Timeline — 1900-1949
62 Entries
From the Biologics Control Act through World War II military vaccination and the race for a polio vaccine
Walter Reed Yellow Fever Commission
Scientific BreakthroughU. S.
First Nobel Prize in Medicine (von Behring)
Nobel PrizeAwarded for serum therapy work on diphtheria.
Camden Smallpox Vaccine Deaths
Safety Event9 children died from contaminated smallpox vaccine.
St. Louis Diphtheria Antitoxin Deaths
Safety Event13 children died from tetanus-contaminated antitoxin.
Brazil Mandatory Vaccination Law
Legal & LegislativeBrazil's Congress passed a mandatory smallpox vaccination law championed by public health director Oswaldo Cruz, sparking the 1904 Vaccine Revolt in Rio de Janeiro.
Biologics Control Act
Regulatory MilestoneFirst federal regulation of biological products. Response to 1901 disasters.
Revolta da Vacina (Brazil Vaccine Revolt)
Anti-Vaccination MovementArmed uprising in Rio de Janeiro against mandatory smallpox vaccination law. Rooted in class tensions and distrust of government health campaigns targeting the urban poor.
Theobald Smith Discovers Anaphylaxis in Vaccine Context
Scientific BreakthroughSmith observed that guinea pigs previously injected with diphtheria toxin-antitoxin mixtures could die from subsequent injections, contributing to understanding of allergic reactions to biological products.
Jacobson v. Massachusetts
Legal & LegislativeU. S.
Nobel Prize: Robert Koch
Nobel PrizeAwarded for TB research and discoveries.
Pure Food and Drug Act
Regulatory MilestoneEstablished federal oversight of food and drug safety. Precursor to FDA.
Nobel Prize: Metchnikoff and Ehrlich (Immune System)
Nobel PrizeShared Nobel Prize for foundational work on immunity: Metchnikoff for phagocytosis (innate immunity) and Ehrlich for humoral immunity (antibody theory). Established the conceptual framework for understanding vaccine mechanisms.
Schick Test for Diphtheria Immunity
Scientific BreakthroughSchick developed a skin test to determine whether a person was immune to diphtheria, enabling targeted vaccination campaigns rather than blanket immunization.
Mass Vaccine Production During World War I
Vaccine Platform / TechnologyWorld War I drove the first industrial-scale vaccine production. Millions of typhoid and tetanus doses were manufactured for military use, establishing principles of large-scale vaccine manufacturing.
First Inactivated Pertussis Vaccine
Discovery & DevelopmentEarly whole-cell pertussis vaccines developed, though efficacy was not definitively demonstrated until Kendrick and Eldering's controlled trial in 1939.
Nobel Prize: Jules Bordet (Complement System)
Nobel PrizeAwarded for discoveries relating to the complement system in immunity. Bordet's work on complement fixation enabled diagnostic tests for many infectious diseases.
Dallas Diphtheria Antitoxin Incident
Safety Event5 children died from contaminated antitoxin.
First BCG Vaccine (Tuberculosis)
Discovery & DevelopmentBCG (Bacillus Calmette-Guerin) first administered to humans. Developed over 13 years of serial passage.
BCG Vaccination Program Begins in France
Public Health CampaignCalmette and Guerin began vaccinating newborns with the BCG vaccine in Paris. Despite the 1930 Lubeck disaster, BCG was gradually adopted worldwide.
Zucht v. King
Legal & LegislativeU. S.
First Diphtheria Vaccine (Toxoid)
Discovery & DevelopmentRamon developed diphtheria toxoid (inactivated toxin) for active immunization.
Diphtheria Toxoid Developed (Ramon)
Discovery & DevelopmentRamon at the Pasteur Institute developed the diphtheria toxoid by inactivating diphtheria toxin with formalin. This approach of converting toxins to safe-but-immunogenic toxoids became a foundational vaccine strategy.
First Tetanus Toxoid
Discovery & DevelopmentInactivated tetanus toxin for active immunization.
Nome Alaska Diphtheria Serum Run
Public Health CampaignTwenty mushers and 150 sled dogs, including lead dog Balto, relayed diphtheria antitoxin 674 miles across Alaska in blizzard conditions to reach the ice-locked town of Nome during an outbreak.
First Use of Aluminum Adjuvant in Vaccines
Vaccine Platform / TechnologyGlenny demonstrated that aluminum salts enhanced immune responses to diphtheria toxoid, establishing the first widely used vaccine adjuvant. Aluminum adjuvants remain in use in numerous vaccines today.
Georgetown Delaware Armed Vaccine Resistance
Anti-Vaccination MovementA retired Army lieutenant and city councilman led an armed mob to force state health officers out of Georgetown, Delaware, preventing a vaccination campaign.
First Pertussis Vaccine
Discovery & DevelopmentFirst whole-cell pertussis vaccine.
First Tetanus Toxoid Vaccine (Human Use)
Discovery & DevelopmentRamon at the Pasteur Institute developed the tetanus toxoid for human immunization. Tetanus toxoid was first widely administered to soldiers during World War II.
First Large-Scale Diphtheria Immunization Campaigns
Public Health CampaignMass diphtheria toxoid immunization campaigns in cities like New York and Toronto dramatically reduced diphtheria incidence, demonstrating the public health impact of organized vaccination programs.
Nobel Prize: Charles Nicolle (Typhus Transmission)
Nobel PrizeAwarded for discovering that epidemic typhus is transmitted by body lice. This knowledge directly informed military vaccination and delousing campaigns during both World Wars.
Alexander Fleming Discovers Penicillin
Scientific BreakthroughNot a vaccine, but revolutionized infectious disease treatment and changed the landscape for vaccine-preventable vs. treatable diseases.
Bundaberg Tragedy
Safety Event12 children died from contaminated diphtheria toxin-antitoxin.
Lubeck Disaster
Safety Event72 infants died from contaminated BCG vaccine.
Nobel Prize: Karl Landsteiner (Blood Types)
Nobel PrizeAwarded for discovery of human blood groups. Landsteiner's work on immunochemistry also contributed to understanding of vaccine antigen-antibody interactions.
Ernest Goodpasture Develops Egg-Based Vaccine Production
Scientific BreakthroughGoodpasture demonstrated that viruses could be grown in embryonated chicken eggs, creating the technique that became the standard for influenza and other vaccine manufacturing for decades.
Kendrick and Eldering Develop and Prove Pertussis Vaccine
Key FigurePearl Kendrick and Grace Eldering, working at the Michigan Department of Health, developed and conducted the first controlled clinical trial of the pertussis vaccine, demonstrating efficacy in 1939.
First Yellow Fever Vaccine
Discovery & DevelopmentTheiler developed 17D attenuated strain. Nobel Prize 1951.
First Live Attenuated Yellow Fever Vaccine (French Neurotropic)
Discovery & DevelopmentThe Pasteur Institute in Dakar developed a neurotropic yellow fever vaccine from mouse brain passages. Used extensively in French Africa until the 1980s, when it was discontinued due to rare encephalitis risk.
Brodie/Kolmer Polio Vaccine Failures
Safety EventTwo experimental vaccines caused paralysis and deaths.
First Attempt at Yellow Fever Mass Vaccination
Public Health CampaignLarge-scale yellow fever vaccination campaigns began in Brazil using the French neurotropic strain and in Africa using Theiler's 17D strain, protecting millions but also revealing safety issues with contaminated lots.
Max Theiler Develops 17D Yellow Fever Strain
Key FigureTheiler attenuated the yellow fever virus through serial passage to create the 17D vaccine strain at the Rockefeller Institute. This strain remains the basis of all yellow fever vaccines used today.
First Influenza Vaccine
Discovery & DevelopmentFirst live attenuated influenza vaccine.
First Typhus Vaccine
Discovery & DevelopmentWeigl developed vaccine using lice. Saved lives during WWII.
March of Dimes Founded
Public Health CampaignNational Foundation for Infantile Paralysis (later March of Dimes) created to fund polio research.
Kendrick and Eldering Prove Pertussis Vaccine Efficacy
Discovery & DevelopmentMichigan Department of Health scientists Kendrick and Eldering completed the first controlled clinical trial demonstrating pertussis vaccine efficacy, reducing infection rates from 15. 1 to 2.
WWII Military Vaccination Programs
Public Health CampaignWorld War II drove the largest military vaccination programs in history, with mandatory immunization against typhoid, tetanus, smallpox, yellow fever, and typhus for millions of Allied soldiers.
Tetanus Toxoid Approved for U.S. Military
Regulatory MilestoneThe U. S.
Yellow Fever Vaccine / Hepatitis B Contamination
Safety EventApproximately 330,000 U. S.
Gruinard Island Anthrax Decontamination (Vaccine Context)
Discovery & DevelopmentBritish biological weapons tests contaminated Gruinard Island with anthrax. The site remained quarantined until 1990 decontamination, informing understanding of anthrax persistence relevant to vaccine development.
Public Health Service Act
Regulatory MilestoneConsolidated all existing public health legislation and established the legal framework for federal quarantine, biologics regulation, and communicable disease control that governs vaccine oversight today.
Influenza Vaccine Licensed (U.S.)
Regulatory MilestoneFirst civilian influenza vaccine licensed after military use during WWII.
Thomas Francis Jr. and Jonas Salk Develop Influenza Vaccine
Key FigureFrancis and Salk at the University of Michigan developed the first effective inactivated influenza vaccine, initially for U. S.
Influenza Vaccine Licensed for Civilian Use
Regulatory MilestoneAfter military use since 1945, the inactivated influenza vaccine was licensed for civilian use, beginning the long tradition of annual influenza vaccination campaigns.
NYC Mass Smallpox Vaccination Campaign
Public Health CampaignAfter a smallpox importation, New York City vaccinated 6. 35 million residents in less than a month, one of the largest and fastest mass vaccination campaigns in U.
Freeze-Drying (Lyophilization) Applied to Vaccines
Vaccine Platform / TechnologyApplication of freeze-drying technology to smallpox vaccine enabled stable storage without refrigeration, critical for the eventual global eradication campaign in developing countries.
NYC Smallpox Vaccine Encephalitis
Safety Event6. 35 million vaccinated; 45 encephalitis cases; 4-6 deaths.
DTP Combination Vaccine
Discovery & DevelopmentPertussis vaccine combined with diphtheria and tetanus toxoids.
Kyoto Diphtheria Vaccine Disaster
Safety Event68 children died from improperly detoxified vaccine.
WHO Founded
International ProgramWorld Health Organization established. Would become central to global vaccination efforts.
Last Naturally Occurring Smallpox Case in United States
Disease EradicationThe last naturally occurring case of smallpox in the United States was recorded, though routine vaccination continued until 1972.
WI-38 Precursor: Human Cell Culture Advances
Scientific BreakthroughEnders, Weller, and Robbins grew poliovirus in non-nervous tissue human cell cultures for the first time, eliminating the need for monkey nervous tissue and enabling safer vaccine production.
Enders/Weller/Robbins Cell Culture Breakthrough
Scientific BreakthroughGrew poliovirus in cell culture. Nobel Prize 1954.