🎯 Central Question

Why are there so few pathogens, given the vast diversity of microbes? And what determines when new pathogens emerge?

🔬 Casadevall’s Model: Biological Requirements

For a microbe to become pathogenic in humans, it needs all three:

1. Survival in host 🧬 → withstand body temperature, immune defenses, etc.
2. Virulence factors 🗡️ → tools to invade, evade immunity, cause damage.
3. Host susceptibility 🧑‍🤝‍🧑 → genetics, immune history, and receptors that microbes can latch onto.

👉 Plus: It must actually harm the host (fitness cost).

Casadevall’s conclusion: these traits are rare and fleeting, which explains the low number of pathogens.

🌱 Drake’s Expansion: Ecological & Evolutionary Accelerants

Biology alone isn’t enough. Drake adds three eco-evolutionary factors:

1. Host availability 🏘️
   • Depends on density, abundance, and social structure.
   • In hunter-gatherer times, small mobile groups = little pathogen spread.
   • Around 10,000 years ago (agriculture revolution), humans settled → denser populations = “crowd diseases” like measles, TB, smallpox.
   • 📊 Estimate: Since Neolithic times, ~1,100 bacterial pathogens emerged. Rate = 1 per 1.4 billion person-years.
2. Exposure to pathogens (Geographic overlap) 🌍✈️
   • Isolated populations = protection (diseases burn out in small groups).
   • Globalization = rapid mixing: trade, travel, migration, shipping.
   • Pathogens follow commerce → e.g. plague, malaria to Americas, COVID-19 spread.
   • Cholera case study 💧: All 7 pandemics tied to human movement. Current pandemic (El Tor strain) began in 1961 in Indonesia, spread via regattas and shipping routes, later across oceans (e.g., to Peru in 1991).
3. Genomic innovation 🧬⚡
   • Microbes can “upgrade” via horizontal gene transfer (HGT) using mobile genetic elements (MGEs: plasmids, phages, transposons).
   • Example: Cholera toxin genes acquired via MGEs.
   • Other examples:
     • Acinetobacter baumannii 🦠 → antibiotic resistance.
     • Vibrio harveyi 🐟 → virulence + resistance via HGT.
   • Global mixing increases opportunities for genetic exchange → faster pathogen evolution.

📊 Big Picture: Pathogens in the Future

• Biological prerequisites (Casadevall) still matter.
• But the 21st century drivers are eco-evolutionary: 🌍 travel, 🛳️ trade, 🧬 gene flow, 🌱 environmental change.
• Prediction: With 10.3 billion people by 2100 → ~504 new bacterial pathogens may emerge (likely an underestimate).
• ⚖️ Counterbalance: Better healthcare + reduced animal contact might lower per capita risk.

📌 Take-Home Points

• Few pathogens exist because the right combination of traits and circumstances is rare.
• But human activity (population growth, globalization, ecological disruption) massively amplifies opportunities for emergence.
• Pathogen emergence = biology (can it infect?) + ecology (can it spread?) + evolution (can it innovate?).