Research Article:In vivo genome-editing
rescues damnatio memoriae in a mouse
model of Titor Syndrome
Mercer E, Hendigger S, Tobbe Q, Ikram R, Supebacker M, Voltz
E, Lemmer T, Musfar R, Olem TS, Yuma G, Lacroix K, Woldeman D1
1Department of
Biological Metaphysics, Harvard Medical School, Boston, Massachusetts 02115,
USA
2 May 2040
Abstract:
First documented in 2010 as the ‘Mandela Effect’, Titor
Syndrome (TS) has eluded rigorous study due to the wide radius of memory
alteration, or damnatio memoriae (d.m.),
which often characterizes its later stages. Here we circumvent these issues by
performing single cell RNA-sequencing on a range of biopsies collected from a still-living
24-year-old female patient of TS. We identify a highly replicable signature of
130 genes dysregulated across tissues. Genome-editing of these genes via the
CRISPR/Cas9 system was sufficient to ablate convulsions and, to a lesser
extent, social defects in mice exposed to Jacksonville soil samples previously
observed to trigger TS. Importantly, researchers retained memory of treated
mice, indicating that d.m. had also been successfully rescued. Future studies
are urgently needed to determine if this treatment regimen could apply to
humans as well.
#
Author Correction
22 May 2040
Due to the accelerated preparation of this manuscript,
Figure panels 4b and S4c were unintentionally duplicated. As the original film
Figure S4 had been assembled from could not be found, the experiment was
repeated, closely replicating the original results. The article has been
corrected in the online version.
#
Technical comment on “In vivo genome-editing
rescues damnatio memoriae in a mouse
model of Titor Syndrome”
Xu L1, Gao M1,
Ye X1, Wong J1, Hu D2,3, Jin T2,3,
Fibrelli B2,3, Xiaolong Y1
1Department of Basic
Medical Sciences, School of Medicine, Tsinghua University, Beijing, 100084,
China.
2Department of Neurobiological
Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts,
USA.
3Artificial
Intelligence and Transcriptomics Program, Broad Institute of MIT and Harvard,
Cambridge, Massachusetts, USA.
14 December 2040
Mercer et al. claimed that symptoms of Titor Syndrome
(TS), most notably damnatio memoriae (d.m.)
could be treated by editing 130 genes in adult mice. Three months of attempting
to replicate Mercer et al.’s results resulted in the recovery of six lab
notebooks, blacked out from cover to cover with permanent marker, along with
hundreds of unlabeled mouse carcasses, from a waste incinerator. The first
author, who security cameras recorded attempting to turn on the incinerator,
has no memory of the incident. Therefore, we are forced to conclude that the Mercer
Protocol does not, in fact, rescue d.m. in a mouse model of TS and, to the
contrary, has resulted in a spread of the syndrome among researchers attempting
to carry out the gene-editing regimen along with bystanders. We note that a
clinical trial conducted by the institution of Mercer et al. is currently
recruiting patients and urge caution in pursuing this treatment.
#
Response to technical
comment on “In
vivo genome-editing rescues damnatio
memoriae in a mouse model of Titor Syndrome”
Mercer et al.
14 December 2040
Xu et al. suggest that, due to their failure to
reproduce our data, that the editing of the gene signature described in our
original study does not alleviate Titor Syndrome (TS), and could conversely
lead to spread damnatio memoriae (d.m.).
We would like to caution Xu et al. in
turn that although involuntary expunging of data often accompanies d.m., it
cannot in itself be taken as evidence of d.m.—especially when factors such as
mental health could also play a role in influencing behavior of involved
researchers. In addition, although the memory of individuals associated with TS
patients is often altered as a result of d.m., TS has never been observed to
spread beyond the originally affected patient. Such fallacies are the basis of the
now-debunked Jacksonville hypothesis, which posits that the Floridian ghost
town in fact thrived until 2036, when it became the center of a Titor Syndrome
‘epidemic’ (see infographic: Using Guidepost Events to Disentangle False from
Altered Memories). We are also happy to report in a forthcoming publication
that the originally described TS patient has now been successfully cured with
the Mercer protocol. Although we agree that Xu et al. that caution is necessary,
we must be equally cautious of not depriving treatment to those in need.
#
Editorial expression
of concern:
6 January 2041
In the May 1 issue, this journal published the Article,
“In vivo genome-editing rescues damnatio memoriae in a mouse model of
Titor Syndrome.” Due to a power surge, the raw data for the Article was lost
from the GEO repository. The authors have since notified the journal that the
data had been inadvertently erased from their lab computers as well. Attempts
are currently being made to re-establish contact with the original patient, who
had been discharged from the hospital, for collection and sequencing of new
samples.
#
Author
correction:
12 March 2041
Since our original study, it has become clear that our
genome-editing protocol merely delays, rather than rescues Titor Syndrome and
its resulting damnatio memoriae (d.m.)1,
2. We also note that although 12 authors appeared on the original study,
only 4 authors could be found in this lab with memory of undertaking the
described research. In addition to having never worked in our department, the
only online record of 5 of the ‘missing authors’ are usernames on early-2000
era message boards. As fictionalization of previously existing entities, such
as the eponymous John Titor, is another anecdotally observed symptom of TS, we
cannot exclude the possibility that d.m. has begun to affect our environment as
well. We are currently working with independent labs across Europe, China, and
the U.S. to reproduce our results and generate an optimized protocol, to be
published as soon as possible.
1. Hart, J., et al. (2041). “Case 9-2041: A 24-Year-Old Missing Woman
with Radiodermatitis, Acute Psychosis and Retrograde Amnesia.” N Engl J Med 424(11):
941-948
A 24-year-old woman previously diagnosed with Titor
Syndrome and successfully treated using the Mercer Protocol reappeared in the
emergency department after being reported missing for two months. There were burns
on the face, arms and back. Although she claimed to have been wounded by
‘gunshots’, these were not consistent with injuries caused by modern firearms,
but instead with prolonged exposure to radioactivity. She additionally reported
hallucinations related to travel between dimensions and ‘collapsing timelines’.
2. Braun, A.C.,
et al. (2041). “Case 10-2041: Group Delusions Related
to a Discontinued Phase I Clinical Trial of the Mercer Protocol.” N Engl J Med
424(12): 1043-1053
All patients scored over 70 on the Mandela Effect Scale,
with 100 indicating full penetrance, most notably the erroneous memory of human
rights activist Mandela becoming president of South Africa rather than dying in
prison in the 1980s.
#
Addendum: Editorial expression of concern
27 April 2042
We previously issued an editorial expression of concern
for our previously published article, “In
vivo genome-editing rescues damnatio
memoriae in a mouse model of Titor Syndrome”. At this time, we are
additionally publishing the results of nine groups who have attempted to
replicate the results of Mercer et al.As
each of these groups has reported cases of damnatio
memoriae ranging from moderate to severe, we are cautioning the readership
against attempting to repeat the Mercer Protocol at this time. Authors E.
Mercer, D. Woldeman and S. Hendigger agree to this expression of concern, while
Q. Tobbe could not be reached.
#
Addendum: Addendum: Editorial expression of concern
30 June 2042
We alert the readership that the Article “In vivo genome-editing rescues damnatio memoriae in a mouse model of
Titor Syndrome” has been flagged, among 233 others, as containing possibly
fabricated data. The errors in this Article include the following:
Interactive Figure 2, allegedly
showing different chimeric mice in sociability cages, in fact shows the same
animal being introduced to the middle chamber three separate times, albeit with
strikingly different results.
Forensic analysis of the
immunoblot in Figure 3b indicated that the background signal on certain lanes
(7, 8, 9) to be too uniform to have been generated from an actual membrane.
The RNA-sequencing data in
Figure 4a could not have come from a human.
Author E. Mercer does not feel that this addendum is
appropriate at the time, maintaining that while the raw data from which the
disputed figures were generated, along with authors D. Woldeman and S.
Hendigger have been ‘lost’, she is attempting to ‘recover’ them. No other authors could be reached.
Corrected online
1 August 2042: We are aware that the spread of damnatio memoriae across the United
States may have impacted flagging of this study and others, and will strive to
take this into consideration in our subsequent investigations.
#
Retraction
25 November 2042
The U.S. Office of Integrity Research has advised retraction of “In vivo genome-editing rescues damnatio memoriae in a mouse model of Titor Syndrome” due to lack of evidence that any such study actually took place. We therefore retract the paper and advise the readership that results contained therein are not valid. None of the authors could be reached for comment. Upon inquiry they appear, along with their department, to be fictional entities. An exploration of the abandoned building in which the lab had been purportedly housed uncovered high levels of radiation, the charred body of a car determined, upon investigation, to be a late 1980s Honda Civic 4WD, and the remains of an IBM-5100 portable computer. We apologize to the scientific community for the damage caused.
~
Bio:
Andrea Kriz is a PhD student in Biological and Biomedical Sciences at Harvard. Her stories are upcoming in Ahoy Comics and have also appeared in Nature, Daily Science Fiction, and Tales to Terrify, among others.
Speculative engineering shakes things up in the ancient world, by Austin Scarberry.
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