1944: Discovery of Streptomycin and First TB Drug (1944)

Tuberculosis killed approximately one in seven people in industrialised nations during the 19th and
early 20th centuries, yet penicillin was entirely inactive against Mycobacterium tuberculosis.
Selman Waksman at Rutgers University had devoted himself since the 1930s to systematically screening
soil actinomycetes for antimicrobial compounds, reasoning that microorganisms in soil must produce
antibiotics to compete with each other.

In 1943, Waksman's laboratory—with graduate student Albert Schatz doing much of the practical work—
isolated streptomycin from Streptomyces griseus. Schatz and Waksman jointly published the discovery
in January 1944. Animal studies confirmed activity against M. tuberculosis, and the drug was rapidly
tested clinically by William Feldman and Corwin Hinshaw at the Mayo Clinic, who treated their first
TB patient in November 1944 with dramatic results.

The British Medical Research Council's 1948 streptomycin trial—the first randomised controlled
trial ever conducted—demonstrated statistically significant survival benefit in tuberculosis. This
trial, designed by Austin Bradford Hill, established the RCT as the methodological gold standard
for clinical evidence, fundamentally reshaping how drug efficacy would be evaluated from that
point onwards.

Streptomycin's clinical use was complicated by rapid emergence of resistance, toxicity (vestibular
and renal), and the discovery that monotherapy was insufficient. These challenges drove the
development of combination antibiotic therapy and eventually the discovery of isoniazid (1952)
and rifampicin (1967), establishing the multi-drug TB regimen still in use today.

Waksman received the 1952 Nobel Prize in Physiology or Medicine. The controversy over Schatz's
contribution—he was omitted from the prize and sued Waksman for recognition and royalties—became
an early landmark case in scientific credit attribution.