This is a long series of extracts from an online, pro-vaccination site. It’s to give scope to understanding the fuller impacts of vaccination history……..
1 – African Use of Variolation
Cotton Mather, a Boston minister (1663-1728), received a gift of a Libyan-born slave named Onesimus, who bore a scar from smallpox variolation in Africa. Mather inquired among other slaves 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.
2 – 1718 – Variolation in Turkey
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.
3 – 4/21/1721 – The First English Variolation
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 %age of the population were “naturally” developing smallpox? That is, the jab killed 2-3% of recipients but, in that time, what percentage of the unvariolated caught and died of smallpox?] What’s more, variolated individuals could pass the disease on to others.
4 – 1721 – Boston Smallpox Epidemic
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%. [See comment above.] [But, also, what percentage of the variolated later developed smallpox?] 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.
5 – 1738 – Promise of Variolation
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. [Same comment again] The results encouraged advocates of variolation. Meanwhile, the same epidemic reportedly killed half of the Cherokee Indian population in the vicinity.
6 – 5/17/1749 – Birth of Jenner
Edward Jenner was born in Berkeley, in Gloucestershire, England.
7 – 1757 – Infectious Nature of Measles Shown
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
8 – 1759 – Spreading Word of Inoculation
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.
9 – 1767 – Chickenpox: Disease Distinguished from Smallpox
English physician William Heberden was the first to give a detailed description that distinguished chickenpox from smallpox. He wrote:
These pocks break out on many without any illness or previous sign: in others they are preceded by a little degree of chillness, lassitude, cough, broken sleep, wandering pains, loss of appetite and feverishness for three days… Most of them are of the common size of the smallpox but some are less. I never saw them confluent nor very numerous. The greatest number which I ever observed was about twelve in the face, and two hundred over the rest of the body.
Heberden also noted that those who had previously had chickenpox “were not capable of having it again.”
10 – 1770 – Jenner Studies at St. George’s Hospital
Edward Jenner began studies at St. George’s Hospital in 1770. He studied for two years with surgeon John Hunter.
11 – 1770 – Protection by Cowpox Infection
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 variolaviruses, which cause smallpox.
12 – 1774 – A Farmer Takes a Chance
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.”
13 – 1776 – Smallpox Becomes a Weapon of War
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.
14 – 1777 – Mandatory Inoculation for Continental Army
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.
15 – 1792 – Stricter Regulations Passed for Inoculation
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.
16 – 1793 – Yellow Fever Decimates Philadelphia
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
17 – 5/14/1796 – Jenner’s Breakthrough
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 variolavirus, 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.
18 – 9/17/1798 – Word of Jenner’s Success Spreads
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.
[Just imagine what this material contained!]
19 – 1802 – Vaccination Endorsed
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.
[And so began the international business in Vaccines]
20 – 1802 – Vaccination vs. Variolation
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.
21 – 5/17/1803 – Origin of the Term Vaccination
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.
22 – 9/1/1803 – A Vaccination Expedition
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.)
[Grim, eh? Would anyone seriously consider doing this today?]
23 – 1805 – First Compulsory Vaccination Attempted
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.
24 – 1810 – Italian Physician Uses Cows for Vaccine Production
Gennaro Galbiati, director of the vaccine service in Naples, Italy, began retrovaccinating cows with human vaccine lymph. [What was this? Pus, presumably?!] He then vaccinated people with the resulting animal lymph. [So, did the cattle then develop pustules, post being retrovaccinated with human pus?] 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.” [But it was still, simply pus.]
“2. Vaccination performed with virus from the cow offers the advantage that no other diseases can be communicated by it.” [Virus? But we didn’t know of viral particles at the time, let alone being able to isolate them. He meant “Pus”….But, anyways, where was their sterile technique? How did they keep their pus clean!]
25 – 1813 – U.S. Vaccine Agency Established
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.”
[Birth of the CDC!!]
26 – 1817 – Cholera: The Pandemics Begin
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. [Ongoing pandemic??!]
27 – 1/26/1823 – Jenner Dies
Jenner died of an apparent stroke at age 73.
28 – 1826 – Diphtheria Given Its Name
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.
29 – 1836 – Method of Increasing Potency
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.
[Thinking this through it has utterly no logic to it. But, hey, that’s no surprise……]
30 – 1840 – Britain Bans Variolation
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.
31 – 1846 – Faroe Islands Yield New Observations
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]
32 – 1853 – Mandatory Vaccination in UK
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.
[Then, 20 years later, there’s the tale of Leicester’s reaction to this act and the appalling death rate associated with the process.]
33 – 9/10/1859 – Pasteur’s Daughter Dies
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
34 – 1861 – Measles Plays a Role in the Civil War
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)
35 – 12/12/1862Smallpox Hospital Loses 110 Patients in 1 Week
-Richmond’s smallpox hospital admitted 250 patients during the week of December 12-19. Of the 250, 110 died.
36 – 1874
German Vaccination Law
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
37 – 1885-Sporadic Epidemics Continue
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
38 – 1891Advances in Vaccine Production
-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
39 – 1893 – Low Vaccination Rates Lead to Outbreak
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
40 – 6/17/1894 – First U.S. Polio Epidemic
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
41 – 1895 – Antitoxin Production in the United States
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 blo
42 – 12/4/1894 – New York City Regulates Antitoxin
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.
43 – 1901 – Antitoxin Contamination
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.
44 – 1904 – Tuberculosis: Attenuation of Bacterium
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.
45 – 1905 – Serum Sickness Described
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
46 – 1905 – North America Sees Last Yellow Fever Epidemic
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.
47 – 1898 – Britain Allows Exemptions
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.
48 – 1905 – A Physician’s Plea
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.
49 – 1905 – Tuberculosis: Fruitless Search for Antitoxin
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.
50 – 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.
51 – 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.
52 – 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.
53 – 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.
54 – 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.
55 – 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.
56 – 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.
57 – 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.”
58 – 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.
59 – 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.
60 – 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.
61 – 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.
62 – 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.
63 – 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.
64 – 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 vac
65 – 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.
66 – 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.
67 – 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.
68 – 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.
69 – 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.
70 – 3/24/1976 – Swine Flu 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.
71 – 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.
72 – 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.
73 – 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.
SOURCE:
All from : https://www.historyofvaccines.org/timeline#EVT_100354
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