What is the history of vaccines?

Definition

Vaccines are substances administered through inoculation, ingestion, or nasal inhalation to stimulate a person’s immune system to fight infection.

Development History

In 1796, Edward Jenner (1749–1823) developed the first successful vaccine. Jenner, as the tale of discovery goes, had heard a milkmaid declare “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” Jenner, after hearing this, took some pus from a cowpox lesion on the hand of a milkmaid named Sarah Nelmes and used it to inoculate an eight-year-old boy. A few days later, the boy had a mild case of vaccinia, a form of cowpox contracted by humans, but he soon recovered. Six weeks later, Jenner inoculated the boy with smallpox, yet the boy was unaffected by this and subsequent exposures; he had gained immunity from smallpox through the inoculation with cowpox.

Jenner’s was the first safe and successful attempt to artificially induce active immunity. To describe this particular style of inoculation, Jenner coined the term “vaccine,” from the Latin word vaccinus, or “of cows.”

About eighty years later, in 1879, Louis Pasteur (1822–1895) furthered the vaccination concept through his work in microbiology. Pasteur was employed to find a solution for chicken cholera, which could wipe out an entire flock in as few as three days. One summer, the cholera cultures used for infecting the test chickens were inadvertently stored in the heat. These cultures produced some symptoms of disease but were no longer deadly to the chickens. When subsequently inoculated with young virulent cultures, the chickens remained unaffected. Pasteur reasoned that the “stale” cultures were actually attenuated (weakened), and with these attenuated organisms, the chickens had become immune.

In the laboratory, Pasteur learned that by prolonged growth and exposure to
oxygen, the microbes could be manipulated to the ideal virulence.
This experiment marked the first time a pathogenic microbe was isolated and used
as a bacterial vaccine. In 1881, applying the methodology he had developed for the
chicken cholera virus, Pasteur and his associates heated anthrax germs, exposed
them to the oxidizing agent potassium dichromate, and inoculated a number of
sheep.

The rabies vaccine was initially created by Émile Roux, a French doctor and a colleague of Pasteur who had been working with a killed vaccine produced by desiccating the spinal cords of infected rabbits. In 1885, Pasteur successfully vaccinated a shepherd boy who had been bitten fourteen times by a rabid dog. He produced his vaccine for rabies by growing the virus in rabbits and then weakening it by drying the affected nerve tissue. The vaccine had been tested only on eleven dogs before its first human trial. The delay in rabies germs reaching the brain enabled the rabies vaccine to be effective after the bite had occurred.

The first toxoid vaccine was for diphtheria. The diphtheria bacillus was discovered by Edwin Klens in 1883. In 1884, Frederick Loeffler isolated it and grew it in culture. In 1890, Emil Von Behring discovered an antitoxin and subsequently developed a vaccine with a combination of diphtheria toxin and antitoxin. However, he did not deem the vaccine safe for widespread use. In 1924, a researcher at the Pasteur Institute weakened diphtheria toxin with formaldehyde to make a “toxoid” to kill the bacteria. He was able to immunize guinea pigs with his toxoid. Mass vaccination began in New York within three years.

As vaccines continued to be developed and released (bubonic plague, 1897;
cholera and typhoid, 1917; pertussis, or whooping cough, 1926; tetanus, 1927; and
tuberculosis, 1927), they became more and more integral to utilitarian and public
health notions of security, productivity, and protection. Licensing of vaccines
began and vaccination became ever more managed by government from the municipal
level to the federal level. For example, vaccination became mandatory for infants
in the United Kingdom in 1853. In the United States, in 1902, the Biologies
Control Act was passed after the deaths of thirteen children in St. Louis,
Missouri, in 1901; the children had received diphtheria antitoxin that had been
accidentally contaminated with tetanus.

Golden Age of Vaccines

The golden age of vaccines began after World War II. Scientific knowledge had developed enough so that large-scale vaccine production was possible, and several important new vaccines were developed in a relatively short time: influenza (1945), polio (1952), measles (1963), mumps (1967), and rubella (1969). The success in preventing diseases such as polio and measles, of which parents had been terrified, was revolutionary. When the polio vaccine was licensed in 1955, its developer, Jonas Salk, was heralded as a hero. In 1967, the World Health Organization (WHO) led a huge campaign against smallpox. Within ten years, naturally occurring smallpox had been vaccinated out of existence.

Important vaccines from the late twentieth century include those against meningitis (1975), chickenpox (1996), rotavirus (1998), and the first acellular vaccine (pertussis, 1997). In acellular vaccine production, only the antigenic part of the microbe (for example, the capsule, the flagella, or part of the cell wall) is used. Prompting the replacement of whole-cell pertussis vaccines by acellular variations was the potential for severe side effects after vaccination and the reported shift in the age distribution of pertussis. Haemophilus influenzae type B (Hib) vaccine is also acellular. Neither killed nor acellular vaccines induce the strongest immune response and may therefore require booster shots, yet they are safer for use in immunocompromised persons.

In the early twenty-first century, vaccines for adults are becoming increasingly common. For example, a shingles vaccine was licensed in 2008. Unlike childhood vaccines, adult vaccines are not mandated. The first formalized adult immunization schedule was published in 2002 and is updated annually.

New Vaccine Development

Researchers have examined many possible approaches for vaccines against malaria. One of the most promising approaches has been a subunit vaccine. Researchers have begun testing another approach: a vaccine that combines killed parasites with an adjuvant to boost immune response.

Researchers also are trying to develop an influenza vaccine that can provide broad protection, including against future strains, so that a single shot would be enough to protect a person from the seasonal flu for ten years or longer.

The human immunodeficiency virus (HIV) is a challenging target for vaccine researchers for many reasons, not the least of which is the virus’s lack of stability. The surface proteins of the virus frequently change, keeping the immune system from recognizing it and keeping researchers from pinpointing a surface protein as a successful target for a vaccine.

A number of other vaccine strategies are under experimental investigation. These include deoxyribonucleic acid (DNA) vaccination and recombinant viral vectors.

In the midst of an Ebola virus disease epidemic that raged in West Africa throughout 2014 and 2015, two promising experimental vaccines was being fast-tracked for development in early 2015. The Ebola virus, like HIV and influenza, can mutate rapidly, making effective vaccination a challenge. Moreover, debate has been waged about the ethics and logistics of such vaccines: whether to administer candidate vaccines in the absence of clinical trials, who should receive the vaccines if they are effective, and whether they truly represent the best means of fighting such deadly diseases in resource-poor regions that lack other health care measures.

Opposition to Vaccination

Vaccination efforts have met with some controversy since their inception. To a great extent, nation-states have responded to this opposition by articulating the right to immunize for the common good. In 1905, for example, the U.S. Supreme Court ruled that the need to protect the public health through compulsory smallpox vaccination outweighed an individual’s right to privacy. This principal has been consistently reiterated and is supported by the concept of herd immunity, whereby a certain target of the population (approximately 90 percent, depending on the disease) must be immunized for protection to be conferred upon the entire group. In the United States, states have granted exemptions to mandatory vaccination for religious beliefs (as, for example, with Christian Science), for medical reasons (such as a compromised immune system), or for philosophical objections (in twenty states).

As a small but vocal antivaccine movement has gained ground, some rates for vaccine-preventable diseases have risen. This is of special concern because many diseases entail complications. In the case of measles, which is extremely virulent, complications include pneumonia and encephalitis. The modern antivaccine movement also claims that vaccines cause autism, either from the additive thiomersal (known in the United States as thimerosol), which has been used as a vaccine preservative since the 1930’s, or from an overload of the combined mumps, measles, and rubella (MMR) vaccine.

The movement was catalyzed by a British doctor, Andrew Wakefield. In 1998, he published a study of twelve children, several of whom developed signs of autism and intestinal symptoms following MMR immunization. He suggested that the vaccine inflamed the gut in a manner that allowed an unspecified toxic substance to cross into the bloodstream. Although he has stated that his paper does not prove an association between the MMR vaccine and autism, his paper does include parental allegations that he adopted as fact. Wakefield recommended separating the components of the injections by a minimum of one year.

The antivaccination movement gained traction because parents tend to first notice symptoms of autism in their child around the time of the MMR; another factor in the movement’s success has been parental fear of mercury: Thimerosol metabolizes to ethyl mercury, which is often confused with methyl mercury, a neurotoxin. A 2006 review of scientific studies found “no convincing evidence” that thimerosol had a causal role in the onset of autism. Also, courts have ruled that there is no connection. After a lengthy investigation by a medical fraternity, Wakefield’s paper was determined unethical. In February 2010, The Lancet retracted Wakefield’s 1998 article, noting that elements of his submitted manuscript had been falsified.

Despite the medical community discrediting Wakefield, the antivaccination movement remains strong in the United States and Britain. Among parents' reasons for not vaccinating children are concern over serious potential side effects from vaccines, fear regarding the number or timing of vaccines in young children, lack of conviction that vaccination is necessary for good health, mistrust of the medical system, or belief that the government is interfering unduly in their medical and parental decisions.

An outbreak of measles occurred in Ohio in 2014, affecting more than 380 individuals, and about 190 sickened were sickened in 2015 outbreaks, the largest of which spread from California to other states. These public health crises reignited debate over the MMR vaccine and the antivaccination movement as the rate of outbreaks had increased significantly year over year from 2008 on, primarily among those who were unvaccinated.

Impact

Jenner’s assertion “that the cow-pox protects the human constitution from the infection of smallpox” laid the foundation for modern vaccination. The principle that guided Jenner in developing vaccines is still followed—namely, develop harmless preparations that will induce immune responses and thereby protect persons from pathogens.

Most vaccines today are safe, highly effective, mass produced, and administered to millions of people for long-term protection against infectious diseases. Nothing, except perhaps clean, safe water, has had a more positive effect on reducing deaths and helping populations around the world than vaccines, making vaccination one of the most important public health advances in history.

Vaccines also contribute significantly to the economic strength of nations. A study in Kenya, for example, concluded that the Hib vaccine remains a cost-effective intervention, having saved that nation close to one million dollars in treatment costs for children born in 2004. Vaccines also enhance economic growth by protecting persons from the long-term effects of an illness on their physical, emotional, and cognitive development. For example, approximately 28,000 cases of pneumonia and meningitis, 5,000 deaths, and 1,000 severe neurologic complications are prevented each year in Uganda alone.

At the end of the nineteenth century, the infant mortality rate in the United States was 20 percent, and the childhood mortality rate before age five was another 20 percent. Infectious diseases such as measles, diphtheria, smallpox, and pertussis once topped the list of childhood killers. Many of these devastating diseases have been contained, especially in industrialized nations, because of the development and widespread distribution of safe, effective, and affordable vaccines.

Before the development of the diphtheria vaccine in 1923, diphtheria accounted for about 15,500 child deaths and 200,000 illnesses. However, there were only fewer than a handful of reported cases of diphtheria between 2003 and 2013, according to the US Centers for Disease Control and Prevention. Likewise, in the 1950’s, about 20,000 people per year in the United States were affected by polio. The number of paralytic polio cases fell to fewer than 100 per year after the introduction of the vaccine.

After a carefully orchestrated and long-fought eradication effort by the WHO, an effort that was supported by national immunization programs, smallpox was eradicated in 1979. This is perhaps the greatest triumph since the development of vaccines. No naturally occurring cases of smallpox have been found since 1977, and smallpox now exists only in two laboratories: one in the United States and one in Russia. Vigorous debate exists on whether these two stores of the virus should be destroyed; were smallpox released into the environment, the results could be devastating. Smallpox vaccination is no longer routine, so the world’s population is once again highly susceptible to the disease, a susceptibility rate that rises each year.

No other pathogen has been eradicated on a global scale, but diphtheria has largely been eradicated in industrialized nations. Also, in 1994, the WHO declared the Western Hemisphere free of the wild-type polio virus.

Compelling evidence of the impact of vaccination on disease incidence was clearly seen in the United Kingdom in 2000. Meningococcal group C infection had been increasing and was responsible for many deaths, particularly in adolescents. In October 1999, the United Kingdom’s health department introduced a vaccination program, and the number of new cases fell from about 145 to about 65 in one year.

Nonimmunized children still die every day from vaccine-preventable diseases. They may also be rendered physically weakened, developmentally delayed, or permanently disabled. As of 2015, 1.5 million children were dying each year worldwide because they did not receive vaccinations against preventable disease.

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