In vivo genome-editing rescues damnatio memoriae in a mouse model of Titor Syndrome

by Andrea Kriz

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.

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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.

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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 D^2,3, Jin T^2,3, Fibrelli B^2,3, 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. 

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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.

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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.

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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.

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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.

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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.

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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.

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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.