The Suresh Linkage Complex is a group of genes essential for the manifestation and use of Evolved abilities. It is named for the scientist who discovered it in 2009, Mohinder Suresh.
Known to All
This information reflects the general status of research on SLC-E (Suresh Linkage Complex-Expressive) molecular biology — in other words, what anyone might uncover from literature searches in databases like PubMed or by following relevant scientific journals. Research that is proprietary, classified, or otherwise unpublished are not included here.
At present, two SLC genes have been conclusively confirmed, both encoding cell-surface proteins. Also of interest is an endogenous retrovirus whose activity appears to be both unique and universal to the SLC-E population, and that has been hypothesized to regulate SLC expression. Efforts are underway to identify other elements of what is referred to as the Suresh or SLC pathway: the molecular network that includes the SLC genes proper, every protein they directly interact with, and an indeterminate number of downstream effectors and upstream regulators. Understanding of this pathway remains at a very early stage, as SLC molecular biology appears to be intractable to many approaches that are standard tools of the field.
SLC Genes
Adynomine Receptor (ADYR)
ADYR encodes a cell-surface protein, the primary receptor of the Suresh pathway. It bears considerable similarity to the NMDA receptor, specifically the NR2B/GRIN2B subunit, but whether it also interacts with that receptor remains unknown. ADYR was initially identified in 2008 not from genetic research, but as a protein distinct to Evolved individuals that could be used in an antibody-based test. Its genetic sequence and genomic location were not confirmed until 2010; this roughly coincided with its identification as the receptor inhibited by adynomine, hence its name.
Prion-like Protein Mirage (PRNM)
PRNM was initially identified in 2011 by a landmark study that employed side-by-side algorithmic annotation of the SLC region and protein interaction studies using ADYR. It appears to have originated as a duplication of the prion protein PRNP. Interestingly, where PRNP is known to bind copper ions, PRNM has been shown to possess a distinct affinity for cobalt ions, suggesting that metal may play an important role in SLC-E neurobiology. PRNM also seems to be required for the cell-surface expression of ADYR; in its absence, ADYR cannot be detected on the outside of the cell.
HERV-K-SLC
This member of human endogenous retrovirus group K was identified by a late-2011 study that aimed to do for noncoding RNAs what the first public studies did for proteins: identify those specific to the SLC-E population. The researchers almost did not consider viral transcripts at all, but ultimately evaluated them because the SLC region contains extensive long terminal repeats — although so does some 40% of the entire genome. Since its discovery, proteins from HERV-K-SLC have been implicated as regulators of SLC genes, but evidence on this front is not entirely conclusive. Recently, viral overexpression has been hypothesized as the mechanism underlying adynomine-associated carcinogenesis.
Overview of SLC Studies
Genetic Research
Characterization of the molecular biology of the Evolved did not begin until after Senator Nathan Petrelli's announcement of their existence in February 2007, giving the lifework of Dr. Chandra Suresh and his book Activating Evolution new legitimacy, along with a great deal of attention in academic circles. It was from intensive evaluation of family pedigree data he'd assembled that the term 'Suresh Linkage Complex' was coined: a set of genes essential to Evolved abilities that are relatively close together on the same chromosome and tend to be inherited as a group (are 'linked'). This was hypothesized to explain why Evolved family members often, but not always, have related abilities. It was also generally accepted that these hypothetical genes needed to be co-regulated, and that they either are only expressed in Evolved individuals or serve other functions in the non-Evolved. However, the location of the SLC within the genome proved difficult to resolve by linkage studies, even using the sample bank Suresh had personally collected over decades.
With the passing of the Linderman Act in June 2007, it became essential to develop a means for reliably distinguishing Evolved from non-Evolved individuals. In the interest of obtaining immediately actionable results, these (mostly commercial) endeavors applied proteomic approaches to blood samples, eventually isolating a unique protein and developing an antibody that recognized it. The first test kits based on that antibody were released late in 2008.
Working backwards from the identified protein — later recognized as the adynomine receptor — researchers predicted the DNA sequence elements that should have created it and attempted to locate its gene in the human reference genome. As with linkage studies, homing in on the SLC region by this method proved to be not just difficult, but outright impossible. It wasn't until well into 2010 that researchers broadened their search scope and discovered that the encoding gene mapped to an unplaced scaffold: a genomic segment whose sequence is known, but whose chromosomal position has yet to be resolved. As most sequencing analysis disregards those problematic areas, no one searching for sequence elements had been looking in the right place.
The nature of the SLC region — the surrounding sequence is highly repetitive and difficult to analyze in many respects — lends itself to controversy over just how many actual genes it contains, and more concerning how many of those are truly part of the SLC. These questions had only begun to be addressed when the Second American Civil War all but halted scientific research in the US. Studies outside the US have predominantly focused on applied research, where they were funded at all, and thus added little to basic knowledge of SLC biology during that period. US-based research only picked back up as of around 2016, when federal science funding became more broadly available — and especially as SESA began offering small grants promoting open, transparent research with potential benefits for the SLC-E population. To this day, most scientific funding from any source remains small and short-term, but SLC-E research is nonetheless one of the hottest fields in genetics.
Animal Research
It remains an open question whether orthologs — equivalent genes inherited from a common ancestor — of SLC genes exist in any other mammals. To date, none have been identified, but most non-human species also have not been sequenced to the same degree of completion as the human genome — and even in the human genome, the SLC region is unplaced. The repetitive sequence that complicates its mapping in humans may also confound its uncovering in other species. The prevailing hypothesis is that no equivalent exists in any other species — that the SLC region is unique to humans — but this negative has yet to be proven beyond reasonable doubt.
Using transgenic animals for the study of SLC genes is another tactic that has largely met with failure. Technically, "knock-in" experiments that insert SLC genes into non-human genomes are successful: the gene sequences can be inserted, and — particularly if driven by a different promoter — the proteins can be expressed. Their failure is that few to no interesting results are observed: the inserted proteins do not spontaneously interact with anything else in the cell, much less reiterate the Suresh pathway entire. This is generally chalked up to there being a great deal more to uncover about the pathway, particularly its downstream components.
All told, animal research concerning the SLC is widely held to be a non-starter and is nearly impossible to acquire funding for. The greatest use for animal studies is in testing the general safety of prospective pharmaceuticals.
Cell Research
"Knock-in" studies using SLC-N cells largely have the same problems as do animal studies, except that knock-in of HERV-K-SLC appears to activate their native SLC genes. Unfortunately, it also turns the cells cancerous, conferring on them very high proliferation rates and extreme genetic instability. HERV-K-activated SLC-N cells have about the same degree of relationship to normal SLC-E biology as HeLa cells do to normal human biology: very, very little. Their high expression levels and resilient growth are positives for protein interaction studies and drug screening, but these converted cells are invasive and likely to contaminate other cell cultures, they vary widely in karyotype and in some respects phenotype, and it is never certain any results obtained from them will translate back to applications in more normal cells.
Accordingly, the vast majority of SLC studies use either primary or immortalized human cells collected from SLC-E individuals. Between the small proportion of the population that is SLC-E and the systemic prejudice experienced by many either recently (in the US) or currently (in many other nations), very few such samples have been collected. The cell lines that are available are either B-cells or fibroblasts, whose expression of SLC cell-surface proteins is very low; furthermore, it is suspected that downstream effectors may not be expressed at all in these cell types, severely limiting their applicability in identifying the rest of the Suresh pathway. Neural cells are expected to be better-suited, but have not been studied because those samples are essentially impossible to obtain, and to date no stem cell line from which they can be derived has been established, whether embryonic or induced pluripotent.
Out of necessity, it is assumed that research done in these cells translates to neural cells, and furthermore to all types of SLC-E abilities beyond the handful represented by existing lines. This also has yet to be confirmed beyond reasonable doubt.
Drug Research
TBD: general overview of drug research
Somewhat after the fact, the internal stem -dy- has been formalized by the World Health Organization to identify SLC-related pharmaceuticals in the International Nonproprietary Name system.
Adynomine and Adynotyline
Adynomine is a competitive inhibitor of ADYR whose binding prevents activation of the Suresh pathway and therefore any use of SLC-E abilities. Adynotyline, brand name Negoxan, is a derivative of adynomine I suitable for pill-based delivery. It is known from evidence and testimony of the Albany Trials that adynomine was developed by the Company and later improved upon by the Commonwealth Institute; however, the particulars of the discovery and production of its various versions are proprietary information that has not been released to the general scientific community. Both drugs received FDA approval in spring 2010, after which adynotyline became available by prescription and was widely used under the policies of the Petrelli and Mitchell Administrations. Use of either drug is associated with substantially increased cancer risk, which also came to light in the Albany Trials and led to their mass production ceasing as of 2014.
Both adynomine I and adynotyline remain invaluable to those studying SLC-E pharmacobiology in general and those attempting to identify other potential negation drugs. They remain in small-scale production, and most major chemical suppliers are able to supply small amounts to vetted customers. In 2015, after the drugs were withdrawn from the pharmaceutical market, an independent researcher published the chemical structures of adynomine I and adynotyline based on data that had implicitly been generated well prior. In 2017, a cell-based study was published showing that adynomine treatment substantially increases expression of HERV-K-SLC, potentially explaining its association with cancer. Similar results were observed for adynotyline.
Zodytrin
Zodytrin is an alternate negation drug approved by the European Medicines Agency in 2014, and by the FDA in mid-2017. Chemically related to phenylpropylaminopentane, it operates by a radically different mechanism, causing a reduction in the release of monoamine neurotransmitters. This effect is not specific to the Suresh molecular pathway, however, leading to potential for neurological side effects. Cell studies support that zodytrin does not have the cancer risks associated with adynomine, and indeed does not directly interact with ADYR or PRNM nor affect HERV-K-SLC expression. To what extent chronic zodytrin use impacts or does not impact risk for psychiatric disorders such as anxiety or depression will remain a subject of study for decades to come.
Neither phenylpropylaminopentane, substituted phenethylamines in general, nor any other drugs affecting monoamine neurotransmitters have so far been identified to have any distinct impact on SLC-E neurobiology.
Refrain
Refrain is a highly addictive hallucinogen only effective upon SLC-E individuals. Although a controlled substance, small amounts may be purchased through major chemical supply companies for research use. In vitro studies have shown Refrain to interact with ADYR and cause a conformational change in the receptor; this is presumed to activate molecular pathways associated with memory, resulting in the drug's characteristic hallucinations.
Amphodynamine
Amphodynamine is half myth, half holy grail to most SLC researchers: it's known to have existed, but nothing about its structure and pharmacodynamics have been released to the greater research community. Amphodynamine is presumed to have been an ADYR agonist, and there is some speculation as to whether its chronic use would have carcinogenic effects similar to adynomine, but its mechanism of action cannot now be independently elucidated. Although produced in quantity by the Commonwealth Institute, it was never approved by the FDA and thus never sold widely nor through standard market channels. Furthermore, it was only available for a two-year period, 2010-2011, and any remaining in storage has long since degraded. It is therefore not available for present study, and development of alternative amplification drugs is proceeding from square one.
Virus Research
HERV-K-SLC
Other HERV-K family members have been independently implicated in both cancer and neurodegenerative diseases in the general population.
Shanti Virus
Pending
Advent Virus
Pending
H5N10 Influenza
Pending
Known to Some
Known to Few
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Related Storylines:
(Book 1, Volume 6) ...And Then There Was Light
(Book 2, Volume 1) Dark Below
(Book 2, Volume 2) The Dragon