Scientific Misconduct:

Introduction of First Principles

and Case Studies

Paul Anderson, MD, PhD

Chief Academic Officer

K. Frank Austen Professor of Medicine

Chief Academic Officer

Senior Vice President of Research and Education

Brigham and Women’s Hospital and

Harvard Medical School

Boston, MA, USA

Famous Misconduct Cases since 1980

Baltimore Case (1984-1996)

Margaret O’Toole, a post doctorate fellow at MIT, was asked by her

supervisor Dr. Imanishi-Kari to do experiments that would extend the work

described in the Journal Cell.

Unable to repeat aspects of the research documented in this paper, O’Toole

came across a laboratory notebook that suggested to her that the Cell study was

wrong and deliberately falsified.

She then challenged the authors of the paper, including the Nobel Prize

winner David Baltimore.

A long investigation followed, during which the NIH and members of

Congress became involved.

During the investigation, Baltimore was forced to resign as president of

Rockefeller University.

Dr. Imanishi-Kari was first found guilty of 19 counts of research misconduct,

but was later cleared of all misconduct charges in 1996 by a Human Health and

Services appeals panel.

Famous Misconduct Cases since 1980

Gallo Case (1984-1994)

In 1984, Dr. Luc Montagnier in Paris announced the discovery of a virus

called LAV, which they thought but could not prove to be the cause of AIDS.

Almost at the same time, Dr. Robert Gallo published a series of four papers in

the journal Science claiming discovery of the AIDS virus, which they named HTLV-

3.

Controversy over this discovery continued for ten years over who could claim

credit for the discovery of the virus; had Gallo’s team isolated the virus described

in the article, or if they had improperly used samples supplied by French

scientists?

The Pasteur Institute took the U.S. government to court over the patented

blood test based on this discovery. The case was finally settled out of court, with

Gallo and Montagnier agreeing on joint credit for the discovery.

Famous Misconduct Cases since 1980

Stem Cell Case (2005-2006)

Dr. Hwang Woo-Suk, a researcher and professor at Seoul National

University, rose to fame after claiming a series of remarkable breakthroughs in the

field of stem cell research.

In 2004 and 2005, Dr. Hwang published two papers in the journal Science

that claimed his team had succeeded in creating human embryonic stem cells

through cloning.

Allegations later followed from a co-worker that these paper was based on

fabricated data.

The papers were editorially retracted, Dr. Hwang lost his position at Seoul

National University, and the South Korean government ended its financial and

legal support of his research.

Motivations for scientific misconduct

Motivations for scientific misconduct

Career pressure

• “Publish or perish” which may be heightened by the desperate

economics faced by research scientists over the past years.

• “Paranoia” of being the first to publish

Ease of fabrication

• Especially in specialty fields that are technically difficult,

expensive, or obscured by noise/artifact. “Even if a scientist

does falsify data, he/she can expect to get away with it or at

least claim innocence” if results conflict with others in the same

field.

Consequences for science and society

Consequences for science and society

• Substantial resources (finances, equipment, person-hours)

from multiple independent groups working to confirm or refute

findings.

• Devastating toll on public/government trust in the research

enterprise, thus jeopardizing future funding to science as a

whole.

• Human health and safety are jeopardized in exploring new

human therapeutics based on fraudulent data.

Integrity in Research

Research misconduct (as defined by 42 CFR Part 93)

Falsification (making up results and reporting them)

Fabrication (manipulating research materials, data, or processes; or

manipulating data such that the research is not accurately represented

in the record)

Plagiarism (the appropriation of another person’s ideas, results, or

words without giving that person appropriate credit)

An honest difference of opinion or an honest error can result in the

occurrence of isolated non-compliance. This is NOT research misconduct.

Misconduct requires deliberate or repeated noncompliance

And even here, life is not black and white.

Ignorance Sloppiness Falsification/Fraud

Unintentional Intentional

Interest in Scientific Misconduct

Putting it in context….

“A pooled weighted average of 1.97% (N = 7, 95%CI: 0.86–4.45) of scientists admitted to

have fabricated, falsified or modified data or results at least once –a serious form of

misconduct by any standard– and up to 33.7% admitted other questionable research

practices.

In surveys asking about the behaviour of colleagues, admission rates were 14.12% (N =

12, 95% CI: 9.91–19.72) for falsification, and up to 72% for other questionable research

practices.”

Fanelli D (2009) How Many Scientists Fabricate and Falsify Research? A Systematic Review and Meta-Analysis of Survey Data. PLoS ONE 4(5):

e5738. doi:10.1371/journal.pone.0005738

Misconduct in the Literature

www.pnas.org/cgi/doi/10.1073/pnas.1212247109

“A detailed review of all 2,047 biomedical

and life-science research articles

indexed by PubMed as retracted on May

3, 2012 revealed that only 21.3% of

retractions were attributable to error. In

contrast, 67.4% of retractions were

attributable to misconduct, including

fraud or suspected fraud (43.4%),

duplicate publication (14.2%), and

plagiarism (9.8%).”

Distributed Impact

www.pnas.org/cgi/doi/10.1073/pnas.1212247109

Responsibilities of authors

“All authors, including coauthors, are expected to have made

reasonable attempts to check findings submitted to academic

journals for publication.”

• Keep all study data for later examination after publication

(journal specific)

• Disclose conflicts of interest

**Gray Area – Authorships and journal submission (not technically

“misconduct”):

• Simultaneous submission of scientific findings to more than

one journal or duplicate publication of findings (Ingelfinger rule)

• Guest/gift authorship: Stated author without significant

contribution

• Ghost authorship: Real author is not listed

Consequences for whistleblowers

Consequences for whistleblowers

Substantial potential for negative consequences of

whistleblowers.

• A whistleblower historically has been alone in the fight –

his/her career becomes completely dependent on the decision

about alleged misconduct.

• If the accusations prove false, there is a perception that his/her

career is completely destroyed; ironically, even in case of

positive decision the career of the whistleblower can be under

question: the reputation of "troublemaker" can prevent many

employers from hiring him.

Responsibilities of research institutions

After allegations are made, academic research institutions are

obliged to conduct a detailed and rigorous investigation.

• Costly and time consuming; the more senior the investigator,

the more likely for conflicts of interest for the institution.

• In some countries (but not the US), acquisition of funds on the

basis of fraudulent data is not a legal offense and no regulator

to oversee investigations.

• In the US, all research institutions that receive federal funds

are obligated to have an official policy of monitoring and

investigating research misconduct; additionally, each such

institution is obliged to name an official in charge of such policy

(Research Integrity Officer = RIO).

The Office of Research Integrity

http://ori.dhhs.gov/

-About ORI

-Assurances

-Conferences

-Forensic Tools

-Handling Misconduct

-International

-Policies/Regulations

-Publications

-RCR Education

-Research

-RIOs

HMS Integrity in Science website

http://hms.harvard.edu/public/coi/policy/integritypolicy.html

Gretchen Brodnicki, JD

Gretchen_Brodnicki@hms.harvard.edu

(617) 432-2496

Partners Research Integrity Policy

Partners Policies onTrove: http://library.partners.org/PartProd/webserver/custom/trovedemoframeset.asp?HU=http://www.partners.org&P2=1&w=800&h=600&c=16

Your RIO

BIDMC Randy Mason

BWH Paul Anderson

CHB Carleen Brunelli

DFCI Beverly Ginsburg Cooper

HMS Gretchen Brodnicki

HSPH Bernita Anderson

Joslin Dianne McCarthy

McLean Peter Paskevich

MGH H. Richard Bringhurst

Spaulding Ross Zafonte

ORI

Notification

ALLEGATION OF RESEARCH MISCONDUCT

Res. Integrity

Officer

Preliminary Assessment

If Sufficient Evidence

Inquiry Stage

Investigation Stage

If Sufficient Findings

BWH: Paul Anderson

MGH: Rick Bringhurst

McLean: Pete Paskevich

If you encounter possible

misconduct:

Call the Research Integrity Officer (RIO)

The RIO will secure all pertinent records, data and materials

Document in writing the steps taken to inform the RIO and

secure materials

Recognize that the institution’s primary obligation is to evaluate

the allegation and NOT to represent individuals

Confidentiality maintained and respected: Don’t talk to anyone

else.

If the Investigation Committee

Finds Misconduct:

RIO presents recommendations to Deciding Official*

Determines sanctions

Notifies relevant agencies, societies, boards, journal editors

and research collaborators

Office of Research Integrity (ORI) may:

Impose additional sanctions on the individual

Require institutional actions * Deciding Officials:

MGH: Peter Slavin

BWH: Betsy Nabel

McLean: Scott Rauch

Responsibilities of scientific journals

Arguably, journals hold the most critical role in dealing with

suspected misconduct as they are responsible for safeguarding

the established research record.

Clear retraction guidelines published by the Committee on

Publication Ethics (COPE)

http://www.publicationethics.org/files/retraction%20guidelines.pdf

• Consider retraction if clear evidence that the findings are

unreliable (misconduct or honest error); redundant publication;

plagiarism; unethical research.

• Consider “expression of concern” from journal editor if

inconclusive evidence of research or publication misconduct or

unreliability (but the authors' institution will not investigate or

will take time for investigation to be complete).

• Consider “correction” if a small portion of an otherwise reliable

publication proves to be misleading or if author list is incorrect.

A more rigorous method for ensuring high-quality

research?

http://reproducibilityinitiative.org/#/home

Case Study #1

Dr. S is an up-and-coming research fellow in your lab with a series of high-

impact publications over the past three years. Much of your lab is focused on work

directly stemming from the findings of those papers.

A technician and graduate student in your lab approach you in private to

discuss an event. They both witnessed Dr. S. labeling data recordings 24 sec, 72

hrs, one week, and two weeks when in reality only minutes had transpired.

As head of your lab, what are your next steps? If you plan to confront Dr. S.,

how would you do so?

Case Study #2

Dr. T is a close colleague of yours, and you have collaborated on multiple

publications together in the past. You are preparing a manuscript, and Dr. T.

approaches you to ask if he could be listed as a co-author. You answer that he

was not originally on this publication because he was not involved in the planning

or execution of any of the experiments. However, Dr. T. is insistent that he should

be listed, since your collaborations through the years were crucial to developing

the ideas that led to these experiments.

Is Dr. T’s request unethical, and how do you address the situation further?

Case Study #3

Dr. D. is a close collaborator of yours, and you are a co-author of a

manuscript from her group that is about to be submitted. Recently, you were

talking about the manuscript with her post-doc and found out that there were

substantial negative pieces of data that were not included in the work but in your

mind would alter the interpretation of the findings. When you bring this up with Dr.

D., she replies that these data are not included because more work needs to be

done for proper interpretation; these will be planned for “future studies.”

What are your next steps?

Case Study #4

Dr. D. is your mentor and immediate supervisor. He has a powerful

international reputation in science and translational research, and over the past

ten years has developed a proteomics system that only a few research institutions

in the world can replicate.

You are a co-investigator on a program project grant about to be submitted to

the NIH. The day before submission, you realize that the crucial preliminary data in

the grant obtained by Dr. Dr. and his technician one week ago are exact duplicates

of data that were obtained one year ago on a separate project. You are unsure if

this was an honest mistake or misconduct. You ask Dr. D. about it who answers,

“Too much time when into this grant to stop it now. Besides it’s preliminary data; no

one will know the difference.”

What do you do?

Definition of scientific misconduct

Violation of the standard codes of scholarly conduct and ethical

behavior in professional scientific research.

A review on Handling of Scientific Misconduct in Scandinavian

countries (Lancet 354 (9172): 57–61) provides the following

sample definitions:

• Danish definition: "Intention or gross negligence leading to

fabrication of the scientific message or a false credit or

emphasis given to a scientist"

• Swedish definition: "Intention[al] distortion of the research

process by fabrication of data, text, hypothesis, or methods

from another researcher's manuscript form or publication; or

distortion of the research process in other ways."

Forms of scientific misconduct

• Fabrication: Making up results and reporting them

• Falsification: Manipulating research materials, equipment,

procedures, raw data such that research is not accurately

represented in the record.

• Suppression: Failure to publish significant findings

because they are adverse to the scientist’s wishes.

• Photo/micrograph manipulation: Gel blots, micrographs

• Plagiarism: Appropriation of another person’s ideas or words

without giving credit.

• Probably the most common form of scientific misconduct

• Self-plagiarism is now much more scrutinized

• For example, in 2006 from Garner lab (UTSW) --Déjà

Vu,[49] an open-access database containing several

thousand instances of duplicate publication; discovered

through the use of text data mining algorithm eTBLAST.

Public interest in scientific misconduct

Protecting whistleblowers

• Whistleblowers are protected under rulings from both the

state and federal governments based on the False Claims

Act (US Code, 1986) –

• New federal regulations have been proposed by the

Department of Health and Human Services (2000) to protect

whistleblowers from retaliation.

• Most institutions, and many professional societies and

journals, offer guidelines to support the role of the

whistleblower.

The degree of scientific misconduct and whether it is

increasing is difficult to estimate.

A meta-analysis published in 2009 covering 18 fraud

surveys, six of which targeted biomedical scientists,

suggests that it may be more common than we suspect.

Although 2% of those participating admitted to having

falsified, fabricated or modified data at least once

themselves, an alarming 14% reported to have noticed this

behavior in colleagues (D. Fanelli, PLoS ONE 4, e5738;

2009).

Nature Cell Biology, 2011, 13(1).

Scientific misconduct is difficult to track

First Principles

• The integrity of science depends on the integrity of

research

• The integrity of research depends in part on self-policing

• A witness to possible misconduct has an obligation to act

• Not all concerns about research conduct should result in an

allegation of research misconduct

• Allegations, once made, should be handled at the

institutional level