The fight against germs in the 20th century

By 1900 scientists could identify many disease-causing bacteria — but had few cures. The 20th century closed that gap. Magic bullets (Salvarsan), the discovery and mass production of penicillin, the development of antibiotics, and the alarming rise of antibiotic resistance are the four parts of this story.

The starting point — 1900

• Germ theory and bacteriology established (Pasteur, Koch).
• Antiseptic surgery (Lister); aseptic surgery (1890s).
• Vaccination growing — Pasteur's rabies, diphtheria toxoid, BCG for TB.
• Public health acts had cleaned cities.

But:

• No way to kill bacteria once inside the body without harming the patient.
• TB, syphilis, pneumonia, diphtheria, meningitis still killed millions.
• Childbirth carried significant risk.

Magic bullets — Paul Ehrlich (1854–1915)

A German chemist who hypothesised: if dyes could stain specific bacteria, perhaps a chemical could target and kill specific microbes — a "magic bullet" (Zauberkugel).

• 1909–10 — Ehrlich's team tested 606 compounds to find one that killed syphilis bacteria without harming the patient.
• The 606th compound — Salvarsan 606 — worked. First effective treatment for syphilis.
• 1932 — German chemist Gerhard Domagk discovered Prontosil — the first sulfa drug — effective against streptococcus.

These chemotherapy agents proved that targeted drugs could work. But sulfa drugs had side effects and resistance soon emerged.

Alexander Fleming (1881–1955) — discovery of penicillin

Fleming was a Scottish bacteriologist at St Mary's Hospital, London. In 1928 he returned from holiday to find a petri dish of staphylococcus bacteria contaminated with mould — and around the mould, the bacteria had died.

• The mould was Penicillium notatum.
• He identified its bacteria-killing property and named the substance penicillin.
• Published in 1929 in the British Journal of Experimental Pathology.

Limits of Fleming's work:

• He could not isolate or mass-produce penicillin.
• He gave up further research within a few years.
• It would take a decade and another team to turn his discovery into medicine.

Florey and Chain — mass production

In Oxford in 1939, Australian pathologist Howard Florey and German biochemist Ernst Chain rediscovered Fleming's paper and began purifying penicillin.

• 1940 — first lab successes.
• 1941 — first patient (Albert Alexander, a policeman with a face infection) treated. Improved dramatically — but supplies ran out and he died.
• 1942 — Florey travelled to America to seek mass-production funding (Britain at war).
• American pharmaceutical companies (Pfizer, Merck) used deep-tank fermentation to scale up.
• By D-Day 1944 — enough penicillin for all Allied wounded.

Impact:

• WWII soldiers' lives saved in vast numbers.
• Pneumonia, meningitis, gangrene, sepsis became treatable.
• Maternal mortality fell sharply.
• Fleming, Florey and Chain shared the 1945 Nobel Prize.

The age of antibiotics 1944–present

Penicillin opened the era of antibiotics:

• 1944 — Streptomycin (first effective TB drug, by Selman Waksman).
• 1948 — Chlortetracycline.
• 1949 — Chloramphenicol.
• 1950s–60s — Rapid expansion of antibiotic classes.

Combined with vaccination programmes, antibiotics ended many infectious diseases as mass killers.

The crisis — antibiotic resistance

Bacteria evolve. From the 1940s onward, antibiotic-resistant bacteria emerged:

• MRSA (methicillin-resistant Staphylococcus aureus) — first identified 1961.
• C. difficile — common hospital-acquired infection.
• TB — multi-drug-resistant strains since 1990s.
• Gonorrhoea — increasing resistance to all antibiotics.

Causes of resistance:

• Over-prescription — antibiotics given for viral infections (which they don't treat).
• Patient non-compliance — stopping the course early.
• Agricultural use — antibiotics in livestock feed.
• Hospital transmission — high concentration of bacteria and antibiotic use.
• Lack of new antibiotics — few new classes developed since 1980s (high cost, low return for pharmaceutical companies).

The WHO has warned of a "post-antibiotic era". Modern strategies:

• Antibiotic stewardship — restricting prescriptions.
• Hand hygiene in hospitals.
• Bacteriophage therapy — using viruses to attack bacteria.
• Alternative treatments — antibodies, probiotics.

Other 20th-century breakthroughs

• Vaccines — polio (Salk 1955, Sabin 1962), MMR (1971), HPV (2006), COVID (2020).
• Antiretrovirals for HIV (1990s).
• Antivirals for influenza, herpes.

Examiner advice

When evaluating breakthroughs, weigh:

• Theory (Ehrlich's magic bullet concept).
• Discovery (Fleming's chance observation).
• Application (Florey, Chain, mass production).
• Limits (resistance threatens 100 years of progress).

Strong answers connect 19th-century germ theory → 20th-century antibiotics → 21st-century resistance crisis as one continuous story.