Scientific Misconduct Investigations are rare

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Scientific Misconduct
What would you do?
Lauren is a postdoc carrying out research on
dopamine receptors in the brain that may yield a
better understanding of Parkinson’s disease. When
the abstract deadline for the national neuroscience’s
meeting approached, her mentor urged her to use
data she presented at a recent lab conference
because it made a good story and she would have
plenty of time to confirm and extend the results
before the meeting. Lauren preferred to hold off
because, as she explained to Dr. Cummings, she
recently has been unable to confirm the main result
fully.
What would you do?
Dr. Cummings insisted, saying that she was
being too timid and that others would get the
credit if she delayed. He added that Lauren
should not be concerned because the
experimental results were consistent with
theory. Dr. Cummings said, “Lauren, you
must be more aggressive with your data if
you are to succeed in the cutthroat world of
contemporary science. After all, it’s publish or
perish! Why don’t you take first authorship on
this abstract?”
What would you do?
Reluctantly, Lauren submitted the abstract and to her
surprise and Dr. Cummings’s delight it was selected
for a plenary slide presentation.
Despite an enormous effort, Lauren could not
replicate or extend the results and announced to Dr.
Cummings that she wished to withdraw the abstract.
Visibly irritated by Lauren’s request, Dr. Cummings
told her harshly that this was not an option and
pressed her to do more experiments.
What do you do ?
A. Present just the experiments that were completed
when the abstract was submitted
B. Withdraw the abstract and your talk officially
C. Just don’t show up for the talk
D. Ask to give a poster instead
E. Give the talk and acknowledge it can’t be repeated
Scientific Misconduct Definition
"Misconduct in Research" means fabrication,
falsification, plagiarism, or other practices that
seriously deviate from those that are commonly
accepted within the scientific community for
proposing, conducting, or reporting research.
It does not include honest error or honest differences
in interpretations or judgments of data. (Source: U.S.
Public Health Service Regulations).
Scientific Misconduct Definition
• Fabrication – making it up
• Falsification – changing the true description
• Plagiarism – taking the words and ideas of others without
citation
• Other practices that seriously deviate from those that are
commonly accepted within the scientific community
Resources about scientific misconduct
Baylor
Vice-President for Research - Jim Patrick
Committee on Scientific Misconduct
National
AAMC - Beyond the Framework
http://www.aamc.org/research/miscon/contents.htm
Government
Office of Research Integrity (ORI)
http://ori.dhhs.gov/
Scientific Misconduct Investigations are rare
4,060 institutions
2001
# of
Institutions
reporting
misconduct
78
# of
New
Cases
Opened
72
Fabrication and Falsification are the most common
charges
Types of Misconduct and Total Number of New Allegations Reported
2001
Fabrication
37
Falsification Plagiarism
46
17
Other
27
Total
127
Process for Scientific Misconduct Investigations
Allegations
Committee on
Scientific
Integrity
VP for
Research
Findings
&
Sanctions
Inquiry
Investigation
Departmental
Appeals
Board
President
Appeal
HSS
Office of Research
Integrity
Independent
Review
Most Inquiries do not lead to investigations
Number of Inquiries and Investigations Conducted in Response to New
Allegations,
2001
Inquiries
67
Investigations
20
There are few findings of scientific misconduct each
year
2001
ORI cases opened
35
ORI cases closed
25
Avg Time
14.6 months
Misconduct Found
14
The PHS found that XXXX, graduate student, SLU Graduate School, engaged in scientific
misconduct by falsifying and fabricating data in research supported by National Institute of
General Medical Sciences. From October 1999 through January 2001, he falsified and
fabricated data in his research notebook and produced false films and graphs of purported
experiments to produce data for his thesis and misrepresent his progress. Mr. XXX
reported the falsified and fabricated data in: (1) laboratory group meetings; (2) a poster
presentation at the American Society for Cell Biology meeting in December 2000; and (3) a
draft manuscript that he was preparing. Mr. XXX also provided falsified data to his mentor,
who unknowingly included it in a draft of a grant application. Given the extensive nature of
Mr. XXX data falsification and fabrication, none of his research after July 2000 can be
considered reliable. His actions adversely and materially affected the laboratory's ongoing
research by creating uncertainty about all his experimental results, necessitating
verification and repetition of experiments, preventing the reporting of results for publication,
and preventing the principal investigator from submitting a competitive renewal application
for a NIH grant. Mr. XXX entered into a Voluntary Exclusion Agreement in which he
voluntarily agreed for a 3-year period to exclude himself from any contracting,
subcontracting, or involvement in grants and cooperative agreements with the U.S.
Government, and to exclude himself from serving in any advisory capacity to PHS.
YYY, Ph.D., engaged in scientific misconduct by falsifying and fabricating data in research
supported by National Institute of Allergy and Infectious Diseases. He falsified Figure 6.2
of his Ph.D. thesis by adding discrete bands where there actually had only been a uniform
smear of radioactivity, the effect suggesting an unobserved result, which was, therefore,
falsified; the falsified image was not published. Dr. YYY committed additional scientific
misconduct while a postdoctoral research fellow. Dr. YYY falsified values in Table 1 of
supplemental web material that accompanied the paper in Science. In Table 1, Dr. YYY
misrepresented that lymphocytes from mice transgenic for ribonuclease H underwent
significantly lower rates of isotope switching, when the actual data showed no such
difference for IgG1, IgG2b, and IgE isotope classes. Dr. YYY also falsified Figures 2 and 4
of the supplemental web material published with the Science paper in that the results were
not representative of multiple independent experiments as he claimed. In addition, Dr. YYY
falsified Figure 2C of the Science paper, which represented a crucial control to establish his
claim that RNA/DNA hybrids were limited to immunoglobulin switch regions, by publishing a
blot that was not representative of his overall results. He also falsified Figures 4 and 7 of a
second paper (EMBO J.) using the PhotoShop computer program to move bands or
regions of a lane vertically relative to the rest of the gel, thus falsifying the size of molecules
described in the paper. Dr. YYY and his coauthors retracted both papers.
Dr. YYY entered into a Voluntary Exclusion Agreement in which he voluntarily agreed for 4
years beginning May 1, 2002, to exclude himself from any contracting, subcontracting, or
involvement in grants and cooperative agreements with the U.S. Government, and to
exclude himself from serving in any advisory capacity to PHS.
A Recent example of a scientific misconduct
investigation at Baylor
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Seven Committee members, administrative assistant, secretarial
support, legal assistance
Five grant applications and five published papers
Nine separate “issues” grouped by scientific relationships
Found scientific misconduct in seven, no misconduct in two
48 separate instances of FFP
Report of 540 pages + separate book of figures
Institutional Appeal
ORI Appeal
DAB Hearing
Civil Lawsuit
Seven YEARS
What would you do?
Dr. Big runs a lab that studies cell motility. Wei is a
graduate student who is making and expressing kinesin
mutants to study kinesin’s motor mechanism in vitro. A
postdoc in the lab, Wayne is using the confocol
microscope to track intercellular movement. Dr. Big
thinks that the two of them could productively
collaborate by introducing Wei’s mutants into cells and
following their effects on vesicle movement. Wei has
never really liked Wayne because he is often
argumentative and rude, but she understands the
advantages to the project. She places one of her
mutants that is defective in ATP hydrolysis into a
mammalian expression vector so that an epitope tag is
added and gives it to Wayne for his experiments.
What would you do?
In two weeks, at a group meeting, Wayne is talking
about the new results he obtained with Wei’s construct.
The pictures show a significant decrease in vesicle
traffic in cells when Wei’s mutant is present. Wayne,
who has been in the lab for two years now without a
publication, has done an exceptional job in a very short
time, with beautiful pictures that document the
decreased activity along with controls showing that the
effect is due to the presence of Wei’s transgene. He
even shows a Western blot of his transfection
experiments proving that Wei’s protein was highly
expressed in his cells but not in wild-type cells.
What would you do?
Dr. Big is very excited and asks Wayne and Wei to write
up the results for publication and indicates that they will
both be authors (Wayne first and Wei second).
Wei is concerned. She knows that she is the only one in
the lab that has the anti-His6 antibody and that Wayne
never asked her for it. In addition, his Western blots
never look very good, but the ones he showed in group
meeting were exceptionally clean, particularly for the
anti-His6 antibody she was using.
What would you do
A.
Stop worrying and help Wayne write the paper.
B.
Talk to Wayne about my concerns that he may have
fabricated or falsified the Western blot.
C.
Tell Dr. Big that you don’t feel that you contributed enough to
the paper and do not want to be an author.
D.
Talk to Dr. Big about your concerns.
E.
Check out Wayne’s notebooks to see where he got the
antibody.
F.
Go to the institutional official in charge of scientific misconduct
investigations and ask them to investigate.
G.
Write an anonymous letter to Dr. Big or to the institutional
official and ask them to investigate.
Whistleblowers
(1) whistleblowers are free to disclose lawfully whatever information supports a reasonable
belief of research misconduct as it is defined by PHS policy,
(2) institutions have a duty not to tolerate or engage in retaliation against good-faith
whistleblowers,
(3) institutions have a duty to provide fair and objective procedures for examining and
resolving complaints, disputes and allegations of research misconduct,
(4) institutions have a duty to follow procedures that are not tainted by partiality arising
from personal or institutional conflict of interest or other sources of bias,
(5) institutions have a duty to elicit and evaluate fully and objectively information about
concerns raised by whistleblower,
(6) institutions have a duty to handle cases involving alleged research misconduct as
expeditiously as possible without compromising responsible resolutions, and
(7) at the conclusion of proceedings, institutions have a responsibility to credit promptly, in
public or private as appropriate, those whose allegations are substantiated
What would you do?
James Gibbons is a respected investigator in the
area of Alzheimer’s disease. His laboratory is
currently trying to develop a new mouse model for
Alzheimer’s by inserting a transgene that can
overexpress the amyloid precursor protein, APP
under the control of an inducible promoter. The idea
is that by conditionally increasing the amount of APP
the mouse will develop dementia more quickly and in
a regulated manner.
What would you do?
The lab has spent considerable time in constructing the model
and have just successfully obtained the long awaited mouse.
Dr. Gibbons serves on an NIH study section and today, he
received copies of the grants he is to review. One of the grants
is entitled “a new inducible model of Alzheimer’s disease. Upon
reading the grant, he finds out that another lab is proposing to
overexpress a protease responsible for processing the APP to
its amyloidogenic form. They show as preliminary data that they
had constructed an alternative model in which the APP was
placed under the control of an inducible promoter.
Unfortunately, this mouse displayed no phenotype after the
promoter was switched on.
Questions
1. What is the ethical dilemma?
2. How should this new knowledge affect the ongoing research in
Dr. Gibbons’ lab?
3. How should Dr. Gibbons handle the review of the grant?
What would you do?
John is writing up his first scientific paper and wants to
be extra careful that he describes all of his experiments
accurately. In describing the results of one of his
experiments he wrote.
“The protein used in these studies was >70% pure by
SDS-Page (data not shown). In addition to the expected
band at 150 kDa, there is an additional band of 18 kDa
that likely represents a degradation product because it is
also recognized by an antibody made against the
protein.”
He gave the draft manuscript to his mentor, Dr. Nice.
When his mentor returned the paper, the text had been
modified to read.
What would you do?
“The protein used in these studies was >95% pure by
SDS-Page (data not shown).”
He pointed out to his mentor that the change in the
description of the protein’s purity was deceptive and
that his qualifying description should be included.
“Nonsense,” said Dr. Nice, “you said yourself that the
only other band was a degradation product. In my way
of thinking that means that all the protein visible on the
gel comes from the same protein, so it’s really quite
pure. Besides, if we included your whole description
the reviewers might think we didn’t purify the protein
well enough to begin with and reject the manuscript.
Questions
1.
Is the mentor’s statement ethical?
2.
What should the student do?
3.
Do we need to report every detail in manuscripts, grants and
abstracts?
What would you do?
Dan, a first-year graduate student is preparing an
application for an NSF fellowship to support his graduate
studies. He did a considerable amount of research as an
undergraduate and his undergraduate research advisor has
told him that he will be the first author on a manuscript he
is planning to submit to the J. Cell Biol. as soon as another
student finishes a group of additional experiments,
probably by January.
What would you do?
Dan knew that his fellowship application would stand a much
better chance if he had demonstrated the quality of his research
by a publication. The application deadline was in November and
since he was sure that a paper was going to be submitted, he
thought it would be OK to give a title for the paper, include the
names of the other authors and list it as “submitted”.
He wrote:
D. Jones, M. Waddle, and H. Thin, “Cellular sorting of a
misfolded glucose transporter,” J. Cell. Biol. (submitted)
Adapted from “On Being a Scientist”, National Academy Press
Questions
• Is this scientific misconduct?
• What are some alternatives?
What would you do?
Dr. Doom was a postdoc in Dr. Able’s lab. They had come
up with an new idea to deliver folded proteins into human
cells using a combination of detergents and polymers. Dr.
Doom developed an assay using a GFP labeled protein and
found that the fluorescence was taken up into cells when a
specific combination of detergents was used. While he
had some difficulty working out the conditions, he has
recently been able to consistently repeat the experiment on
four successive attempts.
What would you do?
Dr. Doom, found a great job in industry and was leaving
the lab soon, but they found time to write up a Science
paper and submit an NIH grant based on the work.
The paper bounced at Science, but they revised and
submitted it to Nature Biotechnology.
The Nature Biotechnology reviewers wanted a couple of
revisions and new experiments, so Dr. Able asked another
postdoc in the lab, Dr. Gloom to do them. Dr. Gloom
couldn’t do the new experiments and also couldn’t make
even the basic technique work.
What would you do?
Dr. Gloom was experienced in the lab but neither she nor
Dr. Able could figure out what was wrong. They
consulted Dr. Doom’s notebook and followed the
procedures he had used as closely as they could, but to no
avail.
In the meantime the NIH grant was reviewed and the
review group loved it. It’s certain to get funded. The
award (and money) should be available in 6 months.
In addition a provisional patent application has been filed.
Questions
• Has Dr. Doom committed scientific misconduct.
• What about Dr. Abel?
• Is there anything else Dr. Abel can do?
• What should Dr. Abel do about the grant and the
patent if the experiments can’t be replicated?
What would you do?
Jeannie is a third year graduate student who is studying
regulation of cell division. She has found a gene that is
essential for cell septation after DNA synthesis. After
expressing the protein in bacteria she had a commercial
lab make an antiserum that she wanted to use to locate
the protein in the cell. Although the antiserum detected
two different sized bands on Western blots, she decided
to perform some preliminary experiments to see what
would it show in cells. She was amazed to see that the
stained cells all showed a protein localized to specific
regions of the plasma membrane near the middle of the
cell - just in the right place to initiate septation.
What would you do?
When she showed her data to Dr. Small, her mentor, he
was excited. “Just the thing we needed for my grant
application. Give me a copy of the pictures to use as a
figure in the grant. This could be the break we’ve been
waiting for.
The grant deadline was a month away so Jeannie decided
to immunopurify the antiserum using the expressed
protein on a affinity column. The purified antibody
recognized a single band of the expected size on Western
blots, but Jeannie was disappointed to find that now the
antibody only visualized diffuse staining on the vast
majority of cells.
What would you do?
However, there were no cells that showed the same
localization of staining that she had seen before.
When she informed Dr. Small of the results, he did not seem
to be too upset and said “We shouldn’t be too concerned about
it at this time, maybe the harsh conditions needed to purify the
antibody altered the specificity. Clearly, we need some more
experiments to find out what’s going on.
Late that evening, she noticed a copy of Dr. Small’s grant
application that he had left laying on the bench outside his
office. Skimming through the grant, she was shocked to see
her original data and read what Dr. Small had written about
her experiments.
What would you do?
“Staining with an antibody raised against the SMAK protein
revealed specific areas of the plasma membrane consistent
with a critical role of SMAK in initiating septation.” He went
on to propose a wide range of further experiments using the
antibody as an assay for following the timing and cellular
requirements for assembling a membrane complex during
septation.
Jeannie confronted Dr. Small the next morning, arguing that
all of her most recent data showed that the antibody did not
recognize a protein at the cell membrane. She had repeated
the experiment with the purified antibody several times and
was confident that it must be some other protein that they had
detected using the immune serum.
What would you do?
Dr. Small said, “You shouldn’t be concerned about the details
at this point. I’m still not sure that the purification didn’t alter
the antibody somehow. This is just a proposal; we don’t have
to be sure of all the details. That’s what a proposal is for - to
let us do all the right experiments before we publish the
findings in a paper.”
Questions?
1. Is there an ethical problem here
2. What is the best way to handle it?
Questions
• Would it change you opinion if you knew that Dr.
Small would get very angry with you and might
dismiss you from the lab?
• Who gets the final say in what decision gets made?
• What recourse would you have as a student?
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