Case studies in scientific reproducibility

There may be hundreds of papers out there reporting on experimental results in cell lines that do not actually exist.

Reese Richardson

A cell line is a population of cells that can be grown in a laboratory culture indefinitely.

Non-verifiable cell lines: immortal or imaginary?

Could the fraudulent work of one researcher be responsible for the rise of curcumin research?

Bharat B. Aggarwal is an Indian-American biochemist who worked at MD Anderson Cancer Center from 1989 to 2015. His research focused on potential anti-cancer effects and therapeutic applications of herbs and spices. Aggarwal was particularly drawn to curcumin, a non-toxic compound found in turmeric that has long been staple in Ayurvedic systems of medicine. He authored more than 120 articles about the compound from 1994 to 2020.

The King of Curcumin: a case study in the consequences of large-scale research fraud

A few months ago, I had the pleasure of giving a talk at Metascience 2023 in Washington D.C. about a strategy research paper mills can use to thwart science integrity measures: journal hopping. You can find the talk below:  If you would like to learn more about research paper mills, I suggest starting with our 2022 review about paper mills in human gene research.

Journal hopping by research paper mills after a preferred journal is de-indexed (Metascience 2023)

Businesses have emerged that sell authorship to aspiring doctors to make their residency applications more competitive.

<em>
 Science
</em>
and
<em>
 Retraction Watch
</em>
just released a large investigation into what I consider a new breed of paper mill.

A new breed of paper mill targeting international medical graduates

Collecting arguments on the stigma surrounding retraction

<em>
 Header image by Sydney Richardson.
</em>
On June 5, head of Research Integrity and Resolutions at Springer Nature Tim Kersjes presented “Requiem for the Retraction: why proposals for ‘honest retractions’ fail in their objective to promote and encourage the self-correction of science” at the 2024 World Conference on Research Integrity (WCRI).  Included was the following slide, later shared by Maria Zalm, senior editor and team manager of

How shameful should retraction be?

A citation manipulation scheme so easy, even a cat can do it.

Before we get to the adventures of
<em>
 Felis domesticus scholasticus
</em>
promised by the title, some important background. A couple of weeks ago, Nick Wise showed me an advertisement from a paper mill offering to boost the buyer’s citation count and h-index on their Google Scholar profile. The advertisement links to several success stories consisting of unredacted “before” and “after” screenshots of clients’ Google Scholar profiles.

Engineering the world’s highest cited cat, Larry

What an minor Wikipedia incident can teach us about the role of authority in the creation of truth

In 2017, Wikipedia editor WikiDan61 changed the flag on Vatican City as it appears on the site, noting that “[all] images of actual Vatican City flags show the “gold” in the keys and tiara rendered in the same hue as the gold/yellow band of the flag, as well as a red opening at the bottom of the tiara”.  However, according to the 2000 revision of the Fundamental Law of Vatican City State, this version of the flag was incorrect.

Truth, authority and the flag of Vatican City

An excerpt from my newly-defended PhD dissertation.

<em>
 The following is an excerpt from the preface of my newly-defended PhD dissertation in Interdisciplinary Biological Sciences, titled “Metascientific studies in reproducibility, bias and fraud”.
</em>
In 1947, a young Osamu Shimomura enrolled in the College of Pharmaceutical Sciences of Nagasaki Medical College [1]. The college had been destroyed in the bombing of Nagasaki and had relocated to a temporary campus near Shimomura’s home.

The scientific enterprise is a human enterprise

*The following is an excerpt from the preface of my newly-defended PhD
dissertation in Interdisciplinary Biological Sciences, titled
"Metascientific studies in reproducibility, bias and fraud".*  
  
In 1947, a young Osamu Shimomura enrolled in the College of
Pharmaceutical Sciences of Nagasaki Medical College \[1\]. The college
had been destroyed in the bombing of Nagasaki and had relocated to a
temporary campus near Shimomura's home. Although he had no interest in
pharmacy at the time, he saw it as his only opportunity to earn an
education. He went on to discover green fluorescent protein (GFP), for
which he was awarded the Nobel Prize in Chemistry in 2008. GFP has since
shaped the design of countless biological experiments \[2\].

On May 10, 1989, a fire began in a mouse breeding facility at Jackson
Laboratory in Bar Harbor, Maine that would grow to consume half of the
breeding laboratories and kill almost half a million mice \[3,4\].
Jackson Laboratory was a leading supplier of mice for biomedical
research in the United States. The fire caused many strains of mice to
suddenly become unavailable to researchers for months, if not years. A
recent analysis found that significantly fewer publications featured the
affected strains in the coming months and scientists whose work relied
on these strains tended to publish less and were more likely to change
their topic of study entirely \[5\]. The authors of this analysis found
that other laboratory disasters showed similar effects on scientific
productivity \[6\].

In the 1990s, a family of proteins called nuclear receptors were
characterized and rapidly earned substantial research attention \[7\].
Researchers believed every member of the family could be a tractable
therapeutic target for one disease or another---hundreds of papers could
be written about each protein. However, over the next couple of decades,
only a small subset of these proteins would be investigated in depth,
receiving thousands more citations than the rest of the family combined.
This subset represents the proteins in this family for which a
protein-specific chemical probe was widely commercially available.
Because such probes have long been unavailable for other members of the
family, biologists have largely elected not to study those members.

Mechanical Turk (MTurk) is a crowd-sourcing service launched by Amazon
in 2005 \[8\]. In the MTurk framework, users ("requesters") temporarily
recruit employees ("workers") to perform menial digital tasks
("microtasks") for wages ("rewards"). These rewards are often pennies
per task \[9,10\]. MTurk has proven to be of great use to social science
researchers as a simple and cost-effective means of gathering
participant data. To date, thousands of studies have been published
featuring data collected through MTurk \[11\]; a 2016 study found that
up to 40% of surveyed social science articles contained at least one
MTurk-aided study \[12\]. However, because workers are paid per task
completed, concerns have recently emerged that an increasing proportion
of MTurk-collected survey responses are low-effort, bad faith, or are
from a single worker using multiple accounts \[13\]. Indian and
Venezuelan workers are suspected of using software to make it appear as
though they are based in the United States, allowing them to participate
in and earn rewards for surveys targeting Americans \[11\]. More
recently, a large number of MTurk survey responses bear signatures of
workers using AI chatbots to expedite their work \[14\]. The extent to
which this widespread contamination of data has affected the social
sciences literature is unclear.

These anecdotes serve to demonstrate what I believe has been the
overarching theme of my doctoral studies: that the scientific enterprise
is a human enterprise. Although trivial to scientists themselves,
science's human aspect is often outright ignored. Popular maxims like
"trust the science", "we believe in science" and "science is
self-correcting" reduce the scientific enterprise to a singular,
infallible entity, withholding due recognition of the human and material
processes behind science's working.

These processes are also neglected when any single scientist is lauded
as a genius or trailblazer. While it is exciting to attribute grand
discoveries to individuals' tenacity or brilliance, this view fails to
capture the mechanics underlying those discoveries. Advances in
understanding are as much because of scientists' individual cleverness
and determination as because certain tools became commercially available
to those scientists, or because standards evolved in response to
changing consumer technologies, or because some funds were allocated to
some program.

Science, and thus our collective knowledge, is inexorably shaped by the
material and practical constraints of its societal context. In the
abstract, a primary goal of metascience (or the science of science) is
to better understand how the scientific enterprise functions within its
human context. Metascientists contend that obtaining such an
understanding allows policymakers to better direct the scientific
enterprise, accelerating innovation and the widening of our collective
knowledge and, in turn, improving human well-being \[15,16\].

Obtaining such a high-level mechanistic understanding is incredibly
difficult. The principal object of analysis in most metascience studies
is the scientific article. However, every scientific article is an
overwrought palimpsest reflecting the intentions of the authors as well
as their institutions, their sources of funding, the peer reviewers, the
editors, and the publisher. Except in rare instances where intermediary
records are available \[17\], this product is the sole lasting
reflection of the scientific process at work. From these records and the
citations that connect them, we are charged with extracting
generalizable insights about scientific productivity, creativity and
innovation.

These difficulties notwithstanding, this challenge has never been more
urgent. Recent global events have strained the relatively strong public
trust in science \[18-20\]. Recent large-scale evaluations have cast
doubts on the reproducibility of large swaths of the published
literature \[21-24\], fueling concerns about a "reproducibility crisis"
\[25\]. Meanwhile, scientific articles are now being retracted at a
record rate \[26\]. At the heart of this trend has been the apparent
emergence of paper mills, businesses that exploit the career pressure on
scientists to publish and serve to fill the peer-reviewed literature
with low-quality and outright fraudulent studies \[27-29\]. These
businesses seem to have found the most customers among academics and
physicians in low- and middle-income countries, where the opportunities
for growth of the scientific enterprise are greatest. In some countries
with burgeoning scientific enterprises, some might argue that such
businesses have completely upended ethical norms of scientific research
and publishing \[30-32\]. In these contexts, even those that wish in
good faith to have impactful and meaningful scientific careers may be
forced into misconduct by their circumstances. Worse still, scientists
trained in these contexts will be subject to the assumption that bogus
science is all they could ever produce; a common reaction to the
discovery of paper mill activity is to conclude that we just cannot
trust any research coming out of China, or Iran, or Russia, or Egypt, or
India, etc. Aspiring and established scientists in the global scientific
periphery deserve better.

One might argue that the development of paper mills and other forms of
systematic scientific fraud is the indirect result of metascientists
creating and popularizing quantifiable heuristics for evaluating
scientists like the h-index and the impact factor \[33,34\] (as an
aspiring metascientist, I would be loath to not cite Goodhart's law,
stated by Strathern as "when a measure becomes a target, it ceases to be
a good measure" \[35,36\]). The scientific enterprise is an unwieldy
behemoth, ever-growing in size and complexity \[37\]. In taking up the
challenge of characterizing this beast, metascientists of the past may
be indirectly responsible for many of its current ills. It is then
incumbent upon metascientists of the present and future to use their
craft to work towards a more equal and more just scientific enterprise
in addition to a more efficient one.

#### References {#references .wp-block-heading}

1.  Osamu Shimomura Nobel Lecture. Dec. 4, 2008.
2.  Aldo Roda. "Discovery and development of the green fluorescent
    protein, GFP: the 2008 Nobel Prize". In: Analytical and
    bioanalytical chemistry 396.5 (2010), pp. 1619--1622.
3.  Joseph Palca. "Fire strikes Jackson Laboratory." In: Nature 339.6221
    (1989).
4.  Elaine Blume. "NCI awards Jackson Lab \$9.5 million to rebuild". In:
    Journal of the National Cancer Institute 82.21 (1990), p. 1674.
5.  Stefano Horst Baruffaldi, Dennis Byrski, and Fabian Gaessler. "Fire
    and Mice: The Effect of Supply Shocks on Basic Science". In: Academy
    of Management Proceedings. Vol. 2020. Academy of Management
    Briarcliff Manor, NY 10510. 2020, p. 14405.
6.  Stefano Baruffaldi and Fabian Gaessler. "The returns to physical
    capital in knowledge production: Evidence from lab disasters". In:
    Max Planck Institute for Innovation & Competition Research Paper
    21-19 (2021).
7.  Aled M Edwards et al. "Too many roads not taken". In: Nature
    470.7333 (2011), pp. 163--165.
8.  Gabriele Paolacci, Jesse Chandler, and Panagiotis G Ipeirotis.
    "Running experiments on Amazon Mechanical Turk". In: Judgment and
    Decision making 5.5 (2010), pp. 411--419.
9.  Paul Hitlin. Research in the crowdsourcing age: A case study. 2016.
10. Douglas J Ahler, Carolyn E Roush, and Gaurav Sood. "The micro-task
    market for lemons: Data quality on Amazon's Mechanical Turk". In:
    Political Science Research and Methods (2021), pp. 1--20.
11. Ryan Kennedy et al. "The shape of and solutions to the MTurk quality
    crisis". In: Political Science Research and Methods 8.4 (2020), pp.
    614--629.
12. Haotian Zhou and Ayelet Fishbach. "The pitfall of experimenting on
    the web: How unattended selective attrition leads to surprising (yet
    false) research conclusions." In: Journal of personality and social
    psychology 111.4 (2016), p. 493.
13. Catherine C Marshall et al. "Who broke Amazon Mechanical Turk? An
    analysis of crowdsourcing data quality over time". In: Proceedings
    of the 15th ACM Web Science Conference 2023, pp. 335--345.
14. Veniamin Veselovsky, Manoel Horta Ribeiro, and Robert West.
    "Artificial artificial artificial intelligence: Crowd workers widely
    use large language models for text production tasks". In: arXiv
    arXiv:2306.07899 (2023).
15. Dashun Wang and Albert-László Barabási. The Science of Science.
    Cambridge University Press, 2021.
16. Santo Fortunato et al. "Science of science". In: Science 359.6379
    (2018), eaao0185.
17. Mohammad Hosseini et al. "Ethical considerations in utilizing
    artificial intelligence for analyzing the NHGRI's History of
    Genomics and Human Genome Project archives". In: Journal of eScience
    Librarianship 13.1 (2024).
18. Viktoria Cologna et al. "Trust in scientists and their role in
    society across 67 countries". In: OSF Preprints (2024).
19. Arthur Lupia et al. "Trends in US public confidence in science and
    opportunities for progress". In: Proceedings of the National Academy
    of Sciences 121.11 (2024), e2319488121.
20. Brian Kennedy and Alec Tyson. "Americans' trust in scientists,
    positive views of science continue to decline". Pew Research Center
    (2023).
21. Open Science Collaboration. "Estimating the reproducibility of
    psychological science". In: Science 349.6251 (2015), aac4716.
22. Colin F Camerer et al. "Evaluating the replicability of social
    science experiments in Nature and Science between 2010 and 2015".
    In: Nature human behaviour 2.9 (2018), pp. 637--644.
23. Timothy M Errington et al. "Investigating the replicability of
    preclinical cancer biology". In: Elife 10 (2021), e71601.
24. Jongwoo Park, Joshua D Howe, and David S Sholl. "How reproducible
    are isotherm measurements in metal--organic frameworks?" In:
    Chemistry of Materials 29.24 (2017), pp. 10487--10495.
25. Monya Baker. "1,500 scientists lift the lid on reproducibility". In:
    Nature 533.7604 (2016).
26. Richard Van Noorden. "More than 10,000 research papers were
    retracted in 2023---a new record". In: Nature 624.7992 (2023), pp.
    479--481.
27. Richard Van Noorden. "How big is science's fake-paper problem?" In:
    Nature 623.7987 (2023), pp. 466--467.
28. Jennifer A Byrne et al. "Protection of the human gene research
    literature from contract cheating organizations known as research
    paper mills". In: Nucleic Acids Research 50.21 (2022), pp.
    12058--12070.
29. Jennifer A Byrne and Cyril Labb´e. "Striking similarities between
    publications from China describing single gene knockdown experiments
    in human cancer cell lines". In: Scientometrics 110.3 (2017), pp.
    1471--1493.
30. Lulin Chen et al. "Knowledge, attitudes and practices about research
    misconduct among medical residents in southwest China: a
    cross-sectional study". In: BMC Medical Education 24.1 (2024), p.
    284.
31. Richard Stone. "In Iran, a shady market for papers flourishes". In:
    Science (2016).
32. Pratap R Patnaik. "Scientific misconduct in India: Causes and
    perpetuation". In: Science and Engineering Ethics 22.4 (2016), pp.
    1245--1249.
33. Jorge E Hirsch. "An index to quantify an individual's scientific
    research output". In: Proceedings of the National academy of
    Sciences 102.46 (2005), pp. 16569--16572.
34. Eugene Garfield. "The history and meaning of the journal impact
    factor". In: JAMA 295.1 (2006), pp. 90--93.
35. Marilyn Strathern. "'Improving ratings': audit in the British
    University system". In: European review 5.3 (1997), pp. 305--321.
36. Charles AE Goodhart. Problems of monetary management: the UK
    experience. Springer, 1984.
37. Lutz Bornmann, Robin Haunschild, and Rüdiger Mutz. "Growth rates of
    modern science: a latent piecewise growth curve approach to model
    publication numbers from established and new literature databases".
    In: Humanities and Social Sciences Communications 8.1 (2021), pp.
    1--15.

*The header image for this post is the Babylonian tablet [Plimpton
322](https://en.wikipedia.org/wiki/Plimpton_322).*


*Header image by Sydney Richardson.*

On June 5, head of Research Integrity and Resolutions at Springer Nature
[Tim Kersjes](https://twitter.com/TimKersjes) presented "Requiem for the
Retraction: why proposals for 'honest retractions' fail in their
objective to promote and encourage the self-correction of science" at
the 2024 World Conference on Research Integrity (WCRI).

Included was the following slide, later shared by [Maria
Zalm](https://x.com/MariaZalm/status/1798304619288047661), senior editor
and team manager of Publication Ethics at PLOS:

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/06/cropped.jpg?w=1024"
class="wp-image-269" data-attachment-id="269"
data-permalink="https://reeserichardson.blog/2024/06/18/how-shameful-should-retraction-be/cropped/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/06/cropped.jpg"
data-orig-size="1955,1100" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="cropped" data-image-description=""
data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/06/cropped.jpg?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/06/cropped.jpg?w=1024"
tabindex="0" role="button" loading="lazy" width="1024" height="576" />
<figcaption><em>Slide from Tim Kersjes’ talk at WCRI
2024.</em></figcaption>
</figure>

> More retraction positivity, less retraction shaming
>
> More and more and more and more
>
> **You want science to be more self-correcting? Stop retraction
> shaming!**
>
> Retractions are normal part of academic publishing and that is **[a
> good thing]{.underline}**
>
> Emphasize that retractions are a signal that editors and publishers
> **[are taking their responsibility]{.underline}**
>
> **[Be careful to jump to conclusions]{.underline}** when you see that
> an article is retracted
>
> Encourage editors to consider that retractions are **[a great
> way]{.underline}** to correct the published record
>
> More importantly: emphasize to authors that they are **[not being
> punished]{.underline}**

Reactions followed. Pseudonymous sleuth
[Morty](https://twitter.com/mortenoxe/status/1798771972555366889) said:

> If this is the final conclusion from \#WCRI2024, so help us God. Most
> of the retractions is due to research misconduct. We need more shaming
> of scientists who commit research misconduct!

Reproducibility researcher and science writer [James
Heathers](https://twitter.com/jamesheathers/status/1801764730031284493)
said:

> I was just thinking about 'stop retraction-shaming' today. While
> reading a 15 month old email thread pleading with an editor to retract
> clearly falsified medical papers.

Sleuth and founder of the 5GH Foundation [WU
Guangheng](https://twitter.com/Dr_5GH/status/1798410890125213868) said:

> We do NOT agree. Honest errors have a very small number, but hundreds
> of thousands of misconduct cases are waiting publishers to handle.
> Both PLoS and Springer Nature should take more effort to "clean up"
> their history, and \[quickly respond\] to new cases.

Maria Zalm
[responded](https://x.com/MariaZalm/status/1798830107425157549):

> To clarify, \[Tim Kersjes\] and I are not suggesting that fraudulent
> research should not be retracted, but rather that unreliable articles
> should be retracted REGARDLESS of misconduct findings.
>
> ...
>
> \[If\] we are truly serious about correcting the scientific
> literature, we need to encourage people to retract their own
> erroneous/unrepeatable results, and this won't happen as long as there
> is such a huge \[stigma\] around all retractions.

Other have written at length about the stigma surrounding retractions:

1.  [Ending the retraction stigma: Encouraging the reporting of errors
    in the biomedical record](https://doi.org/10.1177/1747016118802970)
2.  [Breaking the stigma of
    retraction](https://doi.org/10.1038/s41562-021-01266-7)
3.  [Retraction Stigma and its Communication via Retraction
    Notices](https://doi.org/10.1007/s11024-022-09465-w)

In my own research and in discussions with others, I have encountered
compelling arguments both for why retraction should be more stigmatized
and why retraction should be less stigmatized. I have yet to form a
coherent opinion myself. Here, I wanted to collect and discuss these
arguments to aid my own understanding and invite arguments from others.

We should first frame this debate in terms of a common value: the
essentiality of retractions. Most observers will agree that retractions
are an indispensable part of the scientific process and that it is a
good thing when an unreliable paper is retracted. Most observers will
agree that even though retraction is becoming [increasingly
frequent](https://doi.org/10.1038/d41586-023-03974-8), not enough papers
are retracted and retractions often take far too long. One might argue
that retraction is not an essential part of science publishing (see
["Science is a strong-link
problem"](https://www.experimental-history.com/p/science-is-a-strong-link-problem)
by psychologist Adam Mastroianni), but we need to stick to one framework
by which we can judge our arguments. Thus, we should prefer a position
that improves the efficiency and integrity of retraction as a research
publishing practice.

### Position A: Retractions should be more stigmatized {#position-a-retractions-should-be-more-stigmatized .wp-block-heading}

###### Contention A1: Most retractions are due to misconduct and misconduct should be shameful {#contention-a1-most-retractions-are-due-to-misconduct-and-misconduct-should-be-shameful .wp-block-heading}

Observers agree that most retractions are the result of research
misconduct on the part of one or more authors ([Fang et
al.](https://doi.org/10.1073/pnas.1212247109), [Freijedo-Farinas et
al.](https://doi.org/10.1007/s11192-024-04992-7), [Grieneisen and
Zhang](https://doi.org/10.1371/journal.pone.0044118)). Many retractions
are now the result of particularly egregious forms of misconduct like
paper milling or other systematic research fraud. Research misconduct
should not be tolerated. As such, instances of misconduct should be met
with scorn for the sake of punitive and preventive justice.

There is some evidence that retraction shaming, as an attitudinal
implementation of preventive justice, would work as a deterrent against
research misconduct. [Chen et
al.](https://doi.org/10.1186/s12909-024-05277-6) report that lower
perceived consequences were positively associated with self-reporting of
research misconduct in a large sample of Chinese physicians. [Martinson
et al.](https://doi.org/10.1525/jer.2006.1.1.51) suggest that
scientists' perceptions of organizational injustice may also contribute
to misconduct.

###### Contention A2: Shameless repeat offenders will continue their careers {#contention-a2-shameless-repeat-offenders-will-continue-their-careers .wp-block-heading}

Researchers that have published retracted work can and do lose their
jobs and access to funding, even without official findings of misconduct
from their employers. However, if employers are not diligent in their
background checks or simply do not care, the most ignominious offenders
might be able to keep their jobs or move onto new ones and continue
recklessly polluting the scientific record. I surmise that researchers
that are comfortable violating ethical norms of scientific conduct would
also be more likely to violate professional and personal ethical norms.

Shame should be used to prevent these individuals from continuing to
climb the ranks for protection of the scientific record and possibly the
protection of violators' colleagues, students and patients. An official
finding of misconduct will most likely not appear in a Google search of
a quack doctor's name. A tweet will.

###### Contention A3: Shame is all we have {#contention-a3-shame-is-all-we-have .wp-block-heading}

Retractions happen very infrequently; there were about 10,000 published
retractions to about 10,000,000 published peer-reviewed articles in 2023
(a 1:1,000 ratio). Many retracted articles are not prominently labelled
as retracted by the publisher [despite COPE
guidelines](https://doi.org/10.24318/cope.2019.1.4). Lots of retracted
articles will continue to be cited as if they were not retracted (see
[Hsiao and Schneider](https://doi.org/10.1162/qss_a_00155)). Moreover,
retracted articles are still counted towards bibliometrics like h-index
and citation count in most databases. Beyond retraction, individual
sanctions are exceedingly infrequent. For instance, the [US Department
of Health and Human Services Office of Research Integrity
sanctions](https://ori.hhs.gov/content/case_summary) on the order of 10
individuals every year, often fewer. University investigations often
close without official misconduct findings even as retractions mount.

If these formal measures are woefully insufficient for addressing
research misconduct, we should practice shame as a low-cost and scalable
alternative.

### Position B: Retractions should be less stigmatized {#position-b-retractions-should-be-less-stigmatized .wp-block-heading}

###### Contention B1: Retraction stigma could prevent self-reported retractions {#contention-b1-retraction-stigma-could-prevent-self-reported-retractions .wp-block-heading}

In most cases, authors will be those that most completely understand the
content of their scientific work. Thus, authors are among the
best-prepared to spot errors in their work and move to correct or
retract. A heavy stigma and career penalty associated with retractions,
real or perceived, could discourage authors from retracting their own
work. This might explain why so few retractions are associated with
honest error, as mentioned in Contention A1.

In 2020, Chemistry Nobel laureate Frances Arnold retracted a [2019
*Science* article](https://doi.org/10.1126/science.aaw9068) she
authored,
[noting](https://retractionwatch.com/2020/01/02/nobel-winner-retracts-paper-from-science/):

> For my first work-related tweet of 2020, I am totally bummed to
> announce that we have retracted last year's paper on enzymatic
> synthesis of beta-lactams. The work has not been reproducible.
>
> It is painful to admit, but important to do so. I apologize to all. I
> was a bit busy when this was submitted, and did not do my job well.

Many commentators (rightfully, in my opinion) celebrated Arnold's
transparency and proactiveness. Early-career researchers without a Nobel
prize or a well-earned reputation might be more reluctant to follow this
path exactly because of the perceived personal cost.

###### Contention B2: Retraction stigma impedes the retraction process {#contention-b2-retraction-stigma-impedes-the-retraction-process .wp-block-heading}

Authors will often mount vicious defenses against criticisms and
investigations of their work that could end in retraction. The
perception that a retraction will bring public and personal shame will
undoubtedly fuel this behavior. The threat of shame can prompt authors
to launch lawsuits, spout vitriol or not cooperate with investigations
by journals and employers, tying up proceedings and delaying retractions
for years. James Heathers is not alone in his 15-month quest to get a
paper retracted---experienced sleuths will have endured innumerable
prolonged matches of back-and-forth with editors and authors. Fear of
getting tangled up in these matches will also discourage observers from
reporting errors in the first place.

Editors will be similarly disincentivized against initiating
investigations and executing retractions by the perception of shame. No
editor would want the name of their journal besmirched by calling
attention to a problematic paper with a retraction. Similarly, editors
will want to maintain professional relationships with prestigious
researchers. This is hard to do if the editor is perceived as an agent
of a humiliating witch hunt.

###### Contention B3: Shame can be misdirected {#contention-b3-shame-can-be-misdirected .wp-block-heading}

Retraction notices rarely assign blame for mistakes or misconduct. Many
retraction notices are cartoonishly opaque (e.g. ["\[the\] article...has
been voluntarily retracted by the authors due to a 'non-scientific
reason'"](https://doi.org/10.1096/fj.201700932RRRET)). As a result, it
is very difficult for readers to properly evaluate where shame should be
directed or if it should be employed at all. Obscurant practices by
institutional committees charged with investigating misconduct compound
this difficulty. In this fog, there is always a strong possibility that
the innocent will be targeted for shaming and the guilty will escape
ire.

Junior researchers are already the most likely to shoulder the brunt of
retraction's consequences. [Jin et
al.](https://doi.org/10.1162/rest_a_00780) found that citation losses to
prior works by an author following a retraction of their work are far
less severe for eminent authors. The citation penalty on prior work
(previously described [by the same
team](https://doi.org/10.1038/srep03146)) also implies that other,
unimpeachable work by a group of authors will earn fewer citations
following the retraction of one of their otherwise unrelated articles.
In essence, shame might cause us to disregard valuable work.

How much collateral damage should the scientific community tolerate in
the name of punishing misdeeds?

###### Contention B4: There is not enough shame to go around {#contention-b4-there-is-not-enough-shame-to-go-around .wp-block-heading}

Attention spans are limited. Cultural memory can be short. Even the most
tireless cranks must eventually stop ringing the alarm. There are
undoubtedly tens of thousands of scientific fraudsters out there who
deserve to lose face and never will simply because shame is
rate-limited.

In our cultural context, this also means that the most shame will be
reserved for the most scandalous cases. Hence, headlines will abound for
one [AI-generated rat
penis](https://youtu.be/Bj8IAoTnyNw?si=dViOmf0ZYMm-eGuV) but a case of
[more than 50 medical studies with faked
authorship](https://retractionwatch.com/2024/01/26/journal-retracts-more-than-50-studies-from-saudi-arabia-for-faked-authorship/)
will get comparatively little attention. If we aim the weapon of shame
selectively and illogically, we should hesitate to wield it.

### Position C: We are asking the wrong question {#position-c-we-are-asking-the-wrong-question .wp-block-heading}

The more practically-minded among us will note that we are debating
attitudinal solutions to what is clearly a structural problem.

Not only do these solutions have duller teeth than sweeping systemic
changes, but no one has the authority to force a cultural change in how
something is stigmatized. As retractions become more frequent, it is
also difficult to predict how that stigma might change on its own. We
should direct our effort towards reshaping scientific institutions for
organizational justice instead of litigating how scientists should feel
about science integrity measures.

### What are your thoughts? {#what-are-your-thoughts .wp-block-heading}

Feel free to share your thoughts and arguments for or against retraction
shaming in the comments on this post. As retractions grow exponentially,
discussions like these will shape the future of scientific publishing
and may alter the character of 'self-correction' as a scientific maxim.


In 2017, Wikipedia editor WikiDan61 [changed the flag on Vatican City as
it appears on the
site](https://web.archive.org/web/20190608034347/https://commons.wikimedia.org/wiki/File:Flag_of_the_Vatican_City.svg),
noting that "\[all\] images of actual Vatican City flags show the "gold"
in the keys and tiara rendered in the same hue as the gold/yellow band
of the flag, as well as a red opening at the bottom of the tiara".

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png?w=800"
class="wp-image-220" data-attachment-id="220"
data-permalink="https://reeserichardson.blog/2024/05/21/truth-authority-and-the-flag-of-vatican-city/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png"
data-orig-size="800,800" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1"
data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png?w=800"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png 800w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-41-22-flag-of-vatican-city-wikipedia-1.png?w=768 768w"
sizes="(max-width: 800px) 100vw, 800px" width="800" height="800" />
<figcaption><em>The flag of Vatican City, as uploaded by WikiDan61 in
2017.</em></figcaption>
</figure>

However, according to the [2000 revision of the Fundamental Law of
Vatican City
State](https://www.vatican.va/news_services/press/documentazione/documents/sp_ss_scv/insigne/sp_ss_scv_stemma-bandiera-sigillo_en.html),
this version of the flag was incorrect. Most notably, if the
specifications set out by the Holy See were followed, the inside of the
papal tiara would appear white, not red.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png?w=708"
class="wp-image-222" data-attachment-id="222"
data-permalink="https://reeserichardson.blog/2024/05/21/truth-authority-and-the-flag-of-vatican-city/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3-pdf/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png"
data-orig-size="708,884" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf"
data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png?w=240"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png?w=708"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png 708w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png?w=120 120w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-13-46-43-vatican-flags-keys-crowns-since-1800-the-flags-of-the-papal-states-and-todays-vatican-raven_v25_2018_p089-134_chapter3.pdf.png?w=240 240w"
sizes="(max-width: 708px) 100vw, 708px" width="708" height="884" />
<figcaption><em>The flag of Vatican City, as described by the 2000
revision to the Fundamental Law of Vatican City State. Image from <a
href="https://nava.org/raven-volume-25">Vatican Flags by William M.
Becker.</a></em></figcaption>
</figure>

Wikipedia editors realized this mistake in 2022 and reverted the flag to
a more appropriate version. However, [as the story
goes](https://www.catholicnewsagency.com/news/254032/wikipedia-had-the-wrong-vatican-city-flag-for-years-now-incorrect-flags-are-everywhere),
the incorrect version of the flag had already begun to be downloaded and
used by flag retailers worldwide. To this day, if you want to buy the
flag of Vatican City, most of your options will feature the tiara with
the red interior.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png?w=861"
class="wp-image-225" data-attachment-id="225"
data-permalink="https://reeserichardson.blog/2024/05/21/truth-authority-and-the-flag-of-vatican-city/oop/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png"
data-orig-size="861,710" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="oop" data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png?w=861"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png 861w, https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/05/oop.png?w=768 768w"
sizes="(max-width: 861px) 100vw, 861px" width="861" height="710" />
<figcaption><em><span style="text-decoration: underline">Top
left:</span> an Amazon listing for Vatican City flag from April 2023,
taken by Jonah McKeown of the Catholic News Agency. <span
style="text-decoration: underline">Top right</span>: a Vatican City flag
I spotted in a Seattle bookstore in March 2023. <span
style="text-decoration: underline">Bottom row:</span></em> <em>listings
for the Vatican City flag from Google Shopping in May 2024. Notice that
all of these instances show the tiara with a red interior, not white.
These flags are also in the wrong aspect ratio (the Vatican City flag is
one of two national flags that officially have a 1:1 ratio, alongside
Switzerland’s</em>).</figcaption>
</figure>

I contend that in order for a speaker's message to be accepted as the
truth by a listener, that listener must attribute a minimum amount of
authority to the speaker. For instance, Wikipedia has just enough
authority in the eyes of these flag retailers for its version of the
Vatican City flag to be accepted as the truth. The primacy of authority
is something I think we all intuitively understand, and to rhetoricians,
this observation will come across as trivial (ethos is a vertex of the
[rhetorical
triangle](https://plato.stanford.edu/entries/aristotle-rhetoric/), after
all).

However, the role of authority in the construction of popular truths and
mis-truths cannot be overstated. For instance, you'll often see
anti-vaxxers (like [Peter A.
McCullough](https://x.com/DrNoMask/status/1738618252723417094) and his
fellow industry professional ["5G
GENOCIDE"](https://web.archive.org/web/20230114005531/https://www.youtube.com/watch?v=jIgUJZ7d_Po))
leaning on the fact that an academic paper that they cite is indexed in
PubMed, an organ of the National Library of Medicine and, by extension,
an organ of the United States federal government. This appeal confers
additional authority upon the speaker while playing against the
authority of the government (*"you see, even the vaccine-peddling NIH
can't deny the legitimacy of our research!"*). McCullough's
understanding of authority might also explain why his display name is
followed by his academic degrees, a registered trademark symbol (?) and
a verification badge.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png?w=748"
class="wp-image-227" data-attachment-id="227"
data-permalink="https://reeserichardson.blog/2024/05/21/truth-authority-and-the-flag-of-vatican-city/mccullough/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png"
data-orig-size="748,788" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="mccullough" data-image-description=""
data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png?w=285"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png?w=748"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png 748w, https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png?w=142 142w, https://reeserichardson.blog/wp-content/uploads/2024/05/mccullough.png?w=285 285w"
sizes="(max-width: 748px) 100vw, 748px" width="748" height="788" />
<figcaption><em>Two tweets from January and December 2023 by anti-vaxxer
Peter A. McCullough featuring an appeal to PubMed as an
authority.</em></figcaption>
</figure>

Is PubMed an authority on human health research? No, it is only an
indexing service (read: online library) for the biomedical literature,
and [PubMed itself will be the first to tell you
that](https://pubmed.ncbi.nlm.nih.gov/disclaimer/). However, this bit of
information isn't relevant so long as PubMed is *perceived as* an
authority within these circles.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png?w=879"
class="wp-image-229" data-attachment-id="229"
data-permalink="https://reeserichardson.blog/2024/05/21/truth-authority-and-the-flag-of-vatican-city/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png"
data-orig-size="879,480" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis"
data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png?w=879"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png 879w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/05/screenshot-2024-05-17-at-14-47-03-sars-cov-2-vaccination-and-the-multi-hit-hypothesis-of-oncogenesis.png?w=768 768w"
sizes="(max-width: 879px) 100vw, 879px" width="879" height="480" />
<figcaption><em>PubMed Central’s disclaimer over the full-text of one of
McCullough’s cited articles.</em></figcaption>
</figure>

The primacy of authority is also why commentators have often portrayed
participants in student protests about Gaza and Palestine as
[white](https://www.ocregister.com/2024/04/29/terrorist-sympathizers-are-disrupting-universities-across-the-country/),
[privileged](https://nypost.com/2024/05/01/us-news/arab-activist-rawan-osman-rips-us-college-students-for-hamas-support/)
or [uneducated](https://www.youtube.com/watch?v=0VRqSgQN0Zs). Doing so
does not really challenge the protestors' message itself, but serves to
degrade the authority of the message's source in the eyes of observers,
which can be both more effective and less troublesome.

The Vatican City flag snafu is a valuable case study in how authority
shapes truth because of its unique conclusion. Not only did WikiDan61's
actions change how the truth was reflected by an authority, but arguably
*changed the truth itself*. As a result of WikiDan61's edit, the
red-tiara version of the Vatican City flag has come into common use as a
symbol to represent Vatican City, fulfilling the purpose of an ensign
and become just as effective a flag of Vatican City as the official
version.

This would be a great place to leave this story if the truth wasn't even
more complicated: WikiDan61 was not wholly incorrect. The red-tiara
version of the Vatican City flag has seen use, even official use by the
Holy See, for decades prior to their edit. You may have also noticed
that several of the listings for the flag I showed earlier are not exact
copies of WikiDan61's design (look at the color and handles of the
crossed keys), complicating the story further.

<figure class="wp-block-image size-large">
<a
href="https://www.catholicsun.org/2015/09/23/el-papa-hijo-de-una-familia-de-inmigrantes-le-dice-a-obama-que-esta-listo-para-aprender-en-los-eeuu/"><img
src="https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=1024"
class="wp-image-232" data-attachment-id="232"
data-permalink="https://reeserichardson.blog/2024/05/21/truth-authority-and-the-flag-of-vatican-city/vatican_flag_in_use/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png"
data-orig-size="1178,659" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="vatican_flag_in_use" data-image-description=""
data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=1024"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=1022 1022w, https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png?w=768 768w, https://reeserichardson.blog/wp-content/uploads/2024/05/vatican_flag_in_use.png 1178w"
sizes="(max-width: 1024px) 100vw, 1024px" width="1024"
height="572" /></a>
<figcaption><em><span style="text-decoration: underline">Left:</span>
The Vatican City flag outside Porta Sant’Anna in 1980 (<span
style="text-decoration: underline"><a
href="https://nava.org/raven-volume-25">source</a></span>). <span
style="text-decoration: underline">Upper right:</span> The Vatican City
flag flown aboard Apollo 11 in 1969 (<a
href="https://en.m.wikipedia.org/wiki/File:Vatican-City-Moon-Flag.jpg">source</a>).
<span style="text-decoration: underline">Lower right:</span> The Vatican
City flag flown behind Pope Francis on a visit to the United States in
2015 (<a
href="https://www.catholicsun.org/2015/09/23/el-papa-hijo-de-una-familia-de-inmigrantes-le-dice-a-obama-que-esta-listo-para-aprender-en-los-eeuu/">source</a>).</em>
<em>All feature the tiara with a red interior.</em></figcaption>
</figure>

Have I muddled my thesis by ending with this tidbit? Probably. Will I
jump at the chance to ramble on any vexillological ephemera regardless
of coherence? Absolutely.


A cell line is a population of cells that can be grown in a laboratory
culture indefinitely. Cell lines are an essential tool for biomedical
research because they allow biological experiments to be performed *in
vitro* (i.e. outside of a living organism). For instance, researchers
developing new cancer drugs will certainly test the effect of their drug
candidates on many different cancer cell lines before ever considering
testing the drug candidate on live animals, let alone human patients.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg?w=512"
class="wp-image-115" data-attachment-id="115"
data-permalink="https://reeserichardson.blog/2024/03/14/non-verifiable-cell-lines-immortal-or-imaginary/0-1/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg"
data-orig-size="512,276" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="0-1" data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg?w=512"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg 512w, https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/03/0-1.jpg?w=300 300w"
sizes="(max-width: 512px) 100vw, 512px" width="512" height="276"
alt="SAOS2 cells" />
<figcaption><em>Fluorescence microscope image of <a
href="https://www.cellosaurus.org/CVCL_0548">SAOS2</a>, a cell line
derived from the bone tissue of an 11-year-old osteosarcoma patient.
Image from the <a href="https://doi.org/10.7295/W9CIL9068">Cell Image
Library.</a></em></figcaption>
</figure>

Because cell lines can grow indefinitely, one research laboratory or
laboratory supplier can take a few cells from their cell line stock and
give them to another laboratory for that laboratory to begin culturing
their own stock. By far the most popular cell line is
[HeLa](https://www.cellosaurus.org/CVCL_0030), and the many of thousands
of HeLa cell stocks used in biomedical research around the world can all
be traced back to the original stock of "immortal" cervical cancer cells
taken from [Henrietta Lacks in
1951](https://en.wikipedia.org/wiki/Henrietta_Lacks).

One complication of relying on cell lines for biomedical research is
that stocks will often become cross-contaminated by other cell lines.
For instance, HeLa is extremely aggressive as cancer cell lines go and
HeLa cells will easily overtake other cell line stocks that are stored
nearby. The popular gastric cancer cell line
[BGC-823](https://www.cellosaurus.org/CVCL_3360) is one such victim of
HeLa's aggression; there are no remaining uncontaminated stocks of
BGC-823 and thus it is no longer considered an appropriate experimental
model for gastric cancer. The International Cell Line Authentication
Committee maintains [a register of misidentified cell
lines](https://iclac.org/databases/cross-contaminations/) that is
currently 582 entries long. A good number of these cell lines were
contaminated by cells from a completely different organism, such as
human salivary gland cell line
[CAC2](https://www.cellosaurus.org/CVCL_6883), which is actually made up
of unknown cells from a rat.

Because [different cell lines can have a wide variety of responses to
the same
treatment](https://www.cancerrxgene.org/compound/Paclitaxel/11/overview/ic50),
it is essential that researchers avoid misidentified cell lines and only
work with authenticated cell lines that actually represent their system
of interest.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/03/1.png?w=623"
class="wp-image-116" data-attachment-id="116"
data-permalink="https://reeserichardson.blog/2024/03/14/non-verifiable-cell-lines-immortal-or-imaginary/attachment/1/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/03/1.png"
data-orig-size="623,293" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="1" data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/03/1.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/03/1.png?w=623"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/03/1.png 623w, https://reeserichardson.blog/wp-content/uploads/2024/03/1.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/03/1.png?w=300 300w"
sizes="(max-width: 623px) 100vw, 623px" width="623" height="293"
alt="Cellosaurus entry for BGC-823." />
<figcaption><em>The Cellosaurus entry for <a
href="https://www.cellosaurus.org/CVCL_3360">BGC-823</a> now warns about
the cell line being contaminated by HeLa.</em></figcaption>
</figure>

Thanks largely to the diligent work of Danielle Oste, [~~now available
on bioRxiv~~](https://doi.org/10.1101/2024.02.29.582220) \[UPDATE: May
16, 2024\] [now published in the *International Journal of
Cancer*](https://doi.org/10.1002/ijc.34995), we can now report on a
whole new threat to biomedical research: cell lines that never existed
in the first place.

The names of cell lines are usually just a jumble of letters and numbers
and thus can often be easily confused. For instance, the name of BGC-823
is very similar to that of
[MGC-803](https://www.cellosaurus.org/CVCL_5334), another misidentified
gastric cancer cell line. One might easily misspell these cell lines as
"BGC-803" or "MGC-823". However, we noticed that sometimes these
misspelled identifiers were used to refer to another cell line entirely
distinct from these existing cell lines. Take the 2021 article ["Long
non-coding RNA KCNQ1OT1 promotes the progression of gastric cancer via
the miR-145-5p/ARF6 axis"](https://doi.org/10.1002/jgm.3330) in the
*Journal of Gene Medicine* (Wiley), which refers to experiments in cell
lines "BGC-803" and "BSG-823" in addition to experiments in the
contaminated cell lines BGC-823 and MGC-803.

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/03/2.png?w=557"
class="wp-image-119" data-attachment-id="119"
data-permalink="https://reeserichardson.blog/2024/03/14/non-verifiable-cell-lines-immortal-or-imaginary/attachment/2/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/03/2.png"
data-orig-size="557,478" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="2" data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/03/2.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/03/2.png?w=557"
tabindex="0" role="button" loading="lazy" data-long=""
data-non-coding="" data-rna="" data-kcnq1ot1="" data-promotes=""
data-progression="" data-of="" data-gastric="" data-cancer=""
data-via="" data-the="" data-mir-145-5p="" data-arf6="" data-axis",=""
data-an="" data-article="" data-that="" data-used="" data-several=""
data-non-verifiable="" data-cell="" data-lines."=""
srcset="https://reeserichardson.blog/wp-content/uploads/2024/03/2.png 557w, https://reeserichardson.blog/wp-content/uploads/2024/03/2.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/03/2.png?w=300 300w"
sizes="(max-width: 557px) 100vw, 557px" width="557" height="478"
alt="A graph from " />
<figcaption><em>Adapted from Figure 1 of <a
href="https://doi.org/10.1002/jgm.3330">“Long non-coding RNA KCNQ1OT1
promotes the progression of gastric cancer via the miR-145-5p/ARF6
axis”</a>. Existing non-contaminated cell lines are highlighted in blue,
existing contaminated cell lines are shown in orange, and non-verifiable
cell lines are shown in red.</em></figcaption>
</figure>

Hundreds of articles have referred to experiments in these cell lines
despite there being no indication that these cell lines actually
exist---there are no entries for these cell lines in any cell line
indices, they cannot be found in any supplier catalogs, there are no
articles describing how these cell lines were established, and no one
seems to have produced any genetic profiles of these cell lines to
confirm their identities. We identified eight such "miscellings":
BGC-803, BSG-803, BSG-823, GSE-1, HGC-7901, HGC-803, MGC-823 and TIE-3.
There are certainly many more non-verifiable cell lines out there.

Could these cell lines actually exist? It is possible, and we would love
to see evidence of it, but it seems much more likely to me that each of
these identifiers were born as typos before assuming a life of their own
in the scientific literature due to the sloppy fact-checking of [paper
mills](https://doi.org/10.1093/nar/gkac1139).

Because of non-verifiable cell lines and cell line contamination, the
biomedical literature abounds with experimental results that are
entirely irreproducible by other scientists, wasting the time of
editors, peer reviewers and researchers alike as well as the public
funds that support this research.

To learn more, you can check out [Jennifer Byrne's guest post in
Retraction
Watch](https://retractionwatch.com/2024/03/11/misspelled-cell-lines-take-on-new-lives-and-why-thats-bad-for-the-scientific-literature/)
or read our ~~preprint~~ \[UPDATE May 16, 2024\] newly-published paper:

Danielle J. Oste, Pranujan Pathmendra, Reese A. K. Richardson, Gracen
Johnson, Yida Ao, Maya D. Arya, Naomi R. Enochs, Muhammed Hussein,
Jinghan Kang, Aaron Lee, Jonathan J. Danon, Guillaume Cabanac, Cyril
Labbé, Amanda Capes Davis, Thomas Stoeger, Jennifer A. Byrne.
Misspellings or "miscellings"-non-verifiable cell lines in cancer
research publications. *Int J Cancer*. 2024; 1-12.
doi:[10.1002/ijc.34995](https://doi.org/10.1002/ijc.34995){target="_blank"
rel="noreferrer noopener"}


Bharat B. Aggarwal is an Indian-American biochemist who worked at MD
Anderson Cancer Center from 1989 to 2015. His research focused on
potential anti-cancer effects and therapeutic applications of herbs and
spices. Aggarwal was particularly drawn to curcumin, a non-toxic
compound found in turmeric that has long been staple in Ayurvedic
systems of medicine. He authored more than 120 articles about the
compound from 1994 to 2020. These articles reported that curcumin had
therapeutic potential for a variety of diseases, including various
cancers, Alzheimer's disease and, more recently, COVID-19. In his 2011
book [*Healing Spices: How to Use 50 Everyday and Exotic Spices to Boost
Health and Beat
Disease*](https://www.amazon.com/Healing-Spices-Everyday-Exotic-Disease/dp/1402776632),
Aggarwal recommends "taking a daily 500 mg curcumin supplement for
general health".

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=1024"
class="wp-image-72" data-attachment-id="72"
data-permalink="https://reeserichardson.blog/2024/01/30/the-king-of-curcumin-a-case-study-in-the-consequences-of-large-scale-research-fraud/curcumin_and_turmeric/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png"
data-orig-size="1292,454" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="curcumin_and_turmeric" data-image-description=""
data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=1024"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=1022 1022w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png?w=768 768w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_and_turmeric.png 1292w"
sizes="(max-width: 1024px) 100vw, 1024px" width="1024" height="359" />
<figcaption><em>Left: Chemical structure of curcumin in its keto form.
Right: turmeric powder.</em></figcaption>
</figure>

MD Anderson Cancer Center initially appeared to be fully on board with
Aggarwal's work. At one point, their website's FAQ page recommended
visitors buy curcumin wholesale from a company for which Aggarwal was a
paid speaker [(see "Spice Healer", *Scientific
American*)](https://www.scientificamerican.com/article/spice-healer/).
However, in 2012 (following observations of image manipulation raised by
pseudonymous sleuth [Juuichi
Jigen](http://md-anderson-cc.blogspot.com/)), MD Anderson Cancer Center
launched a research fraud probe against Aggarwal which eventually led to
30 of Aggarwal's articles being retracted. Only some of these studies
were about curcumin specifically, but most concerned similar natural
products.

Retractions rarely number this high for a single author; according to
the [Retraction Watch
leaderboard](https://retractionwatch.com/the-retraction-watch-leaderboard/),
only 26 other people have authored this many retracted studies.
Aggarwal's retracted articles feature dozens of instances of spliced
Western blots and duplicated images, as well as several instances where
mice were implanted with tumors exceeding volumes considered ethical.
[PubPeer commenters](https://pubpeer.com/search?q=Bharat+Aggarwal) have
noted irregularities in many publications beyond the 30 that have
already been retracted. Aggarwal retired from M.D. Anderson in 2015, but
has continued to author articles and appear at conferences.

<figure class="wp-block-image size-large is-resized">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=1024"
class="wp-image-74" style="width:620px;height:auto"
data-attachment-id="74"
data-permalink="https://reeserichardson.blog/2024/01/30/the-king-of-curcumin-a-case-study-in-the-consequences-of-large-scale-research-fraud/aggarwal_presentation/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png"
data-orig-size="1294,339" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="aggarwal_presentation" data-image-description=""
data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=1024"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=1024 1024w, https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png?w=768 768w, https://reeserichardson.blog/wp-content/uploads/2024/01/aggarwal_presentation.png 1294w"
sizes="(max-width: 1024px) 100vw, 1024px" width="1024" height="268" />
<figcaption><em>Aggarwal citing a 2017 paper he wrote, <a
href="https://www.frontiersin.org/articles/10.3389/fphar.2018.00400/full">retracted
in 2018</a>, in a 2022 <a
href="https://youtu.be/0e5Zn62IE_M?t=1854">conference
presentation</a>.</em></figcaption>
</figure>

Curcumin doesn't work well as a therapeutic agent for any disease.
Though it is safe for human consumption in most forms and will show
activity in essentially any in vitro assay you throw at it (via a
process known as [assay
interference](https://doi.org/10.1021/acschembio.7b00903)), no
well-powered clinical trials have ever found it to be an effective
medicine. Consider the following summary from [Nelson et al.
2017](https://doi.org/10.1021/acs.jmedchem.6b00975):

> "\[No\] form of curcumin, or its closely related analogues, appears to
> possess the properties required for a good drug candidate (chemical
> stability, high water solubility, potent and selective target
> activity, high bioavailability, broad tissue distribution, stable
> metabolism, and low toxicity). The in vitro interference properties of
> curcumin do, however, offer many traps that can trick unprepared
> researchers into misinterpreting the results of their investigations."

Despite curcumin's apparent lack of therapeutic promise, the [volume of
research produced on
curcumin](https://pubmed.ncbi.nlm.nih.gov/?term=%28curcumin%5BTitle%2FAbstract%5D%29&sort=date&size=200)
grows each year.  More than 2,000 studies involving the compound are
published annually. [Many of these studies bear signs of fraud and
involvement of paper
mills.](https://pubpeer.com/search?q=%22curcumin%22) As of 2020, the
United States National Institutes of Health (NIH) has spent more than
150 million USD funding projects related to curcumin. Funding increased
drastically in the 2007 fiscal year, shortly after Aggarwal began to
publish in earnest about the compound and the same year he declared
curcumin ["the Indian solid
gold"](https://doi.org/10.1007/978-0-387-46401-5_1).

<figure class="wp-block-image size-large">
<img
src="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=1024"
class="wp-image-79" data-attachment-id="79"
data-permalink="https://reeserichardson.blog/2024/01/30/the-king-of-curcumin-a-case-study-in-the-consequences-of-large-scale-research-fraud/curcumin_aggarwal_story_230913/"
data-orig-file="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png"
data-orig-size="2078,1437" data-comments-opened="1" data-image-meta="{"
aperture":"0","credit":"","camera":"","caption":"","created_timestamp":"0","copyright":"","focal_length":"0","iso":"0","shutter_speed":"0","title":"","orientation":"0"}"=""
data-image-title="curcumin_aggarwal_story_230913"
data-image-description="" data-image-caption=""
data-medium-file="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=300"
data-large-file="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=1024"
tabindex="0" role="button" loading="lazy"
srcset="https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=1024 1024w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=2048 2048w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=150 150w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=300 300w, https://reeserichardson.blog/wp-content/uploads/2024/01/curcumin_aggarwal_story_230913.png?w=768 768w"
sizes="(max-width: 1024px) 100vw, 1024px" width="1024" height="708" />
<figcaption><em>Graphs describing the volume of curcumin research from
various sources. Data collected from PubMed and NIH RePORTER. Data may
be incomplete in recent years.</em></figcaption>
</figure>

This proliferation of research on curcumin has fueled its popularity as
a dietary supplement. Grand View Research estimated the global market
for curcumin as a pharmaceutical to be around [30
million](https://www.grandviewresearch.com/industry-analysis/turmeric-extract-curcumin-market)
USD in 2020. Manufacturers are [routinely scolded by the United States
Food and Drug
Administration](https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters)
for making false claims about the health effects of these supplements.

Curcumin is a valuable case study in how unimpeded fraud can distort an
entire research field to the detriment of genuine research. Despite
indications that Aggarwal's research on curcumin ought not to be
considered reliable, a majority of articles and an even greater majority
of NIH-funded studies about curcumin still cite Aggarwal's work. It
seems unlikely that this explosion in funding and research would have
materialized if Aggarwal had not engaged in large-scale research fraud.

Scientific fraud, especially at this scale, is alarming. However, there
is a common refrain that instances like this are an exceedingly rare,
insular threat and that any harm done to human knowledge by them will
inevitably be neutralized by science's remarkable tendency for
self-correction. Once the history books are written, these instances
will be little more than footnotes, parked between [the Bates
method](https://en.wikipedia.org/wiki/Bates_method) and
[orgone](https://en.wikipedia.org/wiki/Orgone).

However, self-correction has a high cost in the present: hundreds of
millions of taxpayer dollars, countless hours spent toiling by junior
scientists, thousands of laboratory animals sacrificed, thousands of
cancer patients enrolled in clinical trials for ineffective treatments,
and countless people who have eschewed expensive and invasive but
effective cancer treatment in favor of a store-bought spice, encouraged
by research steeped in lies.


A few months ago, I had the pleasure of giving a talk at Metascience
2023 in Washington D.C. about a strategy research paper mills can use to
thwart science integrity measures: journal hopping. You can find the
talk below:

<figure
class="wp-block-embed is-type-video is-provider-youtube wp-block-embed-youtube wp-embed-aspect-16-9 wp-has-aspect-ratio">
<div class="wp-block-embed__wrapper">
<div class="iframe">
<div id="player">

</div>
<div class="player-unavailable">
<h1 id="an-error-occurred." class="message">An error occurred.</h1>
<div class="submessage">
<a href="https://www.youtube.com/watch?v=OsacupPEj_Q"
target="_blank">Try watching this video on www.youtube.com</a>, or
enable JavaScript if it is disabled in your browser.
</div>
</div>
</div>
</div>
</figure>

If you would like to learn more about research paper mills, I suggest
starting with our [2022 review about paper mills in human gene
research](https://doi.org/10.1093/nar/gkac1139).
