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“Shall We All Commit Suicide?” Sir Winston S Churchill ominously warned in his 1924 essay about the alarming progress of biological warfare (BW), where engineered diseases could target humans, animals and agriculture. He wrote, “A study of Disease—of Pestilences, methodically prepared and deliberately launched upon man and beast—is certainly being pursued in the laboratories of more than one great country. Blight to destroy crops, Anthrax to slay horses and cattle, Plague to poison not armies only but whole districts—such are the lines along which military science is remorselessly advancing.” A century ago, Churchill predicted the risks of bioterrorism, foreseeing military strategies using engineered bioweapons that could devastate humanity and ecosystems.

In an op-ed for Business Insider in 2017, Microsoft founder and billionaire philanthropist Bill Gates warned “Infectious virus is a greater risk to humanity than nuclear war. Whether such an outbreak occurs due to a quirk of nature or is deliberately released by a terrorist, epidemiologists say a fast-moving airborne pathogen could kill more than 30m people in less than a year.” Gates emphasized the cataclysmic gravity of BW agents, indicating bioterrorism—the deliberate release of natural or engineered biological agents to harm humans, animals, or environments for terrorist purposes—could become one of humanity’s greatest perils.

Historical perspective

BW dates back to the 6th century BCE when the Assyrians poisoned enemy wells with ergot fungus, causing delusions, cardiovascular issues and death, and has since been a strategic tool in military conflicts. In the 4th century BCE, Scythian archers dipped arrows in animal feces to induce infections, while in 204 BCE, Hannibal used venomous snake-filled clay pots against Pergamene ships. In 1346, the Tatars catapulted plague-infected corpses into Kaffa, contributing to Black Death’s spread across Europe, which killed up to 200m people in the 14th century alone, wiping out nearly half of Europe's population.

During the 16th century, Spanish conquistadors used smallpox-infected blankets to devastate indigenous South American populations. The industrial revolution advanced microbiology, inadvertently enabling the weaponization of pathogens. During World War I, Germany allegedly infected enemy livestock with anthrax.

During World War II, Japan’s Units 731 and 100 weaponized pathogens like B anthrax, Yersinia pestis, V cholera and Shigella in ceramic bombs, dispersing them over Chinese cities via aerosols and testing them on prisoners, causing epidemics and an estimated 10,000 prisoners’ deaths.

The Cold War saw further advancements, with the United States and the Soviet Union developing extensive bioweapons programs.

Despite the 1972 Biological and Toxin Weapons Convention banning bioweapon development, production, and storage, signed by most UN countries, the enduring threat of bioterrorism remains alarming.

Modern bioterrorism

In 1984, the Rajneeshee sect conducted the first known US bioterror attack, contaminating salad bars in The Dalles, Oregon, with Salmonella typhimurium, infecting 751 and hospitalizing 45.

The 2001 US anthrax attacks, where letters containing B anthracis spores were mailed to media and government offices, caused 22 infections, five fatalities and required 30,000 people to undergo antibiotic treatment. The attack fueled widespread fear, prompted biosecurity policy reforms and incurred over $1bn in response costs, highlighting bioterrorism’s social, economic and global security impact.

The US Centers for Disease Control and Prevention classifies biological agents into three categories A, B, and C based on their threat level to public health and national security. Category A agents represent the highest threat due to their high transmissibility, mortality and societal impact, include B. anthracis, Francisella tularensis, Y. pestis, botulinum toxin, smallpox and hemorrhagic fever viruses (Ebola, Marburg).

Category B agents pose a moderate threat, with lower mortality but significant health implications, requiring enhanced diagnostic and surveillance, include Brucella, Clostridium epsilon toxin, Salmonella, Escherichia coli O157:H7, Shigella, Ricin toxin and V cholera.

Viruses are now considered the greatest biothreat in the EU’s expanded list including emerging and re-emerging pathogens—SARS, MERS, WestNile, Mpox and influenza A (H5, H7).

Advancements in biotechnology, CRISPR gene editing and gain-of-function research have reduced barriers to developing bioweapons, raising concerns about non-state actors misusing engineered pathogens or chimera with enhanced virulence or drug resistance. Unlike conventional weapons, BW agents remain silent, invisible and capable of widespread devastation, underscoring the urgency for global biodefense measures.

Biodefense

Biosecurity measures are vital for protecting biological research and mitigating bioterrorism risks. Early detection remains a challenge, as pathogens can spread undetected before symptoms manifest, complicating containment efforts. The Covid-19 pandemic exposed critical gaps in global biodefense, emphasizing the necessity for enhanced surveillance, rapid-response systems and international cooperation. A 2021 Lancet article by Long and Marzi reveals the global biodefense market at $12.2bn in 2019, projected to reach $19.8bn by 2027, growing at a 5.8 percent annual rate.

Strict biosecurity protocols regulate pathogen access, laboratory safety and dual-use research, but inconsistent enforcement and weak compliance mechanisms in many nations create vulnerabilities that could be exploited. A unified global biosecurity framework is essential to ensure scientific advancements benefit humanity, not destruction.

The Biological Weapons Convention prohibits the development, production, acquisition, transfer, stockpiling and use of biological and toxin weapons, yet its enforcement remains inadequate.

Geopolitical tensions complicate biosecurity by fueling mistrust and obstructing global cooperation. Scientific and political debates over SARS-CoV-2’s origins underscore concerns about laboratory safety and accidental pathogen leaks, and the need for stringent oversight in high-containment laboratories.

Safeguarding public health, Nepal’s three-tier health system must enhance surveillance, regulate biotechnology and enforce ethical research standards. Additionally, the Nepali Army and security agencies should develop robust capabilities to detect, prevent and respond to potential bioterrorism threats or bioweapons. This requires coordinated efforts in intelligence gathering, rapid response mechanisms and cross-sectoral collaboration to mitigate hazards and ensure national biosecurity.

Lessons from past pandemics and bioterrorism incidents must inform future biodefense strategies. As Churchill and Gates forewarned, bioterrorism remains an alarming threat. A failure to act now could lead to consequences far more catastrophic than any seen before.

“Death sits in the bowels,” and “bad digestion is the root of all evil,” proclaimed Hippocrates, the Greek philosopher and “father of medicine”, in the fourth century BCE. These quotes resonate profoundly in modern science as researchers continue to unveil the critical role the gut plays in both maintaining health and contributing to disease. Far from being just a digestive bowel, our gut harbors a complex and dynamic microbial ecosystem that influences nearly every aspect of our health.

The anatomy

The gut or gastrointestinal (GI) tract spans from the mouth to the rectum, and is crucial for digestion and nutrient absorption. However, its significance goes far beyond breaking down food. The gut is home to approximately 100 trillion microbes—bacteria, archaea, fungi and viruses—that outnumber human host cells by ten-fold. This bustling microbial metropolis, known as the gut microbiome, is often considered an “essential organ” due to its indispensable functions. 

Weighing roughly two kilograms—comparable to the human brain size—the gut microbiome contains 150 times more genes than the human genome. Over millennia, these microbes have co-evolved with humans, establishing a symbiosis that profoundly influences our physiology, immune system and even mental health.

A landmark study (Almeida et al 2020) published in Nature Biotechnology highlighted the staggering gut microbiome diversity. The study cataloged 204,938 reference genomes and 170m protein sequences from 4,644 bacterial species found in the human gut. Despite these advances, much of the gut microbiome remains an uncharted territory, with 70 percent of its microbial populations still uncultured in the laboratory and poorly understood.

Diverse, complex microbiota

The gut microbiota (GM) is a highly diverse and intricate microbial community, comprising over 1,000 heterogeneous species dominated by six major phyla, Firmicutes (Clostridium, Lactobacillus, Enterococcus), Bacteroidetes (Bacteroides), Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia coli), Fusobacteria, Verrucomicrobia, and Cyanobacteria. Of these, Firmicutes and Bacteroidetes dominate adult gut microbiota, accounting for 80-90 percent composition.

The dominant fungal species are Candida, Saccharomyces, Malassezia and Cladosporium. Meanwhile, the gut virome, the viral counterpart of the microbiome, is vast and largely uncultivated. Enteroviruses, parechoviruses, and sapoviruses are common residents. A Journal of Clinical Microbiology 2012 case report highlighted the gut virome diversity in stools collected from two healthy infant siblings during their first year of life, identified 15 enteric genera Adenovirus, Aichivirus, Anellovirus, Astrovirus, Bocavirus, Enterovirus, Parechovirus, Picobirnavirus, and Rotavirus. Additionally, the gut DNA viromes of Malawian one-year-old infant twins, with severe acute malnutrition, revealed Anellovirus, Picobirnavirus, and HPeV-1/-6 as the most frequently observed viruses.

Archaea are less diverse but highly conserved, with Methanobrevibacter smithii being the most frequently observed species across all six continents.

Each individual’s GM is a unique microbial signature, shaped by genetics, immune function, diet, lifestyle, environment, epigenetics and early microbial exposure during birth and breastfeeding. These microbes colonize different GI tract sections, with the highest biomass found in the caecum and proximal colon.

Health guardians 

GM performs crucial functions for maintaining health. In digestion and metabolism, gut microbes break down complex carbohydrates, synthesize vitamins such as B and K (via Bifidobacterium, Lactobacillus, Salmonella, Streptococcus, Clostridia, and Listeria), and produce short-chain fatty acids (SCFAs) like butyrate, which nourish colonic cells and regulate inflammation.

While humans cannot digest fiber, bacteria possess glycoside hydrolases/ polysaccharide lysases that ferment plant polysaccharides. Gut bacteria Eubacterium, Roseburia, Faecalibacterium and Coprococcus ferment indigestible fibers like resistant starches, and cellulose, generating butyrate, provides energy to colonocytes. Butyrate enhances bowel health by regulating colonic motility, improving blood flow and preventing pathogen overgrowth. GM Bacillus subtilis and E. coli synthesize riboflavin (vitamin B2), essential for cellular metabolism. With 70 percent of the immune system in the gut, microbes train immune cells to differentiate pathogens, ensuring immune balance. Furthermore, they strengthen the intestinal barrier, preventing harmful pathogens and toxins from entering the bloodstream.

Through the gut-brain axis, they influence mood, cognition and behavior, impacting conditions like anxiety and depression. Maintaining a healthy balance of GM, known as ‘normobiosis’, is crucial for overall well-being. Disruptions to this balance, ‘dysbiosis’, fosters pathogen overgrowth triggering health issues.

Declining diversity

Modern lifestyles and urbanization have significantly reduced GM diversity, impacting health. Processed diets, irrational antimicrobial use, sedentary lifestyles, high salt/protein intake and limited exposure to natural environments have caused a multigenerational loss of beneficial microbial signatures, key for immune resilience. A 2024 study in Kazakhstan revealed stark differences in gut diversity between urban and rural populations. Urban microbiomes showed reduced diversity, elevated Firmicutes/Bacteroidetes ratios and higher prevalence of Coprococcus and Parasutterella. Rural populations exhibited greater microbial diversity, with abundant Ligilactobacillus and Paraprevotella, correlating with their fiber-rich diets. Interestingly, a Nepali study (Jha et al 2018) found traditional Himalayan populations (Chepang, Raute, Raji, and Tharu) had distinct microbiome signatures compared to Americans, emphasizing lifestyles impact on gut diversity.

This GM diversity depletion is linked to autoimmune diseases and chronic inflammation. Dysbiosis is implicated in obesity where excessive Firmicutes enhance fat absorption. Inflammatory bowel disease (IBD) (Crohn’s disease, Ulcerative colitis), features reduced alpha diversity and shifts favoring pathogenic Gamma-proteobacteria. Colorectal cancer patients exhibit harmful bacteria, such as Fusobacterium nucleatum, genotoxic E. coli, Enterotoxigenic Bacteroides fragilis, produce metabolites fostering tumorigenesis. Dysbiosis also influences metabolic disorders (diabetes) and neurodegenerative diseases (Alzheimer’s, Parkinson's) through inflammation and the gut-brain axis.

Advancements

Advancements in gut microbiome research herald a new era of personalized medicine. Probiotics/prebiotics restore microbial balance by enhancing beneficial GM, while fiber-rich diets and healthy lifestyles promote gut health reducing inflammation. Conversely, ultra-processed foods, artificial sweeteners and emulsifiers disrupt this balance, decreasing diversity and driving inflammation. Innovations like fecal microbiota transplant treat C. difficile infections and hold promise for IBD.

Despite progress, gut microbiome research is still in its infancy, with challenges in decoding complex host-microbe interactions. Investigating gut microbial signatures of exceptional mountain climbers, like Sherpas, and ethnic Nepali communities could lead to personalized therapies. Technologies like metagenomics/metabolomics offer breakthroughs in diagnostics and therapies. Deepening our understanding of this hidden world within us can unlock new avenues to enhance well-being and resilience.

Recent reports of a Human Metapneumovirus (HMPV) outbreak in China have triggered global concerns, with echoes of the early Covid-19 pandemic raising speculation about a potential health emergency. However, HMPV is not a new or mysterious virus. It has been well-documented for decades as a significant cause of respiratory illness in children, elderly and immunocompromised individuals.

Identified in 2001 at Erasmus Medical Center in the Netherlands, HMPV was initially isolated from children with respiratory illnesses. Published in Nature Medicine, this study indicated all Dutch children were exposed to HMPV by the age of five. Retrospective analyses, however, suggest HMPV has been circulating in humans for 50 years.

HMPV belongs to the Pneumoviridae family along with respiratory syncytial virus (RSV) and the Metapneumovirus genus. This enveloped, single-stranded negative-sense RNA virus has two genetic lineages, A and B, further divided into six sublineages: A1, A2.1, A2.2.1, A2.2.2, B1 and B2. Emerging sublineages A2.2.1 and A2.2.2, were recently identified in pediatric respiratory infections in South India, as reported by the International Society of Infectious Diseases in 2025.

A Virology Journal 2009 genetic study by Vanderbilt University suggests HMPV diverged from Avian Metapneumovirus 200–400 years ago via zoonotic spillover from an avian reservoir, with phylogenetic evidence indicating a spillover event around 200 years ago, emphasizing HMPV’s long-standing presence in human populations.

Symptoms, risk groups and treatment

HMPV is a common etiological agent of respiratory tract infections, affecting infants, children under 15, the elderly, and immunocompromised individuals. Nearly all children are exposed by age five, with reinfections occurring throughout life. According to the US Centers for Disease Control and Prevention (CDC), it spreads via respiratory droplets, close contact, or contaminated surfaces, similar to the transmission of SARS-CoV-2, with an incubation period of 3–6 days. Symptoms vary from mild cough, nasal congestion, fever, and breath shortness to severe pneumonia, bronchiolitis, asthma exacerbations, especially in high-risk groups.

Infants and young children are prone to severe bronchiolitis and pneumonia. The elderly, often with comorbidities like asthma, may experience complications. Immunocompromised individuals face prolonged or severe illness, and pregnant women are at risk of respiratory complications that could affect both maternal and fetal health.

No specific antiviral treatment or vaccine exists for HMPV. Management relies on supportive care, supplemental oxygen, antipyretics and intravenous hydration when needed.

Seasonal outbreaks

HMPV is a seasonal respiratory virus, primarily circulating during late winter and early spring in temperate regions, similar to influenza and RSV. Recent reports of increased cases in China and parts of Asia align with this seasonal pattern. US CDC data also highlight annual outbreaks during these months, influenced by climatic conditions.

Despite comparisons to the Covid-19 pandemic, HMPV is not a novel virus. Identified over two decades back, it has been extensively studied, with over 300 PubMed scientific articles available. While it causes localized outbreaks, its transmission dynamics and clinical severity do not indicate pandemic potential. For instance, HMPV was the predominant virus during the 2002–2003 winter in Norwegian children hospitalized for respiratory infections, as reported in The Pediatric Infectious Disease Journal. Severe pneumonia occurred in some cases, but widespread outbreaks have remained limited to specific populations.

HMPV outbreaks have been documented globally, including Israel (2003), Japan (2003–2004), South Africa (2009-2013), Nicaragua (2011-2016), Western Sydney (2018), South Korea (2022), India (2022), China (2017-2023) and various regions. In Pakistan, HMPV accounted for 5–7 percent of pneumonia admissions in children at Aga Khan University Hospital (2009–2012). HMPV causes 5–10 percent of pediatric acute respiratory infections (ARIs) hospitalizations and is the second most common viral pathogen in certain settings. ARIs are a major global public health problem, causing significant morbidity and mortality, particularly in children.

A 2019 study at Nepal’s Kanti Children’s Hospital revealed a prevalence of 13 percent among children with ARIs, with infections more frequent in those under three years old (22 percent). Symptoms like cough and fever were universally observed.

Besides, data from Nepal’s Sarlahi district (2011–2014) detected HMPV in five percent of infants, identifying three genotypes (A2, B1, B2). A recent Chinese CDC analysis ranked HMPV second among 11 respiratory viruses affecting children under 15 years, with a positivity rate of 6.2 percent in influenza-like illness.

These findings reflect a seasonal uptick, not an unprecedented surge. Factors like colder weather and increased indoor crowding contribute to HMPV’s seasonal prevalence.

Covid-19 lessons

The Covid-19 pandemic highlighted the importance of preparedness, evidence-based communication and robust public health strategies in managing infectious disease outbreaks. While HMPV does not pose the same threat as Covid-19, its current attention emphasizes the need to apply these lessons. Strengthened surveillance systems are essential for early detection, while public education can counter misinformation, reduce anxiety and encourage preventive behaviors. Investment in research on HMPV’s pathogenesis, treatments and vaccine development is key to mitigating its long-term impacts and bolstering public health resilience.

Precautions

The rise in HMPV cases in China and India warrants vigilance but not alarm. Vulnerable populations—infants, rural children, immunocompromised individuals—are particularly at risk, in regions with limited healthcare resources like Nepal. Preventive measures, supportive care and community-driven initiatives are critical to minimizing HMPV’s burden.

Between 2011 and 2014, HMPV infections in rural southern Nepal were associated with adverse outcomes, including an increased risk of small-for-gestational-age births in pregnant women. Interventions targeting febrile respiratory illness in pregnancy could improve maternal and neonatal health in resource-limited settings.

Hygiene practices, regular handwashing and respiratory etiquette, alongside isolation during illness, can reduce HMPV transmission. Enhanced diagnostic capabilities and heightened awareness will support disease management and safeguard at-risk groups.

Policymakers, healthcare providers and community leaders must collaborate to strengthen surveillance systems, improve diagnostics and develop effective preventive strategies. Public health messaging should prioritize education and reassurance, focusing on practical actions to protect vulnerable populations. By taking informed and measured steps, HMPV’s impact can be effectively mitigated, fostering resilience against future viral outbreaks.

The author is a researcher with a PhD degree at Nexus Institute of Research and Innovation