to apply here concerning the accurate
reporting of data and results and the reporting of conclusions which
take into account all experimental data unless scientifically unsound.
The record shows that the reason Dr. Bridges disregarded the accepted
standards of conduct was to deceive others about the development of the
frog series protocols and the conduct of the frog series experiments
because he had plagiarized the PNAS manuscript. Dr. Bridges' deviations
from the accepted standards show a flagrant disregard for those
STANDARDS OF CONDUCT FOR A PRINCIPAL INVESTIGATOR
10. DR. BRIDGES DID NOT ADHERE TO CERTAIN STANDARDS OF CONDUCT
APPLICABLE TO A PRINCIPAL INVESTIGATOR WITH REGARD TO PRIMARY DATA FOR
SCIENTIFIC RESEARCH SUPPORTED BY FEDERAL FUNDS. THESE STANDARDS ARE:
PROMPTLY TO PROVIDE TO THE GRANTEE INSTITUTION ADEQUATE PRIMARY
DATA TO SUPPORT THE EXPERIMENTAL METHODS, DATA, AND CONCLUSIONS
PUBLISHED UNDER THE AUSPICES OF THE GRANTEE INSTITUTION WHEN
NECESSARY TO ADDRESS MATTERS UNDER INVESTIGATION IN ACCORDANCE
WITH FEDERAL REQUIREMENTS.
PROMPTLY TO PROVIDE TO THE FEDERAL GRANTOR AGENCY ADEQUATE
PRIMARY DATA TO SUPPORT THE EXPERIMENTAL METHODS, DATA, AND
CONCLUSIONS PUBLISHED WITH FEDERAL GRANT SUPPORT WHEN NECESSARY
TO ADDRESS MATTERS UNDER INVESTIGATION IN ACCORDANCE WITH
11. DR. BRIDGES DEVIATED FROM THIS STANDARD WHEN HE FAILED TO PROVIDE
ADEQUATE PRIMARY DATA RELATED TO THE FROG SERIES EXPERIMENTS REPORTED IN
THE SCIENCE ARTICLE.
12. DR. BRIDGES' DEVIATION FROM THE STANDARDS OF CONDUCT FOR PRINCIPAL
INVESTIGATORS SHOWS A FLAGRANT DISREGARD FOR THOSE STANDARDS.
DISCUSSION OF STANDARDS OF CONDUCT FOR A PRINCIPAL INVESTIGATOR
A principal investigator has a particular responsibility for activities
under a research grant. The principal investigator is "responsible and
accountable to the recipient institution officials for the proper
conduct of the project or program." Public Health Service Grants Policy
Statement (rev.) (1982), p. 5. The principal investigator is
"responsible for the scientific and technical direction of the project."
42 C.F.R. 52.2(b). More specifically, the responsibilities of a
principal investigator of a research grant include supervising the work
of others on the project, designing the project, interpreting the data,
and accurately reporting the project results. DAB No. 823 (1987) at 53.
Dr. Bridges, as principal investigator for the research grant which
provided funding for the research leading to the Science paper, signed a
statement that he would "accept responsibility for the scientific
conduct of the project." A.Ex. 211.
A grant is not a gift. Under a research grant, the principal
investigator and the grantee institution are accountable to the Federal
Government for the use of the funds provided. 45 C.F.R. 74.3 and 74.4.
Implicit in this responsibility for the scientific conduct of the
research grant is the principal investigator's responsibility to
document the research performed under the grant. Therefore, a principal
investigator must be able to provide adequate primary data to support
experimental methods, data, and conclusions published with federal grant
support to the grantee institution and the granting agency when
necessary to address matters under examination. 45 C.F.R. 74.24(a).
This responsibility flows directly from the receipt of federal grant
It is a fundamental tenet of grant stewardship that records must be
maintained and retained in support of a grant project. 45 C.F.R. 74.20.
The requirement to maintain and retain records applies not only to
financial records in support of costs expended under a grant project but
applies as well to other records necessary to document the nature of
activities conducted with federal funds. This standard of conduct for
maintaining and providing primary data was discussed in "On Being a
Scientist," authored by the Committee on the Conduct of Science,
National Academy of Sciences. A.Ex. 205. This publication states:
After publication, scientists expect that data and other
research materials will be shared upon request . . . But in
those fields in which sharing is possible, a scientist who is
unwilling to divulge research data to qualified colleagues runs
a great risk of not being trusted or respected. Because of the
continued need for access to data, researchers should keep
primary data for as long as there is any reasonable need to
refer to them.
A.Ex. 205, p. 9066 (emphasis added). Consequently, the requirement to
maintain and retain primary data in support of a research grant is not
only a legal requirement, but has far reaching practical applications in
that it offers an objective description of all the experimental methods
and data performed. It allows other scientists to verify and replicate
the results, and prevents the likelihood of just this kind of dispute
occurring. The principal investigator, who is ultimately responsible
for his own work as well as the work of those under his supervision, is
responsible for maintaining and retaining the primary data that will
support the funded research. Therefore, as a practical matter, the
principal investigator has to safeguard this information.
Most importantly, unless a principal investigator is considered as
having a duty to maintain and retain primary data, a principal
investigator could always discard the primary data and be absolved from
fault any time an allegation of misconduct is levied against him or her.
While there may certainly be circumstances where data has been lost or
stolen without fault on the part of the principal investigator, these
circumstances would presumably be rare. Therefore, unless such unique
circumstances are shown to exist, a principal investigator must promptly
provide primary data in support of federally funded research to the
grantee institution and the awarding agency when necessary to address
matters under investigation.
I have concluded that Dr. Bridges violated the standards of conduct for
a principal investigator. Dr. Bridges deviated from the standards of
conduct when, as a principal investigator, he failed to provide adequate
primary data related to the frog series experiments reported in the
In this case, I found that there were no unique or rare circumstances
established to account for Dr. Bridges' failure to produce the primary
data. The absence of Dr. Bridges' primary data is particularly
disturbing since Dr. Bridges did read the PNAS manuscript and the
experimental methods reported in Dr. Bridges' Science article were so
strikingly similar to the PNAS article. Indeed, this debarment dispute
revolves around a relatively simple issue -- when did Dr. Bridges begin
the isomerase research which led to the Science paper -- which could
have been determined at the outset from the primary data if it had been
promptly provided to the Baylor Committee and the NIH Panel. Yet,
because the primary data was not provided, two long and unnecessarily
complicated proceedings were required.
Dr. Bridges offered only changing and confusing reasons about the
absence of the primary data. First, he led Baylor to believe the
primary data was discarded, then he argued it was lost or stolen, later
he provided only bits and pieces of fragmentary data, and then only
months after the investigation began, he provided data related to the
experimental methods (the 66 pages), which is of uncertain evidentiary
value, without any reasonable explanation for why the information was
not produced earlier. Findings of Fact Nos. 59-72. Computer records
can be easily altered. Without the original primary data, it is
impossible to verify the authenticity of the computer pages submitted by
Dr. Bridges. Moreover, while Mr. Thomas indicated he assisted Dr.
Bridges in locating the data in the subdirectory of the Panasonic
computer, he was not present when Dr. Bridges actually printed out the
data. Therefore, he could not verify that the material located on the
hard disk was the material that actually appeared in the 66 pages that
were printed. Furthermore, Mr. Thomas could not verify whether any
information was inputted into the computer just prior to his locating
the files in the subdirectory. 31/ The testimony clearly indicated that
the data had not been deleted and was accessible, at any time, to anyone
with even a smattering of computer experience. Tr. 4862, 4873 (Mr.
Thus, in light of Dr. Bridges' duty as a principal investigator to
provide adequate primary data, which was clearly violated here, it is
reasonable to draw negative inferences. After all, Dr. Bridges had the
responsibility to maintain and retain the primary data. Moreover, the
primary data was in his exclusive control. Therefore, I conclude that
Dr. Bridges' failure to make records available in any reasonable form
meant that the primary data would not support Dr. Bridges' assertions.
I can also reasonably conclude that Dr. Bridges disregarded the accepted
standard in order to protect himself from the allegations of misconduct.
Dr. Bridges' actions show a flagrant disregard for the accepted
standards of conduct.
LACK OF RESPONSIBILITY USING FEDERAL GRANT FUNDS
13. DR. BRIDGES' FAILURE TO ADHERE TO CERTAIN STANDARDS APPLICABLE TO
RESEARCH SCIENTISTS AND PRINCIPAL INVESTIGATORS INDICATES A LACK OF
DISCUSSION OF LACK OF RESPONSIBILITY
In general, a finding that a prospective contractor or grantee is
responsible requires a determination that the contractor or grantee
possesses the requisite competence, capacity, record of satisfactory
performance on other awards, integrity, and ethics to satisfactorily
perform under a given award of federal funds. See generally 48 C.F.R.
9.104-1 et. seq. Here, I consider whether Dr. Bridges' violations of
accepted standards of conduct indicate a lack of responsibility to
receive awards of federal funds.
In accepting federal support, a researcher implicitly agrees to conduct
and report that experimental work in accordance with accepted standards
of conduct for scientific research. DAB No. 823 at 56. Consequently,
in deviating from accepted standards, Dr. Bridges' performance under his
grant award was rendered unsatisfactory.
While it was undisputed that Dr. Bridges is an innovative and productive
scientist who had made a number of important contributions to the vision
research field, this alone is not adequate to establish responsibility.
Nevertheless, Dr. Bridges' violations of the standards of conduct for
research scientists were extremely serious. He disregarded standards
with which he was undisputably familiar and did so to deceive others.
Dr. Bridges' actions formed a pattern of deception and confusion
concerning the development of the frog series protocols and the conduct
of the actual experimental work in his laboratory. These actions are
inconsistent with any presumption of honesty or integrity.
Accordingly, I conclude that Dr. Bridges' violations of accepted
standards of conduct for research indicate a lack of responsibility.
CAUSE FOR DEBARMENT ESTABLISHED
14. DR. BRIDGES' DISREGARD OF CERTAIN STANDARDS OF CONDUCT APPLICABLE
TO RESEARCH SCIENTISTS AND PRINCIPAL INVESTIGATORS ESTABLISHES A "CAUSE
[FOR DEBARMENT] OF SO SERIOUS OR COMPELLING A NATURE THAT IT AFFECTS THE
PRESENT RESPONSIBILITY OF" DR. BRIDGES PURSUANT TO 45 C.F.R. 76.305(D)
AND 48 C.F.R. 9.406-2(C).
DISCUSSION OF CAUSE FOR DEBARMENT ESTABLISHED
I have concluded that Dr. Bridges did not act responsibly when he
disregarded certain standards of conduct for scientific research.
Conclusion of Law 13.
As I pointed out in DAB No. 823 (at 58), grant awards for scientific
research depend "heavily upon the trust which the government places in
the principal investigator to direct and oversee the research conducted
with the support of grant funds." Dr. Bridges' failure to assure that
the research supported by his grant was independent (i.e., not derived
from another's privileged material) and reported in accordance with
accepted standards is a serious breach of this trust. So, too, is his
failure to provide adequate primary data to the grantee institution or
grantor agency. As I concluded earlier, primary data provided early in
this inquiry would have answered unequivocally the pivotal question of
when the frog series experiments began in Dr. Bridges' laboratory. The
failure to make this data available is a serious and compelling matter.
I have drawn an appropriate negative inference from this since I
concluded that the data if provided would not have supported Dr.
Bridges' assertions concerning when this work was done. But I emphasize
for purposes of this conclusion that the safeguarding of such data is an
obligation integral to the proper performance of a grant of federal
Therefore, I conclude that Dr. Bridges' flagrant disregard for the
standards of conduct for scientific research establishes the proposed
cause for debarment since these are "serious or compelling" matters that
affect Dr. Bridges' "present responsibility" to receive awards of
federal funds. This cause was established by a preponderance of the
DEBARMENT IS WARRANTED BY THE CIRCUMSTANCES OF THIS CASE
15. THE SERIOUSNESS OF DR. BRIDGES' ACTS AND THE ABSENCE OF ANY
SUBSTANTIAL MITIGATING FACTORS REQUIRE THAT HE BE DEBARRED FOR A TERM OF
THREE YEARS FROM RECEIVING AWARDS OF FEDERAL ASSISTANCE OR PROCUREMENT
FUNDS IN ORDER TO PROTECT THE INTERESTS OF THE FEDERAL GOVERNMENT IN
CONDUCTING BUSINESS WITH ONLY RESPONSIBLE PERSONS.
DISCUSSION OF THE CONCLUSION THAT DEBARMENT IS WARRANTED BY THE
CIRCUMSTANCES OF THIS CASE
The regulations provide that a determination to debar is made after
consideration of "the seriousness of the . . . acts or omissions and any
mitigating factors." 45 C.F.R. 76.300 and 48 C.F.R. 9.406(1)(a).
I asked the parties to address mitigating factors in their post-hearing
submissions. NIH asserted that there were no mitigating factors present
in this case. Dr. Bridges did not address mitigating factors in his
post-hearing submission or oral argument. While Dr. Bridges alluded to
the fact that he had difficulties with other researchers at Baylor
(A.Ex. 81), no evidence suggests that there were any exceptional
circumstances in Dr. Bridges' laboratory during August 1986 which would
excuse his actions. There is no reason apparent on this record why Dr.
Bridges did not act to maintain the integrity of his work. In fact, it
is reasonable to conclude that his standing in his field and his
position as the head of a laboratory where a number of other scientists
worked created a particular obligation to adhere to accepted ethical
standards. Accordingly, I conclude that there are no substantial
factors which mitigate against a decision that debarment is warranted.
Considering the seriousness of Dr. Bridges' violations of certain
fundamental standards of conduct, I find no reason to refrain from
The scientific misconduct found here strikes at the heart of the system
of scientific research and progress in scientific inquiry. As is
apparent from the earlier discussions in this decision, the scientific
community functions on trust and openness; once that trust is breached,
the harm is far greater from an incident of plagiarism than simply
discrediting the work underlying one paper. Not only did Dr. Bridges
violate fundamental standards of conduct, but he also misrepresented as
his own work that would potentially be considered by the Federal
Government in evaluating Dr. Bridges' grants and in making future
funding decisions. In light of the high degree of trust inherent in
research grants of the type which Dr. Bridges received, under which
performance cannot be readily verified or qualitatively monitored,
there is no lesser sanction that would adequately protect the public
interest. The government has an obligation to award its limited federal
research monies only to those that it determines will use those funds
After considering the circumstances in this case, I recommend a
three-year debarment term, the standard length for an administrative
debarment. 45 C.F.R. 76.320 and 48 C.F.R. 9.406-4. The Debarring
Official, however, has the discretion to select any reasonable and
specified period of time commensurate with the seriousness of the cause
for debarment. In this case, the violations were of a highly serious
nature, and I have found no substantial mitigating factors which support
a decision not to debar. The violations I concluded exist here related
directly to Dr. Bridges' integrity, his willingness to conform to
accepted scientific practices, and his satisfactory performance of his
While a decision to debar is certainly reasonable under these
circumstances, I do not regard the NIH post-hearing submission as
supporting a five-year term in lieu of the standard three-year term.
Although Dr. Bridges' misrepresentation concerning the timing and
conduct of the frog series experiments and his evasive conduct
surrounding the presentation of primary data were not a single, isolated
incident, the misconduct found does concern one set of experiments and
one publication. NIH did not assert that Dr. Bridges' other work
(throughout a distinguished 30-year career) was called into question or
that he could not in the future be found responsible to receive federal
funds. Notwithstanding the seriousness of the violations found in the
recommended conclusions of law, I propose that a standard three-year
term of debarment be imposed. This term would strike a proper balance
between protecting the government's interests and not unduly
disadvantaging Dr. Bridges by virtue of a too lengthy debarment term.
NIH also argued that any debarment term should commence as of the date
of this decision, but agreed to a two-month reduction of the proposed
five-year term based on the time required to resolve NIH's January 1990
request to stay these proceedings. Dr. Bridges did not present any
arguments concerning the commencement of any period of debarment.
Accordingly, I recommend that the debarment period begin as of January
1, 1991, the approximate date this decision would have been issued but
for the time required for the NIH stay request.
For the reasons stated above, I recommend to the Debarring Official that
the Respondent, Dr. C. David Bridges, be debarred for a period of three
years beginning January 1, 1991.
Sparks Ford Hearing Officer Member,
Departmental Appeals Board1. NIH
agreed to a two-month reduction to
reflect the time required to resolve its
January 1990 request to stay these
2. The regulations applicable to grants further provide for a term
longer than three years "[w]here circumstances warrant" (45 C.F.R.
76.320(a)) and both regulations provide that an existing debarment may
be extended if necessary to protect the public interest (45 C.F.R.
76.320(b) and 48 C.F.R. 9.406-4(b)).
3. The five members of the Panel were scientists with distinguished
credentials and experience in vision research and related fields. Dr.
Ralph A. Bradshaw, the Panel chair, is a professor and the chair of the
Department of Biological Chemistry at the University of California,
Irvine. Dr. Alice Adler is a senior scientist at the Eye Research
Institute of Retina Foundation in Boston, Massachusetts. Dr. Frank
Chytil is a professor of biochemistry and assistant professor of
medicine at Vanderbilt University School of Medicine in Nashville,
Tennessee. Dr. Nelson Goldberg is a professor of biochemistry at the
University of Minnesota in Minneapolis. Dr. Burton J. Litman is
chairman of the Department of Biochemistry at the University of Virginia
School of Medicine in Charlottesville. See Agency Exhibits (A.Exs.) 213
through 217. Three of the Panel members, Drs. Adler, Litman, and
Chytil, were among those scientists suggested by Dr. Bridges for
appointment to the Panel. See A.Ex. 81. With regard to the scientific
matters at issue, four of the Panel members were recognized as expert
witnesses, as was Dr. Bridges, for the debarment proceedings. Hearing
Transcript (Tr.) Tr. 1201 (Dr. Goldberg); Tr. 1566 (Dr. Litman); Tr.
2463-2465 (Dr. Bridges); Tr. 2810 (Dr. Chytil); and Tr. 4889 (Dr.
4. Exhibits (Exs.) one through eight were submitted to me by the
Debarring Official. Exhibits denominated A.Ex. were NIH hearing
exhibits, and exhibits denominated CDB Ex. were Dr. Bridges' hearing
exhibits. We also received visual exhibits from both parties which are
indicated as CDB visual exhibits (CDB V. Ex.) and Agency Visual exhibits
(A. V. Ex.) and were lettered sequentially.
5. The Panel report describes in detail the charge to the Panel by
NIH, the conclusions reached and the supporting reasons, as well as what
steps were taken by the Panel to gather information relevant to its
inquiry. The Panel's report is the best and most direct source of
information about these matters. Therefore, they are not explained in
detail here. The Panel report also included a detailed chronology of
events related to this matter.
There are, however, certain hotly contested issues, primarily when Dr.
Bridges began the experimental work reported on in the Science article,
when the experimental protocols were developed for this work, whether
adequate supplies of certain available materials existed in Dr. Bridges
laboratory, and whether Dr. Bridges had the primary data related to the
experimentation in question, that were covered by the Panel's report.
The evidence in the entire administrative record is examined in this
decision when making independent findings on the contested material
facts, regardless of the findings and conclusions made by the NIH Panel.
However, where relevant, the Panel findings and conclusions are
discussed as part of the analysis supporting the factual findings.
6. The protocols and experimental data for the frog series of
experiments were kept on computer by Mr. Alvarez. He, therefore,
labeled the experiments, for example, FROGONE, for the first frog
experiment. The next 14 experiments were labeled for the computer with
sequential numerical labels up to FROG 15 and then to RATONE (the first
7. The abstract is the synopsis of the manuscript that appears either
on the second or third page of a manuscript following the title page and
in some journals the footnote reference page. Tr. 1539-1540 (Dr.
8. I also note that Dr. Bridges referred in both the initial changes
and the published changes to "the present authors" knowledge of the PNAS
manuscript which was untrue. Tr. 4287-4289 (Dr. Bridges). Dr. Bridges
testified that he was responsible for the language "present authors" and
that Mr. Alvarez never saw the PNAS manuscript.
9. While these events are somewhat tangential to the question of the
possible plagiarism of the PNAS manuscript, Dr. Bridges' seeking
publicity is illustrative of the competitive environment. It is of note
that Dr. Dowling testified that he had told Dr. Bridges that "there was
plenty of glory for all . . . [T]here was no sense in causing great
antagonism between groups of investigators by one group claiming all the
credit." Tr. 3089 (Dr. Dowling).
10. Dr. Lin testified that while Dr. Bridges routinely had Monday
morning lab meetings with his staff to discuss the work going on in the
lab, she could not remember Dr. Bridges discussing that project. Tr.
2089 (Dr. Lin). Dr. Bridges had previously discussed with Dr. Lin the
possibility of the isomerase project as a possible thesis project. It
would be more probable than not that since she had some familiarity with
the subject, she would remember if the frog series results were
discussed in the Monday morning lab meetings. On the other hand, Dr.
Bernstein testified in marked contrast that the other staff in Dr.
Rando's lab knew about their positive results with the isomerase
project. Tr. 466 (Dr. Bernstein). It is also curious that Dr. Bridges
did not discuss perhaps the most significant results of his career with
the other more senior members of his lab. Dr. Fong testified that as
the most senior member of Dr. Bridges' lab, Dr. Bridges most of the time
would discuss with him the data produced in the laboratory. Tr. 2132
(Dr. Fong). Yet, Dr. Fong stated that while he had seen the bovine
data, he could not remember discussing the results of the frog series
with Dr. Bridges before August 1986 and had no personal knowledge of
when the experiments actually began. Tr. 2150, 2169, and 2195 (Dr.
Fong). Other members of Dr. Bridges' lab did not recall the isomerase
project being discussed during Monday morning lab meetings. Tr. 960
11. Dr. Adler testified that the Panel never saw "what we would
consider primary data, that is, data in a lab notebook taken on the day
that the experiments were conducted and dated." She further explained
that she "would have expected to see a bound lab notebook, or at least a
looseleaf one, where the date was at the top of the page and the
experiment was listed, a title for it, and a brief protocol . . . a list
of what was actually done, complete with mistakes that were made.
Something written that day when the experiment was done." Tr. 5152-5153
12. Dr. Bridges considered entering certain parts of his personal
diaries into the record before us as CDB Exs. 91 and 91a. Tr. 2465-2468
and 3196. Ultimately, Dr. Bridges determined that the diary segments
introduced should not be moved into evidence because they contained
purportedly proprietary material which Dr. Bridges wanted to ensure
remained privileged. Tr. 4502-4504. Therefore, these exhibits were not
included in the record and I disregarded any testimony related to these
two exhibits. However, certain selected entries were submitted earlier
to the Baylor Committee and NIH Panel and, therefore, were already part
of the record before me. A.Ex. 31 (Item 8L, Attachments (Atts.) F-J).
I did not find these entries persuasive evidence. I agree with the NIH
Panel's judgment that these entries were idiosyncratic and did not
clearly detail information indicating that the isomerase experiments
began in May 1986. Ex. 4, p. 37. Moreover, I could not verify that
these entries were, in fact, made on the date Dr. Bridges alleged.
While I did not have the original diaries to review, the record
indicated that many of the diary entries referred to by Dr. Bridges were
made with different pens and in different colored inks on the same date.
Ex. 4, p. 12. In other instances, the segments referred to by Dr.
Bridges appeared as random entries on the page unrelated to the other
entries. A.Ex. 31 (Item 8L, Atts. F-J).
13. Dr. Bridges refused to allow the Baylor Committee to take
Committee notes at the meetings with him. Tr. 45 (Dr. Knight).
14. While Dr. Bridges did not tell the Baylor Committee until November
12, 1987, that the isomerase experimental materials had been lost or
stolen, the record shows that the Committee may have been indirectly
aware of this from two other sources. The Chair received an October 7,
1987 letter from Dr. Rando. Dr. Rando recounted a recent conversation
with Dr. Bridges wherein Dr. Rando told Dr. Bridges that the issues of
misconduct could be clarified if Dr. Bridges provided Baylor with his
notebook entries. This letter states that Dr. Bridges told Dr. Rando
that he had trouble finding these entries because some of the books may
have been stolen. A.Ex. 156. Mr. Alvarez told the Committee on October
8, 1987 that Dr. Bridges was in possession of Mr. Alvarez's experimental
records and notes. A.Ex. 104 (Item 8).
15. Mr. Thomas testified that while he found the files on the LOTUS
1-2-3 subdirectory, he was not present while they were printed out.
Therefore, he could not verify that what he accessed on January 5, 1988,
was the exact same material that was sent to the Baylor Committee on
January 13, 1988. Tr. 4864 (Mr. Thomas); and Tr. 4238 (Dr. Bridges).
16. Finding 73 is uncontested. Ex. 8 (Item 2); and Tr. 1600 (Dr.
Litman). While the Agency submitted proposed findings of fact regarding
the research methods reported in the two articles, Dr. Bridges submitted
no proposed findings related to these facts. See Agency Proposed
Findings of Fact 57-59, 63; Respondent's Proposed Findings of Fact.
17. While Dr. Bridges contended that the NIH Panel had not asked him
about certain aspects of his experimental design (see September 13, 1989
letter responding to the proposal to debar, Ex. 7, p. 1), Dr. Adler
testified that, during the NIH Panel's Chicago meeting, they had asked
Dr. Bridges to explain the development of the frog series methods. Tr.
4900 (Dr. Adler). In any event, even after Dr. Bridges had clear notice
that his antecedent experimentation was important, he failed to
satisfactorily explain in these debarment proceedings how the frog
series methods were a logical development of his earlier work.
18. Dr. Adler testified that the substrate is the material upon which
the enzyme acts to form a different product. Tr. 4913 (Dr. Adler).
19. Addendum IV to the NIH Panel report is this chart (footnotes
deleted). Ex. 4 at 24.
EXPERIMENTAL CONDITIONS FOR DETECTION OF RETINOL
11/13/85 Science PNAS (Bridges)
(Bridges-Alvarez) (Bernstein- Law-Rando)
Animal Source bovine frog frog
Enzyme Source pigmented pigmented pigmented epithelium
epithelium epithelium Preparation
suspension supernatant supernatant (700 X g/20 min)
(600 X g/10 min) Incubation
Time 4 h 1.5 h and 3 h 3 h
Volume 3.0 ml 1.0 ml 0.5 ml
Alcohol none 1 ul/500 ul 2 ul/500 ul
BSA 3.785 mg/500 ul 2.5 mg/500 ul 2.5 mg/500 ul
Radioactivity 0.24 uCi/500 ul 0.58 uCi/500 ul 2 uCi/500 ul
20. I note that Dr. Adler testified that Dr. Bridges never discussed
retinol colloidal dispersions when he met with the Panel. Tr. 4965 (Dr.
21. Batch analysis sheets are at: Ex. 8, Item 5 (Batch 27), Item 6
(Batch 29), Item 7 (Batch 30), Item 9 (Batch 27 -- Amersham
(nonletterhead) copy), Item 10 (Batch 36 -- Amersham (nonletterhead)
copy), Item 11 (Batch 32 -- Amersham (nonletterhead) copy), Item 12
(Batch 29 -- Amersham (nonletterhead) copy), Item 13 (Batch 24 --
Amersham (nonletterhead) copy), Item 22 (Batch 24); and A.Ex 17 contains
only Amersham (nonletterhead) copies which show the dates batches were
withdrawn from the market for batches 24, 25, 26, 27, 28, 29, 30, 31,
32, 33, 34, 35, 36.
22. The August 1985 and October 1986 orders were requisitioned by Mr.
Alvarez and Dr. Liou and charged to Dr. Liou's grant, No. 03829. The
September 1986 order included other items as well and Mr. Landers and
Dr. Bridges are identified as the requisitioners. Unless otherwise
noted here, the orders in the record were requisitioned by Mr. Alvarez
and Dr. Bridges and charged to Dr. Bridges' grant, No. 02489. There was
no evidence presented concerning availability or unavailability for the
frog series experiments of material ordered other that by Mr. Alvarez
and Dr. Bridges or charged to Dr. Liou's grant. A.Ex. 65. Batch 28 was
withdrawn from the market by Amersham on June 6, 1986 and, therefore,
would not have been available for shipment in August 1986.
23. Dr. Chytil testified that there were a total of 176 incubations in
the Frog series of experiments. Dr. Bridges testified to 81
incubations, Mr. Alvarez testified to 79 incubations, and Dr. Adler
testified to 98 incubations. Tr. 2840-2847 (Dr. Chytil); Tr. 5326-5336
(Mr Alvarez); Tr. 4952 (Dr. Adler); Tr. 3468 et seq. (Dr. Bridges); and
CDB V. Exs. AA1- AA10.
24. Mr. Alvarez testified that he would not use a large quantity of
frogs, for example 50, belonging to another investigator without the
other investigator's agreement and that he would contemporaneously place
an order for additional frogs. Tr. 718 (Mr. Alvarez).
25. While Dr. Bridges claimed that the 66 pages of computer print-outs
and the other documents presented in this matter were not the complete
documentation of the research reported in the Science paper, Dr. Bridges
did not present any other documentation. See generally Tr. 4236-4277
(Dr. Bridges). Most importantly, Dr. Bridges, who had primary control
over the necessary documentation, did not present a reasonable
explanation for why the data was not complete. Tr. 4241 (Dr. Bridges).
26. The protocols of FROGONE and FROGTWO submitted to the Baylor
Committee by Mr. Alvarez in October 1987 also indicate a 600 g spin,
rather than the 700 g spin reported in the Science paper. The use of 2
ul of ethanol and a 600 g spin, however, are identical to the variables
reported in the PNAS article.
27. The Panel Report indicated that none of the printouts showed a use
of 2 ul of ethanol as reported in Science, but instead showed the use of
3 ul, 4 ul, 5 ul, and even 8 ul. Dr. Bridges did not dispute the
Panel's statements which cited recent research results showing ethanol
concentration as a critical variable because this solvent is inhibitory
to the isomerase. Ex. 8, pp. 11-12.
28. It strained credulity to believe that, if Dr. Bridges were as
familiar and involved with the conduct of this research as he contended,
he could overlook a typographical error that listed a volume of ethanol
that had never been used in the conduct of the experiments. The volume
of ethanol, 2 ul, however, is identical to the volume stated in the PNAS
manuscript which Dr. Bridges read.
29. Dr. Litman indicated that customary practice in science is to use
control samples to verify experimental results. Tr. 1607-1608 and 1641
(Dr. Litman). This is the accepted means of determining if there is a
sound scientific basis for excluding data from reported research
results. In this instance, since no control samples were made, there
was no documentation that the results in FROGSIX which were discarded by
Dr. Bridges were excluded because of a sound scientific basis or because
the reported results conflicted with the results reported in FROGEIGHT.
30. There is a contradiction between Dr. Bridges' testimony and his
reply to the Panel's Preliminary Report regarding which frog series
experiments were reported in the Science article. While he testified
that no frog experiments after FROGTEN were reported in Science, he
stated in his reply that the number of dark adapted observations
reported in Figure 3 of the Science article included observations from
FROG 11 through FROG 13, A.Ex. 30, p. 19; and Tr. 3828-3850 (Dr.
31. Dr. Bridges submitted a hard copy printout of the subdirectory
listing in Lotus 1-2-3 for the frog series experiments indicating dates
that the files were last worked on which would be consistent with a May
1986 start date for the frog series of experiments. There was
testimony, however, from a computer expert indicating that dates in a
subdirectory are easily changed. Tr. 1893 (Mr.