PHIL/MBIOL 7570 Case Studies in Research Ethics Fall 2008 Bryan Benham Department of Philosophy

PHIL/MBIOL 7570Case Studies in Research Ethics

Fall 2008

Bryan Benham

Department of Philosophy

Phil 7570: Case Studies in Research Ethics2

Why Research Ethics?

Woo Suk Hwang

S. Korean stem-cell scandal

Success

• Seoul National University• 1999 announced cow cloning

– But, not confirmed.

• Science, March 12, 2004– somatic cloning

• Science, June 17, 2005– 11 hESC lines, patient

matched

• August, 2005– Cloned dog, “Snuppy”

• Leader of World Stem Cell Hub

Failure

• Accused of paying for donated eggs, from lab techs.

• Gerald Schatten (U Pitt.) ceased collaborations, and withdrew name from 2005 Science paper.

• Both Science papers found to have fabricated data; subsequently retracted.

• Also, charges of embezzlement and government collusion.

• Removed from SNU and WSCH.

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Insult to injury

Review of Hwang Woo Suk’s research shows his embryonic stem cell lines were likely the product of parthenogenesis – a form of asexual reproduction.

“It could have been a seminal finding if they hadn’t had their blinders on.”

Kent Vrana, Penn State University

Reported in New York Times, Aug. 3, 2007 and Scientific American, Aug. 2, 2007.Confirmed by Kim et al. 2007: Cell Stem Cell,1(3): 346-352.

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Consequences?

• Misconduct: fabricated data• Financial conflicts of interest (with gov’t involvement)• Coerced lab-members: egg donation*• Missed significant finding – parthenogenesis• Undermined confidence in collaborations with S. Korea• Global public perception of stem cell research affected• Set back stem cell advances by a number of years

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Perceptions?

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But, “Snuppy” is real…

Hwang Suk currently owns/directs a private company that clones pets the Sooam BioTech Research Center which recently announced 5 clones of a pet, Booger, in collaborations with RNL and SNU.

7Houston Chronicle, August 5, 2008: http://www.chron.com/disp/story.mpl/pets/dogs/5926679.html


Outline

• Course Overview• Research Misconduct• Ethical Framework

hum.utah.edu/~bbenham

Course Objectives

• Serves as an “ethics education” component for funding sources and programs across campus.

• Increase ethical sensitivity to research ethics issues and serve the U as a forum and resource for discussing research ethics issues.

hum.utah.edu/~bbenhamPhil 7570: Case Studies in Research Ethics

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Course Requirements

• Course Structure– Ten Week Course (See Schedule)– Lecture and Small Group Discussion of Case Studies– First and last meetings, only lecture*

• Grade Distribution– Readings & Case Studies (Available Online)– Attendance: no less than 8 of 10 to receive credit– Final Paper: Case Study Analysis and Evaluation



Sept. 4 RCR and Misconduct*

Sept. 11 Authorship

Sept. 18 Data Management

Sept. 25 Mentoring Issues

Oct. 2 Animal Subjects

Oct. 9 Human Subjects

Oct. 16 Fall Break - No Meeting

Oct. 23 Social Pressures on Science

Oct. 30 Commerce & Research

Nov. 6 Science’s Effect on Society

Nov. 13 Social Responsibility*

Nov. 20Papers Due

Fall 2008 Schedule

Course Director– Bryan Benham (Philosophy)

Faculty Facilitators– Kathi Mooney (Nursing)– Kim Korinek (Sociology)– Tom Richmond (Chemistry)

– David Grunwald (Genetics)– Michael Kay (Biochem)– Matt Williams (Pathology)– Jody Rosenblatt (OncSci– Alana Welm (OncSci)– Jerry Spangrude (Path)– Scott Rogers (Neuro&Anat)– Lorise Gahring (Path)– Grzegorz Bulaj (MedChem)



Central Dogma

The focus of the course is not merely

understanding “the regulations,” but more

importantly identifying and employing the

underlying ethical principles and values

that guide responsible research, so that

one can (ideally) navigate the rocky shoals

and murky waters of daily research practice.


Examples

• A professor publishes ideas and experiments developed by her graduate student, without giving credit to the student.

• A researcher presents a paper that shows 33 data points that are consistent with his hypothesis, but doesn’t report the other 12 data points that are significantly inconsistent with his hypothesis.

• An experimenter recruits subjects for his study on cognitive effects of stress on children, but advertises it as a study on the role of social interactions in child learning.


Examples

• While waiting to hear from a journal about her latest paper submission, a new assistant professor hears from the editor that the paper is held up by a reviewer who has been “extremely busy,” but professor suspects the reviewer may be delaying her paper in order to publish first with similar findings.

• A researcher published favorable results for a new memory enhancing drug, without disclosing that she serves as a consultant and holds stocks in the company that is developing this new drug.


And a bad grad

A FORMER GRADUATE STUDENT at Michigan State University was sentenced on Monday to 10 months in prison for faking the theft of his own research materials. The student, Scott M. Doree, was supposed to be working on a vaccine to prevent a pneumonialike disease in pigs, but he apparently had not done any research for several years, authorities say.– http://chronicle.com/daily/2003/08/2003082102n.htm.


Central Dogma









Outline

• Course Overview• Research Misconduct• Ethical Framework


Integrity vs. Misconduct

…it is vital for leaders of the academic community to ensure that research conducted on our campuses meets the highest standards of ethics and integrity*…By integrity of the research process, the panel means the adherence by scientists and their institutions to honest and verifiable methods in proposing, performing, evaluating, and reporting research activities**… Integrity in science is perhaps better seen today as an extension of current concerns with quality***… Quality refers to the rigor with which experiments are designed and carried out; statistical analyses performed, and results accurately recorded and reported, with credit given where it is due. Integrity in research means that the reported results are honest and accurate and are in keeping with generally accepted research practices.****


Research Misconduct

Research Misconduct comes in two flavors:

Wide = generally refers to questionable research practices (QRP) and implicates norms of responsible science.

Narrow = federal definition restricted to certain egregious behaviors, FFP.


“Wide” misconduct

• Wide misconduct is the general notion of questionable scientific practice (QRP) and implicitly appeals to norms of responsible science:– Technically competent, creative; and

– Ethically responsible

• Specific norms of responsible research– Critical, Honest, Open, Disinterested, Safe, Responsive, etc.

• Positive ideal is helpful, but limited without some clearer idea about when, e.g., honesty and openness is applicable.

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Norms & Realities

“Many plausible-sounding rules [ideals] for defining ethical conduct might be destructive to the aims of scientific inquiry… Behavior that may seem at first glance morally un attractive can, in a properly functioning system, produce results that are generally beneficial.”

James Woodward and David Goodstein Conduct, Misconduct and the Structure of Science, American Scientist 84(5): 468-478.


Critical Developments

Scientific research is increasingly:• Professional & Career-Oriented• Collaborative• Specialized• Competitive

Each puts stress on accepted norms of responsible science.


“Narrow” misconduct

Federal – Office of Science and Technology Policy, 2000:

"fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results."

a.k.a: FFPThis is not meant to include honest mistake or error in research. But a finding of misconduct does require "that there be a significant departure from accepted practices of the relevant research community" proven by the preponderance of evidence.

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FFP?

Fabrication – is making up results and recording or reporting the fabricated

results.

Falsification – is manipulating research materials, equipment, or processes, or

changing or omitting data or results such that the research is not accurately represented in the research record.

Plagiarism – is the appropriation of another person's ideas, processes,

results, or words without giving appropriate credit and without specific approval, including those obtained through confidential review of others' research proposals and manuscripts.


Please Note

University of Utah

Misconduct is "fabrication, falsification, plagiarism, or other practices that seriously deviate from those practices that are commonly accepted within the research community for proposing, conducting, or reporting research. It does not include honest error or honest difference in interpretations or judgments of data."

Jan Hendrik Schön – Bell Labs(See Science 24 May 2002 and 5 July 2002.)

• September 2002 an investigating committee found that a series of extraordinary advances in molecular-scale transistors by Schön, 32, were based on falsified experimental data.

• Resulted in the retraction of at least 17 papers published in various journals, including Science and Nature, between 1998 and 2001.

• Schön was fired from Bell Labs. No other co-authors were found guilty of misconduct.

• Disheartening because “this was the first case of misconduct at Bell Laboratories;, and the work was of Nobel quality.” 27

Victor Ninov – LBNL(See New York Times, 15 October 2002.)

• Ninov was recognized expert in detecting decay chains of unstable trans-uranium elements; involved in discovery of elements 110, 111, and 112. Hired to compete with German and Russian teams.

• Investigation found that published report of synthesizing element 118 was based on fabricated data. Ninov plus 14 co-authors.

• Ninov denied accusations, but was fired in 2001 from LBNL. Other co-authors reprimanded for “not being vigilant enough.” 28

As reported:(New York Times, 15 October 2002.)

As the final report put it: “The committee finds it incredible that not a single collaborator checked the validity of Ninov’s conclusions of having found three element 118 decay chains by tracing these events back to the raw data tapes.” But members of the group say it is routine in this type of complex experiments to delegate responsibility. “The fundamental assumption is that of trust in the honesty and competence of your colleagues, especially if they have distinguished reputations, as was the case here,”

Note: as a result of the Schön and Ninov cases the American Physical Society adopts more stringent professional ethics guidelines by 2004.

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Plagiarism?


Scientific American

See also Nature 451, 24 January 2008.

What does this tell us about “narrow” misconduct?

• Temptations of modern scientific research– Junior and senior scientists alike

– Competition and Professionalism

• Collaborations pose special problems– Technical specialization in collaborations

– Strains norms of trust and honesty

• Other Issues Involved: – Authorship and Data Management– Peer Review– Mentoring and Institutional Oversight

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FFP Underreported

• Repairing research integrity – Nature 453(19), 2008– Surveyed 2,212 scientists– 8.7% (192) observed or had evidence of one or more incidents of

misconduct over the past three years (2002-05) in their department. (Total of 265 incidents, methodology cut to 201.)

– Equivalent to 3 incidents per 100 researchers per year; Extrapolations to al DHHS-funded researchers = 2,300 observations of potential misconduct (FFP).

– However, reported number of investigations remains low: average 24 institutional reports to Office of Research Integrity (ORI) per year.

• Misconduct (FFP) is underreported…and may be a much larger problem.


Wide Misconduct

FFP is only the tip of the iceberg

Questionable research practices that are not FFP may be more pervasive and erosive for the integrity of the research enterprise.


Two Studies

• Ethics and the welfare of the physics profession – Physics Today, Nov. 2004– Surveyed junior membership of APS and others*– 39% of junior respondents reported observing or having

knowledge of ethical violations– 4% of those incidents were misconduct (see chart)

• Scientists behaving badly – Nature 435, 2005– Surveyed 3,247 early and mid career scientists funded by NIH– 28% early and 38% mid-career (33% overall) reported

engaging in one or more of the top ten questionable research practices

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Distribution of ethics violationsKirby & Houle. 2004. Ethics and the welfare of the physics profession. Physics Today, November. (Figure 1)

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Top 10 ethics violationsMartinson, Anderson, & De Vries. 2005. Scientists behaving badly. Nature 435(9). (Table 1.)

Who Did It?*Early-career = 28%

Mid-career = 38%

Total = 33%*Under-reporting bias

FFP: 1 & 5 = <2%

Others = 5% or higher, often above 10%

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A Culture of Misconduct?

Research suggests misconduct is pervasive, perhaps a “culture” of irresponsible research or unreflective research practice in combination with modern practices of research leads to sloppy science, unethical science, or worse.

History Testifies to Problems:– Human Participation: Nazis, Willowbrook, Tuskegee, etc.– Misconduct: “Baltimore Affair,” S. Korean Debacle, etc.– COI: Jesse Gelsinger & “Global Warming” Policies


Central Dogma









What is “Ethics”?

• Determining what one should do…– Right/wrong, good/bad, better/worse– Principled and Practical– Promotion and Prevention

• Not mysterious, subjective, arcane practice of analysis or deliberation, – but a balancing act…


What is the difference between an ethical and unethical action?

Ethical• Leads to good

consequences.

• Weighs interests fairly.

• In accord with an ethical principle.

Unethical• Leads to bad

consequences.

• Doesn’t weigh interests fairly.

• Violates an ethical principle.

Balancing Three Questions

1. What are the consequences?– Short term and long term consequences.– Consequences to whom? (see next.)

2. Who’s interests are involved?– Who will benefit? Who will be at risk? Who is responsible? Who has the power?– Individuals, groups, society at large– Professional interests, research enterprise, commercial interests, academic

interests, public interests, non-human animals…

3. What principles or rules apply?– General: don’t kill, harm, lie, cheat, steal; do good, protect the vulnerable, etc.– Research Oriented: Honesty, Openness, Disinterested, Safe, Responsive,

Beneficial



Ethical Framework

Principles Consequences

Interests

P C

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Sample Case Study

A researcher presents a paper that shows 33 data points that are consistent with his hypothesis, but doesn’t report the other 12 data points that are significantly inconsistent with his hypothesis.

• Is this falsification of data? Why or why not?

• Does it make a difference if his results are reproducible? Or fail to be exactly reproduced?

• Why is this important for research?

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Robert Andrews Millikan (1868-1953)

• Nobel laureate in physics (1923) for measuring charge on electron and work on photoelectric effect.

• Oil drop experiment:– 1913 paper: error of 0.2% which bested

the current 3%. He reports “…this is not a select group of drops but represents all of the drops experimented upon during 60 consecutive days….”

– But review of notebooks demonstrates he used only 57 of 75-100 trial results. Charges of fraud, “cosmic surgery,” and “…extensively misrepresented his work in order to make his experimental results seem more convincing than was in fact the case.”

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What does this tell us about research ethics?

• A look at Millikan’s notebooks revealed cryptic remarks about why he rejected this or that experiment, including “too high” and “doesn’t fit.” While no one denies Millikan’s finding, they do question the reliability of his experiment and his choice of data points.

• Science is messy…– Frederick Grinnell (2000) argues that “at the edge of knowledge” discovery requires

confounding experiments in which no clear line divides a signal from noise. From the outside it might look like arbitrary decisions, but the final test is whether the science community is convinced.

– Perception is that ethics violations can draw a clear line between acceptable experimental manipulation and unacceptable manipulation.

• Thus the importance of an accurate and reliable research record and an understanding of how science works.

Grinnell, Frederick. 2000. The Practice of Science at the Edge of Knowledge. The Chronicle of Higher Education, March 24; B11.

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Phil 7570: Case Studies in Research Ethics46Repairing research integrity – Nature 453(19), 2008


P C

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Solutions?

• Education and Deterrence

• Institutional Level Response

• Mentoring & Culture of Responsibility

• Zero Tolerance

• Protect Whistleblowers

• Clear Expectations


Consider Perceptions

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Summary

• Why Research Ethics?– Culture and Developments

• Research Misconduct – Wide and Narrow

• Ethical Framework: 3 Questions– Consequences– Interests– Principles


Documents

PHIL/MBIOL 7570 Case Studies in Research Ethics Fall 2008 Bryan Benham Department of Philosophy