The first smallpox vaccine changed the world—but we're still not sure what was in it

It only took 181 years to eradicate smallpox once we had a way to inoculate against it. That cocktail was the first successful vaccine, and the basis for most future immunizations. And we’re still not really sure what was in it.

There’s a story about Jenner that nearly every high school biology student has heard, and it’s only mostly true. The tale goes like this:

Edward Jenner grew up amongst English cow farms during the 1700s, where he noticed that the milkmaids never seemed to catch or die from smallpox. He always considered this odd, especially in a world where infectious diseases regularly killed a significant fraction of the population.

He grew up and became something resembling a doctor, meaning he apprenticed with an apothecarist and a surgeon (and that apparently sufficed as a license). He moved back to his hometown, where other people had also noticed the milkmaid phenomenon.

To test the hypothesis, he took pus from the cowpox blemishes on a sickly bovine and infected the eight-year-old son of his gardener with it. Times were different, but it’s hard to imagine that the gardener was entirely okay with this. Regardless, Jenner waited six weeks and then tried to infect the kid with smallpox. Again, a quick reminder that he was attempting to give a child a deadly disease on purpose.

RELATED: Threats the Centers for Disease Control and Prevention (CDC) have responded to

13 PHOTOS
Threats the Centers for Disease Control and Prevention (CDC) have responded to
See Gallery
Threats the Centers for Disease Control and Prevention (CDC) have responded to
Barbara Smith, a registered nurse with Mount Sinai Medical Health Systems, St. Luke's and Roosevelt Hospitals in New York, demonstrates putting on personal protective equipment (PPE) during an Ebola educational session for healthcare workers at the Jacob Javits Convention center in New York, October 21, 2014. Thousands of healthcare workers representing dozens of clinical and non-clinical positions attended the session that featured experts from the Centers for Disease Control and Prevention (CDC) and other area infection control experts to provide training and information on caring for potential Ebola patients. REUTERS/Mike Segar (UNITED STATES - Tags: HEALTH DISASTER)
A Chipotle restaurant is shown in Federal Way, Washington November 20, 2015. The U.S. Centers for Disease Control and Prevention (CDC) said on Friday that three additional states reported E. coli infections from the same strain as the Chipotle Mexican Grill outbreak, sending shares in the chain down more than 12 percent. REUTERS/David Ryder
A deer mouse in a sawdust, pine needle, and bird feather habitat is seen in this handout photo obtained by Reuters, July 6, 2017. The deer mice are the principal reservoir of Sin Nombre (SN) virus, the primary etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in North America, a relatively-new acute respiratory illness. Centers for Disease Control and Prevention/Handout via REUTERS ATTENTION EDITORS - THIS IMAGE WAS PROVIDED BY A THIRD PARTY.
The cruise ship Balmoral is prepared prior to boarding of passengers going on the Titanic Memorial Cruise in Southampton, England April 8, 2012. An outbreak of the norovirus stomach bug has sickened 160 people aboard a Fred Olsen Cruise Lines ship docked at Norfolk, Virginia, U.S. health officials and the company said on Friday. The norovirus outbreak took place aboard the Britain-based line's Balmoral during a transatlantic cruise, the Centers for Disease Control and Prevention (CDC) said in a statement. REUTERS/Chris Helgren/File Photo
A scientist holds a container filled with blood to feed aedes aegypti mosquitoes at the Laboratory of Entomology and Ecology of the Dengue Branch of the U.S. Centers for Disease Control and Prevention in San Juan, March 6, 2016. Picture taken March 6, 2016. REUTERS/Alvin Baez
A deer tick, or blacklegged tick, Ixodes scapularis, is seen on a blade of grass, in this undated picture from the Centers for Disease Control and Prevention. Scientists have discovered a new bacteria species causing Lyme disease in the U.S. Midwest, the national Centers for Disease Control and Prevention said on Monday, adding to the medical literature on the tick-borne disease. REUTERS/Centers for Disease Control and Prevention/Handout via Reuters THIS IMAGE HAS BEEN SUPPLIED BY A THIRD PARTY. IT IS DISTRIBUTED, EXACTLY AS RECEIVED BY REUTERS, AS A SERVICE TO CLIENTS. FOR EDITORIAL USE ONLY. NOT FOR SALE FOR MARKETING OR ADVERTISING CAMPAIGNS
NEW YORK - 1958: In this handout from the Centers for Disease Control and Prevention (CDC), the skin of a patient after three days of measles infection is seen at a New York hospital in 1958. Measles outbreaks have been reported throughout the U.S., with the latest reported February 5, 2015 at a daycare in suburban Chicago where as many as five children under the age of one have been infected. (Photo by CDC via Getty Images)
NEW YORK, NY - OCTOBER 24: Bio Recovery Corporation employees hand over potentially contaminated materials to the CDC outside of 546 West 147th Street October 24, 2014 in New York City. After returning to New York City from Guinea, where he was working with Doctors Without Borders treating Ebola patients, Dr. Craig Spencer was quarantined after showing symptoms consistent with the virus. Spencer was taken to Bellevue hospital to undergo testing where he was officially diagnosed with the Ebola virus on October 23rd. (Photo by Bryan Thomas/Getty Images)
MIAMI BEACH, FL - SEPTEMBER 13: A Florida Department of Health worker packages up a urine sample to be tested for the Zika virus as they provide people with a free Zika virus test at a temporary clinic setup at the Miami Beach Police Department on September 13, 2016 in Miami Beach, Florida. According to the CDC, 64 locally transmitted cases of the Zika virus have been discovered in Florida. (Photo by Joe Raedle/Getty Images)
FILE PHOTO: A Centers for Disease Control (CDC) scientist measures the amount of H7N9 avian flu virus which was grown and harvested in an unnamed CDC laboratory in 2013. James Gathany/CDC/Handout via REUTERS ATTENTION EDITORS - THIS IMAGE WAS PROVIDED BY A THIRD PARTY. FOR EDITORIAL USE ONLY.
Colonies of E. coli bacteria grown on a Hektoen enteric (HE) agar plate are seen in a microscopic image courtesy of the U.S. Centers for Disease Control (CDC). U.S. health officials on May 26, 2016 reported the first case in the country of a patient with E. coli bacteria carrying the mcr-1 gene, an infection resistant to all known antibiotics. CDC/Handout via REUTERS TPX IMAGES OF THE DAY FOR EDITORIAL USE ONLY. NOT FOR SALE FOR MARKETING OR ADVERTISING CAMPAIGNS. THIS IMAGE HAS BEEN SUPPLIED BY A THIRD PARTY
The Aeromedical Biological Containment System (ABCS) is shown in this undated handout photo provided by the Centers for Disease Control (CDC) in Atlanta, Georgia, August 1, 2014. The ABCS is a portable, tent-like device installed in a modified Gulfstream III (G-III) aircraft, providing a means to perform emergency movement of exposed or contagious CDC personnel from the field, or site of exposure, to a facility that can provide appropriate medical care without risk to passengers or air crew, according to the CDC. The ABCS was designed and built by the Department of Defense (DoD), Phoenix Air Group (PAG), and CDC. REUTERS/CDC/Handout via Reuters (UNITED STATES - Tags: HEALTH DISASTER SOCIETY) FOR EDITORIAL USE ONLY. NOT FOR SALE FOR MARKETING OR ADVERTISING CAMPAIGNS. THIS IMAGE HAS BEEN SUPPLIED BY A THIRD PARTY. IT IS DISTRIBUTED, EXACTLY AS RECEIVED BY REUTERS, AS A SERVICE TO CLIENTS
HIDE CAPTION
SHOW CAPTION
of
SEE ALL
BACK TO SLIDE

Side note: the history of medicine is full of ethically dubious experiments, many of them performed on the disenfranchised and carried out by, let’s be real, rich powerful white dudes, that we choose ignore because society as a whole saw a benefit. It’s only some consolation that in this particular case, it all turned out okay: the little boy didn’t get sick, because his body had become immune to the smallpox virus. Thus a vaccine was born, albeit a much more pus-filled one than the shots we have today.

It’s a nice story, and we even get the name “vaccine” from the cow-based method Jenner used. But it’s a little off on one crucial detail: the virus probably didn’t come from a cow. Jenner did collect pus from a cow, so it might seem safe to assume that the cowpox virus provided that initial smallpox immunity. But with modern genomic sequencing and access to some of the first vaccines, we can tell that the virus within them isn’t most closely related to cowpox. It’s a lot closer to horsepox.

This has been a going theory within the scientific community for some time, and has just recently gotten a boost from another sequencing. It that showed that a 1902 vaccine contained a virus with a 99.7 percent similarity to modern horsepox. The virologists published their findings in a letter in the New England Journal of Medicine on Wednesday.

This is actually all in line with what Jenner himself thought. He noted that he believed the best pus to vaccinate people with came originally from horses, which infected cows, which in turn could be used on people. He even took samples directly from horsepox sores on multiple occasions.

Most of the confusion here stems from the fact that the virus inside smallpox vaccines isn’t found in nature. Vaccinia virus seems to only exist in laboratories, not in any biological hosts. It’s not quite horsepox, and it’s definitely not cowpox, but it’s also not variola virus, which is what causes smallpox in humans. Vaccinia is just close enough to variola that it provides immunity without killing the patient. But not all vaccines contain the same strain of vaccinia.

Modern vaccines are carefully crafted to be as identical as possible. Back in Jenner’s day, and for many years after, the viruses used were passed from host to host and used to create vaccines at various points. This journey created excellent conditions for evolutionary selection, so the vaccinia virus changed a lot—and doctors ended up with many different strains.

So we know that this one vaccine, the Mulford 1902 sample, came from horsepox. We just don’t know exactly where in the world that sample came from, or how many other vaccines originated in horses. More sequencing will help fill in some of the knowledge gaps, but without samples from the very first inoculations, some of this story may be lost to the morally murky history books.

Read Full Story