- Birth name
Constance Olivia Muren
- Known for
Discovering Cariappa-Muren disease (CMD)
Connie Muren (born September 16th 1992 - disappeared March 4th 2040, died October 6th 2049) was a British-born German neurologist, activist, and author whose celebrated work on prion diseases led her to be instrumental in the discovery of Cariappa-Muren disease (CMD) in 2039.
Born in Nottingham, Muren moved to Germany in 2017 and became a research associate at the University of Düsseldorf, where she developed a new diagnosis method and immunotherapeutic treatment for both Creutzfeldt-Jakob disease (CJD) and its acquired variant, winning her team the 2034 Nobel Prize in Medicine.
In 2038, Muren was contacted by Sunil Cariappa about a novel prion disease spread through Lassgard tuna, leading to the shared discovery of CMD. Under the auspices of the World Health Organisation (WHO), Muren became the public face of the international effort to stop the CMD pandemic.
In 2040, Muren went missing while travelling to a conference in Berlin. Despite several arrests and public appeals, Muren’s disappearance has remained unsolved, though many believe it was related to her activism. The case was closed in April 2040 with all charges dropped, and Muren was declared dead in absentia by her family in 2047.
In 2049, Muren’s body was recovered in Zadar, Croatia, with Volya Kirienko identified as her killer and Sofia Peña in custody as a person of interest in Muren’s death and recent whereabouts. Interpol has reopened its investigation into Muren’s disappearance with the intent to prosecute it as a murder case.
Table of contents
Early life and education
Connie Muren was born Constance Olivia Muren on September 16th 1992 in Nottingham, Great Britain. Her mother was Hannah Tildesley, a sales manager, and her father was Richard Muren, an architect who died from an undiagnosed heart condition three months after she was born. In 1995, Tildesley married geneticist Anil Jagtap, whose influence and encouragement Muren credits with inspiring her love of science.  The family moved to London City in 2006, where Muren qualified for her medical degree at UCLC Medical School in 2015 and earned a Master of Science in Clinical Neuroscience in 2016.
In 2016, Muren campaigned for the Remain camp of the Brexit referendum. When the Leave vote won out and negotiations regarding the withdrawal of the United Kingdom (UK) from the European Union (EU) went underway, Muren joined Open Britain, focusing her efforts on highlighting “the unabashed actions of successive Conservative governments to privatise the National Health Service (NHS) by systematically stripping it of resources and staff under the guise of austerity and anti-immigration policies.”
On April 16th 2017, Muren’s stepfather was the victim of a racist assault while he was walking to their home in West Green, which resulted in a punctured dura mater and a paralysed right arm. He urged Tildesley to leave the UK and they emigrated to Germany on a residence permit, settling in Düsseldorf where Muren applied for a research position at the University of Düsseldorf. She was naturalised as a German citizen in 2023.
Muren continued her activism in Germany, taking part in pro-immigration rallies and offering treatment to migrants who had sustained injuries during demonstrations and police raids. On several occasions in 2017 and 2018, Muren travelled to Greece, where she offered medical aid in the refugee encampments and helped migrants cross the border with Macedonia. After Muren and other volunteers were detained by Greek police in November 2018, she reported that she had been beaten during her arrest. Muren has talked openly about being diagnosed with posttraumatic stress disorder (PTSD) as a result of the event.
Research and career
Over the course of her career, Muren published over 150 articles and edited four books. She was also a sought-after peer reviewer. From 2018 to 2022, Muren worked at the University of Düsseldorf on replicating research on a possible new treatment for Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) involving targeted monoclonal antibodies.  Muren’s work eventually led to a breakthrough in long-term neuroprotection during preclinical trials with transgenic mice.
In 2023, Muren was offered to lead her own research group at the university’s Institute of Neuroscience. She started a clinical trial for the antibody treatment, setting up a long-term study over the next decade after initial delays due to difficulties in finding suitable candidates. There continued to be a practical problem with the effective diagnosis of prion diseases in the presymptomatic stage, with Muren’s team ultimately making use of a combination of protein misfolding cyclic amplification (PMCA) and surround optical-fiber immunoassay (SOFIA) to detect infectious prions in blood plasma.  While this method demonstrated a high degree of accuracy, it was considered time-consuming and cumbersome.
During the clinical trial, Muren noticed that increased media reports of the second wave of vCJD in the UK and Europe resulted in people requesting medical screenings in numbers greater than the maximum of 250 additional cases projected by epidemiological models.  In an effort to devise a more efficient diagnostic tool for CJD and vCJD, Muren reached out to Endoptic in 2030, after having learned of the company’s research into AlphaFold-enabled protein targeting for implantable multielectrode arrays (MEAs).  Muren suggested that the MEA bioreactors for the synthesis and expression of cell surface proteins could be used as chemical sensors for the early detection of infectious prions in brain tissue, even when present at extremely low concentrations.
When human trials for Endoptic’s MEA technology started in 2032, Muren’s team worked closely with the company’s research and technological development (RTD) to implement her design for the sensors, leading to a functioning prototype in 2033. Spencer Hagen praised Endoptic’s collaboration with Muren’s team, calling her “an elegant nanoengineer in her own right.” When neural colloids were approved as implantable medical devices (IMDs) in 2038, Muren was unable to release her design for the diagnostic modifications under an open-source license, which Hagen attributed to its use of technology proprietary to Endoptic.
After the completion of its clinical trial in 2034, the antibody treatment was officially approved as a neuroprotector against CJD and vCJD, and made available as a prescription drug under the name daunocycline. On October 3rd 2034, Muren’s research group was awarded the Nobel Prize in Medicine “for its discoveries concerning a novel diagnosis and treatment of Creutzfeldt-Jakob disease and its variant strain.”  Muren initially considered refusing the award because of her disregard for official honours and recent scandals surrounding several Nobel Committees, but ultimately decided to accept, citing Maryam Mirzakhani as an inspiration. 
In 2035, Muren accepted a position as Professor of Translational Neuroscience at the University of Düsseldorf. While her research group at the university’s Institute of Neuroscience was headed by Gerhard Kobl-Thissen after her departure, Muren continued to work with him on applying her findings to other neurodegenerative disorders that act on the prion protein.
Discovery of CMD
In October 2038, Muren was asked to consult on the clinical case of WedgeWoo, an atypical patient of vCJD in Tokyo, Japan. Though initially reluctant to travel to Japan for a medical appraisal, Muren accepted when the patient’s father, Ryota Hasegawa, privately offered to “pay a hefty sum to bring in a foremost authority on prion diseases,” with Muren requesting that he make a donation to a refugee charity instead.
Upon arriving in Tokyo, Muren was immediately puzzled by WedgeWoo’s case. Although a diagnostic colloid had indicated the presence of infectious aggregates that closely matched the molecular structure of vCJD prions, WedgeWoo’s young age was inconsistent with the disease’s long incubation period and repeated doses of daunocycline had no apparent effect. When magnetic resonance imaging (MRI) of WedgeWoo’s brain revealed a lack of spongiosis, Muren initially assumed that WedgeWoo was suffering from a rare case of sporadic fatal insomnia (sFI), which similarly shows no brain spongiosis and acts on the same prion protein that is affected by vCJD.
This was ruled out when the exponential growth rate of the prion aggregates indicated that WedgeWoo’s symptomatic period would take approximately three months before onset of death, whereas sFI patients have an average survival time of eighteen months after becoming symptomatic. In addition, no insomnia was described and genetic testing revealed no markers for the development of sFI or any other known inherited prion diseases. When she returned to Düsseldorf, Muren co-authored an article with Kobl-Thissen and described WedgeWoo’s condition as a novel sporadic prion mutation with rapid progression. 
In November 2038, Muren was contacted by Sunil Cariappa while she was anticipating the results of further genetic tests and a post-mortem examination following WedgeWoo’s death. Cariappa informed her of a possible outbreak of feline spongiform encephalopathy (FSE) in domestic cats that he had documented after his own cat became infected. Necropsies of the affected cats had shown an anomalous lack of spongiosis, which had brought Cariappa to Muren’s article on WedgeWoo’s case because it mentioned the same anomaly.
Additionally, Cariappa had determined that the common link between all FSE-affected cats was their diet, which included Lassgard tuna. While Muren had found no mention of tuna in WedgeWoo’s dietary records, she did uncover a 2034 livestream sponsored by Lassgard Bioteknik, during which WedgeWoo had consumed large amounts of sushi made with Lassgard tuna, which could explain the accelerated neurodegeneration in his case. A later investigation indicated that William Lassgard had taken steps to doctor WedgeWoo’s records and minimise any connection to Lassgard tuna.
Muren asked Kobl-Thissen to take over her classes and invited Cariappa to join her in Düsseldorf so they could confirm their find before raising any alarm. Cariappa suggested they contact Lassgard Bioteknik to request samples of their tuna stock, but Muren anticipated that the company would stonewall or close ranks. She reached out to Hasegawa and told him that, with his financial backing and a guarantee of secrecy, she could confirm a promising theory that might shed light on both WedgeWoo’s death and the suspected existence of a more widespread foodborne outbreak. Hasegawa agreed and arranged for Lassgard tuna from suppliers in East Asia, Europe, Africa, and the United States to be shipped to Düsseldorf.
With the cooperation of the university and members of her research group, Muren analysed brain samples of the delivered tuna and found that a significant proportion of the samples showed aggregates of dystrophic neurites, disorganised dendrites, and extensive deconstruction of microfilaments within the axons. These findings were consistent with advanced amyloidosis, which was most likely the result of a prion infection. Although there was some debate regarding its origin, Muren and Cariappa jointly described the infection as piscine transmissible amyloidotic encephalopathy (PTAE).
On January 13th 2039, Muren sent a report on PTAE to the Global Foodborne Infections Network (GFN) of the World Health Organisation (WHO). She had asked to be involved in any decision-making process prompted by the report, but GFN officials nonetheless reacted by contacting Lassgard Bioteknik about a possible contaminant in its tuna stock without her knowledge. Muren had criticised this move, as it signalled the start of the company’s harassment and misinformation campaign against the WHO. Consequently, the only response to the report was a notice against feeding tuna to pets in the WHO’s monthly Bulletin, with no mention made of Lassgard Bioteknik or the suspected biorisk to people. 
Muren publicly denounced the WHO for acquiescing to pressure from Lassgard Bioteknik, which resulted in the GFN assembling an Outbreak Control Team (OCT) in February 2039. Muren later mentioned that she considered this to be another way for the WHO to avoid having to take any proportional action, as an OCT is considerably limited in scope when compared to an official WHO investigation. The OCT was composed of only four members (Muren, Cariappa, and two food safety officers from the GFN), enjoyed little to no logistical support, and had to work out of facilities provided by the University of Düsseldorf.
On February 18th 2039, legal action was brought against the university when Lassgard Bioteknik uncovered the agreement Muren had made with Hasegawa, which the company’s lawyers cited as grounds for her immediate dismissal. The university’s president, Sam Humleker, came out in support of Muren, who was reappointed as head of her former research group so the OCT could benefit from more resources. Muren proposed a study of PTAE’s transmission potential to humans, which involved the passage of infected brain material from Lassgard tuna to transgenic mice. This study was completed in July 2039 and conclusively demonstrated that PTAE could result in a clinical disease in humans with an infection vector analogous to that between bovine spongiform encephalopathy (BSE) and vCJD.
Muren described the newly discovered disease as acquired prionopathic neurodegeneration syndrome (APNS) and prepared a report for the WHO, which had been suffering a mounting image crisis due to repeated attacks from Lassgard Bioteknik and other Big Fish companies.  On July 20th 2039, the WHO’s Emergency Committee declared a Public Health Emergency of International Concern (PHEIC) and widened the OCT’s scope. This involved coordinating with epidemiologists and laboratory specialists from the GFN, the Public Health Agency of Canada (PHAC), the Swedish National Food Agency (NFA), and the Food Safety Bureau of the Japanese Ministry of Health, Labour, and Welfare, with Muren appointed as chair.
Leadership of OCT
Muren felt uncomfortable with the increased visibility that accompanied her new role, which was magnified when APNS was described and issued to the media as Cariappa-Muren disease (CMD). Muren expressed her dismay at being overruled on the medical name she had chosen, with health communicators in the OCT believing that the eponymous name was easier to grasp, avoided confusion with PTAE, and put a human face on the team’s efforts. Muren dismissed this as “a branding exercise,” though later stated that she understood the decision.
Lassgard Bioteknik often seized on Muren’s attitude to claim there was a lack of scientific consensus in the OCT, with “premature and unfair” aim being taken at Lassgard tuna. Though some internal debate regarding the specific origin of PTAE remained, there was no doubt that Lassgard tuna was the primary method by which it was spreading to humans.
Muren’s working theory on PTAE’s origin was based on a 2009 research study, which had demonstrated that fish infected with BSE could develop a neurodegenerative amyloidosis that was largely consistent with PTAE.  As such, Muren believed PTAE was a variant strain of BSE introduced to Lassgard tuna via the fish meal used during their farming cycle. She was unable to confirm this theory, as Lassgard Bioteknik lawyers were actively fighting all attempts to subpoena the formula for this feed. In addition, the WHO’s campaign for a preventive ban of Lassgard tuna was met with little response from national food agencies due to lobbying efforts from the Aquaculture Advisory Council (AAC).
In October 2039, Muren was contacted by Anse Daems on behalf of World News Wire (WNW), which was working with the International Consortium of Investigative Journalists (ICIJ) to review a data cache of documents and correspondence Daems had received from a source inside Lassgard Bioteknik. Muren coordinated with the GFN and the ICIJ to flag all files relevant to the farming process of Lassgard tuna and make them available to the OCT and fifteen other laboratories. The files revealed that Lassgard Bioteknik had been using waste material of bovine origin to feed its tuna stock, which corroborated Muren’s theory regarding PTAE’s origin.
Between October 10th and 19th 2039, Muren worked with Daems and WNW on editing and vetting a series of articles that would uncover Lassgard Bioteknik’s malpractice. WNW began running the articles on October 23rd 2039, which resulted in the WHO declaring CMD a pandemic and issuing a global alert on October 25th 2039. This granted Muren international media attention akin to celebrity status, which she described as intense.
In December 2039, Zhupao announced a partnership with the WHO to manufacture and supply diagnostic colloids for the WHO’s contact tracing efforts to contain the CMD pandemic. Although Muren publicly endorsed the WHO strategy, she took aim at Zhupao for its patent enforcement on colloid technology, arguing that the company was “appropriating and monopolising” her diagnostic modifications for the early detection of prions in brain tissue. Following a public backlash, Muren delegated her duties as OCT chair and returned to the University of Düsseldorf so she could further her analysis of CMD and PTAE. Her work ultimately laid the foundation for the WHO’s official report on the CMD pandemic, which was released on April 19th 2040 when the pandemic was declared contained.
Refusing to Fold
In November 2039, Daems approached Muren with the idea to expand the interviews they had conducted for the WNW articles into a book. Muren agreed because, while she was not interested in her story being told by the WHO to rehabilitate the organisation’s image, she did trust Daems to be truthful in providing a counternarrative to the misinformation that persisted around her role in identifying CMD. The book, which details Muren’s life as seen through a frame story of her work on CMD, was completed two months later and published on February 7th 2040 under the title Refusing to Fold. It became an unexpected bestseller, with an estimated nine million copies sold in 132 languages.
In February 2040, Muren joined Daems on a digital book tour. When appearing on a livestream for the Lahore Literary Festival on February 25th 2040, Muren was asked how she felt about “having cured CMD with colloids.” In her answer, Muren lamented this misconception “being actively encouraged everywhere” and took aim at China’s announcement of mìngyùn and its integration of IMDs, which she condemned as “a way to turn temporary health measures into permanent fixtures of the surveillance state.”
A clip of Muren’s answer went viral following the livestream, amassing over 120 million views in twelve hours. Muren’s perceived criticism of mìngyùn ended up stalling talks between the WHO and the Chinese Communist Party (CCP) to allow the WHO to assess the CMD pandemic in mainland China. Muren was set to travel to Beijing alongside then-WHO Director-General Yang Jinglei so they could coordinate with the National Health Commission (NHC), but the video’s popularity caused the CCP to withdraw Muren’s invitation.
On February 27th 2040, Muren cut short her participation in the book tour and issued a statement, explaining her concerns that the CCP was extending her an invitation for the sole purpose of legitimising the creation of mìngyùn. While Muren had discussed these and other concerns in private, she was under pressure from the WHO to refrain from voicing them in public, leading her to conclude that the WHO was similarly interested only in her name recognition. Muren also said that she was suffering from a burnout as a result of Cariappa’s dismissal from the OCT on January 27th 2040, and how she was forced to take on his responsibilities.
On March 4th 2040, Muren was scheduled to deliver the opening keynote at the annual Democracy in Europe Movement (DiEM) conference in Berlin. The theme of that year’s event was the threat of the neurocarceral state, and Muren’s public stance on mìngyùn had prompted the organisers to ask her if she was willing to adapt her comments for the keynote.
Muren was booked on a ICE train from Düsseldorf to Berlin, which she boarded four minutes prior to its departure at 09:52 CET. When the train arrived in Berlin at 13:34 CET, she was no longer on it. The driver who had been arranged to collect her from the Berlin Hauptbahnhof waited for half an hour before reporting her absence to DiEM’s event manager, who contacted the Berlin police that evening. An official investigation into Muren’s whereabouts was started on March 5th 2040 when Düsseldorf police found that she was not in her apartment, and all activity on her mobile phone and social media profiles had ceased after she boarded the train.
Analysis of video surveillance inside the train showed Muren’s assigned seat as empty after the intermediate stop in Bochum, though she was not seen disembarking there or at any of the other stops. All passengers on the train were summoned for questioning, but none recalled any unusual activity or having taken specific notice of Muren. When the media picked up on her disappearance, an internet campaign under the tag FindConnie led to rampant speculation and countless unconfirmed sightings in multiple EU countries. Cariappa, who was identified as one of the last persons to speak to Muren, launched a personal appeal, offering crowdfunded rewards for any information that would lead to a break in the case.
On March 9th 2040, three Chinese nationals who were on Muren’s train claimed that they had been held for questioning much longer than other passengers, which led to rumours that Muren had been kidnapped or even murdered by agents operating under orders from China in retaliation for her critical comments. CCP officials issued strong denials of any involvement, and German police stated that foul play was only one of the avenues being pursued.
Interpol took over the investigation on March 13th 2040 and fielded three detectives to coordinate with German police. After the international search effort was called off with no compelling leads or results on April 15th 2040, Interpol ruled Muren’s case as either an accident or a voluntary disappearance, including a possible suicide. All charges made during the investigation were dropped, though FindConnie stayed active until 2042 and maintained that the CCP was responsible or at least involved. Various conspiracy theories have surfaced around Muren’s disappearance, with the prevailing impression that she had discovered “some disturbing secret” about CMD and was silenced for planning to reveal it at the DiEM event.
In April 2040, Daems expressed her dissatisfaction with the Interpol investigation, calling it “rushed” and claiming that Muren’s disappearance had been maliciously orchestrated as a result of her continued activism, though she did concede that a voluntary disappearance was also a possibility. When Daems was asked to adapt Refusing to Fold into Muren in 2042, an early draft of her screenplay included a reveal that would have implicated Zhupao in Muren’s disappearance. Later rewrites excised this part of the screenplay.
Since Muren’s disappearance occurred in circumstances that were not dangerous to her life and her death was uncertain, there was a seven-year waiting period before she could be declared legally dead. This request was lodged and approved by Muren’s family on March 4th 2047.
On October 6th 2049, Sofia Peña issued a livestream from an undisclosed location in Zadar, Croatia, showing that Muren had been murdered by a Russian man identified as Volya Kirienko, and that Peña had managed to kill Kirienko in self-defence. Peña provided no explanation for her presence in Croatia or connection with Muren, mentioning only that Muren’s death, as well as her 2040 disappearance, were part of “an ongoing cover-up.” Local authorities have recovered Muren’s body from the scene and confirmed Peña’s account of the event. On October 9th 2049, a forensic investigation indicated that Deena Kim was also present at the scene of Muren’s death.
Interpol has reopened its investigation into Muren’s disappearance with the intent to coordinate it as a murder case in cooperation with Canadian, Croatian, Spanish, and Russian authorities. On October 8th 2049, an Interpol representative indicated that Kirienko travelled from the Pokrov complex in Innopolis, where he was last seen on September 17th 2049, to Zadar, where he arrived on October 5th 2049. It is believed that he travelled alongside a second individual, possibly Peña or Muren. 
All through her life, Muren remained close to her parents and her half-brother, political philosopher Ekram Jagtap (born 1996). Muren considered Jagtap to be her father, never referring to him as her stepfather and stating that she “[celebrates] him with the life I’m living, and Richard with the name I’m attaching it to.” 
Muren was notoriously private about her personal life. When Muren and Cariappa became well-known after their shared discovery of CMD, rumours of a romanctic involvement between them began to surface. Where Cariappa maintained that they had become no more than friends, Muren never confirmed or denied the rumours, stating that “to address these questions would imply that it was all right to ask them in the first place.”
- Daems, A. (February 2040). “Refusing to Fold.” Standaard Uitgeverij. ↩ ↩ ↩
- White, A; Evener, P; Tayebi, M et al. (March 2003). “Monoclonal antibodies inhibit prion replication and delay the development of prion disease.” Nature. ↩
- Paramithiotis, E; Pinard, M; Lawton, T et al. (July 2003). “A prion protein epitope selective for the pathologically misfolded conformation.” Nature Medicine. ↩
- Rubenstein, R; Chang, B; Gray, P et al. (July 2010). “A novel method for preclinical detection of PrPSc in blood.” Journal of General Virology. ↩
- Boffey, D. (June 2021). “EU to lift its ban on feeding animal remains to domestic livestock.” The Guardian. ↩
- Muren, C. (February 2023). “Overall incidence of variant Creutzfeldt-Jakob disease expected to double after second wave of cases.” News Medical. ↩
- Hagen, S; Gao, K; Lundeen, J et al. (May 2030). “A Non-Invasive Delivery Method for Intracerebral Imaging and Stimulation Electrodes Using Protein Synthesis Pseudocell Bilayers.” Science Translational Medicine. ↩
- Muren, C; Hagen, S; Gao, K et al. (November 2033). “Electrode implant-based ultra-sensitive array for PrP detection in brain tissue.” Nature Nanotechnology. ↩
- Nobel Foundation. (October 2034). “The Nobel Prize in Physiology or Medicine 2034.” nobelprize.org. ↩
- Muren, C; Kobl-Thissen, G; Matthes, B et al. (November 2038). “A Novel Type 5 Sporadic Prion Mutation in Humans.” German Medical Journal. ↩
- World Health Organisation. (January 2039). “Increased cat mortality linked to tuna diets.” Bulletin of the World Health Organisation. ↩
- Cariappa, S; Muren, C. (July 2039). “Acquired Prionopathic Neurodegeneration Syndrome (APNS): Pathology, Transmission, and Epidemiology.” Bulletin of the World Health Organisation. ↩
- Salta, E; Panagiotidis, C; Konstantinos, E et al. (July 2009). “Evaluation of the Possible Transmission of BSE and Scrapie to Gilthead Sea Bream (Sparus aurata).” PLOS Biology. ↩
- Bauer, H. (October 2049). “Interpol reopens investigation into 2040 disappearance of Connie Muren.” Die Welt. ↩