History of Vaccines

Faroe Islands Yield New Observations (1846)

Danish physician Peter Panum was sent to the Faroe Islands (located in the North Atlantic, between Iceland and Scotland) to study a measles epidemic there. He spent approximately five months on the islands, noting that although measles was traditionally a disease of childhood in most parts of the world, it "attacked almost the entire population [of the Faroes] without respect to age." Panum hypothesized that the same isolation that generally protected the Faroes from exposure to illness also led to increased mortality when a disease did reach the islands. He wrote: "It is obvious, then, that prophylactic measures against the introduction and spread of foreign diseases are of very great importance in such places, where they can be put into execution, as, for example, on the Faroes; whereas they are of no importance where they are rendered impracticable by a great conflux of people and by other conditions, as in Copenhagen. Here [In Copenhagen], therefore, an edict of quarantine against measles would seem ludicrous, but the Faroe Islands would probably not have lost nearly 100 inhabitants if an edict directed against the introduction of measles had not been removed some years ago." Panum also took advantage of the isolated nature of the islands to study the transmission of the disease. He observed that the measles rash appeared approximately fourteen days after a person was exposed to infective matter, and that surviving the infection resulted in lifelong immunity against the disease. "The isolated situation of the villages, and their limited intercourse with each other, made it possible in many, in fact in most cases, to ascertain where and when the person who first fell ill had been exposed to the infection, and to prove that the contagion could not have affected him either before or after the day stated... In Fuglefjord, on Østerø, on account of my observations, I acquired the reputation of being able to prophesy. On my first arrival there, the daughter of Farmer J. Hansen, churchwarden, had recently had measles, but had then got up, and, except for a slight cough, was almost entirely well. All the other nine persons in the house were feeling well in every respect and expressed the hope that they would escape the disease. I inquired as to what day the exanthem [rash] had appeared on the daughter, asked for the almanac, and pointed to the fourteenth day after that... with the remark that they should make a black line under that date, for I feared that on it measles would show itself on others in the house... As it turned out I was summoned to Fuglefjord again ten days later and was met with the outcry: 'What he said was correct! On the day he pointed out the measles broke out, with its red spots, on all nine.'" —Peter Panum, Observations made during the epidemic of measles on the Faroe Islands in 1846

1949 Bodian Finds Three Types of Poliovirus

David Bodian, MD, PhD (1910-1992), and Isabel Morgan, PhD (1911-1996), researchers at Johns Hopkins University School of Medicine, published a paper identifying three types of poliovirus. Their work would be crucial for developing a vaccine, as a vaccine would have to produce immunity to all poliovirus types. This initial study was small, but further research (much of it overseen by Jonas Salk, MD) confirmed that there were no more than three immunologically different types of polio.

1994 Diphtheria in the Russian Federation

Declining diphtheria immunization among children and waning adult immunity led to an epidemic in the former Soviet Union. In 1994, the Russian Federation saw 39,703 diphtheria cases. In contrast, in 1990, there had been only 1,211 cases.

1926 Opposition to Vaccination Grows

Despite vaccination's successes against smallpox, opposition to vaccination continued through the 1920s, particularly against compulsory vaccination. In 1926, a group of health officers visited Georgetown, Delaware, to vaccinate the townspeople. A retired Army lieutenant and a city councilman led an armed mob to force them out, successfully preventing the vaccination attempt.

1943 War Breeds Outbreaks

Diphtheria outbreaks accompanied war and disruption in Europe: in 1943, there were 1 million cases in Europe, with 50,000 deaths (not including the USSR).

1935 Changing Standards

Diphtheria toxoid immunization became more widespread during the 1930s, but use of toxin-antitoxin mixture persisted. During this time, some confusion existed among parents and physicians about the need for booster doses and whether immunization was achieved after one or two doses.

1976 Whooping Cough: Fewest Annual U.S. Cases Reported

Reported cases of pertussis (whooping cough) had been dropping in the United States since the introduction of the combined DTP (diphtheria, tetanus, and pertussis) vaccine. The highest recorded number of annual cases had been in 1934, with more than 260,000 cases. By 1976, the number of annual cases was down to 1,010.

Smallpox Hospital Loses 110 Patients in 1 Week (12/12/1862)

Richmond's smallpox hospital admitted 250 patients during the week of December 12-19. Of the 250, 110 died.

1952 Polio Cases Surge

57,628 polio cases were reported in the United States in 1952, more than 21,000 of them paralytic cases. This epidemic heightened parents' fears of the disease and focused public awareness on the need for a vaccine.

Yellow Fever in the American Colonies (1699)

Charleston and Philadelphia suffered the first confirmed yellow fever outbreaks in the American colonies. The death tolls in both cities were high, and life came nearly to a standstill. A Quaker in Philadelphia wrote: "In this distemper had died six, seven, and sometimes eight in a day, for several weeks, there being few houses, if any, free of the sickness. Great was the fear that fell on all flesh! [He] saw no lofty or airy countenances nor heard any vain jesting to move men to laughter....But every face gathered paleness, and many hearts were humbled, and countenances fallen and sunk, as such that waited every moment to be summoned to the bar and numbered to the grave." - Quaker diarist, quoted in John Duffy, Epidemics in Colonial America, Baton Rouge: Louisiana State University Press, 1953.

1981 Chickenpox: Attenuated Strain Licensed in U.S.

Chickenpox had emerged as the most common childhood infectious disease after vaccination reduced rates of measles, mumps, and rubella. Vaccine researcher Maurice Hilleman and his group had long been working on a chickenpox vaccine; in 1981, Merck licensed the "Oka" strain of the varicella virus in the United States, which had been isolated from a three-year-old boy with chickenpox by Michiaki Takahashi. This strain would be further attenuated by Merck and used to develop a U.S. chickenpox vaccine.

10/20/2010 Cholera in Haiti

Cholera emerged in Haiti in the aftermath of January 12, 2010, earthquake there. Notably, cholera had not been reported in Haiti since 1960. Investigations of the epidemic suggest importation of cholera by infected aid workers. The bacteria likely spread through contaminated river drinking water. Many public health authorities have not advocated for widespread use of the cholera vaccine in the Haitian epidemic for several reasons: the difficulty of deploying a multi-dose vaccine regimen in chaotic circumstances, the fact that many people had already been exposed to the bacteria, and the potential to detract from meeting other public health needs. Other groups, however, have urged for deployment of the vaccine in spite of the obstacles. As of April 2011, 4,787 Haitians had died from cholera.

01/29/1991 Cholera: A Return to South America

Cholera made an unexpected return to the South America in 1991, when people in coastal areas of Peru became ill with the disease. It quickly spread inland via contaminated water and food, and then to neighboring countries. Scientists postulate that the epidemic emerged when changing weather patterns enabled the wider reproduction and spread of cholera vibrios found naturally in the ocean environment there. The scope of the epidemic was enormous: As a CDC report stated, "Because of underreporting, the more than 1,000,000 cholera cases and 10,000 deaths reported from Latin America through 1994 represent only a small fraction of the actual number of infections." remain there for the next 10 years. Cholera returned to Haiti in the aftermath of the January 2010 earthquake, possibly imported by foreign aid workers.

The First English Variolation (4/21/1721)

Lady Mary Montagu brought the practice of variolation to England, where she had Dr. Charles Maitland variolate her two-year-old daughter. Lady Montagu would come under considerable criticism for advocating variolation, a practice that slowly began to spread as its ability to protect against smallpox became apparent. The results, however, were sometimes fatal: two to three percent of those variolated died of smallpox (in contrast to 20-30% who died after contracting smallpox naturally). What's more, variolated individuals could pass the disease on to others.

1948 Koprowski Tests Polio Vaccine on Himself

Lederle Laboratories researcher Hilary Koprowski, MD (1916-2013), after testing his attenuated Type II poliovirus vaccine on chimpanzees, drank a concoction of his vaccine. He and his assistant, who also took the vaccine, seemed to suffer no ill effects.

5/8/1955 Polio Vaccination Suspended

Leonard Scheele, MD, the U.S. Surgeon General, suspended the polio vaccination program in order to investigate the safety of all six manufacturers' vaccine. The full review concluded that 11 people died from the vaccine and hundreds were paralyzed. Though the cause of the disaster was never proven, it is likely that certain production methods (which, it turns out, did not follow Salk's instructions) resulted in a failure to completely kill the Type 1 (Mahoney) poliovirus in the vaccine.

London Smallpox Deaths (1751)

London recorded a record 3,538 smallpox deaths for the year.

Pneumococcal: Bacterium Discovered (1881)

Louis Pasteur and U.S. Army physician George Miller Sternberg both independently discovered the Streptococcus pneumoniae bacterium that is responsible for cases of pneumonia and meningitis, as well as other illnesses.

Death of Pasteur (9/28/1895)

Louis Pasteur died in Marnes-la-Coquette, outside Paris, France, at age 72.

Institut Pasteur Inaugurated (11/14/1888)

Louis Pasteur founded the Institut Pasteur in Paris as a center for rabies treatment as well as for the study of science. Soon Pasteur Institutes in other locations would begin to provide rabies vaccination. Today the Institut Pasteur has 30 international locations and 146 research units, focusing on infectious disease, public health, and teaching.

A Royal Death (12/28/1694)

Queen Mary II of England, age 32, died of variola hemorrhagica, a lethal form of smallpox in which bleeding occurs into the pustules, from other body surfaces, and internally. "The havoc of the plague had been far more rapid: but the plague had visited our shores only once or twice within living memory; and the smallpox was always present, filling the church-yards with corpses, tormenting with constant fears all whom it had not yet stricken, leaving on those whose lives it spared the hideous traces of its power, turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the betrothed maiden objects of horror to the lover. Toward the end of the year 1694, this pestilence was more than usually severe. At length the infection spread to the palace, and reached the young and blooming Queen." — Thomas Babington Macaulay, The History of England from the Accession of James the Second

1972 Routine U.S. Smallpox Vaccination Ceases

Recommendations for routine U.S. smallpox vaccination, previously recommended at age 1, ceased. As smallpox disappeared, the risks from complication of vaccination became less acceptable to the medical establishment and to the public. The graphic shows vaccination complications in 1968. The high number of revaccinations stems from the fact that vaccination-induced immunity waned over time. Revaccination was often performed 10-15 years after primary vaccination to ensure continuing immunity.

10/4/1999 Imported Yellow Fever Cases Lead to American Deaths

A 48-year-old Californian died of yellow fever after a trip to Venezuela. Hospitalized on September 28, the man suffered from a 102°F fever, chills, headache, joint pains, nausea, vomiting, seizures, and cardiac arrhythmias—among other symptoms—before dying six days later. Officials later determined that the patient, prior to leaving for Venezuela, had been vaccinated against tetanus, typhoid, hepatitis A, and malaria, but not yellow fever. Similarly, the only other U.S. fatality from yellow fever since 1924 was in 1996, when an unvaccinated Tennessee resident returning from a trip to Brazil died of the disease.

Contamination Leads to Stronger Regulations (1901)

A Camden, New Jersey, a tetanus outbreak was linked to contaminated smallpox vaccine. This incident, along with a Saint Louis, Missouri, tetanus outbreak traced to contaminated diphtheria antitoxin, led to U.S. regulation of biologics products the following year.

Chickenpox: Relationship Between Chickenpox and Shingles Suggested (1892)

A Hungarian professor of pediatrics, James Bokay, described cases of chickenpox developing in individuals who had been in contact with shingles (zoster) patients. Bokay wrote: I would like to bring up the question of whether or not the unknown infectious material of chickenpox could under certain circumstances manifest itself, instead of a generalized skin eruption, as a zoster eruption. Bokay seems to be the first to have documented his suspicions about a connection between chickenpox and shingles. It would be nearly three decades before he would be proven correct, when K. Kundratitz would demonstrate that inoculating children with vesicular fluid from shingles (zoster) patients could produce chickenpox cases.

Low Vaccination Rates Lead to Outbreak (1893)

A Muncie, Indiana, smallpox outbreak illustrated the effect of lower vaccination rates on the spread of disease. A local physician noted that vaccination there had been largely neglected since the last epidemic of smallpox in 1876. The initial cases appeared in a family in which only one member had been vaccinated. Physicians were unsure whether the disease was smallpox or chickenpox, and established a quarantine too late to control disease spread. Despite measures that included a near-quarantine of the city, fumigation of mail, cancellation of public gatherings, and compulsory vaccination, the epidemic spread from May 1893 through October. In the end, 140 people contracted smallpox and 20 died of it. Approximately 13,000 people were vaccinated during the epidemic, with one possible death resulting from post-vaccination tetanus infection. The careful collection of epidemic-related data shown in the images points to the emerging use of statistics to analyze disease spread. This tendency will grow through the 20th century.

Rabies Studies Begin (1880)

A Parisian veterinarian sent Louis Pasteur samples from two dogs that had died of rabies. The number of rabid dogs had increased in Paris, and veterinarians had become concerned about the problem. Pasteur then began careful work on rabies, attempting to infect other animals with rabies and identify the site and cause of infection. One of the difficulties with studying rabies is that the time between introduction of the infectious agent and signs of the disease varies greatly. Pasteur was able to advance his studies by shortening this period: first, he selected for the most lethal, fast-acting strains of the virus, and, second, he injected infectious material directly into rabbit brains (in the wild, the virus is introduced via a bite and travels slowly up a nerve to the brain). Pasteur would continue to work with rabies over the next several years until his successful use of the vaccine in 1885.

8/14/2017 Yemeni Cholera Epidmic

A cholera epidemic began in Yemen in April 2017, raging through a country whose water, sanitation, and health infrastructures had been damaged by conflict. As of mid-August, about 500,000 cases and nearly 2,000 deaths had occurred. The World Health Organization and its partners responded to the epidemic by establishing oral hydration stations and diarrhea treatment facilities, enhancing surveillance activities, strengthening water purification practices, and training health workers. An emergency one-dose cholera vaccination campaign was postponed at the request of Yemeni authorities, who opted to conduct a preventive two-dose vaccination campaign in 2018 in high-risk areas when global vaccine supplies, depleted by cholera epidemics elsewhere, would be expected to rebound.

1999 Whooping Cough: Acellular Vaccine Recommended

A combined dipthertia, tetanus and pertussis (whooping cough) vaccine, DTaP, that used an acellular pertussis vaccine, replaced the DTP vaccination on the U.S. Recommended Childhood Immunization Schedule. The acellular vaccine used only parts of the pertussis pathogen in order to generate immunity, and resulted in fewer side effects than the whole-cell vaccine that had been used in DTP. Eventually, the United States would cease the use of DTP completely in favor of DTaP.

German Vaccination Law (1874)

A compulsory smallpox vaccination and revaccination law went into in effect in Germany. Over the next decades, smallpox deaths there dropped rapidly. "After the law of 1874 went into effect the annual mortality in Prussia fell so that between 1875 and 1886 the average yearly mortality per 100,000 of population was only 1.91. On the other hand, in Austria, where the lax vaccination and revaccination requirements remained unchanged, the mortality of smallpox during about the same period (1872-1884) increased, varying between 39.28 and 94.79 per 100,000 of population.... In 1897, there were but five deaths from this disease in the entire German Empire with a population of 54,000,000." — from Vaccination: A Message from the Medical Society of the State of Pennsylvania

2010 Meningococcal Vaccine Rolled Out in Africa

A conjugate meningococcal group A vaccine began to be used in the African meningitis belt, where epidemics have historically led to thousands of deaths in epidemic years and much disability. This vaccine was developed in a unique collaboration among corporate, governmental, and non-governmental entities for a cost of development that was less than 10% of the $500 million typically required to create a new vaccine. The final cost per dose was only US $0.40. At the close of the 2011 epidemic season, monitoring indicated that there had not been a single case of group A meningitis among those who had received the vaccine. By 2014, meningococcal deaths were at their lowest level in 10 years. More than 220,000,00 people between the ages of 1 and 29 in 15 African countries had received the vaccine by the end of 2015.

1929 Tuberculosis: Lübeck Disaster

A disaster caused by use of Bacillus Calmette-Guérin (BCG) for tuberculosis vaccination struck the German city of Lübeck. During 1929 and 1930, 72 babies died from tuberculosis out of 252 vaccinated. Many other infants were made ill as a result of vaccination. The vaccine used was later found to have been contaminated with a human tuberculosis strain being studied in same lab where the vaccine was produced.

1911 Pneumococcal: Whole-cell Vaccine Tested

A killed whole-cell pneumococcal vaccine was created by Almroth Wright, MD (1861-1947). Wright and collaborators tested the vaccine in more than 50,000 South African gold miners. (Pneumonia from Streptococcus pneumoniae was a massive problem for the miners.) Unfortunately, data from the trials was found to be inconclusive, and the vaccine was abandoned.

1964 Major U.S. Anti-Mosquito Measures Begin

A major effort to eradicate the Aedes aegypti mosquito from the United States began. A pilot program in Pensacola, Florida, helped to determine the method of approach, including spraying insecticide at Aedes aegypti breeding sites and removing containers that could hold standing water (to prevent further breeding). A report issued the following year, however, noted that rural infestations in particular were far more widespread than initially believed, and that while reductions in infestation were achieved, eradication was not.

1918 Anti-Mosquito Methods Control Yellow Fever in Ecuador

A major eradication effort in Guayaquil began. Efforts focused mainly on anti-mosquito measures, with 25 mosquito squads active by the end of the year. By mid-1919, the city had no reported cases of yellow fever. Guayaquil was then declared free of the disease for the first time in approximately a century.

1964 U.S. Rubella Outbreak Infects Millions

A massive rubella outbreak in the United States initially failed to draw serious attention. A Time magazine article encouraged rubella parties, even recommending strategies so that "especially all the little girls get the infection." Unfortunately, despite warnings about keeping infected children away from pregnant women, nearly 50,000 women in vulnerable stages of their pregnancies were infected with rubella during the outbreak, leading to thousands of miscarriages and even more children being born with severe damage. At least 8,000 were born deaf, 3,500 deaf and blind; the total number of congenital rubella syndrome cases reached 20,000. Over the course of the outbreak the country tallied approximately 12.5 million cases of rubella and more than 2,000 deaths. Resulting medical costs reached the billions.

New York Inauguration (10/9/1893)

A new building for the Pasteur Institute in New York City was inaugurated. This Pasteur Institute appears not to have been officially connected to the Institut Pasteur in Paris. Rather, it was a privately established entity that provided rabies treatment and other kinds of medical services. "From its opening in December, 1889, to January, 1900, 1,367 patients were treated at the institute under the direction of Dr. Paul Gibier. Of these 1,367 nine died of rabies notwithstanding the Pasteur treatment; a mortality of 0.65 per cent.... The mortality of rabies, without treatment, varies from 5 to 95 per cent." —George G. Rambaud, M.D. New York Times, February 29, 1908

4/17/2016 Type 2 Oral Polio Vaccine Discontinued

A shift to eliminate vaccine-derived type 2 polio began on this day across the globe. In the approximately 150 countries using oral polio vaccine, all immunization programs were directed to stop using trivalent (types 1, 2, and 3) oral polio vaccine and begin using bivalent (types 1 and 3) vaccine. The switch to bivalent vaccine was designed to eliminate circulating vaccine-derived type 2 polio strains. No wild cases of type 2 polio have been reported since 1999, and the switch means that type 2 polio should die out.

1975 Cutaneous Diphtheria

A significant outbreak of cutaneous diphtheria (diphtheria infection in the skin) occurred in Seattle, Washington. Cutaneous diphtheria is endemic in tropical regions. However, where immunization rates were low and in populations of indigent adults with poor community and personal hygiene, outbreaks could occur. Cutaneous diphtheria infections may co-exist with other types of infections. Antibiotics generally cure the infection. The CDC discontinued reporting cutaneous diphtheria cases around 1979.

Colonial Epidemic (1633)

A smallpox epidemic hit Massachusetts, affecting settlers and Native Americans; among the casualties were 20 settlers from the Mayflower, including their only physician.

Promise of Variolation (1738)

A smallpox epidemic struck Charleston, South Carolina. Of the 441 people who were variolated, almost 4% died, while eighteen percent of people who were naturally infected died. The results encouraged advocates of variolation. Meanwhile, the same epidemic reportedly killed half of the Cherokee Indian population in the vicinity.

Harvard, Adams, and Smallpox (1764)

A smallpox outbreak in Boston led the General Court to flee across the river to Cambridge. Unfortunately, "[they] required such roaring fires in the fireplaces of Harvard Hall that the whole building burned down, destroying the best collection of scientific apparatus and the finest library in the American colonies" (Howard Simpson, New England Journal of Medicine, 1954). The fire took nearly the entire College library with it; one book, which had been taken from the library by a student earlier in the evening, survived. John Adams (1735-1826) underwent variolation during a Boston epidemic. By this time, many doctors performed variolation along with an arduous course of purging, vomiting, and sweats brought on by treatments with mercury and antimony. "In the Winter of 1764, the Small Pox prevailing in Boston, I went with my Brother into Town and was inocculated under the Direction of Dr. Nathaniel Perkins and Dr. Joseph Warren. This Distemper was very terrible even by Inocculation at that time. My Physicians dreaded it, and prepared me, by a milk Diet and a Course of Mercurial Preparations, till they reduced me very low before they performed the operation. They continued to feed me with Milk and Mercury through the whole Course of it, and salivated me to such a degree, that every tooth in my head became so loose that I believe I could have pulled them all with my Thumb and finger. By such means they conquered the Small Pox, which I had very lightly, but they rendered me incapable ... of speaking or eating in my old Age, in short they brought me into the same Situation with my Friend Washington, who attributed his misfortune to cracking of Walnuts in his Youth." — John Adams, Autobiography Part 1, Massachusetts Historical Society

1962 A Killed-Virus Vaccine Fails

A study documenting immune responses to a killed-virus measles vaccine was published in the American Journal of Diseases of Children. Doctors at Merck Sharp & Dohme laboratories had worked with Enders's Edmonston measles strain, hoping to develop a killed-virus vaccine that would result in fewer side effects than the live vaccine. Unfortunately, the study found no evidence that the killed-virus vaccine could offer protection against the measles.

5/27/1955 The Aftermath of the Cutter Incident

A subcommittee of researchers and public health officials made several changes to poliovirus vaccine production methods in order to address the problems made evident by the Cutter disaster. They required manufacturers to test larger samples of each vaccine lot, to lengthen the time the vaccine was treated with formaldehyde, to use filters that would remove clumps of virus that might resist chemical inactivation, and to test the vaccine after bottling, among other changes. The vaccination program resumed, though some locations declined to participate because of potential risks from the vaccine.

The Plague Among Children (1735)

A terrifying diphtheria epidemic swept through New England. In some cases, entire families died of the disease. In one New Hampshire town, 32% of children under 10 died of diphtheria. The case-fatality ratio was almost 40%. Noah Webster (1758-1843) later wrote: "It was literally the plague among children. Many families lost three of four children—many lost all." Treatments were largely ineffective. One approach was described in a Boston newspaper: METHOD OF CURE OF THROAT DISTEMPER. What is used is as follows. First be sure that a vein be opened under the tongue, and if that can't be done, open a vein in the arm, which must be first done, as all other means will be ineffectual. Then take borax or honey to bathe or annoint the mouth and throat, and lay on the Throat a plaister Vngiuntum Dialthae. To drink a decoction of Devil's bitt or Robbin's Plantain, with some Sal Prunelle dissolved therein, as often as the patient will drink. If the body be costive use a clyster agreeable to the nature of the Distemper. I have known many other things used, especially a root called Physick Root, filarie or five-leaved physick; also a root that I know no name for, only Canker Root. But be sure and let blood, and that under the tongue. We havemany times made Blisters under the arms, but that has proved sometimes dangerous. —Boston Gazette, March 18, 1735

1945 Pneumococcal: Vaccine Largely Ignored

A tetravalent pneumococcal vaccine (created with four pneumococcus types) was introduced in 1945. This vaccine, however, appeared during the advent of widespread penicillin use. With penicillin being viewed as an effective treatment for pneumococcal infections, the vaccine did not gain much traction.

2000 99% Reduction in Polio Cases

A total of 719 cases of wild polio were reported in 2000. When the worldwide eradication program began in 1988, there had been 350,000 estimated cases; the reduction in cases from 1988 to 2000 had reached 99%.

1947 Tuberculosis: The International Campaign

A total of 8 million babies and nearly 14 million people were given the BCG vaccine in the International Tuberculosis Campaign, which ran through 1951. The project initially began in Europe in the aftermath of World War II. However, the program extended beyond Europe when UNICEF contributed $2 million to expand the program to other continents.

Death Brings Silence (1732)

A yellow fever epidemic struck Charleston, starting in May and running into the fall, with deaths occurring so frequently that the usual ringing of bells upon a death was forbidden. A smaller outbreak hit New York the same year.

Measles and Smallpox Described Separately (01/01/0910)

Abū Bakr Muhammad Zakariyyā Rāzī (known as "Rhazes" in the Western World), a Persian physician, was the first to publish a written account titled "On Smallpox and Measles" ("al-Judari wa al-Hasbah" in Arabic) in which he describes the two diseases as being distinct and unique from each other.

Yellow Fever Decimates Philadelphia (1793)

After 31 years of absence, yellow fever returned to Philadelphia, killing thousands of city residents over a span of several months. As the then-capital and largest city of the United States, Philadelphia was home to both local and federal governments, most of whose members (including President George Washington) fled to escape the disease. The total number of cases was estimated to be approximately 11,000; the final mortality rate for the city was 10%. Like many others, Philadelphia physician Dr. Benjamin Rush (1745-1813) observed the symptoms and spread of the disease closely, hoping to uncover some definite cause and means of prevention. Rush kept meticulous notes about his individual patients as well as about conditions in the city for many years. His notes ranged from the observation that "A meteor was seen at two o'clock in the morning, on or about the twelfth of September" to several remarks that, curiously, "Moschetoes" were "uncommonly numerous." Rush, however, did not seem to draw any conclusions about the presence of the mosquitoes in relation to yellow fever. He favored the "miasma" theory of the disease—literally "pollution"—which was widely accepted in Philadelphia at the time. Miasmatic theory argued that diseases like yellow fever were the result of bad air. In 1793, its proponents blamed the yellow fever epidemic on the miasma from a shipment of rotting coffee that had been dumped at the docks. Among the other comments Rush made in 1793 was one about refugees from the French West Indies escaping infection from yellow fever as it struck the city. Though Rush did not know it at the time, this was no doubt because the men and women who had come from the West Indies had been exposed to yellow fever before and were thus immune to it. Unfortunately, Rush took a mis-step in his assessment of another group as being immune to the disease: From the accounts of the yellow fever which had been published by many writers, I was led to believe that the negroes in our city would escape it. In consequence of this belief, I published the following extract in the American Daily Advertiser, from Dr. Lining's history of the yellow fever, as it had four times appeared in Charleston, in South Carolina. "There is something very singular (says the doctor) in the constitution of the negroes, which renders them not liable to this fever; for though many of them were as much exposed as the nurses to the infection, yet I never knew of one instance of this fever among them, though they are equally subject with the white people to the bilious fever." --Benjamin Rush, An Account of the Bilious Remitting Yellow Fever, as it Appeared in Philadelphia, In the Year 1793. Shortly after the passage was published, Rush notes, Matthew Clarkson (1733—1800), the mayor of Philadelphia, wrote a response to the printer of the paper: September 6th, 1793 "Sir, It is with peculiar satisfaction that I communicate to the public, through your paper, that the African Society, touched with the distresses which arise from the present dangerous disorder, have voluntarily undertaken to furnish nurses to attend the afflicted; and that, by applying to Absalom Jones and William Gray, both members of that society, they may be supplied. MATTH. CLARKSON, Mayor." Tragically, as Rush noted, he had been mistaken in his belief that African-Americans would be immune to the disease: "It was not long after these worthy Africans undertook the execution of their humane offer of services to the sick before I was convinced I had been mistaken. They took the disease in common with the white people, and many of them died with it." --Benjamin Rush, An Account of the Bilious Remitting Yellow Fever, as it Appeared in Philadelphia, In the Year 1793 . Matthew Clarkson eventually fell victim to the disease as well: his gravestone notes that he "died of the fever in 1800."

1/31/2015 Measles Spreads from Disneyland

After a record year for measles cases in the post-elimination era, measles cases continued to spread in January 2015. Visitors to Disneyland in Anaheim, California, were exposed to measles via an as-yet-unidentified person. The U.S. Centers for Disease Control and Prevention eventually identified 111 cases associated with the Disneyland exposures, most of them in under- or unvaccinated individuals. A total of 188 cases would eventually be reported for 2015.

Contagious Nature of Polio Discovered (1905)

After a series of polio epidemics in Sweden, Ivar Wickman (1872-1914) published two important findings about polio. First, he suggested that polio was a contagious disease that could be spread from person to person. Second, he recognized that polio could be present in people who did not appear to have a severe form of the disease. These cases are known as abortive cases.

1963 Measles Vaccine Licensed

After demonstrating its safety and efficacy, first in monkeys and then humans, John Enders and colleagues declared their measles vaccine capable of preventing infection. Their Edmonston-B strain of measles virus was transformed into a vaccine licensed in the United States in 1963, and nearly 19 million doses would be administered over the next 12 years.

3/26/1953 Salk Becomes a Public Figure

After some media reports suggested that a polio vaccine was nearly ready for widespread use, Jonas Salk went on the radio to deflate the nation's hopes. He insisted, "Although progress has been more rapid than we had any right to expect, there will be no vaccine available for widespread use for the next polio season." Salk thus became the most well-known scientific name behind the search for a vaccine. Some others, working on live, attenuated polio vaccines, objected both to Salk's public profile and to his killed-virus approach. They argued that his vaccine would fail to produce long-term protection from polio and that dangers lurked in Salk's choice of a virulent Type 1 (Mahoney) virus strain.

Word of Jenner's Success Spreads (9/17/1798)

After the Royal Society rejected his report of his achievement, Jenner self-published a pamphlet called "An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease discovered in some of the Western Counties of England, particularly Gloucestershire, and known by the name of the Cow Pox." It outlined Jenner's success in protecting James Phipps from smallpox infection with material from a cowpox pustule, in addition to 22 related cases. Initially, the Inquiry received little attention. This changed when Henry Cline, an associate of Jenner living in London, used dried vaccine material provided by Jenner to demonstrate once again that vaccination with cowpox material prevented future smallpox infection. From this point on, word about the Inquiry quickly spread.

07/18/1921 Tuberculosis: First Human Tests of BCG

Albert Calmette and Camille Guérin began their first tests of their attenuated tuberculosis bacilli in humans. Their preparation is called Bacillus Calmette-Guérin, or BCG in shorthand. BCG is a weakened form of a tuberculosis bacterium that causes the disease in cows.

1959 Soviet Trials of Sabin's Live Poliovirus Vaccine

Albert Sabin forged a bond with Soviet health officials, who were interested in a cheaper alternative to Salk's vaccine. Sabin had spent years studying and attenuating the three types of polioviruses so that they were effective in inducing immunity to polio but weak enough not to cause disease. A massive vaccination campaign began, in which Sabin's oral polio vaccine (OPV) was fed to 10 million Soviet children. Unlike the Salk trials of 1954 in the United States, the trial of Sabin's vaccine used no unvaccinated control group. The OPV had several advantages over the Salk vaccine (IPV). It produced an immune response faster than Salk's vaccine, which meant that it could be used to respond to an epidemic. Because it entered the mouth, it traveled through the digestive system in the same manner as the wild virus. Vaccine recipients shed weakened vaccine virus in their stools, which sometimes had the effect of weakly immunizing those around them. OPV, often delivered on a sugar cube and eaten, was easier to give than the Salk vaccine, which was injected. The IPV, however, retained one major advantage over the OPV: The killed viruses in IPV cannot revert to virulent forms as can the viruses in OPV. And in another resprect, the two vaccines are basically the same: The IPV is as good at OPV in preventing polioviruses from spreading through the bloodstream. Over the next several decades, the medical world would continue to weigh the advanatages and disadvantages of the two vaccines.

8/24/1960 Sabin's Polio Vaccine Licensed

Albert Sabin's live poliovirus vaccine was recommended by the U.S. Surgeon General to be licensed. This vaccine provided protection against Type 1 poliovirus. Soon, vaccines for Types 2 and 3 would be licensed. A 1963 vaccine would combine all three types.

1926 Glenny Develops Adjuvant

Alexander Thomas Glenny (1882-1965) increased the effectiveness of diphtheria toxoid by treating it with aluminum salts. Efforts to improve diphtheria toxoid were necessary because toxoid alone produced a lower level of antibody response than desired. Moreover, the immunity it produced was shorter than desired. Observing that animals achieved better immunity to diphtheria when the injected toxoid created a local inflammatory reaction, Glenny began to add substances to the toxoid to trigger such a response. Today we call these substances adjuvants, and they are used in several types of vaccines.

1927 Cholera: Besredka's Bilivaccine

Alexandre Besredka's (Institut Pasteur) oral bilivaccine was tested in India and China alongside an injected vaccine. The bilivaccine, so-called because it employed bile salts, was as effective as the other vaccine. However, the bile salts caused diarrhea, which led some to conclude that the vaccine was in fact causing cholera. Besredka's bilivaccine was given in doses on three successive days and consisted of a bile tablet followed by a tablet containing cholera vibrios.

10/26/1977 Last Wild Case of Variola Minor

Ali Maow Maalin contracted the last case of naturally occurring smallpox (variola minor). He made a full recovery. Maalin, a cook in Merca, Somalia, worked in a hospital but had never been vaccinated himself. He became an advocate for polio vaccination and worked as a vaccinator in Somalia. He died July 22, 2013, at age 59 of malaria.

2000 Pneumococcal: Conjugate Vaccine for Children Licensed

Although Robert Austrian's polysaccharide vaccine against pneumococcal disease was effective for adults, it did not consistently generate immunity in children less than two years old (nor in individuals with certain immunodeficiencies, such as HIV infection). In February 2000, however, a new conjugate vaccine was licensed in the United States. This vaccine, PCV7 (tradename Prevnar, manufactured by Wyeth, now Pfizer) protected against seven pneumococcal serotypes. Clinical trials showed it to be effective in children less than two years old, and it was recommended for all children aged 2-23 months in 2000. Just a few years later, in June 2004, a population-based study published in the American Journal of Public Health found that "Preliminary evidence shows that in the short study period, the use of PCV7 is correlated with decreased hospital discharge rates for invasive pneumococcal disease." PCV7 has since been replaced by PCV13, licensed in 2010.

1998 Polio Immunization Efforts in Sudan

Although parts of Sudan had weak infrastructures and areas of ongoing armed conflict, the first National Immunization Days against polio began in the country in February. Later that year, the first National Immunization Days were also held in Somalia, a country with conflict and infrastructure problems similar to Sudan's. The World Health Organization considered polio vaccination in countries such as Sudan and Somalia vital to reaching its goal of eradication, but acknowledged that they also presented unique challenges. The CDC's Morbidity and Mortality Weekly Report for July 30, 1999 noted that polio was known or suspected to be circulating in 10 countries with civil conflicts at the end of 1998: Afghanistan, Angola, Democratic Republic of the Congo, Eritrea, Ethiopia, Liberia, Sierra Leone, Somalia, Sudan, and Tajikistan. The United Nations, acknowledging the important role to be played by such countries in polio eradication, advocated for days of tranquility during vaccination activities. However, the MMWR report noted that even without formal cease-fires, efforts against polio could be effectively conducted.

2010 Yellow Fever Vaccination Efforts Continue

Although the 17D yellow fever vaccine is highly effective, vaccination rates in at-risk regions remain lower than is necessary to prevent outbreaks. The World Health Organization warns that epidemics in unvaccinated populations can result in case-fatality ratios of more than 50%. WHO encourages both mass immunization efforts and routine infant immunization, as well as vaccination for travelers to countries where the disease is endemic. American travelers are required by WHO International Health Regulations to receive a yellow fever vaccination before visiting some countries in tropical South America and sub-Saharan Africa.

1939 Whooping Cough Vaccine Shown to Be Effective

American bacteriologist Pearl Kendrick, PhD (1890-1980), and her colleague Grace Elderding, PhD (1900-1988), at the Michigan Department of Public Health published the results of a landmark pertussis (whooping cough) vaccine study. The two scientists demonstrated the effectiveness of a vaccine when compared with a control group that did not receive the vaccine: the annual attack-rates per 100 children were 2.3 in the vaccinated group and 15.1 in the control group, respectively, with no deaths in either group. In addition, the disease was milder in the group that had been vaccinated.

O'Dwyer Uses Intubation (1885)

American physician Joseph P. O'Dwyer (1841-1898) introduced intubation for treatment of obstructed larynx in patients with diphtheria. Not only did O'Dwyer describe the method for the procedure, but he developed instruments to perform it. Within a short time, intubation largely replaced tracheotomy in treatment of diphtheria with airway blockage. O'Dwyer died a few years later from a heart ailment brought on by diphtheria infection most likely acquired from a young patient whom he intubated.

1965 Hepatitis B: The Australia Antigen

American physician and researcher Baruch Blumberg, MD, PhD (1925-2011), was interested in how genes could influence susceptibility to disease. He traveled the world collecting and studying blood samples from different populations. With a new lab technique, he matched a protein found in the blood of an Australian aborigine with an antibody in the blood of a hemophiliac from the United States. He called the protein the "Australia antigen." Blumberg and others were able to connect the presence of the antigen with hepatitis B infection. The Australia antigen proved to be the hepatitis B virus (HBV) surface protein. Later they related HBV infection to liver cancer. The Australia antigen circulates in the blood of a previously infected person not only as part of HBV, but also as a small, independent particle. The discovery of the Australia antigen had an important effect on the study of hepatitis B, in large part because HBV cannot be cultivated in the lab. The Australia antigen could, therefore, serve as a model for the virus as a whole. Moreover, the Australia antigen provided a source for antigen for the vaccine. Blumberg would win the Nobel Prize in Medicine in 1976 for his work on hepatitis B.

1931 Hib Linked to Meningitis

American researcher Margaret Pittman, PhD (1901-1995), classified different types of Haemophilus influenzae bacteria and found that strains that caused meningitis had a capsule composed of a specific polysaccharide (a form of a carbohydrate that has many sugars linked together). Of those strains, Pittman found that type b (called Hib, for Haemophilus influenzae type b) caused nearly all cases of Haemophilus influenzae meningitis. It would later be confirmed that Hib could also cause many other serious diseases, including infections of the blood, bone, and joints.

2/24/2010 Pneumococcal: Vaccine for Children Expanded

Among children younger than five years old, severe pneumococcal disease had dropped by almost 80% since the introduction of the PCV7 vaccine in 2000. In 2010, PCV13 was licensed: a vaccine that protected against an additional six pneumococcal types. (There are more than 90 types of pneumococcal bacteria; PCV13 protects against the 13 that are responsible for the most severe childhood pneumococcal infections.) The Advisory Committee on Immunization Practices recommended that PCV13 replace PCV7 on the childhood immunization schedule.

A Christmas Tale (12/25/1891)

An anecdote that persists even today described the dramatic Christmas recovery of a young girl ill with diphtheria. The story goes that Emil von Behring treated a seriously ill girl with diphtheria antitoxin prepared from a sheep and that she made a full recovery. Though it makes a good story, it is untrue. Systematic use of antitoxin to treat diphtheria did not occur until late 1892.

1938 March of Dimes Born

An enormous fundraising effort began when entertainer Eddie Cantor suggested on the radio that people send dimes to President Roosevelt at the White House to help fight polio. Within a few weeks, people had mailed 2,680,000 dimes to the President. Other celebrities and then grass-roots organizers joined in the campaign. Over the years, this "March of Dimes" raised tens of millions of dollars, much of which went to the effort to find a vaccine.

1997 IPV Returns to U.S. Schedule

An improved version of Jonas Salk's inactivated poliovirus vaccine began to be given to U.S. children before giving the OPV that had been a standard part of the immunization schedule since 1968. An average of 8-10 cases of vaccine-derived polio per year were caused by the OPV (about 1 case per 2.4 million doses distributed). Among OPV recipients, the risk was higher with first doses (1 per 750,000 doses), compared with subsequent doses (1 per 5.1 million doses). In the absence of wild-type disease, the public and authorities began to deem the risk from the vaccine unacceptable. By 2000, transition to an all-IPV schedule would be complete.

1925 The Great Race of Mercy

An outbreak of diphtheria in Alaska led to the famous Nenana-to-Nome dog sled run of antitoxin to treat the sick children. Curtis Welch, a physician in Nome, saw several children die of what he first thought was tonsillitis. As more children reported sore throats, he observed the white pseudomembrane of diphtheria. Welch had no fresh antitoxin on hand; he had only expired antitoxin because the shipment he had ordered in 1924 had not arrived. He sent a telegram requesting mail delivery of antitoxin. A hospital in Anchorage had 300,000 units of antitoxin and shipped it by train to Nenana, 674 miles from Nome. The shipment would need to travel by dog sled to reach the children of Nome. The journey of 20 teams of mushers and sled dogs from Nenana to Nome transfixed the country. The mushers battled near record low temperatures along the way, and they had to stop periodically to warm the serum. Many dogs died during the trip. Several of the mushers suffered frostbite. The antitoxin reached Nome on February 2, when Welch quickly used it to treat the many sick children in his hospital. He reported that five children had died, but thought the toll might have been higher because many native Alaskans might not have reported deaths. Togo and Balto, two of the lead sled dogs, received national attention. A statue of Balto still stands in Central Park in New York City.

Future President Contracts Smallpox (1781)

Andrew Jackson (1767-1845), future U.S. president, contracted smallpox at age 14 while being held prisoner by the British during the War of Independence. His brother Robert, taken prisoner with him, died of the disease.

Britain Bans Arm-to-Arm Vaccine Transmission (1898)

Arm-to-arm smallpox vaccine transmission was banned in Great Britain. As the Royal Commission of 1896 noted, lymph from calves was safer than human lymph, which sometimes contributed to the spread of diseases such as syphilis and hepatitis. Bovine vaccines eliminated the danger of human infections being passed on from the lymph material. Countries on the Continent had been steadily moving to the use animal vaccine since the mid-1860s.

Pasteur Teaches Chemistry (1/20/1849)

Arriving in Strasbourg, France, Louis Pasteur became professor of chemistry at the university there.

Pasteur Observes Rabies (1831)

As a schoolboy in Arbois, France, Louis Pasteur observed at first hand a rabies outbreak spread by the bites of rabid animals.

Regulation of Vaccine Supply Increases (1898)

As smallpox rates declined, the apparent need for vaccination was less pressing, and the occasional adverse reactions to vaccination became more visible. At the same time, developments such as the addition of glycerin to vaccine lymph, the increasing regulation of pharmaceutical suppliers, and the advancements of microbiology led to the generally increasing safety of the vaccine supply. A Pennsylvania commission reporting on inspections wrote: "This [Inspection of Vaccine Propagating Establishments] included a personal inspection of each plant...and a bacteriological examination of the points produced at each place. These points were purchased in open market. The matters investigated were location, size, number and construction of buildings, arrangements for cleanliness, character of animals, mode of operation and of taking of lymph, modes of preparation of virus, precautions taken in packing and bacteriological control. Fourteen of these establishments were visited and the inspectors were uniformly received with courtesy. Of these, four are located in this State. It is somewhat humiliating to find that three of these are not conducted with such regard to hygienic precautions or even to ordinary cleanliness, as to warrant the Board in expressing anything but condemnation of the establishments themselves and of the methods pursued therein. On the other hand it is gratifying to our State pride to be able to point to the fourth as admirable in all its appointments and conducted with the strictest observance of modern surgical asepsis. The establishment referred to is known as the Lancaster County Vaccine Farms, at Marietta, Dr. H. M. Alexander & Co., Proprietors." — Twelfth Annual Report of the State Board of Health and Vital Statistics of the Commonwealth of Pennsylvania, vol. 1 (1896) H.M. Alexander & Company's facilities in Marietta, Pennsylvania, were eventually acquired by Wyeth Pharmaceuticals and played an important role in global smallpox eradication.

Basis for Typhoid Vaccination Is Established (1896)

As with many discoveries in medical history, several different researchers were working on the idea of protection against typhoid fever at the same time in the 1890s. In Germany, Richard Pfeiffer and Wilhelm Kolle in 1896 demonstrated that inoculation with killed typhoid bacteria resulted in human immunity against typhoid fever. Almroth E. Wright published a paper a few months later in 1897, in which he described a similar finding. Reading before the Harvey Society of New York in February 1913, U.S. Army physician Frederick F. Russell stated that "The publication of Pfeiffer and Kolle's investigations antedates Wright's paper by some months," giving credit for the demonstration of typhoid immunity via inoculation to Pfeiffer and Kolle. Wright, however, would be the first to develop an effective typhoid vaccine the following year. Russell developed the first U.S. typhoid fever vaccine in 1909. In the November-December 1981 issue of Reviews of Infectious Diseases, Dieter H. M. Gröschel and Richard B. Hornick conducted a review of original literature related to typhoid vaccination and argued that Wright and Pfeiffer in particular should share the credit for the vaccine.

Cholera: The Pandemics Begin (1817)

Beginning in 1817, a series of deadly cholera pandemics swept over India, Asia, and the rest of the world. Scholars usually refer to a wave of seven cholera pandemics, and generally describe them as occurring 1817-23, 1826-37, 1846-63, 1865-75, 1881-96, and 1902-23, and 1961-present.

1946 Rabies: Virus Adapted to Non-nervous Tissue

At Lederle Laboratories, physician Hilary Koprowski adapted a rabies virus strain in chick embryos. He hoped to avoid using nervous system tissue as a medium for cultivating rabies virus because vaccine containing such tissue could cause serious side effects, such as encephalitis. Additionally, Koprowski wanted to improve upon the immunogenicity of the older vaccines and to create a vaccine that would not result in as many vaccine failures as the older vaccines. Eventually, he would pass his virus strain through chick embryos 180 times. At that point, the virus lost its ability to sicken small animals. Koprowski would use this strain, which he called HEP (for high-egg passage), as he continued to work on a new rabies vaccine.

Studies of Fermentation (1854)

At age 31, Louis Pasteur became professor of chemistry and dean of sciences at the newly established University of Lille. Here he began studying fermentation, which is the chemical process of extracting energy from carbohydrates.

1988 Global Polio Eradication Initiative

At its annual meeting, the World Health Assembly voted to launch a global polio eradication initiative. At the time, polio was endemic in 125 countries. The initiative called for the eradication of the disease by the year 2000.

1910 Flexner Investigates Polio Immunity

At the Rockefeller Institute for Medical Research in New York, Simon Flexner, MD (1863-1946), showed that "germicidal substances" were present in the blood of monkeys that had survived polio. Other researchers reported similar results with humans. These substances were neutralizing antibodies to polio. Researchers took this finding to indicate that a vaccine might be used to induce antibody production to fight the virus.

1936 Growing Poliovirus in Human Nervous Tissue

At the Rockefeller Institute in New York City, researchers Peter Olitsky, MD (1917-1964), and Albert Sabin, MD (1906-1993), demonstrated a new cultivation method for poliovirus. They were able to grow the virus in human embryonic brain tissue. Though their finding was interesting to researchers, it would not lead to immediate practical application. Researchers had long known that making a vaccine from virus bred in nervous system tissues presented challenges. The risk came from possible damage to the vaccine recipient's nervous system.

1951 Cultivation of Poliovirus in Monkey Kidney Tissue

At the University of Pittsburgh, Jonas Salk, MD (1914-1995), and his team developed a method of cultivating poliovirus in monkey kidney tissue. The method would lead to the ability to produce large quantities of virus for vaccine.

1909 Air-Dried Vaccine Developed in Paris

At the Vaccine Institute in Paris, Lucien Camus dried smallpox vaccine pulp in an evacuated chamber, removing all of the moisture from the sample. Such air-dried vaccines were used in tropical areas, where the temperature would destroy non-dried vaccine material. However, this method was not well-suited for large-scale production, and bacterial contamination was often a problem.

Origin of the Term Vaccination (5/17/1803)

At the first meeting of the Royal Jennerian Society, Edward Jenner insisted that the origin of the term vaccination, from the Latin for cow ("vacca"), be credited to his friend and fellow physician, Richard Dunning.

Spreading Word of Inoculation (1759)

At the suggestion of his friend Benjamin Franklin, English physician William Heberden wrote a pamphlet called "Some Account of the Success of Inoculation for the Small-Pox in England and America: Together with Plain Instructions By which any Person may be enabled to perform the Operation and conduct the Patient through the Distemper." In it he encouraged parents to inoculate their children against smallpox, detailing how they could do so themselves. Franklin added an introduction documenting the success of the process in Boston, and distributed the pamphlets in the American colonies for free.

1941 Rubella Implicated in Congenital Defects

Australian ophthalmologist Norman McAlister Gregg noted a surprising number of infants suffering from cataracts in his practice. Gregg later overheard mothers in his waiting room discussing the cases of rubella they'd had during their pregnancies in the midst of an outbreak the year before. After further investigation, Gregg linked rubella during pregnancy to congenital cataracts. His observation was the first of what eventually became a collection of reports linking rubella during pregnancy to various congenital defects. The risks were overwhelming: infection with rubella during the first trimester of a pregnancy resulted in a greater than 2 in 3 chance of a baby afflicted with congenital rubella syndrome. Of the syndrome's various symptoms and complications, ranging from blindness to heart disease to neurological abnormalities, deafness was the most common.

1931 More Than One Type of Poliovirus Proposed

Australian researchers Frank M. Burnet (1899-1985) and Jean Macnamara (1899-1968) infected monkeys with polio from a fatal human case of the disease. The monkeys had recovered from a previous case of polio and yet were paralyzed by the new infection. Their work showed that there was more than one type of poliovirus, and that previous infection with one type did not confer immunity to another type. The implication was clear: a polio vaccine would need to provide protection from all types of polio. It would be 20 years before David Bodian and Isabel Morgan would demonstrate that there are three types of polioviruses.

French Doctors Investigate Animal Vaccine (1864)

Awareness of the danger of the spread of diseases such as syphilis via arm-to-arm transmission of vaccine virus began to grow in France. Several doctors, having read of the Neopolitan practice of serial vaccination of calves with vaccinia, had a vaccinated calf shipped to Paris, where it was used as a source of vaccine. The use of calves for vaccine material came to be widespread, not only in France, but in other parts of Europe and the United States. Great Britain, however, did not adopt the practice in until 1881 and finally banned arm-to-arm transmission in 1898.

2016 Tuberculosis: BCG Today

BCG vaccination for tuberculosis has never been recommended for routine use in the United States. It is, however, frequently used for children in countries where risk of TB infection is high. Three tuberculosis vaccines are currently licensed in the United States. The Advisory Council on Immunization Practices recommends them only for children and certain health care workers who have a high risk of infection with TB (because of ongoing or frequent exposure to TB). Reports of the effectiveness of BCG for tuberculosis immunization vary greatly, though efficacy seems to be best in younger people. It is widely used in countries where the disease burden of TB is high. The World Health Organization states, "[BCG is] is one of the most widely used of all current vaccines, reaching >80%of neonates and infants in countries where it is part of the national childhood immunization programme. BCG vaccine has a documented protective effect against meningitis and disseminated TB in children. It does not prevent primary infection and, more importantly, does not prevent reactivation of latent pulmonary infection, the principal source of bacillary spread in the community. The impact of BCG vaccination on transmission of [tuberculosis] is therefore limited." —WHO, BCG Vaccine WHO estimates that one third of the world's population is infected with the tuberculosis bacillus. In 2014, 9.6 million people became ill with tuberculosis. About 1.5 million people, including about 140,000 children, died from tuberculosis. Drug-resistant tuberculosis is becoming an increasing problem. Researchers continue to try to develop new, more reliable and effective tuberculosis vaccines. Areas gaining a great deal of research attention are DNA vaccines and subunit TB vaccines.

1928 Queensland Disaster

Bacterial contamination of diphtheria toxin-antitoxin mixture in Bundaberg, Queensland, Australia, led to the deaths of 12 children. Five others became critically ill but recovered. The tragedy occurred when a multi-use bottle of TAT, containing no preservative, was improperly stored and reused.

1/30/1934 Roosevelt's Birthday Celebrations

Basil O'Connor (1892-1972), a New York lawyer and Roosevelt advisor, organized the first of many annual Birthday Balls to commemorate Franklin Delano Roosevelt's birthday and to raise money for polio research. The dance contests were enormously successful and led to Roosevelt's creation of the National Foundation for Infantile Paralysis in 1938.

1913 The Schick Test

Bela Schick developed a test to determine if a person had developed some immunity to diphtheria after having been exposed to those bacteria. Schick based his test on developments in the understanding of disease and immunity. He reasoned that the injection of a very small amount of diphtheria toxin under the skin would produce a reddening and slight swelling of the site. This is a positive reaction, and indicated that the patient had not previously been exposed to diphtheria. A negative reaction, based on a lack of reddening of the area, indicated that the patient had previously been exposed to diphtheria and therefore had immunity to it. A negative reaction eliminated the need for treatment for diphtheria if a household contact or schoolmate developed the disease. After Schick left his native Europe and came to New York in 1923, he instituted wide use of his test throughout the city. At that point, immunization was available for those who had not been exposed to diphtheria.

1906 Whooping Cough: Bacteria Isolated

Belgian scientists Jules Bordet (1870-1961) and Octave Gengou (1875-1957) isolated the bacterium Bordetella pertussis, the causative agent of pertussis (whooping cough), which they had first observed in 1900. It would later also come to be known as the Bordet-Gengou bacillus.

Franklin Loses Son (11/21/1736)

Benjamin Franklin's four-year-old son, Francis Folger Franklin, died of smallpox on November 21, 1736. Rumors began to circulate claiming that the boy had been inoculated. Franklin published a denial and advocated inoculation. "In 1736 I lost one of my Sons, a fine Boy of 4 Years old, taken by the Small Pox in the common way. I long regretted that I had not given it to him by Inoculation, which I mention for the Sake of Parents, who omit that Operation on the Supposition that they should never forgive themselves if a Child died under it; my Example showing that the Regret may be the same either way, and that therefore the safer should be chosen." — Benjamin Franklin, quoted in Franklin on Franklin by Paul Zall

A Farmer Takes a Chance (1774)

Benjamin Jesty (1737-1816), English farmer and cattle breeder, inoculated his wife and two sons with matter from a cowpox lesion on one of his cows. Jesty, having already contracted cowpox, believed himself protected from smallpox infection. When a serious smallpox epidemic hit his Dorset village, he, from his "great strength of mind," took it upon himself to protect his family. His wife and children survived, and the boys, when challenged with smallpox inoculation in 1789, showed no symptoms. Jesty, however, had no interest in systematically testing his methods or publishing his results, and so his finding was largely forgotten. Upon his death, Jesty's wife had his tombstone inscribed, "the first person (known) who introduced the cow-pox inoculation."

Waterhouse Brings Vaccination to the States (1800)

Benjamin Waterhouse (1754-1846), a Harvard professor of medicine, performed the first U.S. vaccinations on his children. He went on to put much effort into encouraging public vaccination. Waterhouse began by writing to then-U.S. President John Adams, with whom he had roomed while studying medicine in England. Growing convinced that Adams was either too busy or disinterested in helping to spread the word about cowpox vaccinations preventing smallpox, Waterhouse then wrote to the current Vice President (and soon-to-be-President), Thomas Jefferson, sending a work he titled, "A prospect of exterminating the smallpox." In a letter dated Christmas day, 1800, Jefferson responded: Sir: I received last night, and have read with great satisfaction, your pamphlet on the subject of the kine-pock, and pray you to accept my thanks for the communication of it. I had before attended to your publications on the subject in the newspapers, and took much interest in the result of the experiments you were making. Every friend of humanity must look with pleasure on this discovery, by which one evil more is withdrawn from the condition of man; and must contemplate the possibility, that future improvements and discoveries may still more and more lessen the catalogue of evils. In this line of proceeding you deserve well of your country; and I pray you accept my portion of the tribute due to you, and assurances of high consideration and respect, with which I am, Sir, Your most obedient, humble servant, Thomas Jefferson — from Robert H. Halsey, How the President, Thomas Jefferson, and Doctor Benjamin Waterhouse Established Vaccination as a Public Health Procedure. Waterhouse, on a later letter from Jefferson, noted that he gave the original of the first letter to Edward Jenner as a gift, "Thinking that coming from the Chief Magistrate of the Americas it would not be unpleasing to the originator of vaccination."

1968 A More Efficient Method

Bifurcated needles were demonstrated to be enormously effective for smallpox vaccination, and the World Health Organization encouraged their use. Bifurcated needle vaccination required one-fourth the amount of vaccine needed with previous methods and was simpler to perform. Wyeth waived royalties for needles manufactured for WHO.

1912 Whooping Cough: Killed Vaccine Fails

Bordet and Gengou prepared a pertussis (whooping cough) vaccine from killed whole-cell B. pertussis preparations, but it proved not to be effective. Other scientists would similarly develop other pertussis vaccines through the 1910s.

Animal Vaccine Brought to U.S. (1870)

Boston physician Henry Austin Martin brought what he called true animal vaccine (material produced by inoculating a calf with cowpox lymph) to the United States. He described how he procured the material: "...[M]y special agent [returned] from Paris with ample supplies of animal virus in tubes and on ivory points and squares of glass, collected and sealed by Professor Depaul in his presence, autograph directions from the same distinguished savant, and a full collection of pamphlets and other publications by Professor Depaul and others. My agent returned to Boston on the 23rd of September, 1870. I had secured the use of a farm on which was a herd of nearly fifty young bovine animals, and, on the very day of my agent's return, I vaccinated three of these, on the next day two, and on till I had nearly exhausted my supply of virus in the vaccination of nine or ten animals....I was, of course, put in possession of ample supplies of animal lymph, and devoted myself to daily vaccinations of infants." Martin wrote that he obtained the vaccine from the 258th, 259th, and 260th animals vaccinated from Depaul's series of animal vaccinated with the original Beaugency lymph (see the 1866 timeline entry). Martin reported success with the new method of producing vaccine, and went on to supply vaccine to vaccinators across the country until others began to serially vaccinate cows. His work, however, came with a price: he wrote, "It involved great labor and responsibility, considerable odium, large expenditure, and, in various ways, infinite annoyance, insult, and wrong; which, as it is now past forever, I can only endeavor to forget. As soon as my experiment had proved a success there were not wanting those who eagerly rushed into competition with me; this I expected, and hailed some of these competitors as fellow-workers in a field where much was to be done. I gave them every aid in my power freely, frankly, and fully, and was repaid by ingratitude, slander, and an effort, as futile as it was earnest and persistent, to rob me of the scrap of professional honor and reputation I had worked so hard to win and deserve, in introducing and establishing in America a system which has already conferred infinite though hardly fully appreciated blessings..." --Henry Austin Martin, On Animal Vaccination, 1878

2/8/1960 One Measles Strain, Many Vaccine Attempts

Boston researchers tested their measles vaccine in developmentally delayed children at a New York state school. This time 23 children were given the vaccine. The vaccine still caused too many side effects, but when a measles outbreak hit the school six weeks later, none of the children who had been vaccinated fell ill. At this point, multiple pharmaceutical companies sent representatives to John Enders's lab to obtain material from which to try to develop their own measles vaccines.

Royalty Successfully Inoculated (1768)

Catherine the Great of Russia was inoculated by physician Thomas Dimsdale, with relays of horses at the ready in case the inoculation should go wrong and Dimsdale need to escape from Catherine's angry subjects. The operation was kept secret, and Catherine recovered successfully. Her inoculation later encouraged others to follow suit.

1998 MMR Safety Questioned

British researcher Andrew Wakefield, along with 12 co-authors, published a paper in the Lancet claiming evidence of measles virus in the digestive systems of autistic children. In press conferences after the paper was published, Wakefield suggested a relationship between the MMR (measles, mumps and rubella) vaccine and autism. Wakefield then recommended that the combination MMR vaccine be suspended in favor of single-disease vaccinations given separately over time. Vaccination rates in England dropped in response, from more than 90% to 80% or lower—well below the level required for herd immunity to measles. Measles cases, meanwhile, began to rise: while only 56 cases were confirmed in Wales and England in 1998, 1,348 were confirmed by 2008. In 2004, it was reported that some of the subjects of Wakefield's paper had been recruited by a lawyer involved in a lawsuit against vaccine manufacturers; in response to this and other problems with the paper, 10 of the 12 co-authors eventually retracted the interpretation regarding a link between the vaccine and autism. Numerous epidemiological studies performed since have also provided additional evidence that no such link exists. In 2010, Britain's General Medical Council ruled that Wakefield had engaged in misconduct during the course of conducting and publishing the study. Subsequently, the Lancet formally retracted the paper; in May 2010, Wakefield was banned from practicing medicine in Britain. Despite this and the lack of any evidence to support a link between vaccines and autism, some groups remain convinced of the allegations first raised by Wakefield in 1998.

1933 Influenza: Influenza Virus Isolated

British scientists Wilson Smith, MD, C.H. Andrewes, MD, and P.P. Laidlaw isolated influenza virus. Widespread influenza in early 1933 gave these scientists the chance to demonstrate the cause of the disease. They took throat washings from patients with influenza symptoms and filtered them through a material that bacteria could not pass through. They tested the washings for the presence of bacteria by trying to culture them on a variety of media. The washings proved not to contain any detectable bacteria. Then they tried to infect a variety of animals with the throat washings. Ferrets became ill about three days after exposure and displayed typical symptoms of influenza. Other ferrets became ill when exposed to the ferrets with influenza, either via direct contact or when inoculated with nasal washings. The researchers also demonstrated a finding crucial for future vaccine development: ferrets and humans who had recovered from influenza produced antibodies to the virus. Thus Smith, Andrews, and Laidlaw's work indicated that influenza immunization might be possible. To this day, ferrets remain an important animal model for understanding influenza in humans.

1914 Typhoid Vaccination Becomes Commonplace in the United States

By 1914, typhoid vaccination had moved beyond military forces in the United States and into use for the general public. Parke, Davis & Company sent the letter shown on the left to a Philadelphia physician to suggest the use of typhoid vaccine for travelers. The pamphlet referred to in the letter can also be viewed on the left. The text of the letter reads as follows: Dear Doctor:- Your patients, many of them, will soon be leaving for their vacations and unless protected by vaccination they may incidentally be in some danger of contracting Typhoid Fever. As a preventive of Typhoid Fever the value of Typhoid Vaccine is now well established. It has been used extensively in our own and other great armies with very satisfactory results. Consequently in the U.S. Army anti-typhoid vaccination of recruits is now compulsory. It is a simple matter to use Typhoid Vaccine Prophylactic (P.D. & Co). Three doses are given, injected subcutaneously at ten-day intervals. It is offered in packages containing enough for the protective treatment of one person - three doses in three bulbs, three doses in three syringes or three doses in one graduated syringe. It may also be had in a larger package known as the "hospital size" and containing enough for ten persons. The interesting and important subject of typhoid vaccination is presented concisely in the enclosed booklet which we commend to your careful attention and we shall be very glad to supply additional information if you desire it. Supplies of Typhoid Vaccine Prophylactic, (P.D. & Co.), may be obtained through pharmacists. Very truly yours, Parke, Davis & Co.

1922 School Vaccination Requirements

By this time, many United States schools required smallpox vaccination before children could attend. Some students and their families, however, sought the help of the courts to avoid the requirement. One such case was considered by the U.S. Supreme Court, when Rosalyn Zucht, a student from San Antonio, Texas, was excluded from a public school for failure to present proof of vaccination. The complaint alleged that the city ordinances requiring vaccination to attend public school violated the due process and equal protection clauses of the Fourteenth Amendment. The court dismissed the writ of error that brought the case to them, stating that the constitutional question presented was not substantial in character, and citing previous cases which had determined that a city ordinance was a law of the state—and that it was "within the police power of a state to provide for compulsory vaccination."

Carlos Finlay Identifies a Suspect (08/14/1881)

Carlos Finlay (1833-1915) presented the paper "The Mosquito Hypothetically Considered as the Transmitting Agent of Yellow Fever" to Havana's Academy of Sciences—the first to correctly identify mosquitoes as the ultimate source of the disease. Finlay's theory, however, was initially ridiculed. It was accepted only when U.S. Army scientists working under Walter Reed (1851-1902) demonstrated that it was correct—two decades later.

Serum Sickness Described (1905)

Clemens Pirquet (1874-1929) and Bela Schick (1877-1967) described a clinical illness they called "serum sickness." Understanding this new form of disease helped pave the way for defining and understanding allergy and immunologic diseases. Schick and Pirquet observed that children treated for diphtheria with large quantities (up to 200 mL, almost 7 ounces, or almost 1 cup) of antitoxin derived from horses often went on to experience symptoms such as swelling, fever, rash, and joint pains. We now know that the human immune system mistakes the foreign antibodies in the serum for antigens. The symptoms of serum sickness are the result of a cascading immune reaction. In Pirquet and Schick's practice, serum sickness was not life-threatening, and the children who recovered from diphtheria were not harmed by the treatment.

2000 Endemic Measles Eliminated From U.S.

Continuous transmission of measles was halted in the United States. However, U.S. residents remained at risk for infection from imported cases.

Bladders in the Windpipe (1659)

Cotton Mather (1663-1728), a Boston minister, wrote: "In December 1659 the (until then unknown) Malady of Bladders in the Windpipe, invaded and removed many Children; by Opening of one of them the Malady and Remedy (too late for very many) were discovered." He was most likely describing diphtheria. One family afflicted was that of the Reverend Samuel Danforth. Danforth wrote: "The Lord sent a general visitation of Children by coughs & colds, of which my 3 children Sarah, Mary & Elisabeth Danforth died, all of them with[in] the space of a fortnight."

African Use of Variolation (1706)

Cotton Mather, a Boston minister (1663-1728), received a "gift" of a Libyan-born enslaved person named Onesimus, who bore a scar from smallpox variolation in Africa. Mather inquired among other enslaved people and found that many had been variolated and thought themselves immune to the disease. Later, Mather would read of variolation in English medical journals and promote the practice in Massachusetts.

Diphtheria Given Its Name (1826)

Diphtheria, which had previously been called by a variety of names, gained its official name from French physician Pierre Bretonneau (1778-1862), who called the disease diphtérite. The origin was the Greek word for "leather" or "hide," which describes the coating that appears in the throat (that is, the pseudomembrane). Bretonneau also distinguished diphtheria from scarlet fever. Bretonneau recorded the first successful use of tracheotomy in a case of diphtheria. This procedure, which had been used to treat other conditions, involves cutting an opening in the trachea and inserting a tube through the opening to allow passage of air and removal of secretions. Bretonneau had attempted the procedure several times before, but the patients died. Later, another French physician, Armand Trousseau (1801-1867), showed a survival rate of about 25% in the tracheotomies he performed on diphtheria sufferers.

1919 Dallas Disaster

Dozens of Dallas, Texas, children were sickened and five died from a contaminated batch of diphtheria toxin-antitoxin mixture (TAT). The TAT was manufactured by Mulford & Co., Philadelphia, and the company paid damages to the afflicted families.

7/13/1965 The Bifurcated Needle

Dr. Benjamin Rubin of Wyeth Laboratories patented the bifurcated needle for delivery of smallpox vaccine. Using bifurcated needles for vaccination required less vaccine material for each dose, and was easier than previous methods. This development would have large implications for smallpox vaccination campaigns.

Vaccination vs. Variolation (1802)

Dr. Jean de Carro, a physician who indirectly helped to introduce vaccination to India, suggested that inoculation should be eliminated, saying, "It is inconsistent for a government to encourage vaccination and not forbid inoculation." This was among the first of many efforts to encourage vaccination over variolation for its improved success and safety.

Hopes for Future Eradication (1767)

Dr. Matthew Maty (1718-1776), a physician-turned-librarian, foresaw the eradication of smallpox. Maty wrote: "When once all the adults susceptible of the infection should either have received it or be dead without suffering from it, the very want of variolous matter would put a stop to both the natural and artificial smallpox. Inoculation would then cease to be necessary, and therefore be laid aside." — Matthew Maty, The Advantages of Early Inoculation

New York Doctor Makes an Important Observation (1794)

During a yellow fever outbreak in New York, physician Valentine Seaman (1770-1817) noted that most of the patients "...were either such as resided in the neighborhood of the slips... or whose employment led them to frequent those places...." The observation once again pointed to a connection between yellow fever and seafaring vessels.

11/19/2014 West African Ebola Epidemic

Ebola virus disease (EVD) emerged at unprecedented epidemic levels in 2014. Whereas previous outbreaks had occurred in remote areas and were contained fairly quickly, this epidemic spread to crowded urban areas where long transmission chains occurred. The center of the epidemic occurred in Sierra Leone, Guinea, and Liberia. Nigeria and Senegal saw small outbreaks related to importations from more heavily affected countries, but they were able to contain spread of the disease. Several cases and deaths were reported from Mali in October and November 2014. In total, 15,261 confirmed, probable, and suspected deaths occurred, including two in the United States. More than 28,000 cases of EVD were reported. Several healthcare workers acquired Ebola virus disease outside West Africa from contact with imported cases. Two U.S. nurses and one Spanish nurse became ill. All three recovered. Ebola virus disease has no cure, but supportive care in a hospital setting can increase a patient's chance for survival. Additionally, plasma transfusions from convalescent patients and an experimental antibody preparation have been used to treat certain patients. Several vaccines were advanced rapidly into clinical trials in both African and non-African countries.

Protection by Cowpox Infection (1770)

Edward Jenner (1749-1823), an English doctor, became interested in the idea that previous illness with a disease called cowpox could protect a person from later becoming ill with smallpox. Jenner's biographer claimed that Jenner heard this folk wisdom from a milkmaid: having caught cowpox from a cow, she believed herself, and her smooth skin, safe from smallpox. Cowpox is an uncommon illness in cattle, usually mild, that can be spread from a cow to humans via sores on the cow. During an infection, dairy workers may have pustules on their hands. Sufferers can spread the infection to other parts of the body. We know now that the cowpox virus belongs to the Orthopox family of viruses. Orthopox viruses also include horsepox virus, monkeypox virus and variola viruses, which cause smallpox.

Jenner Studies at St. George's Hospital (1770)

Edward Jenner began studies at St. George's Hospital in 1770. He studied for two years with surgeon John Hunter.

Jenner Returns to Berkeley (1772)

Edward Jenner returned to Berkeley, now as a trained doctor.

2000 A Return to Salk's Vaccine in the U.S.

Forty-six years after the successful Salk poliovirus vaccine trials of 1954, concerns about cases of polio developing from use of the OPV led to the United States adopting an IPV-only vaccine schedule. Sabin's vaccine was still used in other parts of the world where polio still circulated.

Jenner's Breakthrough (5/14/1796)

Edward Jenner tested the hypothesis that infection with cowpox could protect a person from smallpox infection. Cowpox is an uncommon illness in cattle, usually mild, that can be spread from a cow to humans via sores on the cow. During an infection, dairy workers may have pustules on their hands. Sufferers can spread the infection to other parts of the body. We know now that the cowpox virus belongs to the Orthopox family of viruses. Orthopox viruses also include horsepox virus, monkeypox virus, and variola virus, which causes smallpox. On May 14, 1796, Jenner inoculated eight-year-old James Phipps with matter from a cowpox sore on the hand of milkmaid Sarah Nelmes. Phipps suffered a local reaction and felt poorly for several days but made a full recovery. In July 1796, Jenner inoculated Phipps with matter taken from a fresh human smallpox sore, as if he were variolating the boy, in an attempt to challenge the protection from cowpox. Phipps remained healthy. Jenner next demonstrated that cowpox matter transferred in a human chain, from one person to the next, provided protection from smallpox. Jenner was not precisely sure about the nature of the cowpox material he used. He suspected that cowpox actually came from horsepox; in other words, he speculated that cows became infected with the same agent that caused a similar disease in horses. Recent genetic analysis of old samples of smallpox vaccine have revealed that the samples were more closely related to horsepox virus than cowpox virus.

Birth of Jenner (5/17/1749)

Edward Jenner was born in Berkeley, in Gloucestershire, England.

Jenner Apprentices to a Surgeon (1763)

Edward Jenner, then 14 years old, trained as an apprentice to surgeon Daniel Ludlow. The apprenticeship lasted for seven years.

Bacterium Identified (1883)

Edwin Klebs (1834-1913), a Swiss-German pathologist, identified and described the bacterium that causes diphtheria. It was known at first as the Klebs-Loeffler bacterium. The bacterium's club-shaped appearance helped Klebs differentiate it from other microbes. Later, the bacterium became known as Microsporon diphtheriticum, Bacillus diphtheriae, Mycobacterium diphtheriae, and, as it is called now, Corynebacterium diphtheriae.

1927 Diphtheria Strikes Young Hilleman

Eight-year-old Maurice Hilleman nearly died from diphtheria, a disease that would later be virtually eradicated in the United States through immunization.

Tuberculosis: Fruitless Search for Antitoxin (1905)

Emil von Behring attempted to apply lessons and methods developed in the study of diphtheria as he searched for a tuberculosis antitoxin. This search would fail, as Mycobacterium tuberculosis does not excrete a toxin.

1907 Toward Immunization

Emil von Behring published a paper showing that a mixture of diphtheria toxin and antitoxin produced safe and lasting immunity to diphtheria in humans. The combination of toxin and antitoxin needed to be carefully balanced to provide enough toxin to elicit active immunity and the right amount of antitoxin to prevent the toxin from causing disease.

Cholera: Snow's Early Findings (1849)

English doctor John Snow (1813-1858) proposed that cholera was spread by contaminated water in his publication On the Mode of Communication of Cholera. Snow rejected the commonly held idea that "bad air," or miasma, was responsible for cholera. Rather, based on his careful examination of a London outbreak, he suggested that the disease occurred when people ingested certain tiny particles in water. "...[T]he disease is communicated by something that acts directly on the alimentary canal, the excretions of the sick at once suggest themselves as containing some material which, being accidentally swallowed, might attach itself to the mucous membrane of the small intestines, and there multiply itself...." -John Snow, On the Mode of Communication of Cholera

Sydenham Documents Measles Infection (1676)

English doctor Thomas Sydenham, MD, publishes Observationes medicae circa morborum acutorum historiam et curationem (Medical observations on the history and cure of acute diseases). Although the Persian physician Rhazes was the first to attempt distinguishing smallpox from the measles, Sydenham was the first to do so successfully and in detail. He also recorded details about and distinguished the disease from scarlet fever.

Method of Increasing Potency (1836)

English physician Edward Ballard noted that cowpox transmitted from human to human seemed to decline in potency over time. He recommended choosing new strains of cowpox and reintroducing the pustule matter (lymph) back into cows to boost its potency. This method came to be used to supply sufficient material for vaccination.

Advances in Vaccine Production (1891)

English physician S. Monkton Copeman showed that adding glycerin to lymph acts as a germicide. As glycerin came to be widely used, it reduced transmission of harmful microbes via the lymph. These are the steps in harvesting lymph and mixing it with glycerin: "A red heifer calf about two months old, in good flesh and health, is placed upon a bench in a special operating room and strapped on its side with one hind leg fastened vertically against the back of the bench. The area between the thighs, covering about ten inches square and including the teats, is shaved and washed with soap and water, with hydrogen peroxide solution, and finally with sterilized water and then dried with sterilized absorbent cotton. On the area so prepared, one hundred spots are then scarified, each from a quarter to half an inch square. The blood is washed away with sterilized water, and when the bleeding has entirely ceased virus is rubbed on each spot very thoroughly for some minutes; the calf is then returned to its stall. It is examined on the third and following days, and when the vesicles are seen to be at the proper stage of development, which is usually on the sixth day, the calf is again placed upon the bench and the whole shaved area washed twice with sterilized water and once again with peroxide of hydrogen solution. All macroscopic dirt and crust is removed and every scarification is cleansed as thoroughly as possible; then with a sterilized curette each scarification is scraped and every particle of pulp removed into a sterilized glass dish. The pulp taken is weighed, comminuted, and mixed with a measured amount of chemically pure glycerin, by being passed between glass rollers on which the glycerin flows. There is thus produced a brown syrupy homogeneous emulsion, which is then drawn by a filter pump into sterilized glass tubes, which when full are sealed in a flame at both ends. Each of these tubes holds about 20 cubic centimeters." — Annual Report of the Board of Health of the Health Department of the City of New York for the Year Ending December 31, 1896

Chickenpox: Disease Distinguished from Smallpox (1767)

English physician William Heberden was the first to give a detailed description that distinguished chickenpox from smallpox. He wrote: These pocks break out on manywithout any illness or previous sign: in others they are precededby a little degree of chillness, lassitude, cough, broken sleep,wandering pains, loss of appetite and feverishness for threedays... Mostof them are of the common size of the smallpox but some areless. I never saw them confluent nor very numerous. The greatestnumber which I ever observed was about twelve in the face, andtwo hundred over the rest of the body. Heberden also noted that those who had previously had chickenpox "were not capable of having it again."

Philadelphia Lazaretto Is Built (1799)

Erected by the city of Philadelphia's Board of Health, the Philadelphia Lazaretto Quarantine Station on Tinicum Island was built largely in response to the city's 1793 yellow fever epidemic. (The Board of Health itself was created in 1794, also in response to the epidemic.) The Lazaretto was designed to quarantine infected travelers headed for Philadelphia by ship. All passenger and cargo vessels bound for the city were required to dock at the Lazaretto for inspection. Ill passengers were quarantined in its hospital; cargo was stored in a public warehouse. Using this approach offered protection not only against yellow fever, but also against smallpox, typhus fever, and other diseases carried by travelers. The Lazaretto was maintained continuously by the city until 1895, when a State Quarantine Board was created and the station was moved to Marcus Hook, Pennsylvania. The structure remains standing, however--the oldest quarantine structure in the country that still exists to this day.

1906 Lederle Produces Antitoxin

Ernst Lederle, who was formerly New York City Health Commissioner, founded Lederle Laboratories in New York City to make diphtheria antitoxin, and later moved out to a farm in Pearl River, New York. Lederle Laboratories later became a part of Wyeth Laboratories.

1906 Cholera: El Tor Strain Emerges

Felix Gotschlich (1874-1914) isolated what came to be known as the El Tor strain of cholera bacteria from Indonesian pilgrims in Egypt. "Gotschlich isolated organisms resembling V. cholera from 6 dead Mecca pilgrims at the El Tor quarantine station on the west coast of the Sinai Peninsula. The Pilgrims did not have clinical cholera nor post mortem evidence of cholera. The organisms appeared morphologically, biochemically, and serologically like V. cholera. - Rudolf Hugh Though the El Tor strain was not thought at the time to cause clinical disease, further studies and the emergence of the seventh cholera pandemic in 1961 showed that this strain was in fact disease-causing. About 75% of infections are asymptomatic, 18% cause mild diarrhea, and 1-2% cause severe cholera symptoms.

1989 Oral Typhoid Vaccine Licensed in the U.S.

First developed in 1975, the Ty21a oral typhoid vaccine made from an attenuated Salmonella enterica typhi strain was licensed for use in the United States in December 1989. An injected subunit vaccine, the Vi polysaccharide vaccine, would be licensed in November 1994. The previous, traditional typhoid vaccine was made from killed whole typhoid bacteria and was notorious for reactions at the injection site; the two "modern" typhoid vaccines, by contrast, have fewer and milder injection-site reactions. The World Health Organization recommends the use of one of these vaccines in areas where typhoid fever is endemic. Neither typhoid vaccine is recommended as a routine vaccination in the United States, where typhoid fever is not endemic. The Centers for Disease Control and Prevention does recommend vaccination for U.S. citizens traveling to areas where typhoid fever is common, as it is in parts of Asia, Africa, and Central and South America.

1942 Hepatitis Outbreak Prompts Improved Vaccine Safety Measures

Following the use of particular lots of the 17D vaccine among U.S. Army troops, an epidemic of hepatitis appeared. Several deaths and thousands of cases of "yellow atrophy of the liver" (jaundice following yellow fever vaccination) resulted. Following this incident and a similar episode in Brazil, both of which likely resulted from contaminated human blood serum being used in the vaccine, human plasma was completely removed from the 17D vaccine. Meanwhile, the disease remained endemic in parts of Africa and South America, and mosquitoes capable of spreading it were observed in parts of North America, Europe, and Australia.

12/31/2008 American Measles Outbreaks Increase

For 2008, the Centers for Disease Control and Prevention received reports of 134 cases of measles in the United States, the most cases in a year since 1996. Of these cases, more than 90% had not been vaccinated or had an unknown vaccination status. Measles remains a threat throughout the world. The World Health Organization credits immunization efforts for a nearly 75% reduction in global measles deaths from 2000 to 2007, but it's estimated that the disease still causes nearly 200,000 deaths each year.

1941 Poliovirus in Digestive System

For years, many researchers had assumed that polio was a disease of the nervous system alone. Simon Flexner of the Rockefeller Institute had been especially responsible for shaping this view, when he proposed that poliovirus entered the human body through the nasal (inhaled) route. But this year Albert Sabin and Robert Ward, MD, showed that it was very rare to find poliovirus in nasal tissues. Moreover, poliovirus was present not only in the nervous system but also in the digestive system. This meant that the virus entered the body through the mouth, passed into the digestive system, and was then distributed by the blood to the nervous system. This finding gave hope that a vaccine could be developed that would produce antibodies to fight the virus in the bloodstream before it reached the nervous system.

6/21/2002 Polio Eliminated in Europe

Fourteen years after the launch of the global eradication program, the World Health Organization declared polio eliminated in Europe on June 6, 2002. The last case of wild polio in Europe occurred in a young boy. Melik Minas, who lived in Turkey, contracted polio in November 1998. Minas, who had not been vaccinated, was paralyzed as a result of the infection—although he did partially recover.

2011 Measles in France, United States

France experienced a three-year increase in incidence of measles cases from 2008 through 2011. Of the more than 22,000 reported cases during this period, 10 people died, and nearly 5,000 were hospitalized for complications. At the beginning of the outbreak, only about 89% of two year olds had received one dose of MMR vaccine, well below the target of 95%. In the United States, 2011 was a relatively active year for measles as well, with 220 reported cases. The outbreaks began with cases imported from abroad, and then spread locally to at-risk contacts.

8/8/1921 Polio Strikes FDR

Franklin Delano Roosevelt (1882-1945), former New York State Senator, Assistant Secretary to the Navy, and future U.S. president, fell ill with what most historians think was polio. Roosevelt's illness left his legs paralyzed for life. He avoided being photographed in his wheelchair, however, and used braces and canes to appear to walk.

A Physician's Plea (1905)

Franklin Royer (1870-1961), from Philadelphia's Municipal Hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin. Royer was concerned that doctors waited too long before starting antitoxin treatment. He wrote that "[t]he time to give it is when you have clinical evidence of diphtheria. Do not await a culture report; do not wait to see if you will have severe diphtheria. Give it at once." He cited declining diphtheria death rates in New York City and Chicago, where treatment may have been more aggressive, to support his pleas for treatment. "The death-rate in diphtheria hospitals has been greatly reduced and in many instances cut in half by the introduction of serum therapy. We would plead for a dose of antitoxin in proportion to the amount of exudates and location of the exudates. We would urge a large dose of antitoxin in nasal, nasopharyngeal, and laryngeal diphtheria. We would plead for the general use of antitoxin earlier in the disease. We would plead for more general use of antitoxin as a prophylactic measure in a dose proportionate to the amount of exposure and time of exposure." - Franklin Royer, The Antitoxin Treatment of Diphtheria, with a Plea for Rational Dosage in Treatment and in Immunizing

Early Smallpox in North America (1625)

French Jesuits who encountered Native Americans in Canada were confused by the hostility they received from the Indians, who, they said, "observed with some sort of reason that since our arrival in these lands those who had been the nearest to us had happened to be the most ruined by [smallpox], and that whole villages of those who had received us now appeared utterly exterminated" (Ian Glynn and Jenifer Glynn, The Life and Death of Smallpox).

"The Indian Plague" (1679)

French courtier Count de Frontenac Louis de Buade, describing the effects of smallpox on the Iroquois, termed it the "Indian Plague" and continued: "The Small Pox desolates them to such a degree that they think no longer of Meeting nor of Wars, but only of bewailing the dead, of whom there is already an immense number."

Tuberculosis: Attenuation of Bacterium (1904)

French researcher Albert Calmette (1863-1933) acquired the M. bovis strain of tuberculosis, which had been isolated from the milk of an infected cow. In 1908, at the Institut Pasteur in Lille, France, he and veterinarian Jean-Marie Camille Guérin (1872-1961) began attenuating M. bovis by passing it through a growth medium they had developed specifically for this purpose. Their immediate goal was to weaken the bacteria to the point where they could no longer kill a guinea pig. In the end, the researchers hoped to produce a strain of the bacillus that would safely confer immunity to an uninfected host. It would be 13 years before they saw the fruits of their efforts.

1916 Measles-specific Antibodies Identified

French researchers Charles Nicolle, MD, and Ernest Conseil, MD, showed that measles patients have specific protective antibodies in their blood. The researchers then demonstrated that serum from measles patients could be used to protect against the disease.

England Uses Vaccine from Calves (1881)

Government production of nonhumanized vaccine lymph by serial propagation in calves began in London. The vaccine was distributed to public vaccinators.

Loeffler's Contributions (1884)

Friedrich Loeffler (1852-1915), a German bacteriologist, was the first to cultivate Corynebacterium diphtheriae. Loeffler used a set of rules we now know as Koch's postulates to confirm that Corynebacterium diphtheriae was the agent that caused diphtheria. Later in 1884, Loeffler showed that C. diphtheriae produces a toxin. This was the first description of a bacterial exotoxin. (An exotoxin is a toxin excreted into the surrounding environment by a microbe.) When C. diphtheriae colonizes the upper respiratory tract, the bacteria secrete a toxin that injures and then destroys cells. Waste products and proteins form a thick gray substance called a pseudomembrane over the pharynx. The pseudomembrane sticks to tissues and may obstruct breathing. Meanwhile, the toxin may travel to the heart, muscle, kidneys, liver, and other areas. Koch's Postulates Robert Koch and Friedrich Loeffler's steps formed the basis for identifying a disease-causing agent. 1. The microbe is present in every case of the disease. 2. The microbe can be taken from the host and grown independently. 3. The disease can be produced by introducing a pure culture of the microbe into a healthy host.* 4. The microbe can be isolated and identified from the host infected in Step 3. *One exception to Step 3 is that some individuals may be infected with a disease-causing microbe and not show signs of the disease. These are known as asymptomatic carriers.

1923 Ramon and Glenny

Gaston Ramon (1886-1963), a veterinarian at the Pasteur Institute in France, developed diphtheria toxoid. Working independently at the Wellcome Research Laboratories in London, physician Alexander Thomas Glenny (1882-1965) did likewise. Ramon followed in the footsteps of other researchers by attempting to inactivate diphtheria toxin. He treated diphtheria toxin with heat and a solution of formaldehyde called formalin. Formalin inactivated the toxin molecule so that it could no longer attach to cells and cause toxicity. Once injected into humans, however, it was able to induce antibodies that blocked natural toxin from attaching to cells. The substance came to be called diphtheria toxoid. This breakthrough provided the simplest and most effective means to prevent diphtheria.

Italian Physician Uses Cows for Vaccine Production (1810)

Gennaro Galbiati, director of the vaccine service in Naples, Italy, began retrovaccinating cows with human vaccine lymph. He then vaccinated people with the resulting animal lymph. His findings on vaccine from cows were expressed in these chapter titles from his 1810 memoir: "1. Vaccination performed with vaccine from the cow manifests its effects much more energetically, without being more dangerous or less protective than humanized virus." "2. Vaccination performed with virus from the cow offers the advantage that no other diseases can be communicated by it."

Smallpox as War Breaks Out (1775)

George Washington's siege of Boston was complicated by smallpox infection inside the city. British troops occupying Boston had been variolated or exposed to smallpox in the past. But Washington's Continental Army troops were more vulnerable. Most had never been exposed to smallpox and were not previously variolated. Washington himself had survived a case of smallpox while on the island of Barbados in 1751.

Mandatory Inoculation for Continental Army (1777)

George Washington, commander-in-chief of the Continental Army, based at his headquarters in Morristown, New Jersey, ordered mandatory inoculation for troops if they had not survived a smallpox infection earlier in life—possibly in reaction to the inability of Benedict Arnold's troops to capture Quebec from Britain the year before, when more than half of the colonial troops had smallpox. Recruits passing through Virginia were inoculated at Alexandria.

Rubella: The "German Measles" (1740)

German physician Friedrich Hoffmann was the first to give a clinical description of the disease that would later come to be known as rubella. Until that point, however, so many German physicians were involved in identifying and distinguishing the disease from other known maladies (after Hoffmann's description, German physicians de Bergen and Orlow confirmed his work) that it would be referred to as "Rötheln," from the German word Röteln. Thus rubella would also eventually be referred to as "German measles."

Hib: Pfeiffer Discovers Bacterium (1892)

German physician Richard Pfeiffer (1858-1945), once a student of Robert Koch, isolated a bacterium from the lungs and sputum of influenza patients during a pandemic. Pfeiffer believed that he had found the cause of influenza, and the bacterium came to be known as "Pfeiffer influenza bacillus." In the 1930s it was definitively established that influenza was in fact caused by a virus, not a bacterium. Pfeiffer's "influenza bacillus," however, would eventually be named Haemophilus influenzae because of its long-standing, though incorrect, association with influenza.

Ehrlich's Immunity Unit (1897)

German scientist Paul Ehrlich (1854-1915), who would win the Nobel Prize in medicine in 1908 for his work on immunity, developed a standardized unit of measure for diphtheria antitoxin. Ehrlich's development resulted from his recognition that the amount of antitoxin in serum varied greatly among different samples. Physicians could not depend on the potency of any given container of antitoxin when treating a patient, because the containers had no common standard for potency. Ehrlich's immunity unit marked the first standardization of a biological product and paved the way for future work with sera.

Whooping Cough: Epidemic in Paris (1578)

Guillaume De Baillou described an epidemic of pertussis (whooping cough) in Paris, referring to it as "quinte," which he said was a common name for the disease that was circulating. De Baillou suggested the name might have to do with the sound of the characteristic "whoop" cough.

1930 Max Theiler Takes on Yellow Fever

Harvard instructor Max Theiler (1899-1972) and colleagues proved that the yellow fever virus could easily be given to mice. This was an important discovery given that, although previous efforts resulted in the successful infection of monkeys, monkeys were difficult to work with and quite expensive. Mice, on the other hand, were easy both to acquire and to handle. Theiler continued his work and joined the Rockefeller Foundation. (Theiler, incidentally, contracted yellow fever himself—from one of his own mice. Fortunately he suffered only a mild case, and developed immunity to the disease.)

Anthrax Investigations (4/30/1877)

Having begun his studies on anthrax earlier in the year in the midst of an epidemic that was devastating livestock, Louis Pasteur presented a paper on the disease to the Academy of Sciences. This investigation was the beginning of his work in medicine. Just as some of Pasteur's colleagues embraced the idea of spontaneous generation, many of them rejected the idea that microbes played a role in disease. In the case of anthrax, they thought that toxic plants, biting insects, the sun, or hot weather might cause the disease. Pasteur, confirming worked published earlier by Robert Koch, showed that anthrax bacilli were the agent of disease. During these studies, Pasteur also demonstrated that another type of bacteria could cause sepsis (also sometimes known as blood poisoning).

Attenuating the Rabies Virus (1884)

Having tried to attenuate the rabies virus in monkeys, Pasteur turned to a different method to produce the vaccine. He observed a flask, open on both ends, in which his protégé Emile Roux had suspended a piece of rabbit spinal cord. Pasteur predicted that drying of the infected tissue might weaken the virus. Indeed, later experiments showed exactly this. Pasteur was able to use a series of less-attenuated vaccines over several days to prevent rabies in dogs that had been infected. The work was dangerous: he and his assistants often had to handle the rabid animals and take samples from them.

6/17/1916 New York City Polio Epidemic

Health officials announced a polio epidemic centered in Brooklyn, New York. As was typical with polio outbreaks, infections surfaced in the summer months. More than 2000 people would die in New York City alone. Across the United States in 1916, polio took the lives of about 6,000 people, leaving thousands more paralyzed. Summer epidemics would come to be common in this era and would lead to widespread closures of pools, amusements parks, and other places where children gathered.

Typhoid Fever Strikes Royalty (1612)

Henry Prince of Wales, the oldest son of King James I, died at age 18 after a "short illness" which was not identified or described other than as a fever. In 1882, Norman Moore, MD, published "The Illness and Death of Henry Prince of Wales in 1612." Based on his studies of the autopsy on the prince as well as detailed descriptions of the illness, Moore alleged that the prince had died of typhoid fever. If he was correct (today it is generally assumed that he was) this would have been the earliest English case of typhoid fever on record.

1957 Koprowski Begins OPV Tests

Hilary Koprowski, having left Lederle Laboratories where he did his initial work on polio, began a series of attenuated poliovirus vaccine trials in the Congo (now Democratic Republic of Congo). His vaccine included only Type 1 poliovirus, the type responsible for most cases of polio. His team vaccinated hundreds of thousands of people. Other sites in Europe would be included as well. Some of Koprowski's results were difficult to evaluate, though at least one study confirmed efficacy of the vaccine used. The Belgian Congo entered a period of political and social unrest, complicating follow-up of vaccinated individuals.

1968 Vaccine for Hong Kong Influenza Pandemic

Hilleman and colleagues received a new influenza A virus, Type A2, Hong Kong strain, that had caused widespread illness in Hong Kong. They rushed to manufacture a vaccine from the new flu strain. In four months, Merck had manufactured more than nine million doses of vaccine.

1966 Experimental Mumps Vaccine

Hilleman arranged to for his daughter, Kirsten, to receive his experimental mumps vaccine, developed from the virus isolated from her half-sister, Jeryl Lynn.

1968 A Vaccine for Chickens

Hilleman began to work on a vaccine to prevent Marek's disease in chickens. Marek's disease infected nearly 50% of U.S. chickens, causing tumors and artherosclerosis. The risk to humans from consuming infected chickens was unknown. Hilleman used a herpes virus from turkeys to create the vaccine.

1941 College Graduation and Graduate Studies

Hilleman graduated from Montana State University, first in his class and with a degree in chemistry and microbiology. Winning a full scholarship, Hilleman soon began graduate studies in microbiology at the University of Chicago. Hilleman's work focused on Chlamydia, a pathogen that causes a sexually transmitted disease that can damage a woman's reproductive organs. Hilleman established that Chlamydia is an unusually shaped bacterium, not a virus as had been thought. His work eventually led to the discovery of a treatment.

1948 Hilleman Leaves Squibb

Hilleman left Squibb to work as chief of the Department of Respiratory Diseases at the Army Medical Center (renamed the Walter Reed Army Institute of Research in 1953) in Washington, DC.

12/31/1957 Merck Hires Hilleman

Hilleman left the Walter Reed Army Institute of Research to become director of Virus and Cell Biology Research for the Merck Institute for Therapeutic Research in West Point, Pennsylvania.

1967 Hilleman Adopts New Rubella Strain

Hilleman shifted his work on an attenuated rubella vaccine by abandoning the Benoit strain of rubella virus and adopting the Division of Biologics Standards' HPV-77 strain (High-Passage Virus, developed by Paul Parkman and Harry Meyer).

4/2/1974 Meningococcal Polysaccharide Vaccine Licensed

Hilleman ushered a series of meningococcal polysaccharide vaccines to licensure (group A, group C, combined groups A+C, and then a quadrivalent vaccine against groups A, C, Y, and W-135) beginning in 1974 with a vaccine that was effective against meningococcal group A, one of five major types of meningococcal bacteria. The vaccines represented a new approach in vaccine science: using not live or attenuated pathogens, but rather the polysaccharide (complex sugar) outer coating of these bacteria. Much of the work on isolating the polysaccharides for both group A and group C was done at Walter Reed Army Institute of Research by Army researchers at Hilleman's earlier professional base.

1944 Commercial Employment

Hilleman went to work for E. R. Squibb and Sons in New Brunswick, New Jersey.

1967 Studies on Interferon

Hilleman's lab demonstrated that certain nucleic acids can stimulate interferon production in cells. Interferon had been identified in the late 1950s as a substance produced by cells that interfers with virus reproduction. Hilleman and his associates described interferon's properties and developed methods to mass produce and purify it. Today, physicians use various forms of interferon therapy to fight cancers, viral infections, and several other diseases.

1968 Attenuvax: New Measles Vaccine

Hilleman's team developed a new, more attenuated measles vaccine by passaging the virus 40 more times through animal tissues. Hilleman called the new measles virus strain Moraten, for More Attenuated Enders. The new vaccine, Attenuvax, did not require an injection of gamma globulin antibodies to reduce reactions.

Lincoln Contracts Smallpox (11/19/1863)

Hours after delivering the Gettysburg Address, President Abraham Lincoln suffered weakness, fever, and headache on the train back to Washington. Within a few days he developed widespread pustular lesions. Medical historians assert that Lincoln had smallpox, which sickened him for almost four weeks. Lincoln, however, recovered, though his valet caught the disease and died.

Variolation in Turkey (1718)

In 1718, Lady Mary Wortley Montagu (1689-1762) had her son variolated in Constantinople by Dr. Charles Maitland. Lady Montagu, whose husband was ambassador to Turkey, had been disfigured by smallpox around 1715. She had heard about variolation upon her arrival in Turkey, and was anxious that her six-year-old son, Edward, have the procedure. In 1717, she wrote to a friend: "...I am going to tell you a thing that I am sure will make you wish yourself here. The small-pox, so fatal, and so general amongst us, is here entirely harmless by the invention of ingrafting, which is the term they give it. There is a set of old women who make it their business to perform the operation every autumn.... The old woman comes with a nut-shell full of the matter of the best sort of smallpox, and asks what veins you please to have opened.... She immediately rips open that you offer her with a large needle ... and puts into the vein as much venom as can lie upon the head of her needle.... Every year thousands undergo this operation.... There is no example of any one that has died in it; and you may believe I am well satisfied of the safety of the experiment.... I am patriot enough to take pains to bring this useful invention into fashion in England; and I should not fail to write to some of our doctors very particularly about it, if I knew any one of them that I thought had virtue enough to destroy such a considerable branch of their revenue for the good of mankind." — Lady Mary Wortley Montagu, Letters of the Right Honourable Lady M--y W--y M--e: Written During her Travels in Europe, Asia and Africa. . . , vol. 1 (Aix: Anthony Henricy, 1796), pp. 167-69; letter 36, to Mrs. S. C. from Adrianople, n.d.

The Death of Spontaneous Generation (12/1/1862)

In 1860, the French Academy of Sciences had issued a challenge to French scientists: they should try to shed light on the concept of spontaneous generation. Spontaneous generation is the idea, which still persisted in the 1860s, that life can arise from nonliving materials, such as mud or water. Louis Pasteur took on the challenge, using a precise series of experiments to show that flasks of broth and water did not spoil when he prevented organisms from entering the flasks. The Academy awarded him the prize on December 1, 1862, though other scientists continued to object to Pasteur's findings and methods. The Academy elected Pasteur to its membership on December 8.

1/1/2018 Polio Eradication Update

In 2017, only 22 cases of wild poliovirus infection were reported, down from 37 reported cases in 2016. At the end of 2017, polio remained endemic in only three countries: Afghanistan, Nigeria, and Pakistan. Other countries, however, remained at risk for polio cases. These include Cameroon, Central African Republic, Chad, Equatorial Guinea, Ethiopia, Iraq, Kenya, Lao People's Democratic Republic, Liberia, Madagascar, Myanmar, Niger, Sierra Leone, Somalia, South Sudan, and Ukraine. Unfortunately, Nigeria reported two cases of paralytic polio in August 2016, two years after the last previous cases had been reported. These cases were likely to have been caused by the wild polio strain circulating in Nigeria in 2014 and before, meaning that low-level transmission of poliovirus was probably occurring in certain areas. Intensive supplemental immunization campaigns were undertaken, and no new cases have been reported since the initial 2016 outbreak. Vaccination response is difficult in Nigeria, however, because of ongoing violence and humanitarian disturbances in affected areas. These factors make it difficult to reach some children: they remain unvaccinated and thus vulnerable to polio infection. The Global Polio Eradication Initiative, Gavi, the World Health Organization, The Bill & Melinda Gates Foundation, and other organizations continue their efforts against the disease.

Hib: Bacterium influenzae (1896)

In Atlas and Principles of Bacteriology, Karl Lehmann and Rudolf Neuman referred to what would eventually be named Haemophilus influenzae as "Bacterium influenzae," crediting Richard Pfeiffer for its discovery. The book included a colorized smear of a nasal secretion containing the bacteria.

Measles Appears in Boston (1657)

In Boston, John Hull wrote in his diary that "the disease of measles went through the town," but fortunately there were very few deaths.

1/28/1949 Breakthrough in Culturing Viruses

In Boston, the team of John Enders, PhD (1897-1985), Thomas Weller, MD (1915-2008), and Frederick Robbins, MD (1916-2003), showed that they could grow polioviruses in non-nervous tissue—namely human embryonic skin and muscle tissue. This landmark finding would reduce reliance on using live monkeys for growing and testing virus. No longer would polio research be restricted to facilities that could house large numbers of experimental animals. Enders's findings would lead the way to simpler, less expensive methods of producing large quantities of virus for study and eventually vaccine production. Enders and colleagues would win the Nobel Prize in Physiology or Medicine in 1954 for their work on culturing polioviruses.

1948 Kyoto Disaster

In Kyoto, Japan, 68 of 606 children died after diphtheria immunization as a result of improper manufacture of toxoid. Toxoid in the preparation reverted to toxin, with disastrous effects. Toxoid manufacturers instituted safeguards after this event to prevent similar incidents. No similar cases have since been reported.

Boys Sent to France for Rabies Vaccine (12/1/1885)

In Newark, New Jersey, four boys were bitten by a rabid dog. A fundraising effort arose to help send the boys to France for treatment by Pasteur. Donors raised $1,000, which sent the boys overseas via ocean liner. The healthy boys returned home in January 1886 after treatment with the new rabies vaccine. The long incubation period of the rabies virus gave the boys enough time to travel thousands of miles for the post-exposure vaccination.

1908 Poliovirus Identified

In Vienna, Karl Landsteiner, MD (1868-1943), and Erwin Popper, MD (1879-1955), announced that the infectious agent in polio was a virus. Popper and Landsteiner deduced the viral nature of polio by carefully filtering preparations of spinal cord fluid from a person who had died of polio. The filters were known to trap bacteria. When Popper and Landsteiner injected the filtered preparations into monkeys, the monkeys developed polio. The researchers then concluded that an infectious particle smaller than bacteria caused the disease. Poliovirus itself would not be visible to researchers until the 1950s, when the electron microscope was available.

4/12/1955 Polio Vaccine Results Announced

In a press conference at the University of Michigan, Thomas Francis Jr., MD (a scientist with extensive experience with influenza vaccines), and colleagues announced the results of the Salk poliovirus vaccine trial. The vaccine, they said, was 80-90% effective against paralytic polio. The U.S. government licensed Salk's vaccine later this same day. The press conference and licensure paved the way for widespread distribution and use of the vaccine.

1925 Smallpox in Milwaukee

In early 1925, a smallpox epidemic emerged in Milwaukee, Wisconsin. The American Journal of Public Health (1926, no. 12) reported that the epidemic resulted in 386 smallpox cases, of whom 87 people died (about 23%). Of the 386 cases, 327 had never been vaccinated, 46 had been vaccinated 10 or more years previously, 11 had been vaccinated more than 5 and less than 10 years previously, 2 had an uncertain vaccination history, and none had been vaccinated within the previous 5 years. Health workers performed about 400,000 vaccinations during the epidemic, and officials enforced quarantine measures and isolation of those infected. Dr. Merle R. French (d. 1961), a 1921 graduate of the University of Iowa School of Medicine, was, at the time of this outbreak, the Superintendent of the Communicable Diseases Hospital in Milwaukee. Dr. French wrote a note describing one of the patients pictured here: "Picture of smallpox patient taken at S.view Hospital a short time ago. Man was a Christian Scientist who thought that he could by power of mind prevent smallpox. Man died. This is the kind of smallpox we are having." Dr. French was referring to variola major, the more dangerous form of smallpox, rather than variola minor, which came to be the dominant form of smallpox in the 20th century, particularly in the West. This man seems to have suffered from a type of variola major known as hemorrhagic smallpox, of which there were 22 cases in this epidemic. Hemorrhagic smallpox usually was fatal. The other photographs show less severe, but clearly serious, cases.

1/29/1944 FDR Pleads for Victory Against Polio

In his radio-broadcast appeal for donations to National Foundation for Infantile Paralysis, President Roosevelt likened the fight against polio to the Second World War: "The dread disease that we battle at home, like the enemy we oppose abroad, shows no concern, no pity for the young. It strikes—with its most frequent and devastating force— against children. And that is why much of the future strength of America depends upon the success that we achieve in combating this disease."

Quarantine in Boston (1648)

In response to epidemics of yellow fever in Barbados, Cuba, and the Yucatan, a strict quarantine was established in Boston, Massachusetts, for all ships arriving from the West Indies because of "ye plague or like in[fectious] disease."

June 27, 2015 Diphtheria Death in Spain

In spite of overall high vaccination rates, Spain reported its first case of diphtheria since 1986 on May 30, 2015. An unvaccinated six-year-old boy contracted the disease, became seriously ill, and died on June 27 in spite of receiving anti-toxin treatment in a Spanish hospital. Several of the boy's contacts tested positive for carriage of Corynebacterium diphtheriae but did not become ill as they were vaccinated. They were treated with antibiotics to eliminate the bacteria from their bodies.

1917 Hib: Bacterium Described

In the Journal of Bacteriology, C.E.A. Winslow and co-authors published a lengthy report titled "The Families and Genera of the Bacteria." It characterized and classified known types of bacteria; among those listed was "Hemophilus influenza," which has now been standardized as Haemophilus influenzae. It described the Hemophilus group as including "the small non-motile parasites, which will grow only on media in the presence of blood or other body fluids." (Haemophilus means "blood loving.") In fact Haemophilus influenzae have such particular nutritional requirements that researchers still use their need for certain growth factors for laboratory identification today.

1918 Influenza: Spanish Influenza Pandemic and Vaccines

In the deadly Spanish influenza pandemic of 1918-19, investigators attempted to develop vaccines to prevent influenza, though they had not yet correctly identified the causative pathogen. A variety of killed whole cell bacterial vaccines were tested; these vaccines included Bacillus influenzae (now know as Haemophilus influenzae) and strains of pneumococcus, streptococcus, staphylococcus, and Moraxella catarrhalis bacteria. These vaccines would certainly not have prevented influenza infection--as we know now, the pandemic was caused by a new strain of the influenza A virus. Influenza viruses would not be isolated and identified until the 1930s, and the first commercial influenza vaccines were not licensed in the United States until the 1940s.

A Decrease in Mortality (1820)

In the last decade of Jenner's life, the London Bills of Mortality documented 7,858 deaths from smallpox—down from 18,447 deaths in the last decade before vaccination (1791-1800).

Beaugency Vaccine Strain Begun (4/30/1866)

Jean Anne Henri Depaul, Director of Vaccination for the French Academy of Medicine, traveled to Beaugency, France, where he observed a cow that had been inoculated with spontaneously occurring cowpox from another cow. From those vesicles, he gathered lymph and inoculated a cow he had brought with him. He returned to Paris with the inoculated cow and used its resulting lymph for vaccination, thus ensuring a fully animal (that is, non-humanized) vaccine strain. According to an American physician, thus "was inaugurated the method of true and undoubted animal vaccination." This vaccine stock came to be known as the Beaugency stock, which was widely propagated in Europe and America

1916 Typhoid Fever: Focus on Water Supplies and Public Health Grows

In the late 1800s and early 1900s, public health officials in the United States focused their attention on the need for safe water supplies to prevent the spread of typhoid. Many publications highlighted the discrepancy between typhoid deaths in European cities, where filtered water supplies were more prevalent, and the much higher typhoid death rates in U.S. cities where water supplies were less safe. This concern was well-founded. Water supplies contaminated with sewage were a vector not only for typhoid, but also for cholera and other waterborne illnesses. In 1912 Allan J. McLaughlin, a former surgeon for the Public Health and Marine Hospital Service, spoke before the Illinois Water Supply Association and stated that "The average American citizen displays toward sanitary problems a very dangerous apathy." As filtered water supplies became more common in the country, deaths from typhoid fever dropped significantly.

Bacterium Mistakenly Blamed for Yellow Fever (1897)

Italian bacteriologist Giuseppe Sanarelli (1865-1940), a prominent researcher in his field, announced that a bacillus bacterium was the cause of yellow fever. Initial investigations seemed to bear this out; however, United States Army Surgeon Walter Reed eventually demonstrated that Sanarelli's Bacillus icteroides was a secondary invader, and was not the cause of yellow fever.

Cholera: Pacini Links Bacterium to Disease (1854)

Italian physician Filippo Pacini (1812-1883) linked the cholera bacterium to the disease itself. Pacini microscopically observed samples from the intestines of cholera victims and noted the presence of tiny, comma-shaped particles that he suggested were the cause of the disease. (The bacterium is known today is Vibrio cholerae. The genus Vibrio includes several species of comma-shaped or rod-shaped bacteria that are mobile by means of a whip-like flagellum, or tail-like structure.) Pacini expanded on his ideas about cholera in several later publications. He suggested that the cholera vibrio acted on the lining of the intestine to cause massive fluid and electrolyte loss, and he suggested that cholera patients be treated with intravenous injections of water to which salt had been added. Though most of his ideas have been shown to be correct, the scientific world largely ignored his work during his lifetime.

9/11/1978 Smallpox Infection in a Lab

Janet Parker, a photographer employed by the University of Birmingham Medical School in Great Britain, died of smallpox. Parker had worked in a darkroom one floor above a research laboratory where work was being done with the live smallpox virus. In August 1978, she was admitted to the hospital and diagnosed with the variola major type of smallpox. Three hundred of her associates and contacts were quarantined. (Her mother also contracted smallpox, but survived; her father died of a heart attack after learning about Parker's illness.) It was later discovered that the World Health Organization had informed Henry Bedson, the head of the medical microbiology department, that the facilities did not meet WHO's standards. Bedson, however, did not act on WHO's recommendations for changes in lab procedures, and in fact lied about the amount of work being done in the laboratory. On September 6, 1978, Bedson committed suicide at his home, purportedly over the guilt for his part in the tragedy.

1938 Rubella: Researchers Demonstrate Transmission of Disease

Japanese scientists S. Tasaka and Y. Hiro used throat washings from children sick with rubella to transmit the disease to healthy children. The causative agent of the disease, however, remained unidentified.

Jenner Dies (1/26/1823)

Jenner died of an apparent stroke at age 73.

Cholera: The Pump Handle (8/31/1854)

John Snow once again made an important contribution to the understanding of cholera. During an 1854 London cholera epidemic that began in late August, Snow carefully investigated illnesses that occurred near a water pump at Cambridge and Broad streets in the Soho neighborhood. Snow proposed that the water, drawn from a downstream location on the Thames River, was contaminated with the causative agent of cholera. In fact, about 500 cholera deaths had occurred in the neighborhood near the pump in 10 days. In contrast, he showed that a nearby pump, supplied by a different company from water further upstream, did not appear to be associated with cholera.

A Governor's Viewpoint (1634)

John Winthrop, governor of the colony of Massachusetts, wrote that "the natives, they are neere all dead of the small Poxe, so as the Lord hathe cleared our title to what we possess" (Ian Glynn and Jenifer Glynn, The Life and Death of Smallpox).

1968 IPV Phased Out in U.S.

Jonas Salk's inactivated polio vaccine was no longer routinely used in the United States. This would be the case until 1997, when the IPV would be phased in again.

4/24/1955 The Cutter Incident

Just a few weeks after the landmark press conference announcing success of the vaccine trials, an Idaho doctor reported a case of paralytic polio in a recently vaccinated girl. Over the next few weeks, similar reports trickled in to local health authorities. All involved a disturbing detail: paralysis began in the vaccinated arm, rather than in the legs as was more common. It soon emerged that most of the cases of paralytic polio occurred in children inoculated with vaccine produced by Cutter Laboratories in California.

A Vaccination Expedition (9/1/1803)

King Charles IV of Spain commissioned royal physician Francisco Xavier de Balmis to bring smallpox vaccination to the Spanish colonies in the New World. De Balmis departed on a ship with 22 abandoned children and a host of assistants, planning to vaccinate the boys in sets of two throughout the trip so that fresh pustules would be available at any given time. He eventually reached Caracas. Despite only one of the children still having a visible cowpox pustule, De Balmis initiated South American vaccination. (All 22 children were eventually settled, educated, and adopted in Mexico, at the Spanish government's expense.)

1971 Rabies: New Inactivated Vaccine

Koprowski's team of scientists, at the Wistar Institute in Philadelphia, wanted to improve on the antibody response created by the experimental HEP live-virus vaccines. They looked to a cell line created from human embryonic cells as a medium for cultivating the rabies virus. Their initial tests successfully used live vaccine virus, as had the previous HEP tests. But medical resistance was strong to using a live virus rabies vaccine. The risk for inadvertent infection with a fatal illness was seen to be too high. Accordingly, Koprowski's team used a chemical disinfectant to inactivate their rabies vaccine virus. In 1971, Koprowski, veterinarian Tadeusz Wiktor, and American physician Stanley Plotkin inoculated themselves with their experimental rabies vaccine. Plotkin went on to successfully test the vaccine in trials with human subjects.

First Laboratory Vaccine (1879)

Louis Pasteur produced the first laboratory-developed vaccine: the vaccine for chicken cholera (Pasteurella multocida). Pasteur attenuated, or weakened, the bacteria for use in the vaccine. He happened upon the method of attenuation by accident: in his lab, he was studying fowl cholera by injecting chickens with the live bacteria and recording the fatal progression of the illness. He had instructed an assistant to inject the chickens with a fresh culture of the bacteria before a holiday. The assistant, however, forgot. When the assistant returned a month later, he carried out Pasteur's wishes. The chickens, while showing mild signs of the disease, survived. When they were healthy again, Pasteur injected them with fresh bacteria. The chickens did not become ill. Pasteur eventually reasoned the factor that made the bacteria less deadly was exposure to oxygen.

Birth of Pasteur (12/27/1822)

Louis Pasteur was born in Dôle, in eastern France.

The Biology of Fermentation (1857)

Louis Pasteur was named Director of Scientific Studies at the École Normale Supérieure, a prestigious higher education institution in Paris. At the École Normale, Pasteur continued his studies of fermentation. He established the concept that fermentation was a biological process, carried out by tiny organisms. Importantly, his experiments demonstrated that fermentation and rotting could not take place when the organisms were excluded from solutions by heating or by filtering. His ideas would lead to the widespread adoption of what we call pasteurization for the preservation of food, and to increasing attention in surgery to the role of microorganisms in infection. This concept of the activity of microorganisms emerged further in the study of the causes of infectious disease undertaken by Pasteur and others later in the century.

Death of Pasteur's Daughter (9/11/1865)

Louis Pasteur's two-year old daughter Camille died of a liver tumor.

Cholera: Egyptian Investigations (9/17/1883)

Louis Thuillier, a biologist sent to Egypt by Louis Pasteur with other French scientists to investigate a cholera outbreak, died of the disease at age 27. Robert Koch had arrived with his own group of German researchers in Egypt in late August. Both teams were attempting to isolate the causative agent of cholera and to infect experimental animals with the disease. Neither team succeeded, and the French scientists returned home. Koch, however, left Egypt for Calcutta, India, to investigate cholera there.

First Compulsory Vaccination Attempted (1805)

Marianne Elisa of Lucca (Napoleon's sister) became the first ruler to try making vaccination compulsory. She was unable, however, to determine a practical method of enforcement.

1909 The Debut of "Typhoid Mary"

Mary Mallon was first referred to as "Typhoid Mary" by the New York American on June 20, 1909. Mallon, an Irish immigrant who worked as a cook for wealthy New York families, first gained the attention of public health officials in 1906. A Long Island family for whom Mallon had worked as a cook had fallen ill with typhoid fever. Though Mallon was no longer with the family, officials trying to locate her discovered that other families she'd worked for had also developed typhoid fever. In one outbreak at a household of nine in Dark Harbor, Maine, in 1902, Mallon and Mr. Coleman Drayton, head of the household, were the only two not to fall ill (Drayton had contracted typhoid fever years before). Major George A. Soper of the United States Army, after investigating Mallon's past some years later, noted that: Mr. Drayton felt so grateful to the cook for the help which she gave him during the epidemic that at the end of the epidemic he made her a handsome present of money in addition to her wages, little thinking that the cause of the whole trouble lay at her door. - Typhoid Mary, Major George A. Soper, reprinted from the Military Surgeon, July 1919 Eventually, Mary Mallon became the first identified healthy carrier of typhoid: she carried the typhoid bacteria and spread them to others, but did not fall ill herself. In 1907, Mallon was detained by the New York City Department of Health for three years, first at a hospital for contagious diseases in Manhattan, and then at Riverside Hospital on North Brother's Island in the East River to be kept in isolation. She was released in 1910 under the conditions that she would no longer work as a cook and would take steps to prevent spreading typhoid. In 1915, however, Mallon was caught once again working as a cook (this time under the assumed name Mary Brown) after infecting 25 people with typhoid, one of whom died. Mallon was eventually sent back to North Brother Island and remained there for the next 23 years until her death in 1938. Although the phrase "Typhoid Mary" is now used to describe a person or object that brings widespread death and destruction, the number of illnesses and deaths caused by Mary Mallon herself are often inflated. At the time of her death in 1938, she was officially blamed for 10 outbreaks totaling 51 cases of typhoid fever, and three deaths from the disease.

Vaccination Endorsed (1802)

Massachusetts became the first U.S. state to encourage the use of vaccination against smallpox. Dr. Waterhouse, the first doctor in Boston to obtain vaccine material, convinced the city's Board of Health to sponsor a public test of vaccination. Nineteen volunteers were successfully vaccinated. Initially, Waterhouse sought to retain a monopoly over smallpox vaccine in North America, refusing to provide vaccine material to other doctors without a fee or a portion of their profits. This monopoly led to efforts to obtain vaccine material from vaccination pustules on human patients, or via clothing carrying pus from vaccination pustules. In at least one such case, a pustule on the arm of a British sailor used to obtain such material was not, in fact, from vaccination, but from a full smallpox infection. Sixty-eight people died after material from the pustule was used to vaccinate patients in Marblehead, Massachusetts. Eventually, other doctors began receiving genuine vaccine material from sources in England. After his initial monopoly was broken, Waterhouse shared his supplies without complaint.

Vaccination Law Passes (1855)

Massachusetts passed the first U.S. law mandating vaccination for schoolchildren.

6/28/1965 Testing of Mumps Vaccine

Maurice Hilleman and colleagues began to test their experimental mumps vaccine in Philadelphia-area institutions for the mentally retarded. Tests showed that the children developed antibodies to mumps. Later, area nursery schools and kindergartens participated in the tests, and the vaccine was shown to be effective in preventing mumps. While testing of vaccines on mentally retarded children was not uncommon, this practice would be frowned upon today. Other prominent vaccine researchers of time, including Jonas Salk and Hilary Koprowski, tested experimental poliovirus vaccines in mentally retarded children, and a group of researchers at Boston Children's hospital did the same with an experimental measles vaccine. On the other hand, people in these settings had at least as high a risk of infection as their counterparts living in the community, in some respects a higher risk of infection. Clearly, the evolving norms of research ethics is a complex issue.

1962 Attenuated Measles Vaccine Developed

Maurice Hilleman and colleagues developed an attenuated measles vaccine by passaging John Enders's measles virus strain over 80 times through different cell types. The resulting vaccine, Rubeovax, was given with a dose of gamma globulin antibodies to reduce reactions (mainly fever and rash).

1957 Asian Influenza Pandemic

Maurice Hilleman and his colleagues at WRAIR identified a new influenza A virus, Type A2, Asian influenza, that caused a pandemic. Hilleman noticed news reports of a severe influenza in Hong Kong. The number of cases and their description led him to think that a new type of influenza was emerging and that a pandemic threatened. Hilleman and his team obtained a sample of the virus from a U.S. serviceman. They soon determined that most people lacked antibody protection from the new influenza virus. Only a few elderly people who had survived the influenza pandemic of 1889-1890 showed antibody response to the new virus. Hilleman jump-started vaccine production by sending virus samples to manufacturers and urging them to develop the vaccine in four months. Worldwide, from 1957-1958, about 2 million people died from Asian flu, with about 70,000 deaths in the United States. Some predicted that the U.S. death toll would have reached 1 million without the vaccine that Hilleman called for. Health officials widely credited that vaccine with saving many lives.

3/24/1976 Swine Influenza Vaccine

Maurice Hilleman and other scientists met with U.S. President Gerald Ford to discuss a vaccine response to an outbreak of swine influenza at Fort Dix, New Jersey. Congress committed funds to a nationwide vaccination program. Merck intended to produce 50 million swine flu vaccine doses by January 1977 and delivered about 11 million doses in late September 1976. The nationwide vaccination program, however, ended after vaccination was associated with an increased risk of a condition called Guillain-Barré syndrome (GBS). GBS has several causes, the most common of which is infection with bacteria called Campylobacter. But GBS occurred in recipients of the 1976 swine-flu vaccine at a rate higher than usual: beyond the normal "expected" rate for the general population, about one additional case occurred for every 100,000 vaccine recipients. And, despite what first promised to be a widespread outbreak, few cases of swine flu actually developed among the American people.

4/11/2005 Death of Hilleman

Maurice Hilleman died at age 85.

1968 A More Attenuated Measles Vaccine

Merck began to distribute an improved vaccine using John Enders's measles strain, developed by Maurice Hilleman and colleagues. Although the previous vaccine was effective in preventing future measles infections, it had to be given along with gamma globulin—human blood proteins—in order to reduce side effects. Hilleman eliminated the need for giving gamma globulin with the vaccine by passing the virus through chick embryo cells an additional 40 times, weakening it even further. Called the Moraten strain (More Attenuated Enders), it has been the only measles vaccine used in the United States since licensure.

3/23/1963 Hilleman Isolates Mumps Virus

Maurice Hilleman isolated mumps virus from his daughter, Jeryl Lynn, during her illness. Hilleman's five-year-old daughter, feeling ill, woke him in the night. He believed that she probably had mumps, because she had the typical swollen glands and fever of the disease. Worrying about her health, but sensing an opportunity, he quickly drove to his Merck office to pick up cotton swabs and a vial of broth. Back at home, he swabbed Jeryl Lynn's throat and placed the swab in the broth. He drove back to work to freeze the solution and then returned to his daughter. Hilleman needed to attenuate, or weaken, the virus before he could use it to develop a vaccine. To do this, he passed the virus from the broth through chicken eggs several times, and then did the same in chick cells. The virus became better and better at destroying chick cells. Hilleman expected that as the mumps virus became more damaging to chick cells, it would become worse at causing disease in humans. He needed to test his assumption.

1984 Hilleman Retires

Maurice Hilleman officially retired from Merck but maintained regular office hours there for many years.

1944 Vaccine for Japanese Encephalitis

Maurice Hilleman, working at E. R. Squibb and Sons, helped develop a Japanese encephalitis vaccine to protect American troops in the World War II Pacific theater of operations. Hilleman's vaccine was never widely tested. It was given to thousands of U.S. soldiers in wartime and likely prevented disease in many of them. Later, other vaccines replaced it.

1969 Rubella: First Vaccine Licensed

Maurice Hilleman, working at Merck, modified a rubella vaccine virus from Paul Parkman and Harry Meyer, scientists at the Division of Biologics Standards. The vaccine entered commercial use in 1969-1970. A year later, in 1971, the MMR vaccine was licensed, and protection against measles, mumps and rubella was provided at the same time, via one shot.

9/30/1919 Birth of Maurice Hilleman

Maurice Ralph Hilleman was born on a farm near Miles City, Montana. His twin sister died during the birth, and his mother died a few days later.

1936 Max Theiler Develops Yellow Fever Vaccine

Max Theiler and his colleagues developed a live attenuated vaccine for yellow fever using tissue cultures prepared from embryonated chicken eggs. Among the many subcultures of the yellow fever virus in the laboratory, the one designated "17D" was used, giving the vaccine its name. He published results of U.S. vaccine trials in humans in 1937. The vaccine was easily adapted for mass production and became the universal standard.

1931 Steps Taken Toward a Vaccine

Max Theiler demonstrated that mice injected with serum from previously infected monkeys or humans were protected from yellow fever infection.

1951 Theiler Wins Nobel Prize

Max Theiler was awarded the Nobel Prize for Physiology or Medicine for his work in developing the 17D yellow fever vaccine. In the speech given before he was presented with the award, the Chairman of the Nobel Committee for Physiology or Medicine explained the importance of Theiler's work: "The significance of Max Theiler's discovery must be considered to be very great from the practical point of view, as effective protection against yellow fever is one condition for the development of the tropical regions - an important problem in an overpopulated world. Dr. Theiler's discovery does not imply anything fundamentally new, for the idea of inoculation against a disease by the use of a variant of the etiologic agent which, though harmless, produces immunity, is more than 150 years old. Jenner used a natural virus variant, cowpox virus, against smallpox, and Pasteur produced a similar variant of the rabies virus by repeated passage through animals. So far there have been only a few successful attempts to master a disease by such measures, but Dr. Theiler's discovery gives new hope that in this manner we shall succeed in mastering other virus diseases, many of which have a devastating, effect and against which we are still entirely powerless. Max Theiler, therefore, has rendered mankind such a service as Nobel made a condition for the awarding of this prize." —Professor H. Bergstrand, Chairman of the Nobel Committee for Physiology or Medicine of the Royal Caroline Institute, in Nobel Lectures, Physiology or Medicine 1942-1962

1916 Measles Continues to Spread in the U.S.

Measles killed nearly 12,000 people in the United States in 1916, 75% of them younger than five years old. Estimates of the percentage of measles patients who suffer complications from the disease have ranged from 15% to as high as 30%. Serious complications include pneumonia, encephalitis, and corneal ulceration.

Deadly Toll for Prominent Colonist (1713)

Measles killed three of Cotton Mather's children and his second wife. Mather, a prominent Boston clergyman, would later bring smallpox variolation to the colonies. But in 1713 he wrote in his diary of an approaching measles epidemic: "The Measles coming into the Town, it is likely to be a Time of Sickness, and much Trouble in the Families of the Neighbourhood." In short order, as the rest of the town suffered, measles infected most of his family members. It killed his wife, his newborn twins, another daughter, and the family's maid within a few weeks.

Measles Plays a Role in the Civil War (1861)

Measles sickened troops on both sides of the American Civil War. "During the first year of war there were 21,676 reported cases of measles and 551 deaths in the Union Army alone. Deaths were primarily from respiratory and cerebral (brain) involvement. It was recorded, 'This infection is always serious, often fatal either directly or through its sequelae. The Prognosis therefore should be guarded.' . . . . "The American Civil War was the last large-scale military conflict fought before the germ theory of disease was developed... Two-thirds of soldiers who died in that war, 660,000 in all, were killed by uncontrolled infectious diseases. Of these, in the Union Army over 67,000 had measles and more than 4,000 died." -Michael B. A Oldstone, Viruses, Plagues, & History, 146-47 (2009)

11/21/1977 Pneumococcal Vaccine Licensed

Merck licensed a polysaccharide vaccine protecting against 14 types of pneumococcal bacteria in 1977. In 1983, Merck expanded on this work by producing a vaccine against 23 types of pneumococcal bacteria. One challenge in producing a pneumococcal vaccine involved determining which of the more than 90 types of pneumococcal bacteria produced the most disease. Once that work was complete, Robert Austrian, MD, (at the University of Pennsylvania) isolated the types most appropriate for the vaccine and provided this information to Hilleman at Merck. Merck researchers then developed the vaccine from the polysaccharide outer coatings of the bacteria.

1981 Chickenpox Virus Strain Licensed

Merck licensed and attenuated the Oka strain of chickenpox virus (varicella-zoster virus) that would later be used in the licensed chickenpox vaccine. Hilleman's group had long been working on a chickenpox vaccine. Chickenpox had emerged as the most common childhood infectious disease that remained to be tamed after vaccination had reduced rates of measles, mumps, and rubella.

1960 Polio Vaccine and Simian Virus

Merck researchers, under Maurice Hilleman's direction, detected a simian virus in the monkey kidney cells used to grow poliovirus for Merck's polio vaccine. Hilleman later showed that the simian virus, SV40, caused tumors in hamsters. Merck eventually withdrew its polio vaccine from market. By 1963, government screening programs began to look for simian viruses in poliovirus vaccines. In 1960, the link between viruses and cancer was a new idea. Hilleman urged the U.S. Public Health Service Technical Committee to withdraw all Salk-type polio vaccine (IPV) until the problem could be addressed. Today, polio vaccines are screened for known viruses. Many studies have been done to investigate any adverse effects from SV40 in the early polio vaccines, and none has shown a relationship between SV40 and cancer in humans. Hilleman's finding was responsible for a shift away from using monkeys for tissue culture. Researchers would largely use human cells for the next wave of vaccine development.

1969 Rubella Vaccine Licensed

Meruvax, Hilleman's HPV-77 rubella vaccine, was licensed. Later, it would be replaced by vaccines derived from Stanley Plotkin's RA 27/3 strain of rubella virus. Rubella is typically a mild illness. Its symptoms are low fever, rash, and swollen glands. If, however, a pregnant woman contracts rubella, especially early in her pregnancy, the effects can be devastating. Babies exposed to rubella in utero may suffer deafness, blindness, mental retardation and other deformities. A devastating rubella pandemic developed during 1962-1965. In the United States, more than 20,000 babies were born with congenital rubella syndrome. Tens of thousands of women suffered miscarriages or elected to have abortions due to rubella infection. The pandemic focused medical researchers' attention on the need for an effective vaccine.

1926 The Metropolitan Life Diphtheria Campaign

Metropolitan Life, the insurance company, launched an anti-diphtheria campaign in New York. It donated $15,000 to the effort. Louis Dublin, a Met Life statistician, estimated that childhood illnesses, including diphtheria, cost the American economy about $200,000,000 a year in lost parental wages and medical care. Met Life used door-to-door polling, radio and print advertisements, essay contests, parades, and more to spread the immunization message.

1974 Chickenpox: Virus Strain Attenuated for Vaccine

Michiaki Takahashi, MD, successfully attenuated a strain of the varicella zoster virus. This strain would be used to developed a live, attenuated chickenpox vaccine, although a U.S. version of the vaccine would not be licensed until about two decades later.

8/15/2017 Circulating Vaccine-Derived Polio, 2017

Mid-way through 2017, reported cases of wild poliovirus remained low. As of August 2017, only 8 cases of wild paralytic poliovirus were recorded for the year, as compared with 19 cases for the same period in 2016. The cases occurred in Afghanistan and Pakistan. However, clusters of circulating vaccine-derived poliovirus occurred in Syria (27 cases) and in the Democratic Republic of the Congo (4 cases). These clusters illustrate the importance of maintaining high immunization rates in non-endemic countries. This is difficult, though, in areas experiencing war and civil unrest. International health groups have responded by committing to work with national health ministries to conduct supplementary vaccination campaigns in vulnerable areas and to improve surveillance activities.

Antitoxin Production in the United States (1895)

Mulford Company of Philadelphia (later Merck Sharp & Dohme) began to produce and test diphtheria antitoxin in the United States. The New York City Health Department began producing diphtheria antitoxin this year as well. Deaths from the disease began to drop as the treatment was increasingly used. A first step in producing diphtheria antitoxin involved incubating the bacteria and then determining which samples were of adequate strength to produce antitoxin. Workers grew the bacteria in test tubes and then tested the strength of the bacteria on guinea pigs. "In a little animal weighing three hundred grams (about half a pound) we would inject, perhaps, one one-hundredth of a cubic centimeter, or one-fifth of a drop; in another would be injected one-half, and in a third one-quarter of this quantity." "By keeping these animals under observation for a few days, we are enabled to detect just how large a quantity of this bouillon containing the living bacilli from each of the cultures is needed to destroy the life of the animal. When this has been determined, we select four or five of the most virulent cultures to use for the production of the toxines." -WH Park and HM Biggs, Diphtheria Antitoxin Park and Biggs described the method for producing serum from horses for use in diphtheria treatment. The horses were injected over time with increasing amounts of diphtheria toxin, starting with about 0.5 cubic centimeters (about 10 drops). "When we can introduce from two hundred to three hundred cubic centimeters of strong toxine into the horse without producing serious symptoms, we can feel pretty certain that the horse's blood contains anti-toxine in sufficient amount to be used for healing purposes." The serum was then processed and used to treat those suffering from diphtheria.

Smallpox Becomes a Weapon of War (1776)

Of a force of 10,000 Continental Army soldiers in Quebec, about 5,000 fell ill with smallpox. A British commander may have deliberately intended to spread the disease by sending recently variolated civilians into Continental Army encampments. The Continental task force commander, Major General John Thomas, died of smallpox. The unit retreated southward in May 1776. Arguably, this defeat preserved the status of the northern British colonies, permitting Canada to become the separate country it is today. John Adams wrote: "Our misfortunes in Canada are enough to melt the heart of stone. The smallpox is ten times more terrible than the British, Canadians and Indians together. This was the cause of our precipitate retreat from Quebec." — John Adams, quoted in Ian Glynn and Jenifer Glynn, The Life and Death of Smallpox

9/29/1994 Polio Declared Eliminated from the Americas

On August 20, 1994, the Pan American Health Organization had reported that three years had passed since the last case of wild polio in the Americas. A three-year-old Peruvian boy, Luis Fermín, had the last registered case there. The International Commission for the Certification of Poliomyelitis Eradication in the Americas examined this report as well as extensively reviewing lab and surveillance data. Based on the results of these analyses, wild poliovirus was declared eliminated from the Americas in September 1994, making the Americas the first World Health Organization Region to meet the goal of polio elimination.

1/15/2004 Geneva Declaration on Polio Signed

On January 15, 2004, representatives from the six remaining polio-endemic countries (Afghanistan, Egypt, India, Niger, Pakistan and Nigeria) signed the Geneva Declaration for the Eradication of Poliomyelitis, committing themselves to "successfully implementing intensified polio immunization activities to stop transmission of the poliovirus by the end of 2004."

7/11/2017 35 Measles Deaths in Europe, Thousands of Cases

On July 11, 2017, the World Health Organization reported that measles outbreaks in Europe during the past 12 months lead to 35 deaths. Thirty-one of the measles deaths occurred in Romania, which had had years of declining measles-containing vaccine (MCV) coverage. For 2015, the World Health Organization estimated two-dose MCV coverages at 88% of Romanian children, down from a high of 97% coverage in 2003. In most countries experiencing outbreaks in 2017, measles immunization rates are much lower than the 95% coverage needed to support herd immunity. Italy alone recorded 3,300 confirmed cases of measles and one death in the first half of 2017. Ukraine reported 1,000 cases by the end of July 2017. Lawmakers and health officials in European countries have begun to respond: in Germany, legislation is pending that would fine parents for not seeking compulsory advice on child immunization. Italian health officials have made immunization against 12 childhood diseases mandatory for public school attendance. In France, where currently children must be immunized only against diphtheria, tetanus, and polio, 11 childhood vaccines—-including MCV—-will become mandatory in 2018.

1997 Massive Vaccination Efforts in India

On a single January day in 1997, health workers vaccinated 127 million children against polio in India, a country struggling to control the disease. The following year, another 134 million would be vaccinated in a single day.

08/24/2018 Measles Circulates in Venezuela Again

Ongoing economic and civic unrest led to a return of measles to Venezuela in 2018. The World Health Organization had declared the entire Region of the Americas free from circulating measles in 2016, only to have the highly infectious disease return at a time of crisis. According to WHO guidelines, measles is considered endemic when the same type of measles virus has been circulating in a country for more than 12 continuous months. Gaps in vaccination coverage in Venezuela provided an entry point for an imported virus -- of a type present first in Asia and then in Europe -- to circulate in underimmunized populations. The disease has crossed Venezuelan borders to infect people in Brazil, including vulnerable indigenous populations. The WHO and other health groups are responding to the reappearance of measles with vaccination campaigns and increased surveillance.

1989 Low Vaccination Rates Lead to Outbreaks

Over the period 1989-1991, measles outbreaks sickened a reported 55,622 Americans, killing 123. Of all of the cities that suffered from the outbreaks, Philadelphia was hit hardest: 1,500 children fell ill and 9, most of whom had not been vaccinated, died. Many outbreaks were centered in areas where immunization levels were low. In fact, the CDC reported, "Surveys in areas experiencing outbreaks among preschool-aged children indicated that as few as 50% of children had been vaccinated against measles by their second birthday, and that black and Hispanic children were less likely to be age-appropriately vaccinated than were white children" (CDC, Measles, Pink Book). Of all fatalities, 90% occurred in individuals who had never been vaccinated.

Disease of Silkworms (1865)

Pasteur accepted a task to investigate a disease of the silkworm that was ravaging France's silk industry. Pasteur, never having handled a silkworm before, traveled to the south of France to investigate. Soon after, he had isolated the microorganism causing the disease. This work contributed to Pasteur's growing interest in infectious disease.

Rabies Success with Dogs Announced (5/19/1884)

Pasteur announced to the French Academy of Sciences that he had successfully protected dogs from fatal rabies by use of his attenuated rabies vaccine.

Pasteur Promoted (1852)

Pasteur became chairman of the chemistry department at the University of Strasbourg.

Pasteur Completes Bachelor of Science Degree (8/13/1842)

Pasteur earned a degree in science from the Royal College in Besançon, in spite of having failed his examinations in 1841.

Marriage of Pasteur (5/29/1849)

Pasteur married Marie Laurent in Strasbourg, France.

Pasteur Presents Rabies Results (3/1/1886)

Pasteur presented a paper describing results of using his new rabies vaccine in 350 people. He recorded one fatality, and reasoned that this was the result of vaccination begun too late to prevent the disease.

Pasteur Completes Bachelor of Arts Degree (1840)

Pasteur received a bachelor of arts degree from the Collège Royal de Besançon and began to teach.

Another Success with Rabies Vaccine (10/10/1885)

Pasteur repeated his rabies vaccinations on a shepherd who had been severely bitten by a rabid dog. This episode, too, was successful. After Pasteur published word of the success, people fearing rabies from animal bites began to seek him out for the series of vaccinations. Anti-vivisectionists, or what we would today call animal rights activists, objected to Pasteur's use of animal experimentation. They published and spoke widely on the topic.

Rabies Vaccine Used in Human (7/16/1885)

Pasteur successfully prevented rabies in nine-year-old Joseph Meister by post-exposure vaccination. Meister's mother brought the boy, severely bitten by a rabid dog, to Pasteur in hopes of preventing the disease. Several factors made Pasteur's potential involvement in the boy's care controversial. 1. Pasteur had never before successfully used the vaccine on a human. (Pasteur's notebooks indicated that two previous attempts had been made. One involved a 60-year-old man who left the hospital after only one injection and did not return. The other was 10-year-old girl, treated with one injection, who died before the second could be given.) 2. The concept of attenuation of viruses and bacteria was in its infancy at this time. Injecting a human with a disease agent, even a weakened one, was a new and controversial action. 3. Pasteur was not a medical doctor and might have faced serious consequences had Meister not survived the injections. Pasteur felt certain that the boy would die from rabies infection if he did nothing. So he began the course of 13 injections, one each day, of vaccine made from rabbit nervous system tissue. Each successive injection contained less-attenuated (stronger) virus. Meister never developed rabies, and the incident was regarded as a success. Later in life, Meister worked as caretaker of Pasteur's tomb at the Institut Pasteur in Paris.

Pasteur Has a Stroke (10/19/1868)

Pasteur suffered a cerebral hemorrhage. He was treated at home, initially with the application of 16 leeches behind his ears. His family and colleagues feared that he would not survive, but he slowly recovered. His left arm and leg were permanently paralyzed.

Pasteur Continues His Schooling (1844)

Pasteur was admitted to the École Normale Supérieure, where he earned a master of science degree in 1845.

Doctorate Won (8/28/1847)

Pasteur won his doctorate of philosophy degree. He wrote and defended two essays, one in physics and one in chemistry.

Another Tragedy (5/23/1866)

Pasteur's daughter Cécile, age 12, contracted typhoid fever and died.

Pasteur's Daughter Dies (9/10/1859)

Pasteur's daughter Jeanne, age 9, died of typhoid fever. "I cannot keep my thoughts from my poor little girl, so good, so happy in her little life, whom this fatal year now ending has taken away from us. She was growing to be such a companion to her mother and to me, to us all." -Louis Pasteur, letter to his father, from Life of Pasteur, by Rene Vallery-Radot

1929 The Iron Lung

Philip Drinker, PhD (1894-1972), and Charles McKhann, MD (1898-1988), at Boston Children's Hospital and Harvard published a paper describing successful use of an artificial respirator for patients suffering from paralytic polio. The machine, first known as the Drinker respirator and later as the iron lung, would provide temporary and in some cases, permanent breathing support for people suffering paralysis of the diaphragm and intracostal muscles, which are essential for respiration. The Drinker respirator was a sealed tube-like structure, powered by electricity. The patient's head extended from the tube, and the body, with a rubber seal at the neck, was entirely enclosed by the tube. Decreased pressure forced air into the lungs, and increased pressure forced air out.

2/27/1950 Koprowski Tests Polio Vaccine on Children

Researcher Hilary Koprowski at Lederle Laboratories conducted the first human trial of his attenuated oral poliovirus vaccine at a New York State facility for intellectually disabled children and children with epilepsy. He tested his Type II vaccine, developed with co-researcher Herald R. Cox (1907-1986), on 20 children and demonstrated that none of them became ill with polio and all of them developed Type II poliovirus antibodies. At the time, Koprowski's methods generated considerable controversy among others who were working on experimental vaccines. Many thought that the move to testing a live vaccine in human subjects was premature, and some objected to testing the vaccine on institutionalized children, though the practice was frequent in this era.

11/1/1940 Influenza: New Type of Influenza Isolated

Researchers had observed that the blood of some influenza patients did not react with antibodies to the influenza virus that an English team had isolated in 1933. Many therefore suspected that different types of influenza viruses existed. Thomas Francis, Jr, MD (1900-1969), then a researcher at Rockefeller University in New York City, obtained throat washings and blood samples from ill children at a nearby convalescent home for children. Antibodies from the blood samples did not react with a known influenza virus. Francis was able to infect ferrets with throat washings from one of the patients (surname Lee). Ferrets exhibited symptoms identical to typical influenza symptoms. Other tests led Francis to conclude that he had identified a new type of influenza virus. According to a classification system that other researchers had already proposed for any newly identified influenza types, Francis deemed the Lee virus influenza B. He published his results in Science magazine. Francis would go on to play an important role in the testing of the first licensed poliovirus vaccine.

2009 Diphtheria: No U.S. Cases for Five Years

Respiratory diphtheria has almost disappeared in the United States. Since 2004, the CDC has recorded no cases of respiratory diphtheria in the United States. In fewer than 75 years, diphtheria, which was once the leading cause of premature death of children, was virtually eliminated in the United States.

Tuberculosis: Koch's Tests Fail (1891)

Results of Robert Koch's attempts to treat people with preparations of tuberculin were published to disappointment. No real difference emerged in the experimental and control groups of patients.

1983 Pneumococcal: Vaccine Expanded to Provide More Protection

Robert Austrian's pneumococcal vaccine, which had protected against 14 strains of pneumococcal bacteria when it was licensed in 1977, was expanded to offer protection against 23 different strains. The 23-valent polysaccharide vaccine (PPVSV, or sometimes PPSV) is still used today for all adults 65 or older, as well as for individuals aged two or older who are at high risk for disease. (A separate conjugate pneuomococcal vaccine [PCV-13] is available for children and is part of the recommended childhood immunization schedule. It was approved at the end of 2011 for use in adults as well.)

1977 Pneumococcal: Multi-serotype Vaccine Licensed

Robert Austrian, MD (1916-2007), Chair of Medical Research at the University of Pennsylvania, had been convinced for years that the availability of antibiotics to treat pneumococcal infections was not reason enough to abandon a pneumococcal vaccine. Austrian had published a report in 1964 documenting hundreds of fatalities from pneumococcal pneumonia over a 10-year study period despite antibiotic treatment. He was convinced that a vaccine was critical as a preventive measure against the disease. Austrian began identifying different strains of pneumococcal bacteria, eventually finding dozens of serotypes. In 1976, he reported that a pneumococcal vaccine he had developed had proven safe and effective in clinical trials among South African gold miners. The vaccine, offering protection against 14 serotypes, was licensed by Merck in 1977.

Tuberculosis: Koch Isolates and Cultures Bacillii (3/24/1882)

Robert Koch (1843-1910) announced his discovery of the agent that causes tuberculosis. For a time, it was called Koch's bacillus. Today it is called Mycobacterium tuberculosis. Tuberculosis was a widespread, deadly disease in the 1800s. As Koch said when he presented his findings, "One in seven of all human beings dies from tuberculosis. If one only considers the productive middle-age groups, tuberculosis carries away one-third, and often more." Koch began to work on a vaccine for treatment and prevention of tuberculosis. In 1905 Koch would win the Nobel Prize in Physiology or Medicine "for his investigations and discoveries in relation to tuberculosis."

Cholera: Koch Isolates Bacillus (2/2/1884)

Robert Koch (1843-1910), in a letter from India describing his research there, announced his discovery of the agent that causes cholera. For a time, it was called Koch's bacillus (as was tuberculosis) and Koch's comma bacillus. Filippo Pacini had achieved this feat in 1854, but his work was not widely known.

1990 U.S. Military Ceases Routine Smallpox Vaccination

Routine smallpox vaccination of U.S. military recruits ceased.

1952 Salk Begins Early Polio Vaccine Tests

Salk and team, with the support of the National Foundation for Infantile Paralysis, began its first tests on humans of their killed-virus polio vaccine. The subjects were resident children in institutions for the physically and intellectually disabled. Salk tested vaccine for all three strains of polio, some in combination, and some on their own. Their findings showed that vaccine recipients produced antibodies to the virus type in the vaccine they were given. Salk's results provided some evidence on which to base larger trials.

5/16/1953 Salk Gives Vaccine to His Family

Salk injected himself, his wife, and their three sons with his experimental poliovirus vaccine.

10/15/1958 First Measles Vaccine Is Tested

Sam Katz, MD, an infectious disease specialist working with Thomas Peebles and other researchers in the Boston lab, tested the first version of the lab's vaccine on developmentally delayed and disabled children at a school outside of Boston. Each of the 11 vaccinated children developed measles antibodies, but nine also developed a mild rash—the vaccine didn't cause full-blown measles, but it did cause symptoms. The researchers realized the virus used for the vaccine had to be weakened even more.

2005 Meningococcal: New Recommendation

Sanofi's quadrivalent meningococcal polysaccharide-protein conjugate vaccine was licensed in the United States in January 2005. In May of that year, the Advisory Committee on Immunization Practices recommended routine meningococcal vaccination for all adolescents aged 11-12 years, with additional recommendations for persons at increased risk of meningococcal disease. In June 2007 this recommendation would be expanded to include vaccination of all persons 11-18 years of age at the earliest opportunity. Until 2004, 1,400-2,800 cases of meningococcal disease occurred in the United States each year. In 2007, 1,077 cases were reported. Although antibiotics are available and can be successful in treating the disease, the case-fatality ratio for meningococcal disease is 10%-14%. Moreover, between 11%-19% of meningococcal disease survivors suffer neurologic disability, limb loss, and hearing loss. In 2010, ACIP would recommend a booster dose of the meningococcal vaccine at age 16 to help extend protection through the college years.

1961 Rabies: Human Testing of New Live Virus Vaccine

Scientists tested different live virus preparations of Koprowski's HEP rabies vaccine virus in animal and human trials. Most studies showed adequate antibody response and minimal side effects.

Infectious Nature of Measles Shown (1757)

Scottish physician Francis Home, MD, transmitted measles from infected patients to healthy individuals via blood, demonstrating that the disease was caused by an infectious agent. "...Francis Home... attempted to produce mild measles by mimicking the variolation process. This process involved taking blood from an infected patient and inoculating it through the skin of an uninfected person. In this way he was able to transfer measles to ten of twelve patients. This experiment clearly demonstrated the presence of measles virus in human blood..." -Michael B. A Oldstone, Viruses, Plagues, & History

Early Chinese Inoculation (1000)

Several accounts from the 1500s describe smallpox inoculation as practiced in China and India (one is referred to in volume 6 of Joseph Needham's Science and Civilisation in China). Glynn and Glynn, in The Life and Death of Smallpox, note that in the late 1600s Emperor K'ang Hsi, who had survived smallpox as a child, had his children inoculated. That method involved grinding up smallpox scabs and blowing the matter into nostril. Inoculation may also have been practiced by scratching matter from a smallpox sore into the skin. It is difficult to pinpoint when the practice began, as some sources claim dates as early as 200 BCE.

1970 Yellow Fever Mosquito Reappears in South America

South America was re-infested with Aedes aegypti. This, along with increasing air travel, led to fears of the reemergence of yellow fever epidemics in the American continents.

Cholera: Ferrán's Vaccine (1885)

Spanish physician Jaime Ferrán (1852-1929) developed a live, attenuated cholera vaccine. His vaccine was the first to immunize humans against a bacterial disease. Ferrán had worked on veterinary vaccines in Spain following Pasteur's publications on the attenuation of microbes. He created the cholera vaccine by cultivating bacteria taken from the waste of a person ill with cholera and growing the bacteria on nutrient culture at room temperature. The material was then administered to subjects via one to three injections in the arm. Ferrán was soon requested to go to Valencia, where he vaccinated about 50,000 people during a cholera epidemic. Scientific commissions soon descended on Valencia to evaluate the efficacy of the vaccine. The reports were mixed, with some declaring that Ferrán had succeeded, and others that the vaccine was not effective. Ferran was widely criticized for attempting to keep the method of creating his vaccine secret. In his defense, he asserted that he needed compensation for the creation of the vaccine to support his studies and his family. During the rest of his career, Ferrán would develop vaccines for plague, tetanus, typhus, tuberculosis, and rabies.

10/22/1952 IgG Used for Polio Protection

Several researchers had been investigating whether use of human immunoglobulin (IgG, or gamma globulin) could protect individuals from polio. Immunoglobulin is an antibody preparation made from blood pooled from many people who most likely have antibodies to common infections. Their disease-specific antibodies in the IgG, when injected into a person who had recently or would soon be exposed to the disease, had been shown to provide protection. This type of protection is known as passive immunization. William M. Hammon, MD (1904-1989), a University of Pittsburgh researcher, tested gamma globulin in a set of three clinical trials in 1951-52. The trials were carefully constructed and used a double-blind, placebo-controlled design, one of the first of this kind. The trials showed some likely protective effects of gamma globulin use against polio. Use of the preparation presented several problems, though. Gamma globulin was expensive to produce and it gave only temporary protection. It would need to be used again in each subsequent epidemic. Moreover, physicians relied on gamma globulin for protection against measles, hepatitis, and other diseases for which there were no vaccines. The supply was limited, and the need was great. As Time magazine wrote at the time, "It takes almost a pint of blood to make an average shot of G.G. (7 cc). To give protection for a single polio season to all the 41 million U.S. children under 15 might take 100 million shots or more, and there simply is not that much gamma globulin available, nor the blood or plasma to extract it from" (Time, November 3, 1952).

Antitoxin and Serum Therapy (1890)

Shibasaburo Kitasato (1852-1931) and Emil von Behring (1854-1917) immunized guinea pigs with heat-treated diphtheria toxin. Kitasato and von Behring showed that the blood products (sera, or, singular, serum) of the guinea pigs contained a substance that prevented the harmful effects of C. diphtheriae and its toxin when the guinea pigs were re-exposed to lethal doses of the bacteria and toxin. Next, they showed that they could cure diphtheria in an animal by injecting it with the serum of an immunized animal. They called the substance antitoxin and their treatment serum therapy. They realized that they needed to immunize large animals, such as horses and sheep, to produce enough antitoxin to protect humans. Von Behring would win the first Nobel Prize in medicine in 1901 for his work on diphtheria.

2010 Looking to the Future

Since smallpox was declared officially eradicated, the number of official samples of the virus still maintained worldwide dwindled. Now only two officially known laboratory stocks are left: one at the Centers for Disease Control and Prevention, and one at a Russian research center. Both facilities are WHO reference laboratories. Complete destruction of all known stockpiles was recommended by WHO in 1986. Destruction dates were set in both 1993 and 1995. Each time a deadline neared, however, officials postponed destruction of the stocks. Eventually, in 2002, WHO recommended against destruction of the virus.

March 1, 1947 A Massive Vaccination Effort

Smallpox appeared for the final time in New York City. Eugene Le Bar, a merchant traveling from Mexico City to Maine with his wife, arrived in the city by bus, bringing the disease with him. Feeling ill, Le Bar went to Bellevue Hospital. Three days later he was transferred to the city's contagious disease hospital. He died two days later. Le Bar's death was not immediately attributed to smallpox, but when the disease appeared in two other patients who had been at the contagious disease facility at the same time, the hospital staff notified the health department. Eugene Le Bar's case of smallpox launched a massive vaccination program in the city, as the health department attempted to trace his steps before arriving at Bellevue Hospital and vaccinate anyone whose path he may have crossed. Health commissioner Israel Weinstein personally visited New York City Mayor William O'Dwyer to request $500,000 for the purchase of additional vaccine and to hire additional staff. O'Dwyer held a press conference in which he asked all residents who had not been recently vaccinated to be vaccinated against the disease. In the next month, 80% of the city's residents were vaccinated—some 6.35 million people. In the end, the effort was judged a success: the total number of smallpox cases reached only 12, and the final death count was limited to two.

Continuing Colonial Epidemics (1730)

Smallpox epidemics took heavy tolls in Boston, New York, and Philadelphia.

Boston Smallpox Epidemic (1721)

Smallpox raged through Boston in 1721, ending in 844 deaths. During this epidemic, physician Zabdiel Boylston, at Cotton Mather's urging, variolated 248 people, thereby introducing variolation to the Americas. Of those variolated, six died. The case fatality for variolation was about 3%, and the disease case fatality was 14%. About 900 people left town for fear of catching the disease. At Harvard, the chambermaid of Cotton Mather's son Samuel contracted smallpox. Samuel's brother Increase encouraged his father to have Samuel variolated by Boylston, and Samuel survived the procedure. Mather was widely criticized for his role in promoting variolation: a primitive grenade was thrown through a window of his house. The attached note threatened "COTTON MATHER, You Dog, Dam you. I'll inoculate you with this, with a Pox to you." Reacting to the Boston outrage against inoculation, Mather wrote: "I never saw the Devil so let loose upon any occasion. The people who made the loudest Cry...had a very Satanic Fury acting them.... Their common Way was to rail and rave, and wish Death or other Mischiefs, to them that practis'd, or favour'd this devilish Invention." — Cotton Mather, quoted in The Life and Death of Smallpox by Ian Glynn and Jenifer Glynn

2003 Number of Polio-Endemic Countries Dwindles

Somalia reached a full year without a case of polio, the last case having been reported in October 2002. When the worldwide eradication program began in 1988, more than 125 countries were listed as polio-endemic. By the end of 2003, the diseases had been eradicated in so many countries (including Somalia) that only six remained on the list: Afghanistan, Egypt, India, Niger, Pakistan, and Nigeria. Of all of the cases reported in 2003, 90% of them occurred in just three of those countries: India, Pakistan, and Nigeria.

Smallpox Epidemic in India (1545)

Some 8,000 children died in Goa, India, from a smallpox epidemic most likely introduced by the Portuguese.

U.S. Army Researchers Discover the Cause of Yellow Fever (1900)

Spurred by the massive yellow fever-related casualties in the Spanish-American War, members of the U.S. Army Yellow Fever Commission, headed by Walter Reed, traveled to Cuba to study the disease. Commission member Jesse Lazear (1866-1900) met Henry Rose Carter, a surgeon who had studied the incubation period of yellow fever. Carter gave Lazear a draft of a paper he'd authored defining the incubation period for the disease as a range of 10 to 17 days. Lazear reportedly stated that Carter's dates, should they prove to be correct, suggested a living host for yellow fever. Determined to uncover the source of the illness, the Commission members visited Carlos Finlay and decided to test his theory of mosquito transmission. Jesse Lazear hatched Finlay's mosquito eggs and let the mosquitoes feed on patients infected with yellow fever at a Havana hospital. The mosquitoes were then allowed to feed on study volunteers over a period of two weeks—yet no infections resulted. Two days later, however, Lazear once again allowed the mosquitoes to feed. This time, both of the men who were bitten fell ill. These experiments validated the theory Finlay had presented two decades earlier: mosquitoes (specifically, the Aedes aegypti variety) were the transmission vector of yellow fever. The researchers went on to rule out a bacterium as the disease agent. They determined that an infectious particle too small to be filtered with a standard bacterial filter was the source of the disease: the first human virus ever discovered. (German scientists had identified the virus that caused foot-and-mouth disease in animals in 1898.) The two men Lazear exposed to yellow fever via the experiment's mosquitoes recovered. Lazear himself, however, was not so lucky. It is likely that he allowed himself to be bitten as part of the experiment. Lazear contracted yellow fever and died in September 1900, at age 34. The Army experiments, however, continued, with Reed naming newly designed facilities "Camp Lazear." The group proceeded to determine that the mosquitoes could transmit the disease only after a certain period of time had passed since they had fed on another human infected with it (in the range of 12-20 days) and that a victim bitten by an infected mosquito would typically fall ill within six days. William Crawford Gorgas (1854-1920), a Colonel in the U.S. Army Medical Corps, later described the details of the discovery: They... found out that [a man], before he had been bitten by the yellow-fever mosquito, could sleep in the bed in which a patient had died of yellow fever, could be covered with a black vomit from a yellow-fever patient, or be exposed to the emanations from yellow fever in any other way, and as long as he was kept safe from the bite of the mosquito he would not have yellow fever; but this same man, after all this exposure, if afterwards bitten by an infected mosquito, would very certainly catch the disease. ...They had a little frame building built in this camp furnished with jars and the necessary simple material for breeding mosquitoes... Eggs of this particular species of mosquito were obtained and hatched in one of the jars. A female mosquito was taken from the booth thus hatched. The male mosquito will not bite... The female mosquito selected was put into a small glass tube, stoppered with a little cotton, so that she could get air but not escape, taken to Habana, placed on the hand of a patient in the first three days of an attack of yellow fever, and allowed to fill herself with blood. She was then brought back to her former home, placed in a large glass jar, and allowed to digest the blood she had obtained. ...So confident were the men in charge of the mosquitoes that I have known them to put their hands in the jars and let the mosquitoes feed upon them, up to the fifth or sixth day after the mosquito had bitten a yellow-fever patient. The mosquito, you recollect, can not convey the disease till from 12 to 20 days have passed from the time of her biting the yellow-fever case from which she becomes infected. On the other hand, I once saw a party of 12 or 15 doctors in the mosquito room one day, when the mosquito-bar covering of the jar accidentally came off and the insects escaped into the room. These doctors had come from other countries to investigate the subject, and were not then convinced that the mosquito carried yellow fever. Still, they did not care to put the matter to a practical test in their own persons, and got out of the room so rapidly that the wire-screen door was broken down during their exit. It happened that the mosquitoes in this jar had never bitten a yellow-fever patient and were not infected. -- Colonel William C. Gorgas, Medical Corps, United States Army, A few general directions with regard to destroying mosquitoes, particularly the yellow-fever mosquito

1960 Rubella Virus Isolated

Ten-year-old Robert Weller, son of a researcher working at the Harvard School of Public Health, developed what seemed to be rubella, but "much more severe" than the usual case. His father, Thomas Weller, MD, inoculated cultures of human cells with his son's urine, and was eventually able to isolate the causative agent. With his colleague, Franklin Neva, MD, Weller collected urine specimens from patients in a rubella outbreak and similarly isolated the causative agent of their illness. The cell changes Weller and Neva observed in the resulting cultures were similar to those observed in Robert Weller's culture. Weller and Neva, however, were not the only ones trying to isolate rubella. Weller wrote in an addendum to the lecture written at the time of his Nobel prize (which he had won in 1954 for polio research): We then found that we were not alone in the field. Beginning in 1961 a group at the Walter Reed Institute of Research in Washington had isolated viruses from cases of rubella using cultures of monkey kidney cells. No cytopathic changes were seen but application of a viral interference method, originally developed by David Tyrrell in England, demonstrated that the rubella virus was present. With the help of Drs. Albert Sabin and Joe Smadel we exchanged viruses with the Washington group and found the isolates identical. -- Nobel Lectures, Physiology or Medicine 1942-1962, Elsevier Publishing Company, Amsterdam, 1964.

5/19/2006 Hepatitis A: Vaccine Recommended for All Children

The Advisory Committee on Immunization Practices (ACIP) recommended routine hepatitis A vaccination of all children older than age 1 in a two-dose schedule. The U.S. Food and Drug Administration had licensed several inactivated hepatitis A vaccines in 1995 and 1996. After that, vaccination for children was gradually phased in, beginning with children in communities with the highest rates of the disease. Next, in 1999, ACIP recommended routine vaccination for children living in areas with elevated rates of the disease. Finally, in 2006, ACIP widened the recommendations to include all children older than age 1. Between 1980 and 1995, 22,000-36,000 cases of hepatitis A were reported annually in the United States. The actual number of infections was likely closer to 271,000 infections per year (reported cases are often just a fraction of actual cases). After widespread immunization practices, in 2007 there were just 2,979 reported cases of hepatitis A in the United States.

1964 Adjuvant Recommended

The American Academy of Pediatrics recommended use of an aluminum-precipitated form of DTP vaccine. The aluminum adjuvant enhanced the body's antibody response to the toxoids in the combination vaccine.

Anti-Vaccination Arguments Spread (1882)

The Anti-Vaccination League of America held its first meeting in New York. Among the assertions made by the speakers at the meeting was the idea that smallpox was spread not by contagion, but by filth. This became a popular, though incorrect, argument of anti-vaccinationists.

11/26/2007 $200M Pledged to Fight Polio

The Bill and Melinda Gates Foundation gave a $100 million grant to Rotary International to combat polio. Rotary International promised to match the grant over a three-year period, for a total of $200 million to be used in the global eradication campaign.

Early Typhoid Vaccines Used by British Military (1899)

The British Army used early forms of the typhoid vaccine during the Second Boer War in southern Africa. Nearly 15,000 soldiers were immunized; among these men, there were approximately 11 cases of typhoid fever per 1,000 soldiers. In contrast, unimmunized soldiers saw approximately 31 cases of typhoid fever per 1,000 men. Typhoid vaccination would become an important part of military life. Mandatory typhoid vaccination for a division of 15,000 men in the United States Army began in 1911, with the mandate expanded to include all soldiers only a few months later. The vast impact on typhoid fever incidence would become evident during World War I. Just 15 years earlier at the beginning of the Spanish-American War, there were 1,590 typhoid fever deaths at five training camps alone (compared with only 280 battlefield deaths for the entire war). In contrast, with typhoid vaccination in full use during World War I, there were only 227 typhoid fever deaths among more than 4,000,000 American soldiers.

Britain Allows Exemptions (1898)

The British Vaccination Act of this year provided a conscience clause to allow exemptions to mandatory smallpox vaccination. This clause gave rise to the term "conscientious objector," which later came to refer to those opposed to military service. By the end of the year, magistrates had issued more than 200,000 vaccination exemptions. Antivaccinationists in England, other parts of Europe, and the United States were active in publishing, speaking, and demonstrating about their objections to vaccination.

12/31/2014 A Record Year for Measles in Elimination Era

The CDC reported 644 cases of measles in 2014, the highest number of U.S. cases in any year since measles was declared eliminated in 2000. December ended with a threat that would extend into 2015: between December 15 and December 20, visitors to Disneyland in Anaheim, California, were exposed to measles by an as-yet-unidentified index case. Cases quickly spread as primary contacts returned home and spread the illness to secondary contacts across the country. A small, unrelated outbreak of measles in Mitchell, South Dakota, added to the case count as the year ended.

1978 Measles Targeted for Elimination

The Centers for Disease Control and Prevention declared a goal of eliminating measles from the United States by 1982. Although this goal would not be met, widespread vaccination drastically reduced the incidence of the disease, and it would be declared eliminated in the country by 2000.

Founding of The College of Physicians of Philadelphia (1/2/1787)

The College of Physicians of Philadelphia was founded in 1787 by 24 prominent Philadelphians, including John Redman (1722-1808), first president of the College; John Morgan (1735-1789), founder of America's first medical school; and Benjamin Rush (1745-1813), a signer of the Declaration of Independence and vigorous advocate of many humanitarian and social causes. The College was established "to advance the Science of Medicine, and thereby lessen human misery, by investigating the diseases and remedies which are peculiar to our country" and to promote "order and uniformity in the practice of Physick." Dr. Rush declared in a speech to the newly formed College that it should collect and publish medical observations and inquiries on health-related topics, hold regular meetings, cultivate a botanical garden, and create a medical library. When the yellow fever epidemic struck in 1793, members assisted the city in developing steps to combat the disease. The College continues, over 200 years later, to advance the cause of health while upholding the ideals and heritage of medicine.

Stricter Regulations Passed for Inoculation (1792)

The Commonwealth of Virginia passed an act to consolidate previously passed acts regulating smallpox inoculation into one. The new act included a penalty of $1,500 or six months' imprisonment for anyone willfully spreading smallpox in a manner other than specified by the act.

Russian Empress Encourages Vaccination (1801)

The Empress Dowager of Russia encouraged vaccination, going so far as to name an orphan first given the smallpox vaccine "Vaccinoff" and providing the young girl with a pension for life.

10/29/2014 Group B Meningococcal Vaccine Approved

The FDA announced the approval of a vaccine for group B meningococcal disease. The vaccine (generic name meningococcal group B vaccine, trade name Trumenba, manufactured by Pfizer) was advanced on an accelerated approval regulatory pathway. Outbreaks of meningococcal group B disease on several college campuses in 2013-2014 spurred the quicker pathway. The vaccine is approved for use in individuals ages 10-25 years and is given in three-dose series. During 2015, the Advisory Committee on Immunization Practices will consider making a recommendation for the vaccine. This may include recommending it for high-risk groups, for researchers working with the bacteria, for individuals during outbreaks, and/or for the adolescent population at large. During the 2013-14 outbreaks, the FDA approved a different group B meningococcal vaccine (generic name meningococcal group B vaccine [rDNA, component, adsorbed], trade name Bexsero, manufactured by Novartis) for use only in the affected populations at Princeton University and University of California, Santa Barbara. The FDA is considering the approval of that vaccine for more widespread use.

1981 Hepatitis B: First Subunit Viral Vaccine in U.S.

The FDA licensed Hilleman's human-blood-derived hepatitis B vaccine, Heptavax-B. It was the first subunit viral vaccine developed in the United States. Hilleman transformed the hepatitis B surface protein, discovered by Baruch Blumberg and known as the Australia antigen, into an effective vaccine. Hilleman harvested serum from several IV drug users and homosexual men, in whom the disease was sometimes present, to obtain the antigen. He used three methods to purify the blood so that the infectious particles were assuredly killed, but the antigen remained. The vaccine proved effective at preventing hepatitis B. But, because of concerns about HIV infection, it was superseded in 1986 by a product that did not use human serum. This new effort produced the first vaccine based on recombinant technology--in this case, changing yeast cells so that they produced the protein that is the active ingredient in the current hepatitis B vaccine.

1995 Hepatitis A: Vaccine Licensed

The FDA licensed Maurice Hilleman's hepatitis A vaccine. Hilleman had been working on hepatitis A for decades. He was one of the first scientists to detect the hepatitis A virus and its antibodies. Tests in 1992 showed that the vaccine was 100% effective in preventing the disease. Hepatitis A vaccine would later be added to the recommended vaccination schedule for children, and its incidence subsequently decreased by about 75%.

7/23/1986 Hepatitis B: Recombinant Vaccine Licensed

The FDA licensed Merck's Recombivax HB. This hepatitis B vaccine was the first human vaccine produced by recombinant DNA methods. A challenge in creating the vaccine involved avoiding the use of human blood products, as did Maurice Hilleman's first hepatitis B vaccine. Therefore, Merck used an enzyme to remove the virus's surface protein (HBsAg, the Australia antigen). Researchers inserted the code for the antigen into yeast cells, which produced more of the surface protein. The yeast-derived surface protein produced immunity to the hepatitis B virus.

1967 Mumpsvax Licensed

The FDA licensed Merck's mumps vaccine, developed by Maurice Hilleman, on March 30, 1967. Within five years, more than 11 million doses of Mumpsvax would be distributed.

3/17/1995 Chickenpox Vaccine Licensed

The FDA licensed Varivax, the first chickenpox vaccine. Hilleman had adapted a Japanese chickenpox virus for use in the United States. Before the chickenpox vaccine, each year in the United States chickenpox infected 4 million people, leading to about 10,000 hospitalizations and about 100 deaths. In the post-vaccine era, hospitalization and death rates from chickenpox have decreased dramatically.

4/3/2008 Rotavirus: Another Vaccine Licensed

The Food and Drug Administration licensed another rotavirus vaccine, Rotarix, for use in the United States. The recommended schedule for Rotarix involves two doses of the vaccine, given at ages 2 months and 4 months. CDC has carefully monitored incidence of rotavirus disease in the United States since 2000. Their studies show that that the number of positive test results for rotavirus was substantially lower than the median observed during 2000-2006. Additionally, it appears that hospitalization rates for acute gastroenteritis dropped by 16% in 2007 and by 45% in 2008 compared with the earlier period. Researchers have estimated that rotavirus vaccination prevented about 55,000 hospitalizations in 2008. Worldwide, rotavirus continues to take a toll. More than 500,000 children under age 5 die each year from rotavirus illness.

Legion of Honor (8/12/1853)

The French government made Pasteur a member of the Legion of Honor.

Yellow Fever Plagues Panama Canal Workers (1899)

The French officially abandoned efforts to build the Panama Canal and transferred the rights to the project to the United States, in part because of the yellow fever and malaria deaths among the project's workers.

1928 Tuberculosis: League of Nations Recommends BCG

The Health Committee of the League of Nations adopted BCG as a recommended tuberculosis vaccine.

Efforts Increase Vaccine Production (1876)

The New York Board of Health established a vaccine farm in Lakeview, New Jersey. Lymph from calves infected with cowpox virus was harvested and used as vaccine. The use of animal lymph reduced transmission of human illnesses such as leprosy and syphilis.The Wyeth strain of vaccine was later derived from this vaccine.

New York City Regulates Antitoxin (12/4/1894)

The New York City Board of Health told the Health Department to devise a plan to ensure the purity and potency of diphtheria antitoxins sold in the city. At this point, most of the antitoxin came from two suppliers in Germany.

1985 Goal Set for Polio Elimination in the Americas

The Pan American Health Organization (PAHO), which serves as the regional office of the World Health Organization for the Americas, announced a campaign to achieve polio elimination in the Americas by 1990. Its original goal of 1990 would not be met, but the last case of wild-type paralytic polio was reported in the Americas in 1991, and the region of the Americas was certified polio free in 1994.

1915 Rockefeller Foundation's Yellow Fever Commission Forms

The Rockefeller Foundation Yellow Fever Commission was formed, with now-Surgeon General of the U.S. Army, Major General William Crawford Gorgas, named director of its work on the eradication of yellow fever. Their initial plans for eradication in Guayaquil, Ecuador, were delayed by World War I, as Gorgas's energies were focused on his duties as Surgeon General until his retirement in 1918. Initial work on the project, however, did begin.

1959 Assembly Aims for Eradication

The Twelfth World Health Assembly adopted a goal of global smallpox eradication.

8/11/2006 Rotavirus: Vaccine Recommended

The U.S. Advisory Committee on Immunization Practices recommended routine infant immunization with three doses of the recently licensed Rotavirus Vaccine, Live, Oral, Pentavalent (tradename RotaTeq), developed by H. Fred Clark, PhD, Stanley A. Plotkin, MD, and Paul A. Offit, MD. The recommended schedule for immunization with this vaccine is at ages 2 months, 4 months, and 6 months. According to the CDC, "Before introduction of a vaccine in 2006, rotavirus caused an estimated 20 to 60 deaths, 55,000 to 70,000 hospitalizations, and 205,000 to 272,000 emergency department visits in the United States each year."

1948 Whooping Cough: Vaccine Combined with Tetanus, Diphtheria

The first combined DTP (diphtheria, tetanus, and pertussis) vaccines became available in the United States. This type of combined shot used a whole-cell pertussis vaccine; decades later, in the mid-1990s, the whole-cell vaccine would be replaced with an acellular version that resulted in fewer adverse reactions.

U.S. Vaccine Agency Established (1813)

The U.S. Congress authorized and James Madison signed "An Act to Encourage Vaccination," establishing a National Vaccine Agency. James Smith, a physician from Baltimore, was appointed the National Vaccine Agent. The U.S. Post Office was required to carry mail weighing up to 0.5 oz. for free if it contained smallpox vaccine material—an effort to advance Congress's ruling to "preserve the genuine vaccine matter, and to furnish the same to any citizen of the United States."

The Biologics Control Act (7/1/1902)

The U.S. Congress passed "An act to regulate the sale of viruses, serums, toxins, and analogous products," later referred to as the Biologics Control Act (even though "biologics" appears nowhere in the law). This was the first modern federal legislation to control the quality of drugs. This act emerged in part as a response to the 1901 St. Louis and Camden contamination events. The Act created the Hygienic Laboratory of the U.S. Public Health Service to oversee manufacture of biological drugs. The Hygienic Laboratory eventually became the National Institutes of Health.

2/20/1905 U.S. Supreme Court Addresses Vaccination

The U.S. Supreme Court in the case of Jacobson v. Massachusetts upheld the constitutionality of mandatory smallpox vaccination programs to preserve the public health.

1971 Measles, Mumps, Rubella Vaccine Licensed

The U.S. government licensed Merck's combined trivalent measles, mumps, and rubella vaccine (MMR). Combination vaccines have several advantages over single vaccines. They reduce the need for several separate injections, and they reduce costs of stocking and shipping multiple containers. Combination vaccines can help improve overall vaccination rates by simplifying the vaccination process.

1971 MMR Combination Vaccine Debuts

The U.S. government licensed Merck's measles, mumps, and rubella combination vaccine (M-M-R). In an article published in the Journal of the American Medical Association, researchers reported that the vaccine induced immunity to measles in 96% of vaccinated children; to mumps in 95%; and to rubella in 94%. Additionally, initial tests in 1968 had already shown that adverse reactions from the MMR vaccine were no greater than from any of the single vaccines.

1971 Marek's Disease Vaccine Licensed

The U.S. government licensed Merck's vaccine DEPTAVAC-HCT for Marek's disease in chickens. A veterinary vaccine producer was able to produce the vaccine less expensively than Merck, and Merck soon dropped the vaccine.

3/21/1963 Rubeovax Licensed

The U.S. government licensed the Merck measles vaccine, Rubeovax.

2008 Military Uses Vaccine Grown in Cell Culture

The U.S. military shifted its vaccine stock from freeze-dried Dryvax vaccine produced by Wyeth in the 1970s and early 1980s to Acambis's ACAM2000 vaccine. Both vaccines use vaccinia virus, a virus related to cowpox and smallpox viruses. The Acambis product is grown in cell culture rather than on the flanks of calves.

2002 Bioweapon Threat Prompts Vaccination

The U.S. military, after the anthrax attacks of 2001, re-instituted smallpox vaccination for some personnel. A similar program for civilian public health workers was implemented a few months later. The perception of the threat of smallpox as a bioweapon was heightened by its high fatality rate (about 30%) and by the large number of people born after 1972 who had never been vaccinated against it. Between December 2002 and October 2009, more than 1.8 million U.S. service members received smallpox vaccinations.

Mandatory Vaccination in UK (1853)

The United Kingdom Vaccination Act of 1853 made smallpox vaccination mandatory in the first three months of an infant's life. A parent's penalty for not complying was a fine or imprisonment.

2006 HPV Vaccine Licensed in United States

The United States Food and Drug Administration licensed a quadrivalent human papillomavirus (HPV) vaccine for use in 2006. The same year, the Advisory Committee on Immunization Practices recommended it for all US girls age 11-12 and up. In 2011 the vaccine would be recommended for boys age 11-12 and up. The vaccine protects against the two most prevalent cancer-causing HPVs and two wart-causing strains. HPVs cause almost all cervical cancers, and they can also cause anal and head and neck cancers in males and females, vaginal cancers, and penile cancers. A bivalent HPV vaccine, recommended for females, protecting only against cancer-causing HPV types would be approved in 2009. A nine-valent vaccine would be licensed in 2014 and recommended in 2015. All licensed HPV vaccines are subunit vaccines, meaning they use only part of HPVs and cannot infect body cells. The vaccines use L1 protein that self-assembles to form empty shells that resemble HPV virus-like proteins. Adolescents who begin HPV vaccination before age 15 need two doses of vaccine delivered at 0 and 6-12 months; those who begin on or after the 15th birthday need three doses of vaccine delivered at months 0, 1-2, and 6.

1921 Park's Diphtheria Campaign

The United States recorded 206,000 cases of diphtheria in 1921, resulting in 15,520 deaths (a case-fatality ratio of 7.5%). This was worst year for diphtheria in the United States in the 20th century. William H. Park launched a massive program in New York City to Schick-test schoolchildren and immunize the unexposed children with diphtheria toxin-antitoxin mixture (TAT). Park's work was a public-health milestone: he needed not only the cooperation of scores of school administrators and school nurses, but he also had to seek the permission of parents to immunize their children with TAT. Park enlisted a total of 180,000 children in the campaign. Half were not tested for diphtheria immunity, and they were not given TAT. The other half were Schick-tested. If positive (meaning they had not been exposed to diphtheria), they were given two or three injections of TAT to immunize them. In a period of five months, the 90,000 untested children developed four times as many cases of diphtheria as the tested-and-immunized children. Park wanted to extend the benefits of Schick testing and TAT immunization to the younger siblings of schoolchildren, who were most at risk of contracting and dying from diphtheria. He used the school campaign to notify parents of immunization opportunities for babies. Mailing cards such as the one pictured were sent to 45,000 homes in New York City. Italian and Yiddish versions were produced as well.

1953 Chickenpox: Varicella Virus Isolated

Thomas Weller, MD, was the first to isolate the varicella virus. He did so from cases of chickenpox and shingles. The following year, Weller would win the Nobel Prize for his group work with John Enders, PhD and Frederick Robbins, MD involving the growth of polio virus in cell cultures.

4/25/1954 Massive Polio Vaccine Trial Begins in U.S.

The Vaccine Advisory Committee approved a field test of Salk's polio vaccine. The trial began the next day, with the vaccination of thousands of schoolchildren. In all, over 1.3 million children participated in the trial. The trial was a randomized, double-blinded test, meaning that children were randomly assigned to either the control group or the vaccine group. Neither the children (nor their parents) nor health officials knew which children had received the vaccine and which had received the injected placebo fluid. (A smaller control group received no injection. Rather, officials observed them throughout the trial period for signs of polio infection.) It would take almost a year to analyze the results and determine whether the vaccine provided protection against polio.

1918 Freeze-Dried Vaccine Used in Tropical Climates

The Vaccine Institute in Paris produced a freeze-dried vacuum-packed smallpox vaccine that addressed the problems with an air-dried vaccine. The product was used in both French Guiana and the French tropical colonies. Its use continued for decades and became crucial to widespread vaccination programs in tropical areas in the 1970s.

11/18/2016 Zika Virus Emergency Ends

The WHO declared an end to the Zika virus public health emergency of international concern. Effective mosquito control measures and an increasing population of humans previously infected with Zika virus led to a slowing of new cases. However, by the end of the epidemic, more nearly 600,000 cases of Zika virus infection were suspected to have occurred in the Americas, and nearly 4,000 babies were confirmed to have congenital syndrome associated with Zika virus infection. Zika virus will likely continue to circulate in many areas. Several Zika virus vaccines are in the early phases of human clinical trials.

5/8/1980 Smallpox Declared Eradicated

The World Health Assembly accepted the WHO Global Commission's recommendation and declared the world free from smallpox.

9/27/2016 Measles Certified Eliminated from Americas

The World Health Organization Region of the Americas achieved a milestone in disease elimination - the Pan American Health Organization on September 27, 2016, declared the Americas to be free of endemic measles. The Region of the Americas is the first of the six WHO regions to eliminate transmission of measles. The United States was certified measles-free in 2000, and the last cases of endemic measles were reported in other countries of the region in 2002. The International Expert Committee for Documenting and Verifying Measles, Rubella, and Congenital Rubella Syndrome Elimination in the Americas was responsible for collecting reports from region countries to certify that measles had in fact been eliminated. Two-dose measles vaccine coverage in the Americas was estimated at only 46% in 2013, and lower than several other regions, and yet the Americas were able to achieve elimination before the others. This may be due to consistently high regional MCV1 coverage, with region-wide rates of greater than 90% since 1998. This high MCV1 coverage was achieved via many years of programmatic catch-up, follow-up, and speed up immunization campaigns. These immunization activities resulted in a precipitous drop in measles incidence-from 320 cases per million population in the years 1980-86, to 170/million in 1987-1994, to 13/million in 1995-2002, to .2/million in 2003-2009 (incidence figures in recent years include non-endemic transmission from imported cases).

2/1/2016 WHO Declares Zika Virus Emergency

The World Health Organization announced that the spread of Zika virus was a public health emergency of international concern. At the time, the WHO's Emergency Committee had sufficient information to announce that a strong association existed between Zika virus infection in pregnant women and microcephaly and other birth defects in their infants. Over the next months, this evidence, and evidence that Zika virus infection could lead to Guillain Barre Syndrome, would grow more convincing. Zika virus was first detected in the Americas in 2015, and it quickly spread to many countries in South, Central, and to a smaller degree, North America. Zika virus is transmitted mainly via the bite of infected mosquitoes, but it can also be spread sexually.

3/27/2014 South-East Asia Region Polio-Free

The World Health Organization certified the South-East Asia Region polio-free on March 27, 2014. The region includes Bangladesh, Bhutan, Democratic People's Republic of Korea, India, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste. In 2011, India was the last of these countries to report a case of disease from wild poliovirus.

1974 Tuberculosis: WHO Immunization Programme

The World Health Organization included BCG in the list of vaccines recommended for its new Expanded Programme on Immunization for developing countries. In 1974, many childhood diseases had almost disappeared from developed countries. These diseases, however, continued to take many lives in poorer countries. In fact, in 1974 fewer than 5% of children worldwide were immunized by age 1 against diphtheria, polio, tuberculosis, pertussis, measles, and tetanus. The Expanded Programme on Immunization would help bring vaccination against these six diseases to many underserved areas.

1974 WHO Advocates DTP

The World Health Organization included DTP in the list of vaccines recommended for its new Expanded Programme on Immunization for developing countries. In 1974, many childhood diseases had almost disappeared from developed countries. These diseases, however, continued to take many lives in poorer countries. In fact, in 1974 fewer than 5% of children worldwide were immunized by age 1 against diphtheria, polio, tuberculosis, pertussis, measles, and tetanus. The Expanded Programme on Immunization would help bring vaccination against these six diseases to many underserved areas.

1954 Adult Immunization Changed

The concentration of diphtheria toxoid in the adult tetanus-diphtheria booster was reduced. Lowering the concentration of toxoid reduced adverse reactions, such as fever, swelling, achiness, fatigue, headaches, and chills. Geoffrey Edsall, a prominent researcher, described reactions to the original booster: "In adults, reactions to toxoid can be surprisingly severe....[A]n adult [could be] confined to bed for 3 or 4 days, with a massively swollen arm which takes 10 days to 2 weeks to return to normal-all from a standard dose of toxoid..." -G. Edsall, Immunization of Adults Against Diphtheria and Tetanus, 1954

A New Name for a Disease (1741)

The term yellow fever began to be used in the 1740s for the disease we now know by that name. Previously, doctors had referred to the disease, and others that were similar to it, by a variety of names, such as pestilential fever, malignant fever, putrid bilious fever, and the like. The new term would be used along with some of the older names for many years. The name comes from the yellowed appearance of the skin and eyes that results from damage to the liver: toxic materials build up in the blood and cause the tell-tale color to appear.

1/1/1967 WHO Pushes Eradication Efforts

The World Health Organization launched the Intensified Smallpox Eradication Programme. At the time, smallpox was endemic in 12 countries or territories in eastern and southern Africa, 11 in western and central Africa, seven in Asia, and Brazil in the Americas. The WHO program designated two main components to its eradication plan: mass vaccinations using freeze-dried vaccine material of carefully monitored quality, and the development of a system to detect, monitor, and investigate smallpox cases and contain outbreaks. Three principles were vital to the program's success: participation from all countries, with solid coordination; adaptability as national programs were implemented; and ongoing research to evaluate progress and deal with problems that might arise. The United States had already announced plans to coordinate with other countries in a smallpox eradication effort, in accordance with WHO's eradication program. WHO efforts came under criticism from some health workers and human rights advocates. Some public health administrators charged that campaign workers at times bent WHO and local regulations. Some human rights advocates objected to the search and quarantine aspects of the program. Later, some critics claimed that physicians used coercion to ensure vaccination of quarantined individuals.

10/21/2021 World Health Organization Recommends Malaria Vaccine

The World Health Organization recommends RTS,S/AS01 (RTS,S) malaria vaccine for children in sub-Saharan Africa and in other regions with moderate to high P. falciparum malaria transmission. The vaccine was tested in a pilot study in three African nations: Ghana, Kenya, and Malawi. Over 800,000 children participated in that pilot study. From WHO: "WHO considers RTS,S as a pathfinder that could be complemented in the future by other vaccines with similar or higher efficacy. Over the last decade, the partnerships forged by EDCTP with the African research community have contributed to the development of both the RTS,S vaccine and to several new candidate malaria vaccines. Noting that EDCTP had been a "proud supporter" of RTS,S, Mrs Inmaculada Peñas-Jiménez, a co-chair of the forum, introduced panellist discussions around other advances in malaria vaccine research and development. Professor Adrian Hill from the University of Oxford presented the latest data on R21/Matrix-M, a vaccine that has shown promising efficacy results against malaria in a Phase 2 clinical trial among several hundred children in areas with highly seasonal malaria transmission. Dr Stephen Hoffman, CEO of Sanaria Inc. reported on progress in the development of the PfSPZ, a vaccine based on whole sporozoite technology. The successful completion of the clinical trials will be important to assess the safety and efficacy profiles of these 2 vaccines. Dr Özlem Türeci, Chief Medical Officer at BioNTech, spoke of a new effort to create a vaccine using mRNA technology. Inspired by the company's success in producing an mRNA-based vaccine against COVID-19, BioNTech scientists hope to develop a malaria vaccine that will be easy to manufacture, highly potent, well-tolerated and suitable for all age groups. "We have learned from our COVID-19 efforts that mRNA is suited to address the most important challenges in developing malaria vaccines, namely how the malaria parasite evades the immune system," said Dr Türeci. "And it is part of our global strategy to enable production of the vaccine within countries themselves. We are committed to these efforts," she added."

January 19, 2016 Angolan Epidemic Stretches Vaccine Supply

The World Health Organization reported the first cases of a yellow fever outbreak in Angola. Since the last reported yellow fever cases in Angola had occurred more than 30 years previously, this epidemic was alarming to health authorities. As of May 2016, Angola has reported 2536 suspected cases and 301 deaths. A massive yellow fever vaccination drive began in the Luanda, the center of the outbreak, with more than 11 million doses of the vaccine shipped to Angola. Cases related to the Angolan outbreak have been reported in Democratic Republic of the Congo, the People's Republic of China, and Kenya.

Native American Tribes Affected (1878)

The Yuma tribes along the Gila River in southern Arizona noted that measles killed many children from 1878-1879.

1945 Influenza Vaccine Approved

The first influenza vaccine was approved for military use in the United States in 1945 and civilian use in 1946. This whole-virus, inactivated influenza A and B vaccine had been tested in military recruits and college students before approval. Thomas Francis Jr., MD, and Jonas Salk, MD, who would become closely associated with the poliovirus vaccine, were key investigators on much of the influenza vaccine research. Influenza vaccine development was a high priority for the U.S. military after the deaths of approximately 1 in every 67 soldiers from influenza during the 1918-1919 pandemic.

First U.S. Polio Epidemic (6/17/1894)

The first major documented polio outbreak in the United States occurred in Rutland County, Vermont. Eighteen deaths and 132 cases of permanent paralysis were reported. Charles Caverly, MD, noted the appearance of acute nervous system disease in the county. He was one of the first physicians to recognize that polio could occur with or without paralysis. He did not assume, however, that the disease could be spread from person to person. The contagious nature of polio would be established in 1905. "The element of contagium does not enter into the etiology either. I find but a single instance in which more than one member of a family had the disease, and as it usually occurred in families of more than one child and as no efforts were made at isolation, it is very certain that it was non-contagious." —Charles Caverly, MD, Infantile Paralysis in Vermont

Early Medical Pamphlet on Smallpox (1678)

The first medical work published in America was printed in Boston, partly in response to a smallpox epidemic in New England: Thomas Thacher's pamphlet, A Brief Rule to Guide the Common People of New England how to order themselves and theirs in the Small Pocks, or Measels.

Smallpox and the Confederacy (1862)

The first of several smallpox epidemics broke out in the Confederacy during the U.S. Civil War, just after the Battle of Antietam in the fall.

1985 First Vaccine Against Hib

The first vaccine against Haemophilus influenzae type b (Hib) disease was licensed in the United States in 1985. The HbPV polysaccharide vaccine was used until 1988. Porter W. Anderson, Jr, PhD, and David H. Smith, MD (1932-1999), had begun working in 1968 on extracting and purifying the polysaccharide outer coating of the bacteria. A 1975 trial of the vaccine in Finland showed that toddlers, but not infants, mounted a protective response to the bacteria. Unable to interest pharmaceutical companies in manufacturing the vaccine, Smith founded a company to produce it. Before the Hib vaccine was introduced in the United States, severe Hib disease (which includes meningitis, pneumonia, joint infections, bone infections, skin infections, and epiglottitis - an infection and swelling in the throat that can block the airway) affected about 20,000 children younger than five each year, and killed nearly 1,000. Among Hib meningitis cases, 2%-5% are fatal, while 15%-30% of patients who survive have permanent neurological damage such as blindness or deafness. With widespread use of the vaccine, the number of reported cases of invasive Hib diease in US children has been reduced by 99% (MacNeil JR, Cohn AC, Farley M, et al. 2011).

10/15/1999 Rotavirus: First Vaccine Withdrawn

The first vaccine for rotavirus, a common cause of severe childhood diarrheal illness, RotaShield, was licensed and recommended for routine childhood immunization in 1998. Wyeth Pharmaceuticals, however, withdrew the vaccine in 1999 due to safety concerns. Scientists associated the vaccine with a rare intestinal problem called intussusception, a potentially fatal telescoping of part of the bowel.

Jenner Is Orphaned (1754)

The five-year-old Jenner was orphaned in December 1754 when his father passed away at age 52. His mother had died after childbirth two months earlier.

2005 Polio Goal Unmet

The goal of the Geneva Declaration signed in 2004 would not be met. Polio remained circulating at the end of 2004 in four of the six previously endemic countries. Egypt and Niger, however, would make it through 2005 without a single reported case of indigenous polio, and by January 2006, the list of polio-endemic countries would be down to four.

1949 U.S. Success with Vaccination

The last cases of naturally occurring smallpox in the United States developed in an outbreak limited to eight people in Hidalgo Country, Texas. Later, several U.S. smallpox infections occurred through importation from abroad and vaccination. The disease continued to appear in the rest of the world through the 1970s.

10/16/1975 Last Wild Case of Variola Major

The last wild human case of variola major occurred in the village of Kuralia, Bhola Island, Barisal district, Bangladesh. Rahima Banu was the sufferer. She was two years old at the time and made a full recovery, although she was scarred.

North America Sees Last Yellow Fever Epidemic (1905)

The last yellow fever epidemic on the North American continent occurred in New Orleans, Louisiana. The epidemic ended in the fall after a large-scale mosquito eradication program.

Rubella: The Naming of the "Little Red" (1841)

The name "Rubella," meaning "little red," was first used to describe an outbreak at a boys' school in India. Later, this would be referenced by English surgeon Henry Veale in the Edinburgh Medical Journal (Volume 12, 1866) documenting the history of an epidemic of "Rötheln." Veale proposed that the name Rubella replace "Rötheln," citing the need for a name that was easy to write and pronounce.

1948 Changes in Vaccine Production

The newly established World Health Organization issued a report praising the freeze-dried vacuum-packed vaccine from the Vaccine Institute in Paris. Production of the vaccine soon spread around the world.

2013 Syrian Crisis Creates Foothold for Polio

The political crisis in the Syrian Arab Republic, with its disruption of health programs and the displacement of millions of people, led to the reappearance of polio. Syria had not seen polio since 1999 prior to these outbreaks, which began in early fall 2013. The WHO launched an intensive emergency immunization drive to try to control the spread of the disease. By the end of 2013, 25 polio cases had been reported. The virus implicated in the Syrian outbreaks was similar to strains continuing to circulate in Pakistan.

Antitoxin Contamination (1901)

Thirteen St. Louis children died from contaminated diphtheria antitoxin. Investigations showed that a horse used in diphtheria antitoxin production for the St. Louis municipal health authority died of tetanus. Rather than being discarded, some of the antitoxin produced from the diseased horse was sent to physicians. This incident, along with a Camden, New Jersey, tetanus outbreak linked to contaminated smallpox vaccine, led to federal regulation of biologic products.

1980 Rabies: HDCV Licensed

The rabies vaccine produced at the Wistar Institute, called HDCV (human diploid cell vaccine), was licensed in Europe in 1976 and in the United States in 1980. One of its principal advantages was that the vaccine was given in five injections rather than the course of 14-21 injections used in the older vaccines. HDCV is still widely used, but it is expensive to produce. Other rabies vaccines containing viruses grown in other types of cell culture (chick embryo, a cell line derived from African green monkey kidney, fetal rhesus cells, and hamster kidney cells) have been licensed in different parts of the world. A few vaccines created with nervous system tissue continue to be used in Asia, Africa, and South America.

Landmark Anthrax Vaccine Study (6/5/1881)

The results of Pasteur's large study of anthrax vaccination in livestock became evident in dramatic public demonstrations. In a test of his vaccine created by attenuating the anthrax bacteria with carbolic acid, all 25 of the unvaccinated animals died. Only one of the vaccinated animals died, likely as a result of a pregnancy miscarriage rather than anthrax.

1979 Rubella: An Improved Vaccine Is Licensed

The rubella vaccines licensed in 1969 were replaced in the United States by American physician Stanley A. Plotkin's newly licensed RA27/3 vaccine, which had been used in Europe for years and provided superior protection to that of the earlier vaccines. While previous rubella vaccine viruses had been grown in animal cultures (dog kidney, duck embryo and rabbit kidney had each been used for different strains) the RA27/3 strain was cultured in a cell line derived from human fetal cells. Plotkin's vaccine also replaced the original rubella vaccine in the combined MMR shot, and is still used today.

1961 Cholera: Seventh Pandemic

The seventh cholera pandemic emerged in Indonesia and spread throughout Africa and Asia. The El Tor strain was the causative agent in this pandemic. Epidemiologists consider the seventh pandemic to be ongoing today.

A New Post (1863)

The École des Beaux-Arts appointed Pasteur to be a professor of chemistry and geology.

Spanish Epidemic (1613)

This year was known in Spain as "El Año de los Garotillos" ("strangulations") for its epidemic of diphtheria.

1935 Early Polio Vaccine Trials

This year, two separate teams were at work developing and testing a polio vaccine. Both projects came to disastrous ends. At New York University, Maurice Brodie, MD (1903-1939), a young researcher, prepared a killed poliovirus vaccine, testing it on chimpanzees, on himself, and finally on children. He enrolled about 11,000 individuals (in both control and vaccine groups) in his trial. Meanwhile, John Kolmer, MD, of Temple University in Philadelphia developed an attenuated poliovirus vaccine, which he tested in about 10,000 children. The tests proved a disaster. Several subjects died of polio, and many were paralyzed, made ill, or suffered allergic reactions to the vaccines.

U.S. President Stands by Vaccination (5/14/1806)

Thomas Jefferson, an advocate of vaccination, received a copy of Edward Jenner's work from Jenner's nephew, Rev. Dr. G.C. Jenner. He wrote in response: Sir: I have received the copy of the Evidence at large respecting the discovery of the Vaccine inoculation, which you have been pleased to send me, and for which I return you my thanks. Having been among the early converts, in this part of the globe, to its efficacy, I took an early part in recommending it to my countrymen. I avail myself of this occasion of rendering you my portion of the tribute of gratitude due to you from the whole human family. Medecine has never before produced any single improvement of such utility. Harvey's discovery of the circulation of the blood was a beautiful addition to our knowledge of the animal economy, but on a review of the practice of medecine before and since that epoch, I do not see any great amelioration which has been derived from that discovery. You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated. Accept the most fervent wishes for your health and happiness and assurances of the greatest respect and consideration. — TH. JEFFERSON. Letter, Monticello, Virginia, May 14, 1806, to "The Rev. Doctr. G. C. Jenner."

1954 Thomas Peebles Isolates the Measles Virus

Thomas Peebles, MD, working in a laboratory at Boston Children's Hospital, was asked by lab director John Enders to isolate the virus responsible for measles. Peebles learned of an outbreak at a private school outside of Boston and, after getting permission from the principal, collected blood samples from the sick students, telling each boy: "Young man, you are standing on the frontiers of science." Peebles attempted for weeks to obtain the virus, and on February 8, succeeded. He collected blood containing the virus from 13-year-old student David Edmonston. Eventually, the collected measles virus would be isolated and used to create a series of vaccines.

17th Century Smallpox Treatment (1684)

Thomas Sydenham (1624-1689), a noted English doctor, had observed that the rich seemed to have a higher mortality rate from smallpox than the poor. This led him to conclude that contemporary medical treatments, largely inaccessible to the poor, might be more harmful than helpful in mild smallpox cases. Thomas Dover, a future doctor and a patient of Sydenham, however, eventually documented his treatment at Sydenham's hands for a more serious case of smallpox. This is Dover's description: "Whilst I lived in Dr Sydenham's house, I had myself the Small Pox, and fell ill on the Twelfth Day. In the beginning I lost twenty two Ounces of Blood [from bloodletting]. He gave me a Vomit, but I find by Experience Purging much better. I went abroad, by his Direction, till I was blind, and then took to my Bed. I had no Fire allowed in my Room, my Windows were constantly open, my Bed-Clothes were ordered to be laid no higher than my Waste. He made me take twelve Bottles of Small Beer, acidulated with Spirit of Vitriol, every twenty Four hours. I had of this Anomalous Kind [of smallpox] to a very great Degree, yet never lost my Senses one Moment." — Thomas Dover, The Ancient Physician's Legacy to His Country

1925 Whooping Cough: Conflicting Reports of Vaccine Success

Thorvald Madsen (1870-1957), a Danish physician, tested his pertussis (whooping cough) vaccine in children in the Faroe Islands. The vaccine seemed to provide protection against disease. However, another Madsen study, published in 1933, reported that two children died from what may have been reactions to the vaccine.

Sporadic Epidemics Continue (1885)

Though smallpox disease rates dropped throughout the 19th century due to vaccination, suspicion about vaccination remained among some populations. This led to devastating epidemics when the disease reappeared. French Canadians were among those whose mistrust of vaccination would end up costing them dearly when, in 1885, poor policies regarding hospital patients resulted in an epidemic in Montreal: "The disease smoulders here and there and when conditions are favorable becomes epidemic. This was well illustrated by the Montreal outbreak of 1885. For several years there had been no small-pox in the city, and a large unprotected population grew up among the French-Canadians, many of whom were opposed to vaccination. On February 28 a Pullman-car conductor, who had traveled from Chicago, was admitted into the Hôtel-Dieu, the civic small-pox hospital being closed at the time. Isolation was not carried out, and on the 1st of April a servant in the hospital died of small-pox. Following her disease, the authorities of the hospital dismissed all patients presenting no symptoms of contagion who could go home. The disease spread like fire in dry grass and, in nine months 3,164 persons died in the city of small-pox." — Sir William Osler and Thomas McCrae, The Principles and Practice of Medicine

2017 Cholera Vaccines Today

Today, several oral cholera vaccines are available globally and are prequalified by the World Health Organization. A whole-cell killed vaccine Dukoral, or WC-Rbs, first licensed in 1992 and manufactured by French vaccine company Valneva, is internationally licensed but not available in the United States. Shanchol is a killed oral vaccine that is licensed and manufactured in India by Shantha Biotechnics. A very similar vaccine named Euvichol is manufactured in South Korea by EuBiologics. In the United States, an oral cholera vaccine (Cholera Vaccine, Live, Oral, [Vaxchora® ]) is approved for adults age 18-64 traveling to cholera-afflicted areas. All of these vaccines protect against both the classic and the El Tor subtypes of cholera (both 01). The WHO prequalified vaccines also protect against a newer but rare type of cholera, O139. Other cholera vaccines are currently in the development pipeline.

1/31/2014 Group B Meningococcal Disease Outbreaks

Two unrelated outbreaks of disease due to serogroup B meningococcal infection occurred at universities in 2013. The disease clusters at Princeton University and University of California Santa Barbara prompted health officials to pursue an unusual course: from late 2013 to early 2014, the FDA authorized use of a group B meningococcal vaccine at the two campuses that had not yet been approved for use in the United States. The vaccine, manufactured by Novartis, was approved in 2013 for use in the European Union, Canada, and Australia. The vaccine currently approved in the United States does not protect against infection from serogroup B meningococcus. Novartis plans to pursue licensure of the group B vaccine in the United States, and they are also investigating plans to add the group B antigens to their approved quadrivalent vaccine.

Early Use of Antitoxin in U.S. (10/16/1894)

Two young Cincinnati physicians treated a two-year-old girl successfully with diphtheria antitoxin. This is one of the earliest documented uses of diphtheria antitoxin in the United States. G.J. Hermann, MD, and Charles Waugh Reynolds, MD, learned that a local physician had obtained some of the serum on a recent trip to Europe. They begged him to let them use it to treat four children in one family who had taken ill. The physician had enough antitoxin to give only the youngest child, whose disease had not progressed far. The little girl and one of her untreated brothers survived, but two of the untreated children died. Dr. Reynolds's typescript memoir provides a dramatic rendering of the event.

Diphtheria in California (1856)

Victor Fourgeaud (1815-1875), a San Francisco doctor and legislator, described a diphtheria epidemic in California. Fourgeaud treated sufferers with application of a variety of chemicals to the affected areas. It is likely that these applications did not help in the patients' recovery, as they would not have been able to arrest the action of the diphtheria toxin.

A Proclamation in Virginia (1693)

Virginia Governor Edmund Andros issued a proclamation for a "day of Humiliation and Prayer" due to measles there.

1961 A Flock of Chickens Changes Everything

Virologist Harry Rubin developed a method to detect a virus that caused leukemia in chickens. The test proved invaluable to researchers concerned about developing vaccines, including measles vaccine, in chick embryos that might contain a virus known to cause cancer in chickens. (It was later determined that the virus did not cause cancer in humans, but the researchers didn't know that at the time.) Maurice Hilleman, PhD, who was trying to use measles virus obtained from Enders to develop a vaccine for Merck, went in search of chickens known to be free of the leukemia virus for use in developing a measles vaccine. He eventually traveled to Kimber Farms in California, where the director of poultry research, W.F. Lamoreux, initially refused to sell the farm's flock of specially bred leukemia-free chickens. Hilleman prepared to leave empty-handed, only to find that Lamoreux was happy to sell him the chickens when he realized that Hilleman, like Lamoreux, was a native of Montana. Hilleman bought the farm's entire flock of leukemia-free chickens for $1 each. The descendents of that original flock are still being used to create vaccines at Merck.

Cholera: Haffkine's Indian Vaccine Trials (1893)

Waldemar Haffkine arrived in India to conduct tests of his cholera vaccine. In his trials, he employed control and experimental groups, a relatively new practice for the time, and vaccinated more than 40,000 people. Though he was not always able to maintain rigorous controls, his methods would become useful models for future vaccine trials. His vaccine showed efficacy in many of the trial subgroups. By mid-1896, Haffkine had concluded that the use of an initial attenuated vaccine was unnecessary, and so, as his trials continued, he tested only the more potent vaccine.

1911 Haffkine Develops Heat-Killed Cholera Vaccine

Waldemar Haffkine developed a heat-killed cholera vaccine, perhaps in recognition that the vaccine Wilhelm Kolle developed was easier to prepare and standardize.

Royal Support of Inoculation (1661)

When Chinese Emperor Fu-lin died of smallpox, his third son became Emperor K'ang. Having already survived a case of smallpox before he became Emperor, he eventually supported inoculation and wrote about it in a letter to his descendants: "The method of inoculation having been brought to light during my reign, I had it used upon you, my sons and daughters, and my descendants, and you all passed through the smallpox in the happiest possible manner.... In the beginning, when I had it tested on one or two people, some old women taxed me with extravagance, and spoke very strongly against inoculation. The courage which I summoned up to insist on its practice has saved the lives and health of millions of men. This is an extremely important thing, of which I am very proud." — Ian Glynn and Jenifer Glynn, The Life and Death of Smallpox

1951 Massive Epidemic Hits Greenland

When measles was introduced to southern Greenland, an area where the disease had not been endemic previously, it spread rapidly: only five people from an unprotected population of 4,262 escaped the disease, so that it had a final attack rate of 99.9%. However, quick efforts made in Denmark to provide gamma globulin (a type of blood protein—in this case, rich in antibodies) to Greenland had some success: patients receiving gamma globulin had a lower case fatality rate from the disease than those who did not.

2008 Pennsylvania and Minnesota Hib Outbreaks

While the majority of fatalities from Haemophilus influenzae type b disease are currently reported in developing countries where the Hib vaccine is not widely used, fatalities still occur in developed nations when vaccination rates drop. Seven cases of invasive Hib disease were reported in Pennsylvania during a six-month period starting in October 2008. Only one of the children had received a Hib vaccination (and had only received one of the recommended doses). Three of the children died. In Minnesota, five cases of invasive Hib disease in children younger than five were reported in 2008, with three of those cases in children whose parents had refused or deferred vaccination for the child. One of the children died. The 2008 outbreaks demonstrate that while herd immunity may be intact on the large scale, with high immunization rates at the national level, rare diseases can still gain footholds in subsets of the population where immunization rates are low.

1939 Typhoid's Role in Warfare Dwindles

While typhoid had killed thousands of soldiers in the Second Boer War and the Spanish-American War, typhoid vaccination had a profound effect on its incidence in the following decades. The U.S. Army Medical Department noted that during the Second World War, typhoid was "nearly nonexistent" among American soldiers.

1953 Adenoviruses Identified

While working at the Walter Reed Army Institute of Research (WRAIR), Maurice Hilleman flew to Missouri to investigate an influenza outbreak in Army troops. When he returned to his lab, however, he discovered that he had isolated an entirely new type of virus. Today that family of virus is known as the adenoviruses. They cause up to 10% of all upper respiratory infections in children and affect adults as well. Adenoviruses were a major cause of acute respiratory distress syndrome among military trainees during their initial basic combat training. Building on Hilleman's work, an inactivated adenovirus vaccine of marginal value was developed in 1956. A more efficacious live virus vaccine was developed by other scientists in the 1970s and widely used in the military from decades.

Cholera: Kolle's Contribution (1896)

Wilhelm Kolle (1868-1935) developed a heat-inactivated cholera vaccine that came to serve as a model for cholera vaccines for the next century. Kolle was, at the time, an assistant to Robert Koch. He went on to work on rinderpest, leprosy, and other diseases, and ended his career at the Institute for Experimental Therapy in Frankfurt.

Britain Bans Variolation (1840)

William Farr in The Lancet characterized Britain's National Vaccine Act of this year as inadequate, with five London children per day still dying of smallpox. The Act did, however, offer free vaccination for infants (the first instance of free medical service in the country) and banned variolation, a move heralded by the medical profession.

Anti-Mosquito Methods Allow Completion of Panama Canal (1904)

William Gorgas brought the mosquito control methods he practiced in Havana four years earlier to Panama, where the United States was attempting to complete the Panama Canal. Efforts to screen windows and doors, fumigate houses, and prevent mosquitoes from breeding in standing water proved fruitful. The last case of yellow fever in Panama City was reported the following year.

1914 Park's Breakthrough

William H. Park (1863-1939) studied the use of diphtheria toxin-antitoxin mixtures to produce active immunity in animals and then in humans. He adjusted the amounts of the substances until he achieved a balance between lasting immunity and reactions to the mixture. This method was used for immunizing humans until toxoid immunization replaced it.

Philadelphia Avoids an Outbreak (1747)

With Philadelphians aware that yellow fever had been traced to the West Indies, a vessel arriving in the city from Barbados was examined carefully. After the captain reported the death of a sailor as well as a second possible case of yellow fever, the ship was held in anchor more than a mile from the city and prevented from unloading cargo or passengers. Reports later indicated that Barbados was suffering from a serious outbreak of the disease at the time. The authorities' actions in holding the ship may have prevented its further spread into Philadelphia.

1981 Measles Cases Drop Dramatically

With the Measles Elimination Program having set a date to eliminate the disease from the United States by October 1, 1982, current statistics seemed promising. In April of 1981, the number of reported measles cases was down an "unprecedented" 80% from the previous year. The Centers for Disease Control and Prevention noted that only 778 cases were reported in the first 14 weeks of 1981, while 3,897 had been reported during the same period the previous year. Unfortunately, the disease would prove more difficult to conquer than researchers had hoped, and the goal of U.S. measles eradication by 1982 would not be met.

Mosquito Control Efforts Reduce Disease Cases (1901)

With the approval of Walter Reed (his commanding officer), Chief Sanitary Officer Dr. William Crawford Gorgas began to study the effects of removing the Aedes aegypti mosquito population on yellow fever rates. He started his work in Havana in February: workers drained or covered open water containers and fumigated areas to kill adult mosquitoes. Yellow fever cases began to drop, and by October, none were reported. Reports of malaria dropped as well.

1987 Conjugate Hib Vaccine Licensed

Work by American scientists John Robbins, MD, and Rachel Schneerson, MD, led to the first conjugate vaccine against Haemophilus influenzae (Hib) disease being licensed in the United States. Conjugate vaccines are better able to induce an immune response than polysaccharide vaccines in infants and young children, the age group most at risk from Hib. This vaccine replaced a previous polysaccharide Hib disease vaccine. Today there are three conjugate Hib disease vaccines available in the United States, as well as two combination vaccines that provide protection against multiple diseases, including Hib disease. For optimal protection, children need 3-4 doses of the vaccine starting around 2 months of age.

Yellow Fever Cripples the Mississippi Valley (1878)

Yellow fever killed more than 13,000 people in the lower Mississippi Valley. At the time, it was one of the worst medical disasters in U.S. history. The following year, a federal government commission investigated the disaster; Marine Hospital Service Surgeon General John Woodworth (1837-1879) reported to Congress that "Yellow fever should be dealt with as an enemy which imperils life and cripples commerce and industry."

A View of Smallpox Progression (1881)

hese heliotypes (an early photography technique) give a detailed view of the progression of smallpox, from just after eruption of pustules to the late scabbing stage. The publisher noted that the patient made a full recovery. The extent of the patient's rash suggests that he was left with significant scarring. Following is the introduction from the book in which the plates were published: "The following plates represent the appearance of the variola at different stages of the eruption. The first sixteen pictures show its appearance on the same patient, from the third to the fourteenth day, when it began to disappear. The patient entered the hospital on the ninth day of October, 1881, and remained until the second day of November following, when he was discharged well. ...[He was] under the professional care of the City Physician of Boston." — Samuel A. Powers, Superintendent Small-pox Hospital, Boston, from Variola. A Series of Twenty-one Heliotype Plates Illustrating the Progressive Stages of the Eruption

Roux and Yersin Investigate the Diphtheria Bacterium (1888)

Émile Roux (1853-1933) and Alexandre Yersin (1863-1943) showed that a substance produced by C. diphtheriae caused symptoms of diphtheria in animals. Later, HJ Parish described Roux and Yersin's procedure: "Broth, in which the organisms had grown for several days, was filtered through unglazed porcelain; the sterile filtrate caused death following its injection into animals in the same manner as that of the living organisms themselves; moreover, the 'membrane' characteristic of human diphtheria, and the intense local inflammation, oedema and haemorrhage, could often be reproduced by the toxin." --HJ Parish, A History of Immunization