Human Defense Research Articles

Delinquent violence, criminal justice in Mexico, and Erich Fromm in real time

The efforts of the Mexican authorities to defeat insecurity, violence, and crime have not been successful. It seems that the prison system plays a major role in this. Delinquent violence forces us to look for different options and conditions. Proposals that emanated from the humanist psychoanalysis promoted by Erich Fromm, who lived in Mexico for over 20 years from the late 1950s to the mid 1970s, are therapeutic resources and paths of analysis. These allow us to identify both the productive and the creative aspects of the individual personality propelling the person to their social integration. The aim is to guide individuals toward a biophilic character and to the construction of a fair society provided with hope and liberty. The mission of the Instituto Mexicano de Psicoanálisis (IMPAC; Mexican Institute of Psychoanalysis), founded in Mexico City in 1963 by Erich Fromm, is to: spread Fromm’s intellectual legacy through psychoanalytic training; pay specialized attention to persons in need of psychotherapies and analytic psychotherapies; disseminate Fromm’s thoughts by publishing them; undertake professional research; plus, recently, collaborate with federal agencies for justice procurement and human rights defense. This has made it possible to convince us of the appropriateness, validity, and efficacy of humanist psychoanalysis to approach and become involved in benefiting Mexican society.

Evaluation of antioxidant and bioactive phytochemical properties of Achyranthes aspera L.

Archeranthes aspera, a member of the Amaranthaceae family, is now widely distributed. This species has become invasive in Nigeria. Despite the natural antioxidant defense and repair mechanisms present in humans and other organisms, continuous exposure to free radicals inevitably causes biological harm that cannot be entirely mitigated. In a recent study, extracts of Achyranthes aspera were examined for their secondary metabolites, antioxidant properties, and antibacterial effects against several strains including Staphylococcus aureus (NCIB 8588), Bacillus cereus (NCIB 6349), Klebsiella pneumoniae (NCIB 418), and Pseudomonas aeruginosa (NCIB). Phytochemical analysis of the plant leaf revealed the presence of alkaloids, tannins, general glycosides, and terpenoids. Quantitative analysis of secondary metabolites showed that the plant extract contained 7.0 ± 2.5 mg/100g alkaloids, 11.5 ± 2.0 mg/100g tannins, 15.0 ± 3.1 mg/100g general glycosides, and 14.0 ± 1.5 mg/100g terpenoids. The investigation revealed that the concentration of leaf extract enhanced DPPH scavenging activity, albeit to a lesser extent than ascorbic acid. At concentrations of 50 and 100µg/ml, ascorbic acid exhibited scavenging activities of 22.66 ± 2.34% and 40.55 ± 1.55%, respectively, whereas Achyranthes aspera leaf extract displayed activities of 6.33 ± 2.04% and 11.65 ± 6.18%. Furthermore, the study demonstrated that the plant extract inhibited the growth of bacteria, rendering them vulnerable. The minimum inhibitory concentration of Achyranthes aspera ethanol leaf extract was found to be lowest against S. aureus and highest against B. cereus. These findings suggest that the ingredients present in the plant leaf extract hold promise for potential use in chemotherapy.

Enhancement of innate immunity in gingival epithelial cells by vitamin D and HDAC inhibitors.

The human host defense peptide LL-37 is a component of the innate immune defense mechanisms of the oral cavity against colonization by microbes associated with periodontal disease. We have previously shown that the active form of vitamin D, 1,25(OH)2D3, can induce the expression of LL-37 in gingival epithelial cells (GEC), and prevent the invasion and growth of periopathogenic bacteria in these cells. Further, experimental vitamin D deficiency resulted in increased gingival inflammation and alveolar bone loss. Epidemiological studies have shown associations between vitamin D deficiency and periodontal disease in humans, suggesting application of vitamin D could be a useful therapeutic approach. Further, since we have shown the local activation of vitamin D by enzymes expressed in the GEC, we hypothesized that we could observe this enhancement with the stable, and inexpensive inactive form of vitamin D, which could be further increased with epigenetic regulators. We treated 3-dimensional primary cultures of GEC topically with the inactive form of vitamin D, in the presence and absence of selected histone deacetylase (HDAC) inhibitors. LL-37 mRNA levels were quantified by quantitative RT-PCR, and inhibition of invasion of bacteria was measured by fluorescence microscopy. Vitamin D treatment led to an induction of LL-37 mRNA levels, as well as an inhibition of pro-inflammatory cytokine secretion. This effect was further enhanced by HDAC inhibitors, most strongly when the HDAC inhibitor, phenyl butyrate (PBA) was combined with Vitamin D3. This was observed both in solution and in a prototype gel formulation using sodium butyrate. Finally, this combination treatment led to an increase in the antimicrobial activity against infection by Porphyromonas gingivalis and Filifactor alocis, bacteria associated with periodontal lesions, as well as herpes simplex virus, which has also been shown to be associated with periodontal lesions. Our results demonstrate that a combination of inactive vitamin D and sodium butyrate could be developed as a safe treatment for periodontal disease.

Immune Reactions of Vector Insects to Parasites and Pathogens.

This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this Special Issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need for great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is often overlooked with the non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented.

Human Host Defense Peptide LL-37 Suppresses TNFα-Mediated Matrix Metalloproteinases MMP9 and MMP13 in Human Bronchial Epithelial Cells

Introduction: TNFα-inducible matrix metalloproteinases play a critical role in the process of airway remodeling in respiratory inflammatory disease including asthma. The cationic host defense peptide LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood. Here, we examined the effect of LL-37 on TNFα-mediated responses in human bronchial epithelial cells (HBECs). Methods: We used a slow off-rate modified aptamer-based proteomics approach to define the HBEC proteome altered in response to TNFα. Abundance of selected protein candidates and signaling intermediates was examined using immunoassays, ELISA and Western blots, and mRNA abundance was examined by qRT-PCR. Results: Proteomics analysis revealed that 124 proteins were significantly altered, 12 proteins were enhanced by ≥2-fold compared to unstimulated cells, in response to TNFα. MMP9 was the topmost increased protein in response to TNFα, enhanced by ∼10-fold, and MMP13 was increased by ∼3-fold, compared to unstimulated cells. Furthermore, we demonstrated that LL-37 significantly suppressed TNFα-mediated MMP9 and MMP13 in HBEC. Mechanistic data revealed that TNFα-mediated MMP9 and MMP13 production is controlled by SRC kinase and that LL-37 enhances related upstream negative regulators, namely, phospho-AKT (T308) and TNFα-mediated TNFAIP3 or A20. Conclusions: The findings of this study suggest that LL-37 may play a role in intervening in the process of airway remodeling in chronic inflammatory respiratory disease such as asthma.

The Plethora of Microbes with Anti-Inflammatory Activities.

Inflammation, which has important functions in human defense systems and in maintaining the dynamic homeostasis of the body, has become a major risk factor for the progression of many chronic diseases. Although the applied medical products alleviate the general status, they still exert adverse effects in the long term. For this reason, the solution should be sought in more harmless and affordable agents. Microorganisms offer a wide range of active substances with anti-inflammatory properties. They confer important advantages such as their renewable and inexhaustible nature. This review aims to provide the most recent updates on microorganisms of different types and genera, being carriers of anti-inflammatory activity.

Native architecture of a human GBP1 defense complex for cell-autonomous immunity to infection.

All living organisms deploy cell-autonomous defenses to combat infection. In plants and animals, large supramolecular complexes often activate immune proteins for protection. In this work, we resolved the native structure of a massive host-defense complex that polymerizes 30,000 guanylate-binding proteins (GBPs) over the surface of gram-negative bacteria inside human cells. Construction of this giant nanomachine took several minutes and remained stable for hours, required guanosine triphosphate hydrolysis, and recruited four GBPs plus caspase-4 and Gasdermin D as a cytokine and cell death immune signaling platform. Cryo-electron tomography suggests that GBP1 can adopt an extended conformation for bacterial membrane insertion to establish this platform, triggering lipopolysaccharide release that activated coassembled caspase-4. Our "open conformer" model provides a dynamic view into how the human GBP1 defense complex mobilizes innate immunity to infection.

Maternal-Foetal/Infant Interactions-Gut Microbiota and Immune Health.

In recent years, the number of scientific publications on the role of intestinal microbiota in shaping human health, as well as the occurrence of intestinal dysbiosis in various disease entities, has increased dynamically. However, there is a gap in comprehensively understanding the factors influencing a child's gut microbiota. This review discusses the establishment of gut microbiota and the immunological mechanisms regulating children's microbiota, emphasising the importance of prioritising the development of appropriate gut microbiota in a child from the planning stages of pregnancy. The databases PubMed, Web of Sciences, Cochrane, Scopus and Google Scholar were searched to identify relevant articles. A child's gut microbiota composition is influenced by numerous factors, such as diet during pregnancy, antibiotic therapy, the mother's vaginal microbiota, delivery method, and, later, feeding method and environmental factors. During pregnancy, the foetus naturally acquires bacterial strains from the mother through the placenta, thereby shaping the newborn's immune system. Inappropriate maternal vaginal microbiota may increase the risk of preterm birth. Formula-fed infants typically exhibit a more diverse microbiota than their breastfed counterparts. These factors, among others, shape the maturation of the child's immune system, impacting the production of IgA antibodies that are central to cellular humoral immune defence. Further research should focus on identifying specific microbiota-immune system interactions influencing a child's immune health and developing personalised treatment strategies for immune-related disorders.

Role of innate host defense proteins in oral cancerogenesis.

It is nowadays well accepted that chronic inflammation plays a pivotal role in tumor initiation and progression. Under this aspect, the oral cavity is predestined to examine this connection because periodontitis is a highly prevalent chronic inflammatory disease and oral squamous cell carcinomas are the most common oral malignant lesions. In this review, we describe how particular molecules of the human innate host defense system may participate as molecular links between these two important chronic noncommunicable diseases (NCDs). Specific focus is directed toward antimicrobial polypeptides, such as the cathelicidin LL-37 and human defensins, as well as S100 proteins and alarmins. We report in which way these peptides and proteins are able to initiate and support oral tumorigenesis, showing direct mechanisms by binding to growth-stimulating cell surface receptors and/or indirect effects, for example, inducing tumor-promoting genes. Finally, bacterial challenges with impact on oral cancerogenesis are briefly addressed.

Episodic versus thematic media framing of violence against social leaders and human rights defenders in Colombia.

Social leaders and human rights defenders (SLHRD) in Colombia have been under increasing attack for defending the rights of communities affected by violence. From 2016 to 2022, over 600 SLHRD were assassinated, resulting in a serious violation of both individual and community human rights. The media's portrayal of these attacks can shape public perceptions and influence efforts towards peacebuilding and promoting human rights. This study examines the media's framing of violence against SLHRD in Colombia between 2016 and 2020, a period marked by an escalation of violence after the signing of the 2016 peace accord between the Colombian government and the Revolutionary Armed Forces of Colombia (FARC). We analysed 1506 textual publications from seven media outlets using a lexicometric approach and identified two frames of news articles: episodic and thematic. Our findings suggest that the episodic media framing may present a simplistic and non-political perspective of the issue, which can impede peacebuilding efforts, while the thematic frame can raise awareness of violence against SLHRD and promote human rights defence. Our study highlights the media's significant role in shaping public opinion on violence against SLHRD, offering practical implications for advocacy and activism.

Music as aposematic signal: predator defense strategies in early human evolution.

The article draws attention to a neglected key element of human evolutionary history-the defense strategies of hominins and early humans against predators. Possible reasons for this neglect are discussed, and the historical development of this field is outlined. Many human morphological and behavioral characteristics-musicality, sense of rhythm, use of dissonances, entrainment, bipedalism, long head hair, long legs, strong body odor, armpit hair, traditions of body painting and cannibalism-are explained as predator avoidance tactics of an aposematic (warning display) defense strategy. The article argues that the origins of human musical faculties should be studied in the wider context of an early, multimodal human defense strategy from predators.

Analisis Kebutuhan E-Modul Biologi Terintgrasi Nilai Imtaq Pada Materi Sistem Pertahanan Tubuh Manusia

This research aims to find out information about the needs of teachers and students in student learning on the material of the human body's defense system. This research was conducted at MAN 2 Pekanbaru using a qualitative descriptive method using a population of 35 students from class XI MAN 2 Pekanbaru and using a sample of 10 students from class XI MAN 2 Pekanbaru. The instruments used were teacher and student interviews and documentation. analyzed using descriptive statistical data analysis techniques. Descriptive statistical analysis techniques are statistics that describe or describe an object that has been examined from the sample or population data obtained. The results of this research are obtained from teacher interviews that teachers have not used e-modules integrated with IMTAQ values ​​and only use learning media in the form of books and videos that are in accordance with the material and results from student interviews, it was found that interest in studying biology was very high and some stated that they had already used e-modules, differing in opinion from teachers who had never used e-modules and it turned out that students only used e-modules when studying at home. . Researchers concluded from the needs analysis that teachers and students need integrated e-modules with IMTAQ values.

Pseudomonas aeruginosa two-component system CprRS regulates HigBA expression and bacterial cytotoxicity in response to LL-37 stress.

Pseudomonas aeruginosa is a highly pathogenic bacterium known for its ability to sense and coordinate the production of virulence factors in response to host immune responses. However, the regulatory mechanisms underlying this process have remained largely elusive. In this study, we investigate the two-component system CprRS in P. aeruginosa and unveil the crucial role of the sensor protein CprS in sensing the human host defense peptide LL-37, thereby modulating bacterial virulence. We demonstrate that CprS acts as a phosphatase in the presence of LL-37, leading to the phosphorylation and activation of the response regulator CprR. The results prove that CprR directly recognizes a specific sequence within the promoter region of the HigBA toxin-antitoxin system, resulting in enhanced expression of the toxin HigB. Importantly, LL-37-induced HigB expression promotes the production of type III secretion system effectors, leading to reduced expression of proinflammatory cytokines and increased cytotoxicity towards macrophages. Moreover, mutations in cprS or cprR significantly impair bacterial survival in both macrophage and insect infection models. This study uncovers the regulatory mechanism of the CprRS system, enabling P. aeruginosa to detect and respond to human innate immune responses while maintaining a balanced virulence gene expression profile. Additionally, this study provides new evidence and insights into the complex regulatory system of T3SS in P. aeruginosa within the host environment, contributing to a better understanding of host-microbe communication and the development of novel strategies to combat bacterial infections.

Monitoring Memory B Cells by Next-Generation ImmunoSpot® Provides Insights into Humoral Immunity that Measurements of Circulating Antibodies Do Not Reveal.

Memory B cells (Bmem) provide the second wall of adaptive humoral host defense upon specific antigen rechallenge when the first wall, consisting of preformed antibodies originating from a preceding antibody response, fails. This is the case, as recently experienced with SARS-CoV-2 infections and previously with seasonal influenza, when levels of neutralizing antibodies decline or when variant viruses arise that evade such. While in these instances, reinfection can occur, in both scenarios, the rapid engagement of preexisting Bmem into the recall response can still confer immune protection. Bmem are known to play a critical role in host defense, yet their assessment has not become part of the standard immune monitoring repertoire. Here we describe a new generation of Bcell ELISPOT/FluoroSpot (collectively ImmunoSpot®) approaches suited to dissect, at single-cell resolution, the Bmem repertoire ex vivo, revealing its immunoglobulin class/subclass utilization, and its affinity distribution for the original, and for variant viruses/antigens. Because such comprehensive Bcell ImmunoSpot® tests can be performed with minimal cell material, are scalable, and robust, they promise to be well-suited for routine immune monitoring.

Cationic human defence peptides and cornea HSV‐1 infections: Results of a rabbit study

In this study, we evaluated the potential of LiQD cornea glue supplemented with LL37‐derived peptide GF19, delivered through Silicium nanoparticles (SiNP) to prevent herpes simplex virus type 1 (HSV‐1) infection in a rabbit corneal model. SiNP‐GF19 was synthesized using a hydrophobic core, a hydrophilic shell, and a reactive surface that allowed covalent bonding to the collagen‐like peptides of our developed LiQD Cornea glue. Our results showed that SiNP‐GF19 was able to effectively release GF19 in a sustained manner, with approximately 60% of the peptide being released over 24 h. The remaining 40% of GF19 is trapped in the SiNP and can only be released upon complete degradation of the nanoparticles, which may occur via cellular uptake and enzymatic degradation. This ensures the prolonged release of GF19. The mechanism of action of GF19 against HSV‐1 may involve preventing the binding of the virus to host cells. Previous studies have shown that LL37, from which GF19 is derived, can block HSV‐1 binding to host cells, leading to decreased viral infection. However, in our study, we did not see reduced viral shedding, furthermore, nanoparticles coated with the GF19 peptide or nanoparticles themselves may have an eye irritant effect. Nevertheless, LiQD Cornea supplemented with SiNP‐GF19 or LiQD alone were effective in promoting corneal regeneration and healing. Specifically, it led to the formation of a relatively mature epithelium composed of 2–3 epithelial layers, expressing CK3 in the outermost epithelial layer, compared to the absence of epithelium or a monolayer of unstructured CK3‐negative epithelium in the cyanoacrylate adhesive control group. LiQD Cornea formulation without SiNP‐GF19 also displayed significantly lower α‐SMA staining than the rest of the experimental groups in the implant area, which overexpression is associated with abnormal extracellular matrix deposition and scar formation. In terms of nerve regeneration, all LiQD Cornea formulations showed βIII tubulin expression, indicating immature neuronal microtubule structures. In summary, all three experimental treatment strategies were significantly more effective compared to the cyanoacrylate adhesive control group, significantly smaller scar tissues without ingrown vascular networks were formed, though, only mild antiviral properties of SiNP‐GF19 were observed.

Anti-Quorum Sensing Efficacy of Mangifera indica Kernel Extract against Biofilm Formation in Pseudomonas aeruginosa

P.aeruginosa (PA) is responsible for causing both acute and chronic infections in immune compromised individuals. Multi-drug resistance among them is a very common phenomenon due to their complex biofilm forming nature enabling the bacteria to evade antibiotic treatment as well as human immune defence mechanism. In the present study, biofilm inhibition in P.aeruginosa was analysed using mango peel (MPE) and kernel extract (MKE). MKE has a greater content of phytoconstituents such as tannin and phenol (1.6458± 0.07 mg g-1 TAE; 1.56± 0.007 mg g-1 GAE) than MPE (0.2938± 0.05 mg g-1 TAE; 1.31± 0.003 mg g-1 GAE). MKE at 12.5-200μg ml-1 showed significant reduction of biofilm (70-75%) and quorum sensing (QS) (35-65%) against PA and C. violaceum whereas MPE showed only 20-23% of biofilm and 5-15% of QS inhibition. Epi-fluorescence and CLSM micrographs demonstrated the efficacy of MKE in inhibiting surface adhesion and biofilm thickness. As a result, MKE at 50μg ml-1 (1/4 BIC) suppressed PA biofilm formation without impairing planktonic cell growth, reducing the possibility of the emergence of multi-drug resistance. Additionally, MKE inhibited the production of pyocyanin and had a negative impact on swarming and twitching motility. Eight distinct phytochemicals were found in MKE after it was characterised, but 2(3h)-furanone, 3-(15-hexadecynylidene)dihydro-4-hydroxy-5-methyl, 4r-(3e,4.alpha.,5.beta) represented 33.75% of the peak area and is presumed to be the antibiofilm compound.

CIVIL-MILITARY COOPERATION AND GENDER PERSPECTIVES

The article is primarily aimed at studying and analysing social relations, roles, and dynamics in the field of civil-military cooperation and gender policy. The authors analyze various social stereotypes, political decisions, legislation, and its impact on gender equality and interaction between civil society and the military. In turn, empirical data is used to confirm or refute hypotheses about gender imbalances, challenges and achievements in these areas, but this research is focused on social analysis and understanding of current challenges in the chosen field. The research presupposed the use of various scientific methods, but its base was formed by general and special scientific and philosophical methods. Particular emphasis was placed on the formal-legal approach that facilitated in-depth analysis of international legal statutes, doctrinal perspectives, and rulings from the European Court of Human Rights concerning gender policies embedded within the framework of civil-military cooperation. The authors conduct a theoretical legal examination of civil-military cooperation within the framework of human rights defense, elucidating its distinctive features. Additionally, the paper places considerable emphasis on gender equality in the context of armed conflicts and civil-military cooperation, drawing upon international legal perspectives and scholarly methodologies.

Immunological Aspects of Infertility-The Role of KIR Receptors and HLA-C Antigen.

The mechanisms of immune tolerance of a mother against an antigenically foreign fetus without a concomitant loss of defense capabilities against pathogens are the factors underlying the success of a pregnancy. A significant role in human defense is played by killer immunoglobulin-like receptor (KIR) receptors, which regulate the function of the natural killer (NK) cells capable of destroying antigenically foreign cells, virus-infected cells, or tumor-lesioned cells. A special subpopulation of NK cells called uterine NK cells (uNK) is found in the uterus. Disruption of the tolerance process or overactivity of immune-competent cells can lead to immune infertility, a situation in which a woman's immune system attacks her own reproductive cells, making it impossible to conceive or maintain a pregnancy. Since the prominent role of the inflammatory response in infertility, including KIR receptors and NK cells, has been postulated, the process of antigen presentation involving major histocompatibility complex (MHC) molecules (HLA) appears to be crucial for a successful pregnancy. Proper interactions between KIR receptors on female uNK cells and HLA class I molecules, with a predominant role for HLA-C, found on the surface of germ cells, are strategically important during embryo implantation. In addition, maintaining a functional balance between activating and inhibitory KIR receptors is essential for proper placenta formation and embryo implantation in the uterus. A disruption of this balance can lead to complications during pregnancy. The discovery of links between KIR and HLA-C has provided valuable information about the complexity of maternal-fetal immune interactions that determine the success of a pregnancy. The great diversity of maternal KIR and fetal HLA-C ligands is associated with the occurrence of KIR/HLA-C combinations that are more or less favorable for reproductive success.

The immune response of the whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) when parasitized by Eretmocerus eremicus (Hymenoptera: Aphelinidae).

In insects, the innate immune system is subdivided into cellular and humoral defenses. When parasitoids attack insects, both reactions can be activated and notably, the phenoloxidase (PO) cascade and lytic activity are part of both cellular and humoral defenses. However, to our knowledge, no study has characterized any immune response of the whitefly Trialeurodes vaporariorum (Hemiptera: Aleyrodidae) to the attack of Eretmocerus eremicus (Hymenoptera: Aphelinidae). Therefore, the first objective of the present study was to determine whether whitefly nymphs recently parasitized by E. eremicus exhibit any immune response. For this, we estimate the level of prophenoloxidase (proPO), phenoloxidase (PO), and lytic activity by colorimetric assays. A second objective was to assess whether the observed whitefly immune response could be related to a previously reported preference of the predator Geocoris punctipes (Hemiptera: Lygaeidae) for non-parasitized nymphs. We therefore offered non-parasitized and recently parasitized nymphs to the predator. Our results show that parasitism of whitefly nymphs by E. eremicus induced a highly estimated level of proPO and PO, and a lower level of lytic activity. In addition, we found that G. punctipes did not show a preference for non-parasitized over recently parasitized nymphs. The nymphs of T. vaporariorum activated the PO pathway against E. eremicus; however, the increase in proPO and PO levels was traded-off with decreased lytic activity. In addition, the previously reported preference for non-parasitized nymphs was not seen in our experiments, indicating that the induced immune response did not affect predator behavior by G. punctipes.

Gene-based COVID-19 vaccines: Australian perspectives in a corporate and global context

Pandemic management requires societal coordination, global orchestration, respect for human rights and defence of ethical principles. Yet some approaches to the COVID-19 pandemic, driven by socioeconomic, corporate, and political interests, have undermined key pillars of ethical medical science. We explore significant mistakes that may have occurred in recent pandemic control, in order to better navigate the future. Within corporate and geopolitical infrastructure, we review the COVID-19 pandemic and novel mRNA and viral-vector DNA COVID-19 vaccines, deployed by wealthy western countries. The pandemic, together with rollouts of unconventional, gene-based vaccine technology, has provided experimental opportunity to engineer social control of entire populations. The haste and scale of development, production, and distribution of these new pharmaceuticals is unprecedented in history. Key phase III clinical trials for these products are yet to be fully completed, despite administration to billions of people. Mass vaccination of workforces has been mandated, and vaccine mandates correlate with excess mortality. Many independent data sets concur - we have experienced a pandemic of viral illness, followed by a pandemic of vaccine injury. For Australia, matters have operated the other way around. Vaccination followed later by the main viral wave. Australian excess mortality data correlates with this. Neither risk nor cost can justify these products for the vast majority of people. Lack of efficacy against infection and transmission, and the equivalent benefits of natural immunity, obviate mandatory therapeutics. With the many gene-based pharmaceuticals planned, a new era of pathology lies ahead. We should pause, reflect, and reaffirm essential freedoms, welcome the end of the COVID-19 pandemic, embrace natural immunity, and lift all mandated medical therapy.