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09/02/2014

Holding Institutions Responsible for Research Misconduct: the recent case of a death of stem cell scientist

This article is being published simultaneously on the Alden March Bioethics Institute blog, the Knoepfler Lab Stem Cell blog and Signals Blog

Scientist
Yoshiki Sasai, age 52, committed suicide and was found dead on August 5, 2014.
Sasai was deputy director of the Center for Developmental Biology (CDB) at
RIKEN in Kobe, Japan, and coauthor on two recently retracted Nature papers about an easier way to
make induced pluripotent stem cells. The papers were retracted due to duplication
and manipulation of images done by the main researcher and lead author on the
two papers – Haruko Obokata. Although cleared of any direct involvement, Sasai was
under immense pressure and heavily scrutinized by the media, public and peers. This
involved speculation about Sasai’s intentions to orchestrate a media frenzy,
and for being overly ambitious and motivated to win future grants overlooking
the integrity of the science.

According
to colleagues at RIKEN, Sasai was receiving counseling since the scandal broke headlines
and he was also hospitalized for about a month in March (1). He was found hanging
in a stairwell of a neighboring building and beside him were three letters
addressed to CDB management, his laboratory, and Obokata. On August 12,
Kazuhiro Nakamura, the family lawyer explained the contents of Sasai’s suicide
note left for the family. Sasai was “worn out by the unjust bashing in the mass
media and the responsibility he felt towards RIKEN and his laboratory” (2). But
unsubstantiated claims in the media were not the only source of stress for
Sasai. The speculation in tabloids might have also influenced how RIKEN and
other colleagues behaved towards Sasai. In June, a report released by an
independent RIKEN reform committee criticized CDB leaders for hyping the
science and did not interview Sasai about such accusations. Their final
recommendation was to dismantle CDB. According to the family lawyer, this was a
tremendous shock for Sasai (2).

In this
blog, I want to discuss the responsibilities research institutions have over
research integrity and misconduct. Zimbardo’s Stanford prison experiments (3) and
other social psychology research has taught us that ethical behavior is not
only shaped by dispositional attribution (an internal moral character), but it
is also influenced by many situational (environmental) features. Similarly, our
understanding about the causes of research misconduct is shifting from the idea
of a few “bad apples” to the realization that the immense pressure to publish,
translate research findings, and poor institutional support are factors that influence
research misconduct. This is not to excuse misbehavior by researchers; rather,
it is about moral responsibility, and research institutions are also
accountable in cases of research misconduct. While scholars on research
integrity are aware of the responsibility of research institutions, the institutions
themselves have taken few measures to promote research integrity and prevent
misconduct; they remain virtually blameless in high profile cases of research
misconduct (4). The tragic death of Dr. Yoshiki Sasai should cause us to consider
the role of institutions. How well do research institutions handle investigations?
Do they take measures to protect researchers and others involved in the case? How
do institutions promote research integrity and prevent misconduct? I think the
short answer to these questions is that institutions still do the minimum to
promote the responsible conduct of research and likely react punitively to
individual researchers by removing the bad apples and then taking corrective
measures. This myopic view of research misconduct needs to change, and
institutions need to be held morally accountable along with scientists who
commit fraud.

The Case

There
has been no shortage of news surrounding misconduct in stem cell research. I
have given lecture
s to science trainees in stem cell
research (5) and blogged about several relatively recent scandals (6; 7). The
pattern of misconduct seen in stem cell research might be due to the heightened
attention it receives in the media and interest by the public. Moreover, ways
to detect misconduct are becoming widely used by journals and other scientists,
and publishing in top-tier journals like Science
and Nature certainly draws
attention.

In January of this year, Haruko Obokata in
the CDB, RIKEN reported that she was able to convert mouse cells to a
pluripotent state simply by exposing cells to stress, the procedure called
stimulus triggered acquisition of pluripotency (STAP). Soon after its
publication, allegations of plagiarism, and figure manipulation and duplication
were reported. Additionally, other researchers were unable to reproduce the STAP
experiments. In April, an investigative committee at RIKEN found Obokata had
committed research misconduct. While she admitted to being sloppy, Obokata
continued to defend the results. The investigative report also concluded that
while Sasai was not directly involved in misconduct, he bore “heavy responsibility”
(8). A reform committee, chaired by a University of Tokyo emeritus professor
Teruo Kishi, faults Sasai and a former CDB researcher, now at another
university, for accepting Obokata’s data without question or further
examination (9). The reform committee found that inadequate oversight extended
to the highest leadership of CDB due to the desire of a major breakthrough and the
committee recommended that CDB be completely reformed.

It is
evident that Yoshiki Sasai, a leader in the scientific community and at CDB,
was under massive pressure. I will neither speculate on the toll this incident
had on Sasai or whether the investigation was handled well and the
recommendations sound. Instead, I want to shift focus to look more at the
research environment scientists work in more generally and consider what
research institutions do (or can do) to promote research integrity.

Shifting the Culture of Science.

The espoused norms of science we learn in
the past seem incongruent with current practices today. The ideals of science –
openly sharing materials/methods, being motivated by discovery and not personal
gain, judging one’s own work and others rigorously through strict standards –
are being replaced with secrecy, self-promotion, and fierce competition (10, 11,
12). Competition in science creates a pressure to publish, and perhaps more
recently to translate and commercialize research (13, 14). A recent survey by New Scientist reported that of 111 stem
cell scientists who responded, 56% felt stem cell research was put under more
intense scrutiny than other areas of biomedical science, and of those that
replied positively, 56% said that this affects their work (15). Moreover, almost
17% of the stem cell researchers reported that they felt pressure to submit a
paper for publication they believed was incomplete or needed verification. Combining
the pressure to produce results in a hyper competitive and bleak job market
creates a stressful environment for anyone. It remains empirically unclear
however, whether such a competitive environment is a recipe for research
misconduct. Given the culture of science today, what are institutions doing to
create a healthier environment?

Globally, several research institutions
promote research integrity but differ in their approach. Some have robust
policies, training, and provide resources while I suspect many only have a
suite of policies and a non-transparent mechanism to address allegations of
misconduct. I believe research institutions can do several things to promote
research integrity and help prevent misconduct.

For starters, institutions can raise
awareness and help promote a culture of research integrity by educating
trainees, faculty, and research administrators and staff. Education can provide
scientists with the tools they need to deal with ethical issues in a
constructive manner when they arise. Michael Kalichman explains that the
primary goal of education should be to “foster a research culture in which
conversations about the responsible conduct of research are expected and
acceptable” (16). Efforts to restore and rehabilitate researchers found to
engage in misbehavior is likely going to incorporate education as part of the
program. Education about the responsible conduct of research needs to be more
than a minimum requirement scientists have to undertake and institutions are
obligated to offer.

In addition to fostering a culture of
integrity, some scholars advocate that research institutions can perform random
or for-cause (when misconduct is suspected) data audits (17). However, it seems
scientists have little appetite for such audits because they fear it would
inhibit scientific freedom, and be burdensome and costly. While there is
virtually no evidence to demonstrate whether such a policy decreases research
misbehavior within an institution, it does not have to be a taxing effort on
scientists or research administration (17).

Institutions should also make transparent
a mechanism of how allegations should be handled, but also to provide resources
like an ombudsperson as trusted broker for researchers to confidentially
discuss potential problems amicably prior to raising a formal allegation
requiring investigation. And if a formal investigation is needed, institutions
must make serious efforts to ensure there are no reprisals against the
complainant, witnesses, investigators, or the accused. In cases where
scientists are under tremendous duress during an investigation, appropriate
accommodations for researchers should be made.

UC San Diego is one example of an
institution that has made significant efforts to promote the responsible
conduct of research by having several research ethics policies, a hotline to
report research fraud, a transparent mechanism to address potential allegations,
and provides courses, seminars and resources to faculty and students (18). The
tools are available – university and college administrators need to seek them
out and implement them at their respective institutions.

Empirical research on institutional
integrity climates is beginning to be performed (19). While journals, funding
agencies, integrity scholars, scientific societies and other players can all do
their part to promote a culture of research integrity, research institutes are
well poised to promote integrity not only within their organization, but also
to the larger institution of science. Research institutions should do more than
simply remove the bad apples as they too bear some moral responsibility over
research misconduct.

Acknowledgements: I would like to thank
Dr. Paul Knoepfler, Ms. Lisa Willemse, and Ms. Tina Muratovic for helpful
feedback.

Web Links

1. http://www.japantimes.co.jp/news/2014/08/05/national/embattled-stap-study-co-author-dies-after-apparent-suicide-bid/#.VADIBE10ymQ

2. http://www.nature.com/news/stem-cell-pioneer-blamed-media-bashing-in-suicide-note-1.15715?WT.ec_id=NEWS-20140819

3. http://www.prisonexp.org/

4. http://mitpress.mit.edu/books/research-misconduct-policy-biomedicine

5. http://ori.hhs.gov/images/ddblock/march_vol22_no2.pdf

6. http://www.signalsblog.ca/rush-to-publish-and-the-repercussions-of-carelessness-in-science/

7. http://www.amc.edu/BioethicsBlog/post.cfm/not-another-stem-cell-scam-alleged-fabrication-false-affiliation-plagiarism-and-poor-publication-ethics-all-in-a-single-shot

8. http://www.nature.com/news/research-integrity-cell-induced-stress-1.15507

9. http://news.sciencemag.org/asiapacific/2014/06/japanese-stem-cell-debacle-could-bring-down-center

10. http://jama.jamanetwork.com/article.aspx?articleid=194592

11. http://www.ncbi.nlm.nih.gov/pubmed/12712166

12.http://www.jstor.org/discover/10.1525/jer.2007.2.4.3?uid=2129&uid=2&uid=70&uid=4&sid=21104081253391

13. http://genomemedicine.com/content/1/2/22

14. http://genomemedicine.com/content/4/2/17

15. http://www.newscientist.com/data/doc/article/dn25281/stemcellsurveypdf1.pdf

16. http://www.ncbi.nlm.nih.gov/pubmed/24073608

17.http://www.tandfonline.com/doi/abs/10.1080/08989621.2013.822259?journalCode=gacr20#preview

18. http://blink.ucsd.edu/research/policies-compliance-ethics/responsible-conduct.html

19. http://link.springer.com/article/10.1007%2Fs11948-012-9409-0

The Alden March Bioethics Institute offers a Master of Science in Bioethics, a Doctorate of Professional Studies in Bioethics, and Graduate Certificates in Clinical Ethics and Clinical Ethics Consultation. For more information on AMBI’s online graduate programs, please visit our website. 

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