1678 Early Medical Pamphlet

Timelines — History of Vaccines

National Library of Medicine

A 1721 (approximate date) printing of Thomas Thacher's pamphlet on colonial smallpox

1678

Early Medical Pamphlet on Smallpox

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.

1898 Regulation of Vaccine Supply Increases

Timelines — History of Vaccines

The Historical Medical Library of The College of Physicians of Philadelphia

This invitation to an inspection of the vaccine farms of Dr. H. M. Alexander illustrates the emerging regulation of vaccine production. Page 1.

1898

Regulation of Vaccine Supply Increases

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.18

1879 First Laboratory Vaccine

Timelines — History of Vaccines

Harper's Weekly, January 3, 1895. Laboratory worker using autoclave to sterilize chicken broth.

1879

First Laboratory Vaccine

Louis Pasteur produced the first laboratory-developed vaccine: the vaccine for chicken cholera.

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 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.

1870 Animal Vaccine Brought to US

The Historical Medical Library of The College of Physicians of Philadelphia

Title page of Martin's On Animal Vaccination, 1878

1870

Animal Vaccine Brought to U.S.

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 distinguishedsavant, 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

1633 Colonial Epidemic | First American Accounts

Timelines — History of Vaccines

Library of Congress

Massasoit (a leader of the Pokanoket Native American tribe) and his warriors

1633

Colonial Epidemic

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

1777 Mandatory Inoculation for Continental Army

Timelines — History of Vaccines

National Library of Medicine

George Washington

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.

1721 Boston Smallpox Epidemic

Timelines — History of Vaccines

The Historical Medical Library of The College of Physicians of Philadelphia

Cotton Mather

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%. 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.”