Early smallpox vaccine is tested

Early smallpox vaccine is tested

Edward Jenner, an English country doctor from Gloucestershire, administers the world’s first vaccination as a preventive treatment for smallpox, a disease that had killed millions of people over the centuries.

While still a medical student, Jenner noticed that milkmaids who had contracted a disease called cowpox, which caused blistering on cow’s udders, did not catch smallpox. Unlike smallpox, which caused severe skin eruptions and dangerous fevers in humans, cowpox led to few ill symptoms in these women.

READ MORE: How an Enslaved African Man Helped Save Generations from Smallpox

On May 14, 1796, Jenner took fluid from a cowpox blister and scratched it into the skin of James Phipps, an eight-year-old boy. A single blister rose up on the spot, but James soon recovered. On July 1, Jenner inoculated the boy again, this time with smallpox matter, and no disease developed. The vaccine was a success. Doctors all over Europe soon adopted Jenner’s innovative technique, leading to a drastic decline in new sufferers of the devastating disease.

In the 19th and 20th centuries, scientists following Jenner’s model developed new vaccines to fight numerous deadly diseases, including polio, whooping cough, measles, tetanus, yellow fever, typhus, and hepatitis B and many others. More sophisticated smallpox vaccines were also developed and by 1970 international vaccination programs, such as those undertaken by the World Health Organization, had eliminated smallpox worldwide.

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Four Times in History Vaccines Failed (Lessons for a Coronavirus Vaccine?)

According to the Centers for Disease Control and Prevention, since 2011, vaccines have averted 23.3 million deaths from disease worldwide. Such numbers surely deserve praise, but there certainly have been several hiccups along the way—mistakes that scientists have surely used as a learning experience.

From biotech and pharmaceutical companies like Moderna to Pfizer, the race is indeed heating up for a COVID-19 vaccine.

But while many would love to have access to it right now, scientists across the world are making sure that a potential vaccine is both effective and safe—with a strong emphasis on the latter.

According to the Centers for Disease Control and Prevention, since 2011, vaccines have averted 23.3 million deaths from disease worldwide. Such numbers surely deserve praise, but there certainly have been several hiccups along the way—mistakes that scientists have surely used as a learning experience.

With that in mind, here are four instances in which vaccines failed the public big-time.

In the 1955 Cutter Incident, some batches of polio vaccine given to the public contained live poliovirus—even though they had passed the required safety testing. More than 250 cases of polio were attributed to vaccines produced by one company, Cutter Laboratories. The mistake resulted in many cases of paralysis, and the vaccine was recalled as soon as new cases of polio were detected.

The Cutter Incident became a defining moment in the history of vaccine manufacturing and led to the creation of a more robust system of regulating future vaccines.

In 2017, the Philippines stopped a school-based dengue fever vaccination program after reports of complications and several deaths linked to the product called Dengvaxia. The French manufacturer, Sanofi Pasteur, later stated that the vaccine posed a risk to those without prior infection from one of the disease’s four stereotypes. The result was that it actually increased the risk that a child would contract a more severe form of the disease.

Next on the list is the widespread vaccination against the childhood disease measles. In the early 1960s, thousands of children received a particular inactivated vaccine, so if they were exposed to the actual measles virus, they developed atypical measles. This was characterized by high fever, severe abdominal pain and lung inflammation and often required hospitalization. That particular vaccine was eventually withdrawn.

The final case deals with the vaccination attempt of the respiratory syncytial virus (RSV). Children treated with one type of vaccine in the 1960s developed an enhanced form of the disease, often suffering from high fever, bronchopneumonia and wheezing. Dozens ended up being hospitalized and two died. There still is no vaccine to prevent RSV infection, but scientists are working hard to develop one, according to the CDC.

Ethen Kim Lieser is a Minneapolis-based Science and Tech Editor who has held posts at Google, The Korea Herald, Lincoln Journal Star, AsianWeek and Arirang TV. Follow or contact him on LinkedIn.

A brief history of vaccines from smallpox to COVID-19

The following is a brief history of vaccines starting with the first known vaccine (smallpox) to the vaccines that are being used now for COVID-19.

1796 — Smallpox vaccine. Edward Jenner used cowpox material to create immunity to smallpox. It was the first vaccine to be developed against a contagious disease. Mortality during outbreaks was as high as 35% before the vaccine. Smallpox is estimated to have killed 300 to 500 million people before 1900. From 1958 to 1977, the World Health Organization conducted a global vaccination campaign that eradicated smallpox. Although the vaccine is no longer given to the public, the vaccine is kept on hand to guard against bioterrorism and biological warfare.

1885 — Rabies vaccine. Louis Pasteur and Emile Roux developed the vaccine. 9-year-old Joseph Meister was the first to receive it after been mauled by a rabid dog. The rabies vaccine is considered very expensive and three doses can cost over $1,000 in the U.S.

1926 — Pertussis (whooping cough) vaccine. Developed by pediatrician Leila Denmark. Controversial during the 1970s and 80s because many believed the vaccine could cause permanent brain injury in rare cases. The rate of risk was very low though and doctors recommended it because of the overwhelming health benefit. Pertussis would kill thousands of Americans each year before the vaccine was introduced.

1926 — Diphtheria vaccine. Recommended by World Health Organization since 1974. Usage of the vaccine resulted in more than a 90% decrease in the number of cases globally between 1980 and 2000. Considered very safe.

1938 — Tetanus vaccine. Deaths from tetanus in newborns decreased from 787,000 in 1988 to 58,000 in 2010 and 34,000 in 2015. Before the vaccine, there were about 550 cases per year in the U.S. There are about 30 cases per year now.

** Vaccines for pertussis, diphtheria and tetanus combined in 1948 and became the DTP vaccine

1940s — Influenza vaccine. Also known as flu shots. New versions are developed twice a year. WHO and CDC recommend yearly vaccination for nearly all people over the age of six months. The Spanish flu epidemic in 1918 killed anywhere between 20 and 50 million people, which made it one of the deadliest pandemics in human history. The death rate is high among infants who catch influenza. During the 2017-18 flu season the CDC believes 85% of the children who died most likely had not been vaccinated. There are usually millions of infections and thousands of death each year during flu season. In the 2019-2020 flu season, between 24,000 and 62,000 people lost their lives because of the flu.

1950 — Polio vaccine. The first successful demonstration of a polio vaccine was by Hilary Koprowski. Another vaccine was developed by Jonas Salk in 1955. Albin Sabin also developed a vaccine in 1961. During the early 1950s, there were about 25,00 cases per year in the U.S. with around 3,000 deaths. The development of two vaccines led to the first modern mass inoculations. However, in April 1955, the surgeon general began receiving reports of patients who contracted paralytic polio about a week after being vaccinated with the Salk polio vaccine. An investigation unveiled that the vaccine caused 40,000 cases of polio and killed 10 people. This led to a drop in public confidence in the polio vaccine. The WHO led a global effort to eradicate polio in 1988 and by 1994, polio was eliminated in the Americas. By 2000, it had been eliminated in 36 Western Pacific countries, including China and Australia. Europe was declared polio-free in 2002. There were only 3 countries as of 2017 with polio cases — Pakistan, Afghanistan, and Nigeria. Those cases are a result of the people in those countries refusing to be vaccinated.

1963 — Measles vaccine. The first version was developed in 1963. The second version, which became the one used in the U.S., was created in 1968. Before the vaccine, there were three to four million cases per year with hundreds of deaths. By the 1980s, there were only a few thousand per year. An outbreak in 1990 led to a renewed push for vaccination. No more than 220 cases were reported between 1997 and 2013. Within the first 20 years, the vaccine is estimated to have prevented 52 million cases, 17,400 cases of intellectual disability, and 5.200 deaths.

1967 — Mumps vaccine. Initially not considered a serious public health issue. Men began suffering from debilitating testicular inflammation, which became an issue during wartime. During World War II, the U.S. targeted mumps for scientific research.

1969 — Rubella vaccine. Epidemic in Europe between 1962 and 1963 and the United States between 1964 and 1965. Countries with high rates of immunizations no longer see cases of rubella. However, the vaccination level must remain at 80% to keep rubella at bay. As of 2009, more than 130 countries have included it in their routine vaccinations.

** The measles, mumps and rubella vaccines were combined into the MMR vaccine by Dr. Maurice Hilleman in 1971

1977 — Haemophilus influenzae type B vaccine, also known as Hib vaccine. In countries that include it as a routine vaccine, rates of severe infections have decreased more than 90%. Recommended by both the WHO and the CDC. Two or three doses should be given before six months of age. As of 2013, 184 countries include it in their routine vaccinations.

1980s — Pneumococcal vaccine. In the year 2000, doctors recommended all children ages 2-23 months and at-risk children 24-59 months receive the vaccine. In February 2010, another vaccine was introduced that provided even more protection from various types of pneumococcal. The pneumococcal polysaccharide vaccine gives at least 85% protection to those under age 55 for five years or longer.

1981 — Hepatitis B vaccine. Research began in 1963 by American physician/geneticist Baruch Blumberg. In 1976, Blumberg won the Nobel Prize in Physiology or Medicine for his work on the hepatitis B vaccine. However, the first field trials didn’t happen until the late 1970s. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. The vaccine is recommended for anyone with poor immune functions and healthcare workers. In healthy people, routine immunizations result in more than 95% of people being protected.

1981 — Chickenpox vaccine. World Health Organization recommends countries keep more than 80% of the population vaccinated to prevent outbreaks. As of 2017, 33 countries recommended all non-medically exempt children receive the vaccine. Before the introduction of the vaccine in the U.S. in 1995, there were around four million cases per year, mostly children. Between 11,000 and 13,000 were hospitalized and 100 to 150 children died each year as a result. 10 years after it was introduced, the CDC reported a 90% drop in chickenpox cases.

2000 — Hepatitis A vaccine. Effective in around 95% of cases and lasts for 15 years to life. Two doses recommended before age 2. WHO recommends universal vaccination in areas where the disease is moderately common.

2006 — Rotavirus vaccine. It is on the WHO's List of Essential Medicines. A 2009 review estimated the vaccine would prevent about 45% of deaths due to rotavirus gastroenteritis, or about 228,000 deaths annually worldwide. More than 100 countries offer the vaccine. The vaccine was first developed in 1998. However, it was withdrawn from the market in 1999 after it was discovered it contributed to the risk of bowel obstruction in one out of every 12,000 vaccinated infants.

2006 — Human papillomavirus vaccine or HPV. Recommended by the WHO as part of routine vaccinations in all countries. Requires two to three doses depending on the person’s age and immune status. As of 2017, 71 countries include it in routine vaccinations, at least for girls.

2021 -- COVID-19 vaccine. Three vaccines have been developed in response to a new, deadly version of the coronavirus (SARS‑CoV‑2). Development began in 2020 in response to the global pandemic. There are currently three vaccines that are being administered — Moderna, Pfizer-BioNTech and Johnson & Johnson. As of April 2021, there are 14 vaccines that have been authorized by at least one national regulatory authority for public use. As of May 1, more than 1.15 billion doses have been administered worldwide. In just over a year, there have been 156,326,916 cases diagnosed with 3,260,983 deaths.

More vaccines followed in the 1960s — measles, mumps and rubella

In 1963, the measles vaccine was developed, and by the late 1960s, vaccines were also available to protect against mumps (1967) and rubella (1969). These three vaccines were combined into the MMR vaccine by Dr. Maurice Hilleman in 1971.

Late 1960s | Recommended Vaccines

Polio (OPV)
* Given in combination as DTP


Sixty years ago, a monstrous hepatitis experiment was performed on mentally disabled children at Willowbrook State School that raises serious ethical questions about vaccine challenge trials for Covid-19.

N ina Galen was ten years old when she became part of one of the most controversial human experiments in American history. Her mother, Diana McCourt, was looking for an institution that could care for her severely autistic daughter. “I was just desperate,” McCourt says now, more than 50 years later. “I think I was having a breakdown because I was just trying to take care of everything.”

McCourt finally settled on Willowbrook State School, a home for severely developmentally challenged children and adults on Staten Island, New York. In order to get Nina a spot at the overcrowded facility, however, she had to make a Faustian bargain—consenting to allow her daughter to be part of a quest to find a vaccine for hepatitis. "I had no choice,” McCourt says, “I had tried so many different places and so many arrangements, and they didn't work out, so I went along with it."

Nina became one of more than 50 mentally disabled children, ages 5 to 10, under the care of Dr. Saul Krugman, a respected pediatrician from New York who wanted to determine if there were multiple strains of hepatitis, and whether a vaccine could be created to protect against the disease. Krugman and his partner, Dr. Joan Giles, used the Willowbrook residents to test a preliminary vaccine for this disease that had killed millions worldwide. From 1955 to 1970, the children were injected with the virus itself or made to drink chocolate milk mixed with feces from other infected children in order to study their immunity.

For much of human history, hepatitis caused some of the deadliest outbreaks in the world. The symptoms, including fever, liver damage and yellow skin, were written about by Hippocrates in the fifth century B.C.E. While we now know that there are multiple viruses (most famously, hepatitis A, B and C), in the first half of the 20th century researchers only knew of one form of the disease, which was then called epidemic jaundice.

Finding a vaccine became particularly important for the United States during World War II, when hepatitis outbreaks affected more than 50,000 American troops. To fight this disease and others, the Surgeon General’s office established the Armed Forces Epidemiological Board.

School for Scandal: In addition to conducting hepatitis experiments, Willowbrook's staff physically abused residents.

In the early 1950s, Dr. Krugman, a former flight surgeon for the U.S. Army Air Corps, went to the Epidemiological Board with a proposition: he wanted to create a vaccine for hepatitis, and knew the perfect place where he could do his research. Willowbrook was overcrowded, already rampant with disease, and at the time it wasn’t uncommon to test vaccines on children.

The idea goes back to the grandfather of vaccines himself, Edward Jenner, who used an 8-year-old boy as the first test subject of his groundbreaking smallpox vaccine in the late 18th century. The Willowbrook hepatitis experiments would be vaccine challenge experiments, so-called because the body is intentionally “challenged” with a direct exposure to the virus to see if a particular treatment prevents someone from getting the disease.

“He believed he was helping the children at this school deal with the epidemic,” says Dr. Krugman’s son Richard, a pediatrician at the Children’s Hospital Colorado and former head of the U.S. Advisory Board on Child Abuse and Neglect. “He certainly thought he was making a contribution to infectious disease research.”

Although there’s little doubt that Dr. Krugman accelerated the discovery of a hepatitis vaccine, the ethics of his experiment have resurfaced as vaccine challenge trials are being debated for Covid-19. Many politicians, medical ethicists and scientists have come out in favor of the idea, which would include giving healthy volunteers a dose of an unproven vaccine, and then deliberately exposing them to Covid-19 to see if it offers protection against the virus.

While the vaccine challenge trials would be done with healthy adult volunteers, the Covid-19 vaccine challenge trial and the Willowbrook hepatitis experiments beg the same question: Is it really necessary—or right—to risk the health of a few for the benefit of many?

S aul Krugman arrived at the bucolic Willowbrook campus in 1955. Nestled on almost 400 acres on Staten Island, the large, U-shaped brick buildings were surrounded by a lush green forest. A painted yellow and blue carousel sat at the entrance to the grounds, and first-time visitors described it as enchanting, like a summer camp. Inside, however, Willowbrook was a nightmare.

Do No Harm: RFK described Willowbrook's conditions as "less comfortable and cheerful than the cages in which we put animals in a zoo."

The school opened in 1947 and was built to hold 4,000 residents, but for years that number was over 6,000. Disease and neglect were everywhere, and multiple residents died from untreated illness and abuse. In 1965, Robert F. Kennedy, then a New York Senator, made an unannounced visit to Willowbrook and left appalled. “There are no civil liberties for those put in the cells of Willowbrook,” he later testified before Congress, calling the institution a “snake pit.”

When Dr. Krugman and Dr. Giles began the Willowbrook hepatitis experiments, they used the conditions of Willowbrook to their advantage for recruiting new families. Despite its well-documented horrors, Willowbrook was still one of the only options for children with severe disabilities, and there was a long waitlist. Dr. Krugman offered several parents, including Nina Galen’s, the ability to jump the line and have their children put in the newer, cleaner research wards with more staff—if they joined the experiments. “I did feel coerced,” McCourt says, “I felt like I was denied help unless I took this [opportunity].”

Krugman also told parents that since hepatitis was already prevalent at Willowbrook, their children may as well have the chance for a vaccine. McCourt remembers being told her daughter could get an “antidote” to hepatitis if she joined the experiment. When she asked why the hepatitis studies couldn’t be done on primates, she was told that using animals would be “too expensive.”

Despite understanding the optics of infecting mentally disabled children with a potentially deadly disease, Dr. Krugman felt the risk was worth the reward. “The decision to feed hepatitis virus to patients at Willowbrook was not undertaken lightly,” he wrote in a 1958 paper published in the New England Journal of Medicine. He noted that the strain of hepatitis in Willowbrook wasn’t very severe, that many of the children would get infected anyway, and that any knowledge gained from the experiment would in fact help other Willowbrook residents. He also emphasized that the study was sanctioned by the New York State Department of Mental Hygiene, and the Armed Forces Epidemiological Board of the Surgeon General’s Office.

“I don’t think you’re ever justified to inoculate a child with an infectious virus that might kill them,” says pediatrician Paul Offit.

Some of Dr. Krugman’s trials built on previous research that giving children antibodies from patients who had recovered from hepatitis could prevent new infections. (A similar concept, using convalescent plasma of recovered Covid-19 patients to treat sick patients, is being explored today.)

The experiments also involved infecting healthy children with the virus through the chocolate milk concoction. The doctors eventually learned how much it took for the children to show symptoms of hepatitis, allowed them to recover, and then gave them the virus all over again. These experiments were done to test if someone who had recovered from hepatitis would remain immune or if they could be reinfected again.

As each trial concluded, Dr. Krugman published the results in prominent medical journals including the New England Journal of Medicine, the Lancet, and the Journal of the American Medical Association. From the time of the first publication, the experiments were controversial within the medical community. In 1966, renowned medical ethicist Henry K. Beecher published an article titled, “Ethics and Clinical Research,” which listed Willowbrook as an example of an unethical clinical experiment and concluded that “there is no right to risk an injury to one person for the benefit of others.”

Five years later, the editorial board of the Lancet apologized for publishing Dr. Krugman’s studies without greater skepticism. “The Willowbrook experiments have always carried a hope that hepatitis might one day be prevented,” the editors wrote, “but that could not justify the giving of infected material to children who would not directly benefit.” A year later, Krugman had to ward off protesters at a medical conference in Atlantic City.

Bad Form: Willowbrook often accepted children in exchange for parental permission to conduct hepatitis testing.

The College of Staten Island Archives and Special Collections

“I think he got a lot of flak for it from people who didn’t understand the context or the reality of the institution,” Richard Krugman says. “It certainly got caught up in the politics of the day.”

But Dr. Krugman had as many fans as he did detractors. New York State Senator Seymour Thaler, originally a critic of the hepatitis experiments, later said that Krugman had “done a magnificent thing.” Dr. Franz Ingelfinger, a former editor of the New England Journal of Medicine, also supported the research. “How much better to have a patient with hepatitis, accidentally or deliberately acquired, under the guidance of a Krugman than under the care of a zealot,” he wrote.

In addition to discovering the hepatitis A and B strains, Dr. Krugman “certainly did speed up the development of a hepatitis B vaccine,” says Paul Offit, a pediatrician and director of the Vaccine Education Center at The Children's Hospital of Philadelphia. But, Offit adds, “I don’t think you’re ever justified to inoculate a child with an infectious virus that might kill them.”

As members of the medical community protested Krugman’s experiments, a greater force was mobilizing to close down Willowbrook for good.

In 1972, Geraldo Rivera, then a local television reporter in New York, snuck into the grounds of the school and broadcast the inhumane conditions of Willowbrook. He had been tipped off about the residents’ living conditions by Michael Wilkins, a doctor at the school who was not involved in the hepatitis trials.

“It’s almost 50 years and speaking about it still makes me cry,” says Rivera, now a roaming correspondent-at-large at Fox News. “The conditions were so horrible.” Rivera remembers seeing children naked, smeared in their own feces and hitting their heads against the wall. “I would imagine that the situation I had was similar to the GIs that freed the concentration camps.”

The Last Great Disgrace: As a result of Geraldo Rivera's 1972 investigation of Willowbrook, a federal law was passed to protect people in institutions.

At roughly the same time, a whistleblower exposed the infamous Tuskegee syphilis study in which researchers deliberately let hundreds of Black men go untreated and several died from the disease, even though there was a known cure. Willowbrook was one in a long line of human experimentations on children, prison inmates, people in mental health facilities, and minority communities, and Tuskegee was the tipping point.

Dr. Krugman, however, was rewarded for his work at Willowbrook. That year, he became president of the American Pediatric Society.

In 1974, the National Research Act was passed in an effort to create regulations that protected subjects in human research trials. One measure it implemented was the creation of an ethics task force, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. "The National Commission might never have come into being were it not for Willowbrook and Tuskegee and several other instances," says Karen Lebacqz, one of the original members of the commission.

By 1979 the commission had published the Belmont Report, a comprehensive guideline of basic ethical principles that guide modern clinical trials. The National Research Act also established the practice of Institutional Review Boards (IRBs), independent committees that must take time to review the ethical aspects of human clinical trials to this day.

A side from potential ethical dilemmas, today’s coronavirus vaccine challenge trials have something else in common with the Willowbrook hepatitis experiments: they may not even be necessary. While Dr. Krugman is credited for speeding up the development of a hepatitis vaccine, other researchers were not far behind. In the late 1960s, Dr. Baruch Blumberg independently discovered the hepatitis B virus, and together with Dr. Irving Millman submitted the first patent for a hepatitis vaccine in 1969. Blumberg did all his research by taking blood samples and testing the liver functions on children and adults who were already infected, and his work earned Blumberg a Nobel Prize for Medicine.

"Whenever people are desperate,” ethics professor Karen Lebacqz says, “they always want to relax ethical standards."

Similarly, even if a challenge trial for coronavirus gets approved, there’s no guarantee that it will lead to a faster vaccine development. The U.S. government’s initiative to develop a coronavirus vaccine may be called “Operation Warp Speed,” but Christine Grady, Chief of the Department of Bioethics at the National Institutes of Health Clinical Center, says that a lot of time and thought have to be put into properly designing a trial.

“Whether or not doing a challenge trial would even speed up the trial is a question that is not exactly clear,” says Grady, who is married to Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. Paul Offit agrees. “You have to have the right dose. And to get the right dose, you have to have these mini-challenge trials,” he says. “I don’t think it’s going to happen.”

Karen Lebacqz, one of the original Belmont Report authors, also has concerns about the accelerated Covid-19 vaccine protocols. "Whenever people are desperate,” she says, “they always want to relax ethical standards."

Saul Krugman’s controversial experiments at Willowbrook were only the beginning of his illustrious career. He later became the head of pediatrics at New York University School of Medicine, was elected to the National Academy of Sciences, authored a classic textbook of pediatric infectious diseases, received the prestigious Lasker Award, and helped to develop the first rubella and measles vaccines.

He defended the Willowbrook trials his whole life, writing in 1986, “I am as convinced today as I was at that time that our studies were ethical and justifiable.” Krugman passed away in 1995, and his obituary in the New York Times has only a small mention of his experiments at Willowbrook.

To this day, while many modern-day ethicists use the Willowbrook studies as an example of unjust human experimentation, there are always second opinions. “It’s complicated,” Grady says. To her knowledge, “Krugman’s first goal was to understand the disease. but I think there are some things about it that certainly don’t look good and would be hard to get approval today.”

Mike Wilkins, the Willowbrook doctor who helped organize parents to shut down the institution in 1987, also doesn’t think that the experiments are black-and-white. "I'm not wanting to crucify Krugman,” he says now, “hepatitis B, for God sakes, is an international disease that there's now a vaccine for. But let's never ever do that again."

Relative risks and benefits

Do the benefits of the smallpox vaccine outweigh its risks?

No. Smallpox infections no longer occur in the world. Currently, the risks of the vaccine clearly outweigh its benefits. However, if smallpox infections were to occur again in the United States, the relationship between vaccine risks and benefits would change dramatically.

Disease risks

  • Although this disease is deadly, no cases occur anywhere in the world, so the risk today is zero. Because there is no risk of disease, this is a situation in which the use of a vaccine does NOT outweigh the risks of disease.

Vaccine risks

  • Inflammation of heart or tissues surrounding heart
  • Infection of the inoculation site
  • Inadvertent inoculation of another site or other people
  • Swelling of brain or spinal cord
  • Severe allergic reaction
  • Rarely death

Rumors and Fears

There was a widespread belief that vaccination was responsible for a variety of ailments, from diarrhea to syphilis. In 1892, Edward Joshua Edwardes wrote a report on smallpox in England and the need for compulsory vaccination. In this report, he referred to the rumors spread by these &lsquoignorant layman&rsquo:

A vast amount of nonsense is talked on the subject of the risks of vaccination. Nearly all young children, are vaccinated nearly all suffer from some ailment or other in the course of the next few months or years, but it is perfectly unreasonable to attribute any such ailment to vaccination merely because vaccination is antecedent.

We might equally attribute street accidents to previous vaccination! Diarrhea was ascribed to vaccination at one time!

Edwardes writes about the dangerous ideas of Dr. Creighton, who &ldquohas his own theory about syphilis after vaccination&rdquo, and &ldquodoes not even touch upon the protective influence against small-pox.&rdquo

1803: Smallpox

In 1796, once the scientist Edward Jenner discovered that people infected with cowpox became immune to smallpox, doctors went from town to town in England, deliberately spreading cowpox by scratching infected material into people’s arms.

The rollout worked on a local level, but how could it be distributed to people in faraway places, like in the Americas, where smallpox had devastated populations? In 1803, the Spanish government put 22 orphans on a ship to its territories in South America. The lead doctor, Francisco Xavier de Balmis, and his team injected cowpox into two of the boys, and then, once cowpox sores developed, took material from the sores and scratched it into the arms of two more boys.

By the time the team arrived in the Americas, only one boy was still infected, but that was enough. Vaccine distribution in the Spanish territories was unsystematic, but eventually, members of the Spanish expedition worked with local political, religious and medical authorities to establish vaccination clinics. More than 100,000 people in Mexico received free vaccinations by 1805, according to a journal article, “The World’s First Immunization Campaign,” in the Bulletin of the History of Medicine.

Great reads: POX — a history of vaccine resistance

To revist this article, visit My Profile, then View saved stories.

To revist this article, visit My Profile, then View saved stories.

A swiftly moving contagious disease threatens children. The government urges parents to vaccinate. But parents are suspicious: They believe the vaccine has unpredictable side-effects and they distrust the government's motives. When persuasion fails, coercion takes its place. The government demands vaccination — and a showdown looms.

In many aspects, that vignette sounds like today, when pertussis and measles are spreading through unvaccinated children. But what it actually describes is a lost episode of history: not 2010, but 1900, when smallpox spread across the country and life-saving universal — and compulsory — vaccination was imposed on the US population.

In a new book, POX: An American History (The Penguin Press, $27.95) historian Michael Willrich describes what happened next.

I wrote a history of US public health, and so I thought I knew something about vaccines, but I had never heard this story. I asked Willrich, an associate professor at Brandeis University, to answer some questions about it.

Among all the vaccine-preventable diseases, smallpox was uniquely deadly — and so I always assumed there was wide agreement over eliminating it. But POX tells the story of a broad, and surprisingly little-known, resistance movement against smallpox vaccination. Tell us that history briefly.

Today’s heated controversies over childhood immunization pale in comparison to the vaccine war that took place in the United States at the turn of the twentieth century – at the height of a nationwide wave of smallpox epidemics. Smallpox killed 730 people in New York, 400 in Philadelphia, 270 in Boston, and 500 in New Orleans (to name just a few of the most serious urban outbreaks). A new, milder form of the virus spread across the entire country, infecting hundreds of thousands of people, wreaking havoc on local economies, and putting the country’s emerging public health departments to the test. Struggling to control smallpox, local, state, and federal health officials enforced vaccination aggressively – all too often with brute force – in factories, work camps, crowded tenement districts, aboard steamships and trains, and in the public schools.

Smallpox vaccination 110 years ago was a risky and invasive procedure, with virtually no government controls on vaccine quality and safety. Many Americans regarded compulsory vaccination as a threat to their health and an invasion of their individual rights. They formed antivaccination leagues, demanded state laws to abolish compulsion, challenged compulsory vaccination in the courts, rioted, forged vaccination certificates, staged school boycotts, and hid sick children from the authorities to prevent them from being hauled off to the local “pesthouse.” POX tells the story of this forgotten civil liberties struggle and its legacy for American society and law.

__The epidemic you focus on in POX leads to the government decreeing "universal compulsory vaccination" against smallpox — and to the spread of resistance that is both organized and individual. Who wins, if anyone does? __

In a sense, both sides win. The struggle culminates in a series of major court decisions that put public health power on a firmer constitutional foundation while also recognizing important safeguards for individual liberties. For example, even as the courts upheld the collective right of a state government or local health board to compel vaccination in order to protect the entire population during an epidemic, the courts also held that such measures could not target particular racial minorities, that health officials could not lawfully use physical force to vaccinate unwilling individuals, and that individuals whose medical condition made vaccine particularly dangerous for them had the right to seek an exemption.

Significantly, in 1902 Congress responded to the crisis of public confidence in vaccine by establishing the first federal system of licensing and regulation of vaccines, antitoxins, and other commercial “biologics.” That law made vaccines safer and helped create a measure of confidence in vaccines. It was a victory for all of us.

__You argue that the vaccine resisters of the 1900s had a point: The vaccines in use then had significant side effects, and the measures used to contain spread infringed on civil liberties. Since then, vaccines have been refined, and legal vaccine exemptions are abundant. So does the vaccine dissent of a century ago have relevance today? __

Absolutely. The story resonates with many contemporary issues – from concerns about bioterrorism to childhood immunization to the debate over “Obamacare.” I think the single biggest lesson from my historical story may be that the public health community (and I include science and medicine journalists) must always strive to present the case for childhood immunization with candor and a measure of respect for parents’ fears.

We have to remember that most parents have the best interests of their children at heart. Vaccines still seem mysterious and unnatural to many people. And the best way to reach skeptics is through reason and persuasion, rather than condescension and coercion. This was the hard-bought lesson of the turn-of-the-century vaccine war.

__The vaccine-resistance movement of the 1900s was driven in part by colorful personalities, including a Lutheran minister who was a movement leader. That was 100 years before social media and 40 years before television. How did their influence spread so widely, and can you draw parallels to today? __

The organized antivaccinationists were part of a colorful transatlantic movement with roots in a broader tradition of libertarian radicalism that claimed the mantle of the nineteenth-century antislavery movement. (British antivaccinationists were so successful that Parliament in 1898 created a special exemption in the vaccination law for “conscientious objectors” – the first political use of that term.) They produced a fascinating literature of books, pamphlets, and alternative medical journals. They turned local school board elections into referenda on vaccination policy.

And a lot of concern about vaccines simply spread by word of mouth, particularly among working-class communities. Public health officials tried to dismiss antivaccinationists as a bunch of cranks and loners. But their concerns about individual liberty in an era of rising state intervention and corporate power resonated with many working-class and middle-class people.

Today’s opposition to vaccinationists seems to me both much more narrow – it’s almost entirely a question of parents and young children – and far more technologically advantaged. The Internet is, of course, an unbelievable force for the spread of information and misinformation about vaccines. The British medical researcher Andrew Wakefield’s infamous 1998 paper, suggesting a possible link between the MMR vaccine and autism has been thoroughly debunked. But every time I write or say something positive about vaccination, I receive angry e-mails filled with web links to Wakefield’s work. It’s all still out there.

__There is an increasing amount of evidence that current vaccine resistance is leading to the resurgence of once-quelled preventable diseases, such as pertussis in California and measles in Minnesota. How would you balance this modern conflict between personal liberty and public health? Are you concerned at all that your book will be interpreted as supporting vaccine resistance? __

In POX, I certainly give both sides their due. And I argue that the historical “vaccination question” posed a serious question of civil liberties. American judges of the day certainly thought it did. And I think today’s antivaccine activists might be interested to learn more about the history of their movement. On the other hand, I’m very much on the record in support of childhood immunizations today. My sense is that the balance of personal liberty and public health is much more carefully drawn today that it was at the dawn of the twentieth century. In fact, I think we are all the beneficiaries of that earlier civil liberties struggle.

Excerpt: 'Pox: An American History'

Pox: An American HistoryBy Michael WillrichHardcover, 400 pagesPenguin Press List Price: $27.95

Manhattan's West Sixty-ninth Street no longer runs from West End Avenue to the old New York Central Railroad tracks at the Hudson River's edge. In the space now occupied by aging high-rise condominium towers and their long shadows, there once stood a low-slung street of tenements and houses. At the turn of the twentieth century, it was said to be the most thickly populated block in the most thickly populated city in the United States of America. Someone called it "All Nations Block," and, being a pretty fair description of the place, for a while the name stuck.

A brisk walk from the fashionable hotels of Central Park West, All Nations Block was a rough world of day laborers, bricklayers, blacksmiths, stonemasons, elevator runners, waiters, janitors, domestic servants, bootblacks, tailors, seamstresses, the odd barber or grocer, and, far outnumbering them all, children. Each morning, the children streamed east to Public School No. 94 at Amsterdam Avenue or to the crowded kindergarten run by the Riverside Association at 259 West Sixty-ninth Street. That same foot-worn building housed the charitable association's public baths in any given week, four hundred men or more paid a nickel for a towel, a piece of soap, and a shower that had to last. The tenement dwellers of All Nations Block did not choose their neighbors. It was the kind of place where an itinerant black minstrel actor, feeling feverish and far from his southern home, could find a bed for a few nights, in a great warren of rooms whose other occupants were Italian, Irish, Jewish, German, Swedish, Austrian, African American, or simply, so they said, "white."

The men of the West Sixty-eighth Street police station knew the block and its ways well. The policemen came when the neighbors brawled, when jewelry went missing in an apartment by the park, or when the Irish boys of the All Nations Gang got too rough with the Chinese laundryman on West End Avenue. The police came once again on the night of November 28. A forlorn and drunken stonemason named Michael Healy, imagining himself to be under attack in his room ("They're after me," he had shouted, "See those black men!"), had hurled himself through a fourth-floor window and fell, in a cascade of glass, to, or rather through, the ground below. The Irishman made a two-by-two-foot hole in the surface, breaking through to some long-forgotten trench near the building's cellar. A neighborhood boy ran to the Church of the Blessed Sacrament on West Seventieth Street and summoned a priest. When the priest arrived, he crawled right through the hole and into the trench, which was already crowded with police, an ambulance surgeon, and Healy's broken but still breathing body. Before this subterranean congregation, the priest administered last rites. That was the way things went on All Nations Block. It was the night before Thanksgiving, the first of the new century.

New Yorkers of a certain age would remember that Thanksgiving as the day the smallpox struck the West Side. The outbreak had in fact started quietly a few days earlier, on All Nations Block. The city health officers found the children first: twelve-year-old Madeline Lyon, on Tuesday, and on Wednesday, a child just across the street, identified only as a "white boy four years old." For the health officers to diagnose the cases with any confidence, the children must have been suffering for days, with raging fevers, headaches, severe back pain, and, likely, vomiting, followed by the distinctive eruption of pocks on their faces and bodies. Once the rash appeared and the lesions began their two-week metamorphosis, from flat red spots to hard, shotlike bumps to fat pustules to scabs, the patients were highly contagious. The health officers removed the children, stripped their rooms of bedding and clothing, and disinfected the premises.

The health department followed the same procedure with the five other cases that were reported elsewhere in Manhattan within hours of the Lyon case. One was a white domestic servant named Mary Holmes, who worked in an affluent apartment house on West Seventy-sixth Street. The other four were black, evidently from the neighborhood of the West Forties. They were Adeffa Warren, Lizzie Hooker, Susan Crowley, and Crowley's newborn daughter — these last two had been removed in haste from the maternity ward at Bellevue Hospital. Through interviews, health officers had established that the four black patients had come into contact with an unnamed infected "negress," who remained at large. How any of these patients might have been connected to the children on West Sixty-ninth Street, about a mile and a half uptown, remained uncertain. But the authorities were working on the assumption that the outbreak started on All Nations Block.

The officers of the internationally renowned New York City Health Department, medical men given broad powers to police and protect the public health in one of the world's most powerful centers of capital, were not easily shaken by the odd case of smallpox among the wage earners. Now and then an infected passenger got past the U.S. government medical inspectors at Ellis Island or crossed into the city on one of its many railroad tracks, waterways, roads, footpaths, or bridges. Most New Yorkers had undergone vaccination for smallpox at one time or another — on board a steamship crossing the Atlantic, in the public schools, in the workplaces, in the city jails and asylums, or, if they possessed the means, in their own homes under the steady hand of a trusted family physician. When an isolated case of smallpox triggered a broader outbreak, the health officials took it as an unmistakable sign that the population's level of immunity had begun to taper off, as it did every five to ten years. The time had come to sound the call for a general vaccination. "We are not afraid of smallpox," said Dr. F. H. Dillingham of the health department, when the news broke that smallpox had reappeared on Manhattan. "With the present facilities of this department we can stamp out any disease."

On Thanksgiving Day, as the Columbia University football team took the field against the Carlisle Indian School and three thousand homeless people lined up for a hot dinner at the Five Points House of Industry, a vaccination squad from the health department's Bureau of Contagious Diseases moved into West Sixty-ninth Street. The four doctors began a quiet canvass of All Nations Block, starting with the immediate neighbors of the infected children. Health department protocol called for a thorough investigation of each case, in order to trace its origin, followed by the immediate vaccination of all possible contacts. In a place as densely inhabited as All Nations Block, everyone would have to bare their arms for the vaccine.

With a willing patient, the vaccination "operation," as doctors called it, lasted just a minute or two. The doctor took hold of the patient's arm, scoring the skin with a needle or lancet. He then dabbed on the vaccine, either by taking a few droplets of liquid "lymph" from a glass tube or using a small ivory "point" coated with dry vaccine. Either way, the vaccine contained live cowpox or vaccinia virus that not long before had oozed from a sore on the underside of an infected calf in a health department stable. In the coming days, the virus would produce a blister-like vesicle at the vaccination site. In due course, the lesion would heal, leaving a permanent scar: the distinctive vaccination cicatrix. If all went well, the patient would then enjoy immunity from smallpox for five to seven years, sometimes longer. And, of course, as long as a person was immune, she could not pass along smallpox to others.

The health department's plan was to secure All Nations Block first and then follow the same procedure on the surrounding streets. In the coming days, health officers and police would maintain a quarantine on the block and enforce vaccination in the neighborhood schools. The health department would use all the available methods to fight the disease: total isolation of patients, quarantine of their living environment, vaccination of anyone exposed to the disease, disinfection of closed spaces and personal belongings, and close surveillance of the infected district and its residents.

It was a sensible protocol, born of medical science and the city's long experience with the deadliest contagious disease the world had ever known. Historically, smallpox killed 25 to 30 percent of all those whom it infected most survivors were permanently disfigured with the dreaded pitted scars. Decades after the scientific revolution known as the germ theory of disease, biologists and doctors were still searching in their laboratories for the specific pathogen that caused smallpox. But they felt confident they had a strong understanding of the microbe's behavior: its pathological course in the human body, its epidemiological effects in a population, and the immunological power of vaccination to prevent the virus from attacking an individual or proliferating across an entire community. According to the state-of-the-art scientific knowledge, the "infecting germs" of smallpox spread unseen from one nonimmune person to another, communicated in a cough, a brush of bodies, or across the folds and surfaces of everyday things: an article of clothing, a Pullman porter's whisk broom, a piece of mail, a newspaper, a library book, a bit of currency, a shared cigarette. Because smallpox had an incubation period of ten to fourteen days, during which the infected person presented no noticeable symptoms, health officers strived to retrace the circuits of human contact in order to identify probable carriers and contain the outbreak.

The vaccination corps had not been on the block long before the doctors realized the need for reinforcements, men armed with more than vaccine. As the physicians moved from door to door, rapping loudly and calling for the occupants to come out and be vaccinated, many residents refused to cooperate. The doctors tried to explain the danger, which could not have been easy given the many tongues spoken on the block. But many people would not submit to having their own or their children's arms scraped by the vaccinators without, according to The New York Times, "loud wails and even positive resistance." Receiving word of the worsening situation on All Nations Block, the commander of the West Sixty-eighth Street station dispatched a detail of six policemen to assist the doctors in "enforcing the vaccination."

Well into the cool autumn night, All Nations Block echoed with the rapping of nightsticks on doors, the shouting and pleas of the residents within, and, through it all, the rattle of the horse-drawn ambulance wagons as they moved to and from the infected district. By midnight, the vaccination corps had discovered another twenty-two cases on the block, many of them little children, all of them, in the health officers' view, requiring immediate isolation. The ambulance wagons carried the patients five miles over rough city roads to the Willard Parker Hospital, the health department's contagious diseases facility at the foot of East Sixteenth Street on the East River, where the doctors gave them a fuller examination. From there they were ferried off Manhattan and many more miles upriver to the city smallpox hospital, the "pesthouse" on North Brother Island, a nineteen-acre wooded island situated between Rikers Island and the Bronx mainland. Pesthouses, public hospitals used to isolate poor people suffering from infectious diseases, were the most dreaded of American institutions. The trip to North Brother Island was a grim journey into unknown territory. No known cure for smallpox existed. The pesthouse doctors could do little more than treat the patients' symptoms. It was up to the virus, and to each patient's own resources, to determine who among the infected would die in the seclusion of North Brother Island.

Author's footnotes have been omitted.

Excerpted from An American History by Michael Willrich. Reprinted by arrangement of The Penguin Press, a member of Penguin Group (USA), Inc. Copyright (c) 2011 by Michael Willrich.