Thalidomide: From Morning Sickness Miracle to Tragic Teratogen

Thalidomide (Contergan, Distaval) was marketed in 1957 as a safe sedative and anti-emetic for pregnancy nausea. By 1961, it was linked to phocomelia (severe limb reduction defects) and other malformations (ear, eye, cardiac, GI) in >10,000 children worldwide.

Mechanism of Teratogenicity

Binds cereblon (CRBN) E3 ubiquitin ligase → degrades transcription factors (SALL4, others) critical for limb bud and organogenesis. Critical window: days 20–36 post-fertilization.

Regulatory Legacy

• US: FDA reviewer Frances Kelsey blocked approval; 1962 Kefauver-Harris Amendments mandated efficacy proof + informed consent.
• Global: Strengthened pharmacovigilance, pregnancy categorization, teratogenicity testing requirements.

Modern Use (Strictly Controlled)

• Multiple Myeloma: With dexamethasone (FDA 2006).
• ENL (Leprosy): WHO essential medicine.
• REMS Program (US): Mandatory pregnancy testing, contraception, registry, prescriber/pharmacy certification.

Thalidomide reshaped drug regulation forever—proving that "safe in adults" ≠ safe in development.