UNSC Marine Expeditionary Reconnaissance

"Les peuples comme les astres ont le droit d’éclipse. Et tout est bien, pourvu que la lumière revienne et que l’éclipse ne dégénère pas en nuit."

- Les Misérables (1862), Myrmidon Program motto

The Myrmidon Detachment, formally known as SPARTAN Detachment IV, was an advanced special operations force operated by the UNSC Office of Naval Intelligence and the UNSC Special Operations Command.

Instigated in 2578, the Myrmidon initiative was the "second epoch" of the SPARTAN Program, integrating novel biological augmentations, warfighting technologies, and combat philosophies to create futuristic special forces that fulfilled the UNSC's requirement for advanced special forces to enable mankind's survival in an evolving and demanding galaxy.

The Myrmidons would partake in some of the climatic events of UNSC history, notably participating in the Midgard Campaign, the Beyond Veil's Azure Crisis, and the Dashan Campaign.

Overview
The Myrmidon Detachment was a battalion-scale joint special warfare unit operated by the UNSC Office of Naval Intelligence and the UNSC Special Operations Command.

It was centered around the "Myrmidons", fourth-generation SPARTAN child soldiers that represented the futuristic iterations of their predecessors, the SPARTAN-Is, the SPARTAN-IIs, and the SPARTAN-IIIs of the Human-Covenant War Era. The Myrmidons were the second iteration of the SPARTAN paradigm, the epitome of mankind's technologies and strategic doctrines in the Post-War Era.

The Myrmidon initiative drew from nearly one century of SPARTAN warfare and lessons learned from all three previous SPARTAN battalions. However, because the conceptual advances and core values of the fourth-generation Myrmidons were so striking different from the preceding three SPARTAN programs, instead of merely being labeled "SPARTAN-IVs", the Office of Naval Intelligence would name these fourth-generation soldiers as "Myrmidons", in honor of the Myrmidons of Greek mythology, another Greek warfighting tribe similar to the Spartans in ancient times.

Although the Myrmidon Detachment was centered upon these futuristic child soldiers, the successors to the prior SPARTANs, the detachment as a whole was a combined-arms unit, integrating forces from all services of the UNSC armed forces. The entire formation, on the battalion scale, was a fully independent special warfare unit that was a three-star command, directed by a Vice Admiral of the UNSC Navy.

Formally known as "SPARTAN Detachment IV", the Myrmidon Detachment was officially subordinated under the UNSC Naval Special Warfare Command (NAVSPECWARCOM) and the UNSC Progressive Warfare Command (PROGWARCOM). The detachment was a member of UNSC Special Warfare Group SPARTAN, reflecting the heritage of the Myrmidons from their ancestral SPARTAN precedessors.

Casus genesis
The causation of the formation of the Myrmidons, their casus genesis, lay simply in the state of galactic affairs.

At the time of the nucleation and formation of the Myrmidons, it was the late 2570s — in the nearly three decades that had passed since 2552 and the closure of the Human-Covenant War, the state of UNSC and mankind had substantially changed after the Great War. Although the UNSC's military forces would continue to resume their force projection during the Vector Era (2560s—2570s), no longer were galactic affairs dependent on military strength.

By the 2570s, the truce between the UNSC and the reformed Covenant was strong, and the two galactic superpowers were bound together by cords of fealty, with strong political and commercial collaboration between the two massive governments. The threat to the UNSC was no longer posed by the Covenant; it was now internal, with domestic threats at home consisting of organized rebel movements and freelancer pirates and mercenaries operating on the Outer Rim.

Kimberly Ivy Blackburn's actions during the Vector Era as an augmented ONI field operative had demonstrated that small, highly-trained, and augmented special forces teams were an ideal solution to the domestic threats that plagued the UNSC and the Covenant in the 2570s. The massive armies of the UNSC Marine Corps and the UNSC Army were simply unequipped to fight intense guerilla wars against rebels and insurgents. Instead, UNSC special forces, highly-trained operatives, would be required for these elite counterinsurgency and counterterrorism activities.

Organization
The Myrmidon Program has a highly atypical command structure and internal organization. One of the major design philosophies of the Myrmidons was counterterrorism; the usage of a small number of highly-trained elite light infantry for highly-intensive counterterror and counterinsurgency operations.

Thus, the Myrmidon Program as of 2590 maintained only one company of infantry, numbering approximately one hundred strong. While this was an extremely small number of operators for any conventional special forces group, it was in accordance with the UNSC's need for a covert and specialized counterterrorism task force.

The ideation of the Myrmidons began with Kawika Son and Beah Schore, who both drew heavily from the success of Kimberly Ivy Blackburn, who indeed served as the proof of concept for the Myrmidon Program. Dr. Schore would only participate in the planning and initiation of the Myrmidons, his lack of military experience and his pacifistic ideals making him unable to participate in the active military mobilization of the Myrmidons. Son would be heavily involved in the creation, training, and the mobilization of the Myrmidons; this would earn him a senior position within the Myrmidon command structure.

Command Detachment
The position of Senior Commander, Myrmidon Detachment was traditionally held by a three-star Vice Admiral ( O-9 ). The detachment's senior commander was responsible for the training, oversight, direction, and operation of the entire Myrmidon unit as a whole, including its command, mobility, and support elements, and would be a member of the Headquarters & Headquarters Company (HHC) of the Myrmidons. The remainder of the HHC section was primarily comprised with the primary staff officers and their staffs, along with the staff officers of the support and auxiliary elements.

The first commander of the Myrmidon Detachment was Vice Admiral Kawika Son, Commander-in-Chief, UNSC Naval Special Warfare Command and a flag officer of the UNSC Navy. Son would begin his tenure as the Myrmidon unit's commander in 2578 as a two-star Rear Admiral, and would relinquish his command in 2600, several years after the closure of the devastating Beyond Veil's Azure crisis.

Mobility Detachment
The actual Myrmidon infantry company proper, known as the "mobility detachment", was approximately one hundred Myrmidons strong, and was responsible for prosecution of the unit's special warfare missions in the field.

The mobility detachment would be commanded by a Navy Captain ( CAPT, O-6 ), the company commander, and a Master Chief Petty Officer ( MCPO, E-9 ), who would serve as unit's senior enlisted NCO.

The remainder of the hundred-odd company was divided into four operational squadrons, Myrmidon Squadron ALPHA ("A"), Myrmidon Squadron BRAVO ("B"), Myrmidon Squadron CHARLIE ("C"), and Myrmidon Squadron DELTA ("D"). Each squadron was comprised of between twenty to thirty operators. The operational squadron was the fundamental deployment unit of the Myrmidons; typically, Myrmidons units were deployed to their respective theater of operations in the squadron-size formation.

Each operational squadron was under the leadership of a Navy Commander ( CMDR, O-5 ) and the squadron's senior enlisted, a Chief Petty Officer ( CPO, E-7 ). While the O-5 would serve as the squadron's commanding officer (CO) and the E-7 would serve as the squadron chief, the two were augmented by a squadron executive officer (XO), typically a Navy Lieutenant ( LT, O-3 ), and a squadron operations officer, typically a Lieutenant, Jr. Grade ( LTJG, O-2 ). The remaining fifteen to twenty-five operators were generally enlisted, special warfare specialists between the ranks of Petty Officer Third Class ( PO3, E-4 ) and Petty Officer First Class ( PO1, E-6 ), although there were a few exceptions.

Beneath the squadron-level formation, their hierarchical organization was not formally defined; instead, sub-squadron units were formed to meet mission requirements. While the majority of missions required either individual Myrmidons solo or a Myrmidon fire team (two-three operators), larger missions employed Myrmidon squads (four-six operators) or whole Myrmidon troops (eight-twelve operators).

A single operation, no matter on what scale, almost never could employ an entire squadron in the field — however, regular squadron-integration exercises were continually scheduled so that the entire squadron could perform as a cohesive warfighting unit, should massive open warfare arise.

All four Myrmidon squadrons were "direct action" capable, that is, that they fulfilled elite counterterrorism and counterinsurgency roles within the UNSC Special Operations Command, practicing even advanced special operations such as in extremis hostage rescue. However, all squadrons carried a secondary certification to further augment the infantry company as a whole. Myrmidon Squadron ALPHA ("A") and Myrmidon Squadron BRAVO ("B") was specially certified for heavy assault, Myrmidon Squadron CHARLIE ("C") was specially certified for dedicated reconnaissance roles, and Myrmidon Squadron DELTA ("D") was specially certified for covert action.

By 2594, Captain Raphael-M064 would serve as Commander, Myrmidon Mobility Detachment.

Support Detachment
The Myrmidon Support Detachment was an integral component of the Myrmidon Detachment, typically commanded by a Marine Corps Colonel ( COL, O-6 ).

The Myrmidon operators were extensively supported on all levels; the individual level, the team level, the squadron level, and the company level. The unit, with its high operations tempo (OPTEMPO), invariably required extensive auxiliary support to continue sustained operations. The Support Detachment was comprised of a Special Operations Air Wing, a Logistical Detachment, an Intelligence Detachment, a Training Detachment, a Communications Detachment, and a Medical Detachment.

The Special Operations Air Wing (SOAW) was responsible for operating attack and transport aviation assets in support of the Myrmidons, and was comprised of elite pilots, technicians, and ground crews from the UNSC Army's Reconnaissance Aviation Expeditionary Force (RAVEN) and also elite UNSC Navy squadrons. The Air Wing was directed by a Navy Captain ( CAPT, O-6 ) from the naval starfighter community.

The Logistical Detachment was responsible for the continued resupply and rearmament of the Myrmidons, and was integral to the sustained deployment of the Myrmidons across the myriad battlefields of the Milky Way Galaxy; it was commanded by a Marine Corps Lieutenant Colonel ( LTCOL, O-5 ).

The Myrmidon unit operated its own independent Intelligence Detachment; on most operations, the Myrmidons received extensive intelligence support. The Myrmidon Intelligence Detachment was strongly affiliated with the UNSC Office of Naval Intelligence, with high-confidence ONI intelligence supporting most Myrmidon field actions. The intelligence section was led by an ONI Commander ( CMDR, O-5 ).

The Myrmidon Training Detachment, based on Asphodel Meadows, was commanded by a Navy Commander ( CMDR, O-5 ). Lieutenant Commander Simon-G294 would serve as the Executive Officer of the Training Detachment during the training of the Myrmidons on Asphodel Meadows in the 2580s.

The Myrmidon Communications Detachment, responsible for long-range cohesive integration of the Myrmidons on a galactic scale as well as fielding short-range planetary and regional communications for Myrmidon field units, was commanded by a Marine Corps Major ( MAJ, O-4 ).

The Myrmidons also operated their own independent clinical unit, the Medical Detachment, which was affiliated with the UNSC Medical Corps and was directed by a Navy Lieutenant Commander ( LCDR, O-4 ).

Augmentations
"We took twenty years to step back, rethink everything. To change all the augmentations from biological to small-molecule chemical compounds, with augmentations specifically tailored to each child. The entire Myrmidon objectives, core fundamentals, all different. It’s a new world. New SPARTANs for a changing time."

- Rear Admiral Kawika Son, 2578

The Myrmidon augmentation philosophy was highly nestled with an advanced understanding of human developmental biology and chemical biology.

An extensive knowledge of mammalian and human developmental biology and stem cell biology allowed for the manipulations of the in utero human embryo, allowing for extensive modifications of the child soldiers prior to birth.

A chemical biology approach was employed for the augmentation regiment, utilizing small-molecule probes to specifically perturb specific biological targets to produce defined phenotypic effects. The usage of small-molecule chemical compounds opposed to biological agents (i.e. peptides or recombinant vectors) maximized the safety of Myrmidon augmentation as well as its reproducibility from human to human. Computational modeling of chemical systems was substantially simpler than modeling of biological factors, which were invariably multiplex, simplifying modeling of chemical modifications of each human subject.

The Myrmidon philosophy, championed by the chemical biologist Beah Schore, advocated the usage of small-molecule chemical compounds as specific perturbers of human biology at the embryonic, postnatal, and adult stages of life. Chemical agonists and inhibitors of biological targets were used to provide quantifiable and dose-responsive control over human physiology and psychology with defined desired phenotypic effects and defined off-target side effects.

Manipulation of the human embryo
Chemical augmentation of Myrmidons began at the embryonic stage, with in utero catherization of pregnant women to perfuse developing human embryos with small-molecule compounds to elicit specific effects on human developmental biology.

Phase I: Inhibition of pluripotent stem cell differentiation
Firstly, compounds were employed to inhibit the maturation of the human pluripotent inner cell mass (ICM) to the epiblast, maintaining the "ground state" pluripotency of authentic pluripotent cells in the human inner cell mass. This blockade of embryonic maturation allowed for the continual self-renewal and expansion of human embryonic stem (hES) cells, enlarging the pluripotent progenitor pool and allowing for increased numbers of differentiated cells to be formed in embryonic and adult life, increasing mean body size and organ mass.

In order to employ chemical probes to blockade pluripotent stem cell differentiation and maturation, Beah Schore composed a collection of compounds known to either enhance embryonic stem cell self-renewal or to specifically block the differentiation of embryonic stem cells to certain lineages.

Finally, ten small-molecule compounds were chosen for final employment.

An Activin receptor and Nodal receptor inhibitor, A-83-01 ("A8"), was employed to block stem cell differentiation to the definitive endoderm. A bone morphogenetic protein receptor (BMPR) inhibitor, Dorsomorphin ("DM"), was employed to block stem cell differentiation to the mesodermal lineage. A fibroblast growth factor receptor (FGFR) inhibitor, SU5402 ("S5") and an extracellular signal-regulated kinase (ERK) inhibitor, PD184352 ("P1"), were employed to block stem cell differentiation to both the neuroectodermal and mesodermal lineages. Cells that managed to escape the chemical blockade and begin differentiation were rapidly de-differentiated by a mitogen-activated protein kinase (MAPK) and a nonmuscle myosin II heavy chain inhibitor, Reversine ("RV").

Overexpression of Nanog, a key member of the pluripotent transcriptome, has been shown to render stem cells refractory to differentiation, whereas deficiency of Nanog (Nanog-/-) has been shown to render pluripotent cells towards differentiation to multiple lineages, including the primitive endoderm. Because β-catenin and canonical Wnt signaling has been shown to increase Nanog expression, a glycogen synthase kinase 3 (GSK3) inhibitor, CHIR99021 ("C9"), was employed to inhibit the global differentiation of pluripotent stem cells.

A p160-Rho-associated coiled-coil kinase (ROCK) inhibitor, Y-27632 ("Y2"), was employed to inhibit the apoptosis of pluripotent stem cells and to enhance their survival.

Finally, three final compounds were chosen to specifically induce the self-renewal of stem cells. These included a Ras GTPase-activating protein (RasGAP) and an extracellular signal-regulated kinase (ERK) inhibitor, Pluripotin ("SC"), and two natural products with uncharacterized biological targets, Theanine ("TN") and Flurbiprofen ("FP").

Thus, in conclusion, combinatorially, these ten compounds potently blocked the maturation of the inner cell mass (ICM) and the loss of pluripotency by blockade of differentiation, enhancement of stem cell survival, and enhancement of stem cell self-renewal.

Inhibitors of stem cell differentiation

 * A-83-01: Chemical inhibitor of TGFβ/Activin receptors, specifically the activin receptor (ALK4), the TGF-β receptor (ALK5), and the nodal receptor (ALK7)
 * Chemical Name: 3-(6-Methylpyridin-2-yl)-1-phenylthiocarbamoyl-4-quinolin-4-ylpyrazole
 * Biological Target: ACVR1B (ALK4), TGFβRI (ALK5), ACVR1C (ALK7)
 * Biological Activity: Blockade of embryonic stem (ES) cell differentiation to the definitive endoderm, maintaining the pluripotency of human pluripotent stem cells and expanding the pluripotent progenitor pool
 * Biological Annotation: Activin and Nodal signals of the TGFβ family are responsible for the differentiation of pluripotent stem cells to the definitive endoderm. Suppression of TGFβ signals leads to blockade of endodermal differentiation.


 * Dorsomorphin: Chemical inhibitor of TGFβ/BMP receptors, specifically ActRIA (ALK2), BMPRIA (ALK3), and BMPR1B (ALK6)
 * Chemical Name: 6-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine
 * Biological Target: ActRIA (ALK2), BMPRIA (ALK3), and BMPR1B (ALK6)
 * Biological Activity: Blockade of embryonic stem (ES) differentiation to the mesoderm, maintaining the pluripotency of human pluripotent stem cells and expanding the pluripotent progenitor pool
 * Biological Annotation: Dorsomorphin is a specific inhibitor of ALK2, ALK3, and ALK6, serving to block transmission of BMP signals, specifically BMP-2, BMP-4, BMP6, and BMP-7 and subsequent phosphorylation of SMADs. The requirement of BMP signals in gastrulation for mesodermal specification means that suppression of BMP signaling in the pluripotent inner cell mass leads to repression of the mesodermal lineage.


 * SU5402: Chemical inhibitor of fibroblast growth factor receptor 1 (FGFR1)
 * Chemical Name: 3-[(3-(2-carboxyethyl)-4-methylpyrrol-2-yl)methylene]-2-indolinone
 * Biological Target: FGFR1 (Fibroblast Growth Factor Receptor 1)
 * Biological Activity: Blockade of embryonic stem cell (ES) differentiation to the endoderm and mesoderm, maintaining the pluripotency of human pluripotent stem cells and expanding the pluripotent progenitor pool
 * Biological Annotation: Fgfr1 and Fgf4 are extensively implicated in stem cell biology and developmental biology. FGF4, an FGFR1 ligand, activates the ERK pathway in embryonic stem cells and inhibits their self-renewal, instead inducing differentiation to the mesodermal and endodermal lineages. Blockade of FGFR1 by SU5402 leads to repression of differentiation-inducing FGF signaling and reduces the competence of embryonic stem cells to differentiate, instead promoting self-renewal.
 * Structural Mechanism: Competitively binds to the ATP-binding site on FGFR1 protein, inhibiting kinase activity by competing with ATP. Interacts with FGFR1 trough three separate intermolecular interactions with the kinase domain in a hydrophobic haven, and demonstrates even electron distribution.


 * PD184352: Chemical inhibitor of the MAPK/ERK pathway
 * Chemical Name: 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
 * Biological Target: Mitogen-activated protein kinase kinase (MKK1)
 * Biological Activity: Blockade of embryonic stem cell (ES) differentiation to the endoderm and mesoderm, maintaining the pluripotency of human pluripotent stem cells and expanding the pluripotent progenitor pool
 * Biological Annotation: ERK is phosphorylated upon FGF4 signaling, triggering lineage commitment of embryonic stem cells, and phospho-ERK is indeed required for endodermal or mesodermal differentiation of embryonic stem cells. Inhibition of the MAPK/ERK pathway with PD184352 leads to repression of the autoinductive FGF4 signal, encouraging pluripotency and embryonic stem cell self-renewal.


 * CHIR99021: Chemical inhibitor of GSK3β, activator of canonical Wnt signaling and Nanog expression
 * Chemical Name: 6-(2-(4-(2,4-dichlorophenyl)-5-(4-methyl-1H-imidazol-2-yl)pyrimidin-2-ylamino)ethylamino)nicotinonitrile
 * Biological Target: Glycogen synthase kinase 3 (GSK3α/β)
 * Biological Activity: Globally blocks pluripotent stem cell differentiation to all lineages, leading to the maintenance of pluripotency of human pluripotent stem cells and expanding the pluripotent progenitor pool
 * Biological Annotation: GSK3β is a biological inhibitor of Wnt signaling, and Wnt signaling is implicated in stem cell self-renewal, controlling the embryonic stem cell transcriptome and cell cycle. The role of Wnt signaling in stem cell self-renewal is believed to be through activation of Nanog transcription, and Nanog is a core member of the pluripotency transcriptome, actively suppressing differentiation and safeguarding against loss of pluripotency. GSK3 inhibition and Wnt signaling has been shown to blockade stem cell differentiation and lead to embryonic stem cell self-renewal.


 * Reversine: Polypharmacological inhibitor of multiple kinases and receptors
 * Chemical Name: 2-(4-morpholinoanilino)-N6-cyclohexyladenine
 * Biological Target: Aurora kinase A, Aurora kinase B, Adenosine receptor A3, MEK1, and Myosin II Heavy Chain
 * Biological Activity: De-differentiates differentiating cells, leading to reprogramming of differentiated cells to authentic pluripotent stem cells and maintenance of the pluripotent progenitor pool through indirect inhibition of differentiation
 * Biological Annotation: Reversine has been shown to de-differentiate myoblasts to a putative multipotent mesenchymal stem cell (MSC)-like intermediate, relaxing lineage specificity and leading to ectopic expression of mesodermal and neuroectodermal transcripts.

Inhibitors of stem cell apoptosis

 * Y-27632: Chemical inhibitor of p160-Rho-associated coiled-coil kinase (ROCK)
 * Chemical Name: (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide
 * Biological Target: p160-Rho-associated coiled-coil kinase (ROCK)
 * Biological Activity: Blocks apoptosis of cells of the pluripotent inner cell mass, leading to increased numbers of pluripotent progenitors
 * Biological Annotation: ROCK family kinases are responsible for cell cycle regulation and control of apoptosis. Blockade of ROCK signaling through Y-27632 has been shown to improve the survival of dissociated human embryonic stem cells, putatively through the inhibition of chemically-induced apoptosis. Y-27632 is believed to play a similar role in enhancement of the survival of pluripotent human inner cell mass.

Enhancers of stem cell self-renewal

 * Pluripotin: Polypharmacological inhibitor of both RasGAP and ERK1/2
 * Chemical Name: N-(3-(7-(1,3-dimethyl-1H-pyrazol-5-ylamino)-1-methyl-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide
 * Biological Target: Ras GTPase-activating protein (RasGAP) and extracellular signal-regulated kinase (ERK)
 * Biological Activity: Sustains self-renewal of embryonic stem cells, leading to increased numbers of pluripotent progenitors
 * Biological Annotation: Murine embryonic stem cells spontaneously differentiate, and require both leukemia inhibitory factor (LIF) and murine embryonic fibroblast (MEF) feeder layers to sustain self-renewal. Pluripotin replaces the dual requirement for LIF and feeders, and stem cells cultured in the presence of pluripotin maintain their pluripotency and can be expanded indefinitely in culture in chemically-defined conditions.


 * Theanine ( 2-amino-4-(ethylcarbamoyl)butyric acid ): Small-molecule compound derived from pharmacognosy and natural sources (Camellia sinensis and Boletus badius) that is a psychoactive agent of uncharacterized molecular mechansisms, although putatively it acts by increasing central nervous system (CNS) concentrations of γ-aminobutryic acid (GABA), among other molecular neural effects. Identified as an enhancer of human embryonic stem cell (hES) self-renewal through a high-throughput screen assay, and confirmed to increase transcriptional levels of Nanog. The significance of autocrine GABAergic signaling endogenously in ES cells and its role in maintenance of ES self-renewal confirms a likely GABAergic mechanism for theanine activity in ES cells.
 * Flurbiprofen ( 2-(3-fluoro-4-phenyl-phenyl)propanoic acid ): Small-molecule compound that is a non-steroidal cyclooxgenase 2 (COX2) inhibitor, acting as an anti-inflammatory agent. Enhances human embryonic stem cell (hES) self-renewal through an unknown mechanism, as identified through high throughput-format screening. Molecular mechanisms remain ambiguous, but anti-inflammatory molecular mechanisms include but are not limited to: inhibition of protein and leukocyte migration, inhibition of prostaglandin synthesis, stabilization of the cell membrane, and activation of mitochondrial ATPase.

Neural stem cell self-renewal

 * Sulpiride ( N-[(1-ethylpyrrolidin-2-yl)methyl]-2-methoxy-5-sulfamoylbenzamide ): Small-molecule compound agonist of the D2 dopamine receptor, promoting neural stem cell proliferation and self-renewal, countering the antiproliferative phenotypic effects of D2 and D3 dopamine receptor agonist bromocriptine.
 * Hh-Ag1.2 ( 3-chloro-N-((4'-cyano-6-methoxybiphenyl-3-yl)methyl)-N-(4-(methylamino)cyclohexyl)benzo[b]thiophene-2-carboxamide ): Small-molecule agonist of Smo and is an agonist of hedgehog signaling.

Haematopoietic stem cell self-renewal

 * 16,16-dimethyl Prostaglandin E2

Pancreatic progenitor specification

 * (—)-Indolactam V

Neuroectodermal differentiation

 * Phosphoserine ( 2-amino-3-phosphonooxy-propanoic acid ): Small-molecule orphan ligand for metabotropic glutamate receptor (mGluR4), identified to promote neural stem cell (NSC) differentiation to neurons and fate neurosphere differentiation to a neuronal lineage, as assayed by Tuj1 expression.
 * G-strophanthin ( 1β,3β,5β,11α,14,19-Hexahydroxycard-20(22)-enolide 3-(6-deoxy-α-L-mannopyranoside) ): Well-characterized cardiac glycoside derived through pharmacognosis that is a putative promoter of neural stem cell differentiation to a neuronal lineage.
 * L-AP4 ( L-(+)-2-Amino-4-phosphonobutyric acid ): Specific small-molecule agonist to the type III glutamate receptor family, including mGluR4, instructively directing neuronal differentiation of neural stem cells putatively through similar molecular mechanisms of phosphoserine. Identified through functional clustering.
 * G-strophanthin ( 1β,3β,5β,11α,14,19-Hexahydroxycard-20(22)-enolide 3-(6-deoxy-α-L-mannopyranoside) ): Well-characterized cardiac glycoside derived through pharmacognosis that is a putative promoter of neural stem cell differentiation to a neuronal lineage.
 * Endothall ( 7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid ): Dicarboxylic acid that is a protein phosphatase 2A (PP2A) inhibitor and an insectile pesticide with low acute toxicity believed to be a putative promoter of neural stem cell differentiation to a neuronal lineage.
 * All-trans retinoic acid (ATRA): Potent endogenous small-molecule compound with endogenous biological targets with pleiotropic activity. During development, retinoic acid is involved in patterning the anterior-posterior (AP) axis in the mammalian and insectile body plan, inducing caudalization and neuralization during the early stages of development, with numerous other later roles, including expansion, proliferation, and self-renewal of various pancreatic progenitors.
 * Neuropathiazol ( ethyl 4-[methyl-(2-phenyl-1,3-thiazol-4-yl)amino]benzoate ): Small molecule chemical compound of the disubstituted 4-aminothiazole classification that is an organic sulfurous heterocyclic that chemically induces neuronal differentiation of adult hippocampal neural progenitor cells (HCN) and suppresses astrogliogenesis. Molecular mechanisms uncharacterized.
 * D-cysteine
 * D-phenylalanine

Mesodermal differentiation

 * QS11: 2,6,9-trisubstituted purine compound

Endodermal differentiation
Directed differentiation of embryonic stem (ES) cells to definitive endoderm (DE) lineage, believed to be canonically regulated with a threshold of Wnt signaling to specify plastic mesendoderm (ME), which is specified by TGFβ signals (Activin A, Nodal) to definitive endoderm, as assayed by SOX17 transcription factor expression and cytoskeletal marker Claudin-6 (Cldn-6).


 * BIO-Acetoxime ( [[(2Z)-2-(6-bromo-2-oxo-1H-indol-3-ylidene)indol-3-yl]amino] acetate ): Small molecule of the bis-indolo (indirubin) structural family that is a specific inhibitor of GSK3β, inducing stabilization of nuclear-localized β-catenin and artificial activation of Wnt/β-catenin signaling, inducing mesendodermal (ME) specification of embryonic stem (ES) cells and subsequent specification of anterior definitive endoderm (DE), as assayed by Brachyury, followed by FOXA2 and Cerberus-1 (CER1) expression, respectively.
 * Cymarin ( (3S,5S,8R,10S,13R,14S,17R)-5,14-dihydroxy-3-((2R,4S,5S,6R)-5-hydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yloxy)-13-methyl-17-(5-oxo-2,5-dihydrofuran-3-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene-10-carbaldehyde : Pharmagnosis-derived secondary plant metabolite that is a Na+/K+ pump inhibitor, acting through unknown molecular mechanisms to strongly induce directed differentiation to the definitive endoderm lineage (as assayed by strong SOX17 expression), comparable to treatment with recombinant Activin A. Cardiac glycoside to increase cardiac contraction strength, is also is a cardiac mutagen and carcinogen.
 * Sarmentogenin ( 4-[(3S,5R,8R,9R,10S,11R,13R,14S,17S)-3,11,14-trihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]-5H-furan-2-one ): Steroid aglycon of sarmentocymarin, chemical analog digitoxigenin with a hydroxyl modification at organic position 11, acting through unknown molecular mechanisms to strongly induce directed differentiation to the definitive endoderm lineage (as assayed by strong SOX17 expression), comparable to treatment with recombinant Activin A. Similarly, is a cardiac glycoside.

Chemical Control of the Adult Psychology

 * (+)-WIN-55212: CB1 and CB2 cannabinoid receptor activator, described by Compton et. al (2002) to have an in vitro biological activity at a Ki of of 62.3 ± 31 nM for human CB1 and a Ki of 3.30 ± 0.40 nM for human CB2 against 0.5 nM [3H]CP 55940
 * 2C-E: substituted phenethylamine and presumptive dopamine active transporter (DAT) inhibitor
 * A-769662: 5' adenosine monophosphate-activated protein kinase (AMPK) activator, described by Cool et. al (2006) to have an in vivo biological activity at a dosage of 30 mg/kg and an in vitro biological activity at an IC50 of 3.2 μM
 * GW1516: peroxisome proliferator-activated receptor (PPARδ) activator, described by Sznaidmann et. al (2003) to have an in vitro transactivation activity at a concentration of 1.0 nM for human PPARδ
 * JZL184: monoacylglycerol lipase (MAGL) inhibitor that increases 2-arachidonoylglycerol (2-AG) transmission, described by Long et. al (2009) to have nearly-complete inhibitory activity at 1.0 nM
 * O-1783: dopamine active transporter (DAT) inhibitor, described by Meltzer et. al (2003) to have an IC50 of 17 nM competitively inhibits [3H]WIN 35,428 binding to the transporter in the rhesus monkey (Macaca mulatta)
 * Selegiline: monoamine oxide-B (MAOB) inhibitor, described by Engberg et. al (1991) to inhibit MAOB and increase dopa accumulation following 3-hydroxybenzyihydrazine administration at an in vivo concentration of 30mg/kg through intraperitoneal (I.P.) administration

Neurocytoarchitectonics

 * BPIQ-II: small-molecule chemical inhibitor of epidermal growth factor receptor (EGFR) that inhibits endogenous inhibition of axonal regeneration through myelin and chondroitin sulfate proteoglycans

Musculoskeletal and Metabolism

 * BMP7: 28.8 kDa homodimeric glycoprotein, which correspond to amino acid residues 316 to 431 of the full-length BMP7 precursor, solubilized in hydroxyapatite
 * Myf5-PRDM16shRNA: promoter-driven gene system ligated into non-replicative, transiently-expressed, non-integrating adenoviral expression vector for specific promoter-driven expression
 * Snai-MyoD: promoter-driven gene system built ligated non-replicative, transiently-expressed, non-integrating adenoviral expression vector for specific promoter-driven expression

Nucleation
The Myrmidon Program would formally have its genesis in 2578. Conceptualized by Dr. Beah Schore of the Harvard Stem Cell Institute and Rear Admiral Kawika Son of the UNSC Naval Special Warfare Command, it would be authorized in early 2578 by the UNSC Office of Naval Intelligence, given the highest priority to train and operate the next iteration of SPARTAN child soldiers, the fourth generation of the SPARTAN Program.

Almost immediately, Admiral Son would begin the nucleation of a core cadre of individuals to train the Myrmidons. While Schore's team would begin investigation of the chemical biology necessary to augment the future warriors, Son would authorize Operation: MARSHAL YELLOW on Hekate and Operation: RALLY VIOLET on Bifröst, gathering ex-SPARTANs such as Simon-G294, Cassandra-G006, Apollo ("Agent 2994"), and Artemis ("Agent 2995") to serve as program advisors and dedicated drill instructors (DIs) to teach the future Myrmidons where their predecessors, the SPARTANs, had gone astray.

Birth and Embryonic Augmentation
The birth of the Myrmidons was founded on their precedent, Kimberly Ivy Blackburn; artificial selection of optimal gamete donors and recipients to ensure that the progeny borne would be of unparalleled caliber on a genetic scale. One hundred sperm donors were chosen from decorated members of the UNSC special warfare community and conscientiously-accepting chosen women were artificially inseminated to produce artificial genetic crosses between the most exceptional that mankind had to offer.

Selection of gamete donors was carried out intensively, with extensive bioinformatics and high-throughput genetic sequencing employed to ensure that only the most exceptional humans were selected to be the parents of the future Myrmidons. Gamete donors were selected from a pool of decorated UNSC special warfare veterans of appropriate age, and these primary donors were intensively screened for physical, mental, and genetic fitness by the Myrmidon Program staff. Highly-fit individuals, secondary donors, were further screened with bioinformatics; genetic sequencing was employed to sequence small nucleotide polymorphisms (SNPs) and restriction fragment length polymorphisms (RFLP) to identify individual polymorphisms linked to disease susceptibility and also referenced against polymorphism sequence records obtained from the SPARTAN-Is, SPARTAN-IIs, SPARTAN-IIIs, and Kimberly Ivy Blackburn.

From the secondary pool, tertiary donors were finally selected based on bioinformatic analysis to confirm that they had few to none polymorphisms associated with disease susceptibility and that they had moderate to high homology to the polymorphism arrays of prior SPARTANs. What remained were two hundred-odd highly-fit UNSC special warfare veterans of both sexes; genetic crosses were made utilizing algorithms to calculate fitness post-breeding. These willing donors were matched, and sperm collection and artificial insemination of female hosts was performed.

Several days after artificial insemination and zygote formation, the first phase of chemical augmentation began — while the future Myrmidons were still in the uterus. Prior to implantation, sterile catheters were surgically integrated into the host uteruses, and a cocktail of small molecule compounds were perfused to inhibit the differentiation of the pluripotent inner cell mass (ICM) and to retain pluripotency, expanding the human pluripotent progenitor pool to increase the number of differentiated cells formed in postnatal and adult life. These compounds included inhibitors of differentiation (A-83-01, Dorsomorphin, SU5402, PD184352, Reversine, and CHIR99021), enhancers of embryonic stem cell self-renewal (Pluripotin, Theanine, and Flurbiprofen), and an inhibitor of stem cell apoptosis (Y-27632).

After sufficient expansion of the pluripotent inner cell mass, chemical blockade of differentiation was relieved, and the differentiating embryos underwent the second phase of embryonic augmentation; the embryos now underwent long-term latent chemical perfusion with a compound cocktail that chemically directed the embryonic specification or amplification of multipotent stem cell pools to increase downstream differentiated cell formation. The Hedgehog (Hh) agonist Hh-Ag1.5 and the D2 receptor antagonists Sulpiride or L-741,626 were employed to specify and amplify multipotent neural stem cells (NSCs) in the nervous system, 16,16-Dimethyl Prostaglandin E2 was employed to specify and amplify haematopoietic stem cells (HSCs) in the bone marrow, and a protein kinase C (PKC) inhibitor, (—)-Indolactam V, was employed to specify pancreatic progenitor cells.

By the closure of 2578, all the Myrmidon progeny were successfully borne.

Order of Battle



 * Command Element
 * Senior Commander: VADM Kawika Son (Vice Admiral, O-9)
 * Mobility Element
 * Detachment Commander: CAPT Raphael-064 (Captain, O-6)
 * Detachment Senior Enlisted: MCPO (Master Chief Petty Officer, E-9)
 * Alpha Squadron (Direct Action / Assault)
 * Alpha Squadron Commander: CMDR (Commander, O-5)
 * Squadron Senior Enlisted: CPO (Chief Petty Officer, E-7)
 * Alpha Squadron XO: LT (Lieutenant, O-3)
 * Squadron Operations Officer: LTJG (Lieutenant Jr. Grade, O-2)
 * Bravo Squadron (Direct Action / Assault)
 * Bravo Squadron Commander: CMDR (Commander, O-5)
 * Squadron Senior Enlisted: CPO (Chief Petty Officer, E-7)
 * Bravo Squadron XO: LT (Lieutenant, O-3)
 * Squadron Operations Officer: LTJG (Lieutenant Jr. Grade, O-2)
 * Charlie Squadron (Direct Action / Reconnaissance)
 * Charlie Squadron Commander: CMDR (Commander, O-5)
 * Squadron Senior Enlisted: CPO (Chief Petty Officer, E-7)
 * Charlie Squadron XO: LT (Lieutenant, O-3)
 * Squadron Operations Officer: LTJG (Lieutenant Jr. Grade, O-2)
 * Delta Squadron: (Direct Action / Covert Action)
 * Delta Squadron Commander: CMDR Florian-021 (Commander, O-5)
 * Squadron Senior Enlisted: CPO Eve-005 (Chief Petty Officer, E-7)
 * Delta Squadron XO: LT (Lieutenant, O-3)
 * Squadron Operations Officer: LTJG Bjorn-047 (Lieutenant Jr. Grade, O-2)
 * Team Loki
 * PO1 Alyssa-028 (Petty Officer 1st Class, E-6)
 * PO2 Gordon-055 (Petty Officer 2nd Class, E-5)
 * Team Valkyrie
 * CMDR Florian-021 (Commander, O-5) — Squadron commander
 * CPO Eve-005 (Chief Petty Officer, E-7) — Squadron leading petty officer
 * LTJG Bjorn-047 (Lieutenant Jr. Grade, O-2) — Squadron operations officer
 * PO2 Daphne-097 (Petty Officer 2nd Class, E-5)

Behind the Scenes

 * The Myrmidons are named after the Myrmidons of Greek mythology, another Greek warfighting tribe similar to the Spartans in ancient times.