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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 # of Institutions reporting misconduct 78 # of New Cases Opened 72

2001

Fabrication and Falsification are the most common charges

Types of Misconduct and Total Number of New Allegations Reported Fabrication 37 Falsification Plagiarism 46 17 Other 27 Total 127

2001

Process for Scientific Misconduct Investigations

Allegations

VP for Research

Findings & Sanctions

Committee on Scientific Integrity

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
• • • • • • • • • • • 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. B. C. D. Stop worrying and help Wayne write the paper. Talk to Wayne about my concerns that he may have fabricated or falsified the Western blot. Tell Dr. Big that you don’t feel that you contributed enough to the paper and do not want to be an author. Talk to Dr. Big about your concerns.

E.
F.

Check out Wayne’s notebooks to see where he got the antibody.
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. 2. 3. Is the mentor’s statement ethical? What should the student do? 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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