Module 0 · Foundations

Discovery & the Tree of Life

1. Leeuwenhoek’s 1676 “Animalcules”

Antonie van Leeuwenhoek was a Delft cloth merchant who built single-lens microscopes of unprecedented quality — ground glass beads ~1 mm across, mounted in brass, that achieved ~270× magnification at a time when compound microscopes managed ~50×. In a 1676 letter to the Royal Society of London (Letter 18), he described tiny moving creatures in pepper-water infusions, calling them animalcula. His drawings are unmistakable: he had seen rod-shaped, spiral, and cocci bacteria. The Society sent the visiting microbiologist Robert Hooke and others to verify; the observations were confirmed.

For nearly two centuries, Leeuwenhoek’s animalcules were a curiosity. The question of what they actually did would wait for Pasteur and Koch.

2. Pasteur and the Germ Theory

Louis Pasteur (1822–1895) used elegant experiments — the swan-neck flask of 1859 the most famous — to show that microorganisms cause fermentation, spoilage, and disease, and do not spontaneously generate from broth. Boiled broth in a flask whose long neck blocked airborne dust remained sterile indefinitely; broken the neck and it spoiled within days. The result demolished the spontaneous generation theory that had survived Aristotle.

Pasteur went on to demonstrate that specific microbes cause specific diseases (the germ theory), invented attenuated-strain vaccines for chicken cholera, anthrax, and rabies, and gave his name to pasteurisation. His most far-reaching contribution was philosophical: disease is not punishment, miasma, or imbalance — it is biology.

3. Koch’s Postulates (1884)

Robert Koch worked out, between his 1876 anthrax paper and his 1882 identification of Mycobacterium tuberculosis, the formal logic by which a microbe is proven to cause a disease. Now known as Koch’s postulates:

  1. The organism must be found in all diseased individuals and absent from healthy ones.
  2. The organism must be isolated and grown in pure culture.
  3. Inoculation of the cultured organism must reproduce the disease in a healthy host.
  4. The organism must be re-isolated from the experimentally diseased host.

Modern microbiology relaxes these (asymptomatic carriers, organisms that won’t culture, viruses, the human microbiome), but the postulates remain the gold standard of causal evidence. Koch shared the 1905 Nobel Prize for the work on tuberculosis.

4. The Three Domains: Carl Woese 1977

Until 1977, biology recognised two great divisions of life: prokaryotes (no nucleus) and eukaryotes (nucleus). Carl Woese, sequencing small-subunit ribosomal RNA (16S/18S rRNA), discovered that the prokaryote group was actually two deeply divergent lineages. He called the second group Archaea and proposed three domains:

  • Bacteria — the “classic” bacteria including E. coli, Bacillus, Mycobacterium, cyanobacteria.
  • Archaea — methanogens, halophiles, hyperthermophiles, and the apparent ancestors of the eukaryotic cytoplasm (Asgard archaea, 2015).
  • Eukarya — everything with a nucleus, mitochondria from a once-free α-proteobacterium, chloroplasts from a once-free cyanobacterium.

16S rRNA works as a universal molecular clock because the ribosome is essential, ancient, and evolves slowly. The classification by 16S sequence has reshaped microbiology entirely — the gut microbiome, environmental shotgun metagenomics, and uncultured-organism surveys all depend on it.

5. Bacteria vs Archaea vs Eukarya: A Quick Compare

FeatureBacteriaArchaeaEukarya
Membrane lipidsester-linked, straightether-linked, isoprenoidester-linked
Cell wallpeptidoglycanpseudopeptidoglycan / S-layercellulose / chitin / none
Ribosome70S (50S + 30S)70S, eukaryote-like factors80S (60S + 40S)
Initiator tRNAfMetMet (no formylation)Met
DNA packagingHU/H-NS, no histoneshistone-likehistones in nucleosomes

The differences matter clinically: most antibiotics targeting bacterial ribosomes, cell wall, or DNA replication exploit features absent in eukaryotes. Archaea are insensitive to most antibacterials — a fact that leaks usefully into modern microbiome work and into hyperthermophile biotechnology.