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Polio vaccine

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization (WHO) recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 33 in 2018.

The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccines cause about three cases of vaccine-associated paralytic poliomyelitis per million doses given. This compares with 5,000 cases per million who are paralysed following a polio infection. Both types of vaccine are generally safe to give during pregnancy and in those who have HIV/AIDS but are otherwise well. However, the emergence of circulating vaccine-derived poliovirus (cVDPV), a form of the vaccine virus that has reverted to causing poliomyelitis, has led to the development of novel oral polio vaccine type 2 (nOPV2) which aims to make the vaccine safer and thus stop further outbreaks of cVDPV2.

The first successful demonstration of a polio vaccine was by Hilary Koprowski in 1950, with a live attenuated virus which people drank. The vaccine was not approved for use in the United States, but was used successfully elsewhere. The success of an inactivated (killed) polio vaccine, developed by Jonas Salk, was announced in 1955. Another attenuated live oral polio vaccine was developed by Albert Sabin and came into commercial use in 1961.

Polio vaccine is on the World Health Organization's List of Essential Medicines.

Medical uses
Interruption of person-to-person transmission of the virus by vaccination is important in global polio eradication, since no long-term carrier state exists for poliovirus in individuals with normal immune function, polio viruses have no non-primate reservoir in nature, and survival of the virus in the environment for an extended period of time appears to be remote. There are two types of vaccine: inactivated polio vaccine (IPV) and oral polio vaccine (OPV).

Inactivated
When the IPV (injection) is used, 90% or more of individuals develop protective antibodies to all three serotypes of polio virus after two doses of inactivated polio vaccine (IPV), and at least 99% are immune to polio virus following three doses. The duration of immunity induced by IPV is not known with certainty, although a complete series is thought to provide protection for many years. IPV replaced the oral vaccine in many developed countries in the 1990s mainly due to the (small) risk of vaccine-derived polio in the oral vaccine.

Attenuated
Oral polio vaccines were easier to administer than IPV, as it eliminated the need for sterile syringes and therefore was more suitable for mass vaccination campaigns. OPV also provided longer-lasting immunity than the Salk vaccine, as it provides both humoral immunity and cell-mediated immunity.

One dose of OPV produces immunity to all three poliovirus serotypes in roughly 50% of recipients. Three doses of live-attenuated OPV produce protective antibodies to all three poliovirus types in more than 95% of recipients. OPV produces excellent immunity in the intestine, the primary site of wild poliovirus entry, which helps prevent infection with wild virus in areas where the virus is endemic. The live virus used in the vaccine can rarely shed in the stool and can rarely spread to others within a community. The live virus also has stringent requirements for transport and storage, which are a problem in some hot or remote areas. As with other live-virus vaccines, immunity initiated by OPV is probably lifelong.

The trivalent (against wild types 1, 2, and 3) OPV has been used to nearly eradicate polio infection worldwide. Led by the Global Polio Eradication Initiative, 155 countries switched to use the bivalent (against wild types 1 and 3) between 17 April and 1 May 2016. The bivalent OPV is more effective against types 1 and 3, but does not cover type 2. The switch to the bivalent vaccine and associated missing immunity against type 2 strains, among other factors, led to outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2), which increased from 2 cases in 2016 to 1037 cases in 2020.

An improved oral vaccine (Novel oral polio vaccine type 2 - nOPV2) began development in 2011 and was granted emergency licencing in 2021, and subsequently full licensure in December 2023. This has greater genetic stability than the traditional oral vaccine and is less likely to revert to a virulent form.

Schedule

In countries with endemic polio or where the risk of imported cases is high, the WHO recommends OPV vaccine at birth followed by a primary series of three OPV doses and at least one IPV dose starting at 6 weeks of age, with a minimum of 4 weeks between OPV doses. In countries with >90% immunization coverage and low risk of importation, the WHO recommends one or two IPV doses starting at 2 months of age followed by at least two OPV doses, with the doses separated by 4–8 weeks depending on the risk of exposure. In countries with the highest levels of coverage and the lowest risks of importation and transmission, the WHO recommends a primary series of three IPV injections, with a booster dose after an interval of six months or more if the first dose was administered before 2 months of age.

Side effects
The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccine results in vaccine-associated paralytic poliomyelitis in about three per million doses. They are generally safe to be given to those who are pregnant and those who have HIV/AIDS but are otherwise well.

Allergic reaction to the vaccine
Inactivated polio vaccine can cause an allergic reaction in a few people since the vaccine contains trace amounts of antibiotics, streptomycin, polymyxin B, and neomycin. It should not be given to anyone who has an allergic reaction to these medicines. Signs and symptoms of an allergic reaction, which usually appear within minutes or a few hours after receiving the injected vaccine, include breathing difficulties, weakness, hoarseness or wheezing, heart rate fluctuations, skin rash and dizziness.

Vaccine-induced polio
A potential, adverse effect of the original OPV is its known ability to recombine to a form that causes neurological infection and paralysis.

The vaccine-derived attenuated virus used in the OPV is normally excreted from vaccinated people for a limited period. Thus, in areas with poor sanitation and low vaccination coverage, it can spread to other unvaccinated individuals. Over time, and after passing through numerous hosts, it can potentially revert to a virulent form. This genetic reversal of the pathogen to a virulent form takes a considerable time (at least 12 months) and does not affect the person who was originally vaccinated. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses. Outbreaks of vaccine-associated paralytic poliomyelitis (VAPP), caused by a circulating vaccine-derived poliovirus (cVDPV), have been reported, and tend to occur in areas of low coverage by OPV, presumably because the OPV is itself protective against the related outbreak strain. With wild polio cases at record lows, 2017 was the first year where more cases of cVDPV were recorded than the wild poliovirus, a trend that is expected to continue.

To combat this, the WHO in 2016, decided to switch from the trivalent polio vaccine to the bivalent polio vaccine. This vaccine no longer contains the type 2 polio virus because it was eradicated in 1999.

In December 2023 an improved oral vaccine - nOPV2 - with greater genetic stability received full licensure. This is less likely to recombine to a form which can cause paralysis.

Contamination concerns
In 1960, the rhesus monkey kidney cells used to prepare the poliovirus vaccines were determined to be infected with the simian virus-40 (SV40), which was also discovered in 1960 and is a naturally occurring virus that infects monkeys. In 1961, SV40 was found to cause tumors in rodents. More recently, the virus was found in certain forms of cancer in humans, for instance brain and bone tumors, pleural and peritoneal mesothelioma, and some types of non-Hodgkin lymphoma. However, SV40 has not been determined to cause these cancers.

SV40 was found to be present in stocks of the injected form of the IPV in use between 1955 and 1963. It is not found in the OPV form. Over 98 million Americans received one or more doses of polio vaccine between 1955 and 1963 when a proportion of vaccine was contaminated with SV40; an estimated 10–30 million Americans may have received a dose of vaccine contaminated with SV40. Later analysis suggested that vaccines produced by the former Soviet bloc countries until 1980, and used in the USSR, China, Japan, and several African countries, may have been contaminated, meaning hundreds of millions more may have been exposed to SV40.

In 1998, the National Cancer Institute undertook a large study, using cancer case information from the institute's SEER database. The published findings from the study revealed no increased incidence of cancer in persons who may have received vaccine containing SV40. Another large study in Sweden examined cancer rates of 700,000 individuals who had received potentially contaminated polio vaccine as late as 1957; the study again revealed no increased cancer incidence between persons who received polio vaccines containing SV40 and those who did not. The question of whether SV40 causes cancer in humans remains controversial, however, and the development of improved assays for detection of SV40 in human tissues will be needed to resolve the controversy. During the race to develop an oral polio vaccine, several large-scale human trials were undertaken. By 1958, the National Institutes of Health had determined that OPV produced using the Sabin strains were the safest. Between 1957 and 1960, however, Hilary Koprowski continued to administer his vaccine around the world. In Africa, the vaccines were administered to roughly one million people in the Belgian territories (now the Democratic Republic of the Congo, Rwanda, and Burundi). The results of these human trials have been controversial, and unfounded accusations in the 1990s arose that the vaccine had created the conditions necessary for transmission of simian immunodeficiency virus from chimpanzees to humans, causing HIV/AIDS. These hypotheses, however, have been conclusively refuted. By 2004, cases of poliomyelitis in Africa had been reduced to just a small number of isolated regions in the western portion of the continent, with sporadic cases elsewhere. Recent local opposition to vaccination campaigns have evolved due to lack of adequate information, often relating to fears that the vaccine might induce sterility. The disease has since resurged in Nigeria and in several other African nations without necessary information, which epidemiologists believe is due to refusals by certain local populations to allow their children to receive the polio vaccine.

Inactivated
The Salk vaccine, IPV, is based on three wild, virulent reference strains, Mahoney (type 1 poliovirus), MEF-1 (type 2 poliovirus), and Saukett (type 3 poliovirus), grown in a type of monkey kidney tissue culture (Vero cell line), which are then inactivated with formalin. The injected Salk vaccine confers IgG-mediated immunity in the bloodstream, which prevents polio infection from progressing to viremia and protects the motor neurons, thus eliminating the risk of bulbar polio and post-polio syndrome.

In the United States, vaccine is administered along with the tetanus, diphtheria, and acellular pertussis vaccines (DTaP) and a pediatric dose of hepatitis B vaccine. In the UK, IPV is combined with tetanus, diphtheria, pertussis, and Haemophilus influenzae type b vaccines.

Attenuated
OPV is an attenuated vaccine, produced by the passage of the virus through nonhuman cells at a subphysiological temperature, which produces spontaneous mutations in the viral genome. Oral polio vaccines were developed by several groups, one of which was led by Albert Sabin. Other groups, led by Hilary Koprowski and H.R. Cox, developed their own attenuated vaccine strains. In 1958, the National Institutes of Health created a special committee on live polio vaccines. The various vaccines were carefully evaluated for their ability to induce immunity to polio, while retaining a low incidence of neuropathogenicity in monkeys. Large-scale clinical trials performed in the Soviet Union in late 1950s to early 1960s by Mikhail Chumakov and his colleagues demonstrated safety and high efficacy of the vaccine. Based on these results, the Sabin strains were chosen for worldwide distribution. Fifty-seven nucleotide substitutions distinguish the attenuated Sabin 1 strain from its virulent parent (the Mahoney serotype), two nucleotide substitutions attenuate the Sabin 2 strain, and 10 substitutions are involved in attenuating the Sabin 3 strain. The primary attenuating factor common to all three Sabin vaccines is a mutation located in the virus's internal ribosome entry site, which alters stem-loop structures and reduces the ability of poliovirus to translate its RNA template within the host cell. The attenuated poliovirus in the Sabin vaccine replicates very efficiently in the gut, the primary site of infection and replication, but is unable to replicate efficiently within nervous system tissue. In 1961, type 1 and 2 monovalent oral poliovirus vaccine (MOPV) was licensed, and in 1962, type 3 MOPV was licensed. In 1963, trivalent OPV (TOPV) was licensed, and became the vaccine of choice in the United States and most other countries of the world, largely replacing the inactivated polio vaccine. A second wave of mass immunizations led to a further dramatic decline in the number of polio cases. Between 1962 and 1965, about 100 million Americans (roughly 56% of the population at that time) received the Sabin vaccine. The result was a substantial reduction in the number of poliomyelitis cases, even from the much-reduced levels following the introduction of the Salk vaccine.

OPV is usually provided in vials containing 10–20 doses of vaccine. A single dose of oral polio vaccine (usually two drops) contains 1,000,000 infectious units of Sabin 1 (effective against PV1), 100,000 infectious units of the Sabin 2 strain, and 600,000 infectious units of Sabin 3. The vaccine contains small traces of antibiotics—neomycin and streptomycin—but does not contain preservatives.

History
In a generic sense, vaccination works by priming the immune system with an 'immunogen'. Stimulating immune response, by use of an infectious agent, is known as immunization. The development of immunity to polio efficiently blocks person-to-person transmission of wild poliovirus, thereby protecting both individual vaccine recipients and the wider community.

The development of two polio vaccines led to the first modern mass inoculations. The last cases of paralytic poliomyelitis caused by endemic transmission of wild virus in the United States occurred in 1979, with an outbreak among the Amish in several Midwest states.

1930s
In the 1930s, poliovirus was perceived as especially terrifying, as little was known of how the disease was transmitted or how it could be prevented. This virus was also notable for primarily impacting affluent children, making it a prime target for vaccine development, despite its relatively low mortality and morbidity. Despite this, the community of researchers in the field thus far had largely observed an informal moratorium on any vaccine development as it was perceived to present too high a risk for too little likelihood of success.

This shifted in the early 1930s when American groups took up the challenge: Maurice Brodie led a team from the public health laboratory of the city of New York and John A. Kolmer collaborated with the Research Institute of Cutaneous Medicine in Philadelphia. The rivalry between these two researchers lent itself to a race-like mentality which, combined with a lack of oversight of medical studies, was reflected in the methodology and outcomes of each of these early vaccine development ventures.

Kolmer's live vaccine
Kolmer began his vaccine development project in 1932 and ultimately focused on producing an attenuated or live virus vaccine. Inspired by the success of vaccines for rabies and yellow fever, he hoped to use a similar process to denature the polio virus. In order to go about attenuating his polio vaccine, he repeatedly passed the virus through monkeys. Using methods of production that were later described as "hair-raisingly amateurish, the therapeutic equivalent of bath-tub gin," Kolmer ground the spinal cords of his infected monkeys and soaked them in a salt solution. He then filtered the solution through mesh, treated it with ricinolate, and refrigerated the product for 14 days to ultimately create what would later be prominently critiqued as a "veritable witches brew".

In keeping with the norms of the time, Kolmer completed a relatively small animal trial with 42 monkeys before proceeding to self experimentation in 1934. He tested his vaccine upon himself, his two children, and his assistant. He gave his vaccine to just 23 more children before declaring it safe and sending it out to doctors and health departments for a larger test of efficacy. By April 1935, he was able to report having tested the vaccine on 100 children without ill effect. Kolmer's first formal presentation of results would not come about until November 1935 where he presented the results of 446 children and adults he had vaccinated with his attenuated vaccine. He also reported that together the Research Institute of Cutaneous Medicine and the Merrell Company of Cincinnati (the manufacturer who held the patent for his ricinoleating process) had distributed 12,000 doses of vaccine to some 700 physicians across the United States and Canada. Kolmer did not describe any monitoring of this experimental vaccination program nor did he provide these physicians with instructions in how to administer the vaccine or how to report side effects. Kolmer dedicated the bulk of his publications thereafter to explaining what he believed to be the cause of the 10+ reported cases of paralytic polio following vaccination, in many cases in towns where no polio outbreak had occurred. Six of these cases had been fatal. Kolmer had no control group but asserted that many more children would have gotten sick.

Brodie's inactivated vaccine
At nearly the same time as Kolmer's project, Maurice Brodie had joined immunologist William H. Park at the New York City Health Department where they worked together on poliovirus. With the aid of grant funding from the President's Birthday Ball Commission (a predecessor to what would become the March of Dimes), Brodie was able to pursue development of an inactivated or "killed virus" vaccine. Brodie's process also began by grinding the spinal cords of infectious monkeys and then treating the cords with various germicides, ultimately finding a solution of formaldehyde to be the most effective. By 1 June 1934, Brodie was able to publish his first scholarly article describing his successful induction of immunity in three monkeys with inactivated polio virus. Through continued study on an additional 26 monkeys, Brodie ultimately concluded that administration of live virus vaccine tended to result in humoral immunity while administration of killed virus vaccine tended to result in tissue immunity.

Soon after, following a similar protocol to Kolmer, Brodie proceeded with self experimentation upon himself and his co-workers at the NYC Health Department laboratory. Brodie's progress was eagerly covered by popular press as the public hoped for a successful vaccine to become available. Such reporting did not make mention of the 12 children in a New York City Asylum who were subjected to early safety trials. As none of the subjects experienced ill effects, Park, described by contemporaries as "never one to let grass grow under his feet," declared the vaccine safe. When a severe polio outbreak overwhelmed Kern County, California it became the first trial site for the new vaccine on very short notice. Between November 1934 - May 1935, over 1,500 doses of the vaccine were administered in Kern County. While initial results were very promising, insufficient staffing and poor protocol design left Brodie open to criticism when he published the California results in August 1935. Through private physicians, Brodie also conducted a broader field study, including 9,000 children who received the vaccine and 4,500 age- and location-matched controls who did not receive a vaccine. Again, results were promising. Of those who received the vaccine, only a few went on to develop polio. Most had been exposed prior to vaccination and none had received the full series of vaccine doses being studied. Additionally, a polio epidemic in Raleigh, North Carolina provided an opportunity for the U.S. Public Health Service to conduct a highly structured trial of the Brodie vaccine using funding from the Birthday Ball Commission.

Academic reception
While their work was ongoing, the larger community of bacteriologists began to raise concerns regarding the safety and efficacy of the new poliovirus vaccines. At this time there was very little oversight of medical studies, and ethical treatment of study participants largely relied upon moral pressure from peer academic scientists. Brodie's inactivated vaccines faced scrutiny from many who felt killed virus vaccines could not be efficacious. While researchers were able to replicate the tissue immunity he had produced in his animal trials, prevailing wisdom was that humoral immunity was essential for an efficacious vaccine. Kolmer directly questioned the killed virus approach in scholarly journals. Kolmer's studies however had raised even more concern with increasing reports of children becoming paralysed following vaccination with his live virus vaccine and notably, with paralysis beginning at the arm rather than the foot in many cases. Both Kolmer and Brodie were called to present their research at the Annual Meeting of the American Public Health Association in Milwaukee WI in October 1935. Additionally, Thomas M. Rivers was asked to discuss each of the presented papers as a prominent critic of the vaccine development effort. This resulted in the APHA arranging a Symposium on Poliomyelitis to be delivered at the Annual Meeting of their Southern Branch the following month. It was during the discussion at this meeting that James Leake of the U.S. Public Health Service stood to immediately present clinical evidence that the Kolmer vaccine had caused several deaths and then allegedly accused Kolmer of being a murderer. As Rivers recalled in his oral history, "All hell broke loose, and it seemed as if everybody was trying to talk at the same time....Jimmy Leake used the strongest language that I have ever heard used at a scientific meeting." In response to the attacks from all sides, Brodie was reported to have stood up and stated, "It looks as though, according to Dr. Rivers, my vaccine is no good, and, according to Dr. Leake, Dr Kolmer's is dangerous." Kolmer simply responded by stating, "Gentlemen, this is one time I wish the floor would open up and swallow me." Ultimately, Kolmer's live vaccine was undoubtedly shown to be dangerous and had already been withdrawn in September 1935 prior to the Milwaukee meeting. While the consensus of the symposium was largely skeptical of the efficacy of Brodie's vaccine, its safety was not in question and the recommendation was for a much larger well-controlled trial. However, when three children became ill with paralytic polio following a dose of the vaccine, the directors of the Warm Springs Foundation in Georgia (acting as the primary funders for the project) requested it be withdrawn in December 1935. Following its withdrawal, the previously observed moratorium on human poliomyelitis vaccine development resumed and there would not be another attempt for nearly 20 years.

While Brodie had arguably made the most progress in the pursuit of a poliovirus vaccine, he suffered the most significant career repercussions due to his status as a less widely known researcher. Modern researchers recognize that Brodie may well have developed an effective polio vaccine, however the basic science and technology of the time was insufficient to understand and utilize this breakthrough. Brodie's work using formalin-inactivated virus would later become the basis for the Salk vaccine, but he would not live to see this success. Brodie was fired from his position within three months of the symposium's publication. While he was able to find another laboratory position, he died of a heart attack only three years later at age 36. By contrast, Park, who was believed in the community to be reaching senility at this point in his older age, was able to retire from his position with honors prior to his death in 1939. Kolmer, already an established and well respected researcher, returned to Temple University as a professor of medicine. Kolmer had a very productive career, receiving multiple awards, and publishing countless papers, articles, and textbooks up until his retirement in 1957.

1948
A breakthrough came in 1948 when a research group headed by John Enders at the Children's Hospital Boston successfully cultivated the poliovirus in human tissue in the laboratory. This group had recently successfully grown mumps in cell culture. In March 1948, Thomas H. Weller was attempting to grow varicella virus in embryonic lung tissue. He had inoculated the planned number of tubes when he noticed that there were a few unused tubes. He retrieved a sample of mouse brain infected with poliovirus and added it to the remaining test tubes, on the off chance that the virus might grow. The varicella cultures failed to grow, but the polio cultures were successful. This development greatly facilitated vaccine research and ultimately allowed for the development of vaccines against polio. Enders and his colleagues, Thomas H. Weller and Frederick C. Robbins, were recognized in 1954 for their efforts with a Nobel Prize in Physiology or Medicine. Other important advances that led to the development of polio vaccines were: the identification of three poliovirus serotypes (Poliovirus type 1 – PV1, or Mahoney; PV2, Lansing; and PV3, Leon); the finding that prior to paralysis, the virus must be present in the blood; and the demonstration that administration of antibodies in the form of gamma globulin protects against paralytic polio.

1950–1955
During the early 1950s, polio rates in the U.S. were above 25,000 annually; in 1952 and 1953, the U.S. experienced an outbreak of 58,000 and 35,000 polio cases, respectively, up from a typical number of some 20,000 a year, with deaths in those years numbering 3,200 and 1,400. Amid this U.S. polio epidemic, millions of dollars were invested in finding and marketing a polio vaccine by commercial interests, including Lederle Laboratories in New York under the direction of H. R. Cox. Also working at Lederle was Polish-born virologist and immunologist Hilary Koprowski of the Wistar Institute in Philadelphia, who tested the first successful polio vaccine, in 1950. His vaccine, however, being a live attenuated virus taken orally, was still in the research stage and would not be ready for use until five years after Jonas Salk's polio vaccine (a dead-virus injectable vaccine) had reached the market. Koprowski's attenuated vaccine was prepared by successive passages through the brains of Swiss albino mice. By the seventh passage, the vaccine strains could no longer infect nervous tissue or cause paralysis. After one to three further passages on rats, the vaccine was deemed safe for human use. On 27 February 1950, Koprowski's live, attenuated vaccine was tested for the first time on an 8-year-old boy living at Letchworth Village, an institution for physically and mentally disabled people located in New York. After the child had no side effects, Koprowski enlarged his experiment to include 19 other children.

Jonas Salk

The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, which required years of subsequent testing. Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later, the results were published in JAMA. Leone N. Farrell invented a key laboratory technique that enabled the mass production of the vaccine by a team she led in Toronto. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania.

Salk's vaccine was then used in a test called the Francis Field Trial, led by Thomas Francis, the largest medical experiment in history at that time. The test began with about 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and eventually involved 1.8 million children, in 44 states from Maine to California. By the conclusion of the study, roughly 440,000 received one or more injections of the vaccine, about 210,000 children received a placebo, consisting of harmless culture media, and 1.2 million children received no vaccination and served as a control group, who would then be observed to see if any contracted polio.

The results of the field trial were announced 12 April 1955 (the tenth anniversary of the death of President Franklin D. Roosevelt, whose paralytic illness was generally believed to have been caused by polio). The Salk vaccine had been 60–70% effective against PV1 (poliovirus type 1), over 90% effective against PV2 and PV3, and 94% effective against the development of bulbar polio. Soon after Salk's vaccine was licensed in 1955, children's vaccination campaigns were launched. In the U.S., following a mass immunization campaign promoted by the March of Dimes, the annual number of polio cases fell from 35,000 in 1953 to 5,600 by 1957. By 1961 only 161 cases were recorded in the United States.

A week before the announcement of the Francis Field Trial results in April 1955, Pierre Lépine at the Pasteur Institute in Paris had also announced an effective polio vaccine.

Safety incidents
In April 1955, soon after mass polio vaccination began in the US, the Surgeon General began to receive reports of patients who contracted paralytic polio about a week after being vaccinated with Salk polio vaccine from the Cutter pharmaceutical company, with the paralysis starting in the limb the vaccine was injected into. The Cutter vaccine had been used in vaccinating 409,000 children in the western and midwestern United States. Later investigations showed that the Cutter vaccine had caused 260 cases of polio, killing 11. In response, the Surgeon General pulled all polio vaccines made by Cutter Laboratories from the market, but not before 260 cases of paralytic illness had occurred. Eli Lilly, Parke-Davis, Pitman-Moore and Wyeth polio vaccines were also reported to have paralyzed numerous children. It was soon discovered that some lots of Salk polio vaccine made by Cutter, Wyeth, and the  other labs had not been properly inactivated, allowing live poliovirus into more than 100,000 doses of vaccine. In May 1955, the National Institutes of Health and Public Health Services established a Technical Committee on Poliomyelitis Vaccine to test and review all polio vaccine lots and advise the Public Health Service as to which lots should be released for public use. These incidents reduced public confidence in polio vaccine, leading to a drop in vaccination rates.

1961
At the same time that Salk was testing his vaccine, both Albert Sabin and Hilary Koprowski continued working on developing a vaccine using live virus. During a meeting in Stockholm to discuss polio vaccines in November 1955, Sabin presented results obtained on a group of 80 volunteers, while Koprowski read a paper detailing the findings of a trial enrolling 150 people. Sabin and Koprowski both eventually succeeded in developing vaccines. Because of the commitment to the Salk vaccine in America, Sabin and Koprowski both did their testing outside the United States, Sabin in Mexico and the Soviet Union, Koprowski in the Congo and Poland. In 1957, Sabin developed a trivalent vaccine containing attenuated strains of all three types of poliovirus. In 1959, ten million children in the Soviet Union received the Sabin oral vaccine. For this work, Sabin was given the medal of the Order of Friendship of Peoples, described as the Soviet Union's highest civilian honor. Sabin's oral vaccine using live virus came into commercial use in 1961.

Once Sabin's oral vaccine became widely available, it supplanted Salk's injected vaccine, which had been tarnished in the public's opinion by the Cutter incident of 1955, in which Salk vaccines improperly prepared by one company resulted in several children dying or becoming paralyzed.

1987
An enhanced-potency IPV was licensed in the United States in November 1987, and is currently the vaccine of choice there. The first dose of polio vaccine is given shortly after birth, usually between 1 and 2 months of age, and a second dose is given at 4 months of age. The timing of the third dose depends on the vaccine formulation, but should be given between 6 and 18 months of age. A booster vaccination is given at 4 to 6 years of age, for a total of four doses at or before school entry. In some countries, a fifth vaccination is given during adolescence. Routine vaccination of adults (18 years of age and older) in developed countries is neither necessary nor recommended because most adults are already immune and have a very small risk of exposure to wild poliovirus in their home countries. In 2002, a pentavalent (five-component) combination vaccine (called Pediarix) containing IPV was approved for use in the United States.

1988

A global effort to eradicate polio, led by the World Health Organization (WHO), UNICEF, and the Rotary Foundation, began in 1988, and has relied largely on the oral polio vaccine developed by Albert Sabin and Mikhail Chumakov (Sabin-Chumakov vaccine).

After 1990
Polio was eliminated in the Americas by 1994. The disease was officially eliminated in 36 Western Pacific countries, including China and Australia, in 2000. Europe was declared polio-free in 2002. Since January 2011, no cases of the disease have been reported in India, hence in February 2012, the country was taken off the WHO list of polio-endemic countries. In March 2014, India was declared a polio-free country.

Although poliovirus transmission has been interrupted in much of the world, transmission of wild poliovirus does continue and creates an ongoing risk for the importation of wild poliovirus into previously polio-free regions. If importations of poliovirus occur, outbreaks of poliomyelitis may develop, especially in areas with low vaccination coverage and poor sanitation. As a result, high levels of vaccination coverage must be maintained. In November 2013, the WHO announced a polio outbreak in Syria. In response, the Armenian government put out a notice asking Syrian Armenians under age 15 to get the polio vaccine. As of 2014, polio virus had spread to 10 countries, mainly in Africa, Asia, and the Middle East, with Pakistan, Syria, and Cameroon advising vaccinations to outbound travellers.

Polio vaccination programs have been resisted by some people in Pakistan, Afghanistan, and Nigeria - the three countries as of 2017 with remaining polio cases. Almost all Muslim religious and political leaders have endorsed the vaccine, but a fringe minority believes that the vaccines are secretly being used for sterilization of Muslims. The fact that the CIA organized a fake vaccination program in 2011 to help find Osama bin Laden is an additional cause of distrust. In 2015, the WHO announced a deal with the Taliban to encourage them to distribute the vaccine in areas they control. However, the Pakistani Taliban was not supportive. On 11 September 2016, two unidentified gunmen associated with the Pakistani Taliban, Jamaat-ul-Ahrar, shot Zakaullah Khan, a doctor who was administering polio vaccines in Pakistan. The leader of the Jamaat-ul-Ahrar claimed responsibility for the shooting and stated that the group would continue this type of attack. Such resistance to and skepticism of vaccinations has consequently slowed down the polio eradication process within the two remaining endemic countries.

Travel requirements

Travellers who wish to enter or leave certain countries must be vaccinated against polio, usually at most 12 months and at least 4 weeks before crossing the border, and be able to present a vaccination record/certificate at the border checks. Most requirements apply only to travel to or from so-called 'polio-endemic', 'polio-affected', 'polio-exporting', 'polio-transmission', or 'high-risk' countries. As of August 2020, Afghanistan and Pakistan are the only polio-endemic countries in the world (where wild polio has not yet been eradicated). Several countries have additional precautionary polio vaccination travel requirements, for example to and from 'key at-risk countries', which as of December 2020 include China, Indonesia, Mozambique, Myanmar, and Papua New Guinea.

Cost
, the Global Alliance for Vaccines and Immunization supplies the inactivated vaccine to developing countries for as little as €0.75 (about US$) per dose in 10-dose vials.

Misconceptions
A misconception has been present in Pakistan that polio vaccine contained haram ingredients and could cause impotence and infertility in male children, leading some parents not to have their children vaccinated. This belief is most common in the Khyber Pakhtunkhwa province and the FATA region. Attacks on polio vaccination teams have also occurred, thereby hampering international efforts to eradicate polio in Pakistan and globally.

title: Polio vaccine


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Jimmy Dean

Jimmy Ray Dean (August 10, 1928 – June 13, 2010) was an American country music singer, television host, actor and businessman. He was the creator of the Jimmy Dean sausage brand as well as the spokesman for its TV commercials, and his likeness and voice continue to be used in advertisements after his death.

He became a national television personality starting on CBS in 1957. He rose to fame for his 1961 country music crossover hit into rock and roll with "Big Bad John" and his 1963 television series The Jimmy Dean Show gave puppeteer Jim Henson his first national exposure with his character, Rowlf.

His acting career included appearing in the early seasons in the Daniel Boone TV series as the sidekick of the famous frontiersman played by star Fess Parker. Later, he was on the big screen in a supporting role as billionaire Willard Whyte in the James Bond film Diamonds Are Forever (1971), starring Sean Connery.

He lived near Richmond, Virginia, and was nominated for the Country Music Hall of Fame in 2010, but died before his induction that year at the age of 81.

Early life
Dean was born on August 10, 1928, in Seth Ward, Texas and raised in nearby Plainview, the son of George Otto Dean and his second wife, the former Ruth Taylor. Ruth taught Jimmy how to play piano at the age of 10. He attributed his interest in music to the Seth Ward Baptist Church. He dropped out of high school and became a professional entertainer after serving in the U.S. Air Force in the late 1940s. Dean was 22 and just starting in show business when he married his first wife, Mary Sue, in 1950.

Entertainment career
Dean had his first hit, "Bumming Around", in 1953 on the 4 Star label (written by Pete Graves, credited to "C. Graves" on the Quality label). Dean signed with Columbia Records in 1957.

He had minor pop hits, such as "Little Sandy Sleighfoot" (a Christmas novelty song) and "Sing Along", later used as the theme for TV's Sing Along with Mitch, hosted by chorus leader Mitch Miller.

In 1954, Dean hosted the popular Washington, D.C., radio program Town and Country Time on WARL-AM, and with his Texas Wildcats became popular in the Mid-Atlantic region. Patsy Cline and Roy Clark got their starts on the show. Although Cline and Dean became good friends, Clark (Dean's lead guitarist) was fired by the singer for what was explained as his chronic tardiness. Dean replaced Clark with Billy Grammer. In 1955, Town and Country Time moved to WMAL-TV (now WJLA-TV) on weekday afternoons. Dean and the Texas Wildcats also appeared during 1957 on Town and Country Jamboree on WMAL-TV on Saturdays, which was also carried by TV stations in neighboring Maryland and Virginia on a regional network.

Also during 1957, while he lived in Arlington County, Virginia, Dean hosted Country Style on WTOP-TV (now WUSA-TV). CBS picked up the show nationally from Washington for eight months in 1957 under the name The Morning Show. Then from September 14, 1958, to June 1959, CBS carried The Jimmy Dean Show on weekday and Saturday afternoons.

Dean became best known for "Big Bad John", his 1961 recitation song about a heroic miner. Recorded in Nashville, the record went to number one on the Billboard pop chart and inspired many imitations and parodies. It sold over one million copies and was awarded a gold disc. The track peaked at number two in the UK Singles Chart. The song won Dean the 1962 Grammy Award for Best Country & Western Recording. He had several more top 40 songs, including a top 10 in 1962 with "PT-109", a song in honor of President John F. Kennedy's bravery in World War II, with the sinking of his PT-boat in the South Pacific Ocean by the Japanese.

In the early 1960s, he hosted The Tonight Show on occasion (he was the first guest host during Johnny Carson's tenure, hosting for the first time on January 14, 1963) and one night introduced country singer Roy Clark, with whom he had remained friendly. In the mid-1960s, Dean helped bring country music into the mainstream with his 1963–66 variety series The Jimmy Dean Show. It presented country music entertainers including Roger Miller, George Jones, Charlie Rich, Buck Owens, and some (such as Joe Maphis) who seldom received network exposure. In 1964, he hosted Hank Williams Jr. in Williams' first television appearance at the age of 14. He sang several songs associated with his father, Hank Williams. The program also featured comedy and a variety of popular music artists, and Dean's sketches with Rowlf the Dog, one of Jim Henson's Muppets. Henson was so grateful for this break that he offered Dean a 40% interest in his production company, but Dean declined on the basis that he had done nothing to truly earn it and Henson deserved all the rewards for his own work. For the rest of his life, Dean made it clear that he never regretted this decision.

Dean appeared on several TV talk shows and game shows in the 1960s and performed on variety programs, including The Ed Sullivan Show, The Pat Boone Chevy Showroom and The Hollywood Palace. Dean turned to acting after his television series ended in 1966. His best-known role was as a reclusive Las Vegas billionaire Willard Whyte, inspired by Howard Hughes, in the James Bond movie Diamonds Are Forever (1971) with Sean Connery as Bond. He also appeared in 14 episodes of Daniel Boone (1967–70) in three different roles (one episode as "Delo Jones," two as "Jeremiah," and 11 as "Josh Clements"); as Charlie Rowlands in two Fantasy Island episodes (1981–82); and on other television shows including a semi-regular role as Charlie Bullets on J.J. Starbuck starring Dale Robertson (1987–1988).

Dean's singing career remained strong into the mid-1960s; in 1965, he achieved a second number one country hit with the ballad "The First Thing Ev'ry Morning (And the Last Thing Ev'ry Night)", and he had a top 40 hit that year with "Harvest of Sunshine". In 1966, Dean signed with RCA Victor and immediately had a top 10 hit with "Stand Beside Me". His other major hits during this time included "Sweet Misery" (1967) and "A Thing Called Love" (1968). He continued charting into the early 1970s with his major hits, including "Slowly" (1971), a duet with Dottie West, and a solo hit with "The One You Say Good Morning To" (1972).

In 1976, Dean achieved a million-seller with another recitation song called "I.O.U.", a tribute to his mother and mothers everywhere. The song was released a few weeks before Mother's Day and quickly became a top 10 country hit, his first in 10 years, and a top 40 pop hit, his first in 14 years. The song was re-released in 1977, 1983, and 1984, but with minor success each time.

In January 1978, Dean hosted an all-star tribute to Elvis Presley titled Nashville Remembers Elvis on His Birthday, during which he reminisced about his friendship with the recently deceased singer and performed his own hit "Big Bad John" and "Peace in the Valley".

Business career
In 1969, he founded the Jimmy Dean Sausage Company with his brother Don. The company did well in part because of Dean's own extemporized, humorous commercials.

The success of the company led to its acquisition in 1984 by Consolidated Foods, later renamed the Sara Lee Corporation. Dean remained involved as spokesman for the company, but the new corporate parent immediately began phasing him out of any management duties. In January 2004, Dean said that Sara Lee had dropped him as the spokesman for the sausage brand because he was too old. In March 2004, Dean revealed that he had sold all but one of his shares in Sara Lee stock. In 2018, several years after his death, the sausage company began re-airing some classic commercials featuring the voice of Dean introducing himself and praising the product.

Later years and death
In the 1980s, he and his wife and family were residents of Tenafly, New Jersey.

A Virginia resident from 1990, Dean was inducted into the Virginia Country Music Hall of Fame in 1997. Former Virginia governor Jim Gilmore appointed Dean to the Virginia Board of Game and Inland Fisheries, which oversees the state's wildlife efforts and boating laws. Dean owned a 110-foot yacht, Big Bad John, on which he hosted President George Bush on numerous occasions. The two had originally met on Dean's cable show in Nashville, where Bush did an impression of Dean selling sausage.

In the fall of 2004, he released his blunt, straight-talking autobiography 30 Years of Sausage, 50 Years of Ham. Dean lived in semi-retirement with his second wife, Donna Meade Dean, a singer, songwriter, and recording artist he married in 1991, who helped him write his book. The couple lived on their property at Chaffin's Bluff overlooking the James River in Henrico County, on the outskirts of Richmond, Virginia. On April 20, 2009, the main house was largely gutted by a fire, although the Deans escaped injury. The Deans rebuilt their home on the same foundation and returned early in 2010.

Dean announced on May 20, 2008, a donation of $1 million to Wayland Baptist University in Plainview, the largest gift ever from one individual to the institution. Dean said: "I've been so blessed, and it makes me proud to give back, especially to my hometown." Dean and his wife also donated generously to Varina High School to reward academic scholars.

On February 23, 2010, Dean was nominated for the Country Music Hall of Fame; he was scheduled to be inducted in October 2010, but this occurred after his death.

Dean had three children, Garry, Connie and Robert, with his first wife Mary Sue (Sue) (née Wittauer) Dean, and two granddaughters, Caroline Taylor (Connie's daughter) and Brianna Dean (Robert's daughter). He married his first wife in 1950; she divorced him in 1990 because of his affair with country-singer Donna Meade who became his second wife. Donna Dean married her childhood sweetheart Jason Stevens two years after Dean's death.

Dean died on June 13, 2010, at the age of 81 at his home in Varina, Virginia. He was survived by his second wife Donna. She told the Associated Press that he was doing well health-wise, so his death came unexpectedly. She recollects that he was eating dinner while watching television, she left the room, and when she came back in he was unresponsive. He was declared dead at 7:54 pm. His estate was estimated to be worth over $50 million.

He was entombed in a 9 ft piano-shaped mausoleum overlooking the James River on the grounds of his estate. His epitaph reads "Here Lies One Hell of a Man", which is a paraphrased lyric from the uncensored version of his song "Big Bad John".

On June 24, 2014, a groundbreaking was held for the Jimmy Dean Museum, which opened two years later on the grounds of Wayland Baptist University in his hometown of Plainview, Texas. Dean's widow, Donna Dean Stevens, was present for the ceremony. The museum houses much of Jimmy Dean's memorabilia as well as a larger-than-life-size bronze statue created by Richmond sculptor Paul DiPasquale and funded by Hillshire Brands, owner of the Jimmy Dean sausage brand. The museum is funded by a gift from the Dean Family Foundation.

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H.R. Pufnstuf

H.R. Pufnstuf is an American children's television series created by Sid and Marty Krofft. It was the first independent live-action, life-sized-puppet program, following on from their work with Hanna-Barbera's program The Banana Splits Adventure Hour. The seventeen episodes were originally broadcast Saturday from September 6, 1969, to December 27, 1969. The broadcasts were successful enough that NBC kept it on the schedule as reruns until September 4, 1971. The show was shot at Paramount Studios and its opening was shot at Big Bear Lake, California. Reruns of the show returned on ABC Saturday morning from September 2, 1972, to September 8, 1973, and on Sunday mornings in some markets from September 16, 1973, to September 8, 1974. It was syndicated by itself from September 1974 to June 1978 and in a package with six other Krofft series under the banner Krofft Superstars from 1978 to 1985. Reruns of the show were featured on TV Land in 1999 as part of its Super Retrovision Saturdaze Saturday morning-related overnight prime programming block and in the summer of 2004 as part of its TV Land Kitschen weekend late-night prime programming block, and it was later shown on MeTV from 2014 until 2016.

In 2004 and 2007, H.R. Pufnstuf was ranked #22 and #27 respectively on TV Guide's Top Cult Shows Ever.

Fast food chain McDonald's later plagiarized the series' concept for its long-running advertising campaign McDonaldland, and the company was successfully sued by the Krofft brothers for copyright infringement.

Overview
The Kroffts created the H.R. Pufnstuf character for the HemisFair '68 World's Fair, where they produced a show called Kaleidoscope for the Coca-Cola pavilion. The character's name was Luther, and he became a mascot for the fair.

H.R. Pufnstuf introduced the Kroffts' most-used plot scenario of a fairy tale of good versus evil, as well as their second plot scenario of the stranger in a strange land. The show centered on a shipwrecked boy named Jimmy, portrayed by teenage actor Jack Wild. He is 11 years old when he arrives on the island and turns 12 in the episode called "The Birthday Party." Jimmy and a talking flute named Freddy take a ride on a mysterious boat, but the boat is actually owned by a wicked witch named Wilhelmina W. Witchiepoo (portrayed by Billie Hayes) who rides on a broomstick-vehicle called the Vroom Broom. She uses the boat to lure Jimmy and Freddy to her castle on Living Island, where she intends to take Jimmy prisoner and steal Freddy for her own purposes.

The Mayor of Living Island is a friendly and helpful anthropomorphic dragon named H.R. Pufnstuf, performed by Roberto Gamonet and voiced by the show's writer Lennie Weinrib, who also voiced many of the other characters. The dragon rescues Jimmy and protects him from Witchiepoo, as his cave is the only place where her magic has no effect.

All of the characters on Living Island were realized by large, cumbersome costumes or puppetry of anthropomorphic animals and objects. Everything was alive on the island, including houses, boats, clocks, candles, and so forth; virtually any part of the Living Island sets could become a character, usually voiced in a parody of a famous film star such as Mae West, Edward G. Robinson, or John Wayne.

Main

 * Jimmy (portrayed by Jack Wild) – A young English human who was lured to Living Island by an enchanted boat. Witchiepoo controlled the boat with the aim of stealing Jimmy's magic talking flute named Freddy.
 * H.R. Pufnstuf (performed by Roberto Gamonet, voiced by Lennie Weinrib in a West Ohio accent) – A friendly dragon who is the Mayor of Living Island.
 * Freddy the Flute (voiced by Joan Gerber) – A magic talking flute that is owned by Jimmy. He is often targeted by Witchiepoo.
 * Cling and Clang (performed by Joy Campbell and Angelo Rossitto) – Two short mute police officers who work for H.R. Pufnstuf as his Rescue Racer Crew. Cling wears red and Clang wears green. Although they appear vaguely animal-like with their beaked faces, and furry three-toed feet, the Kroffts have said they are actually bells, hence their names.
 * Wilhelmina W. Witchiepoo (portrayed by Billie Hayes) – The primary antagonist of the series, inspired by Margaret Hamilton's portrayal of the Wicked Witch of the West. Witchiepoo is a wicked but ineffective witch who has been targeting Freddy the Flute. She rides a large rocket-powered broom with a steering wheel called the Vroom Broom. She is cruel to everyone around her, even her henchmen, whom she constantly whacks with her wand. Yet when faced with failure, Witchiepoo usually starts to pity herself by asking "Why me"?
 * Orson Vulture (performed by Joy Campbell, voiced by Lennie Weinrib) – A stuffy, somewhat inept vulture who is one of Witchiepoo's henchmen. As her favorite flunky, he multitasks as her sounding board operator, butler, and co-pilot on her Vroom Broom. Orson once made the mistake of asking what the W. in his boss's name stood for. The answer: WHACK!
 * Seymour Spider (performed by Angelo Rossitto, voiced by Walker Edmiston) – A dim-witted "spider" (appearance as a furry orange ogre with eight limbs) who is another of Witchiepoo's henchmen. As her second favorite flunky, he primarily serves her as her hairdress and an alternative sounding board operator when Orson was busy.
 * Stupid Bat (performed by Sharon Baird, voiced by Lennie Weinrib) – A bat who is the least favorite and least seen of Witchiepoo's henchmen. He mainly serves as her messenger. As his name implies, Stupid Bat is not very bright and his messages are usually delivered one second too late.
 * Skeleton Guards – Two skeletons who guard Witchiepoo's castle. They are easily spooked and will often run from danger in a flash, but not before their armor and capes fly off in a cartoonish fashion.

Others

 * Dr. Blinky (performed by Johnny Silver, voiced by Walker Edmiston impersonating Ed Wynn) – An owl who is Living Island's local physician and scientist. Dr. Blinky is also the head of H.R. Pufnstuf's "Anti-Smog, Pollution, and Witch Committee". Other characters (including Polka-Dotted Horse) fear his medical incompetence and are terrified at the prospect of being treated by him.
 * Judy Frog (performed by Sharon Baird, voiced by Joan Gerber) – A singing, dancing frog who is one of H.R. Pufnstuf's friends and the resident entertainer. Judy is based on Judy Garland, whom Sid Krofft had previously toured with and opened for.
 * Pop Lolly (voiced by Lennie Weinrib) – A living lollipop who makes and sells candy and other sweet goods.
 * Cheese Guards – Two guards that are living pieces of cheese who work for Pop Lolly. They would often help Pop Lolly fend off a group of Hippie Ants who want to have free candy.
 * Ludicrous Lion (performed by Johnny Silver, voiced by Walker Edmiston impersonating W. C. Fields) – A lion who works as a peddler and owns a horse-drawn wagon. He is quite cunning and not always so honest when it comes to money. Although slightly shady and greedy, he is officially one of the Good Guys since he would often help to thwart Witchiepoo's plots.
 * Polka-Dotted Horse (performed by Felix Silla, voiced by Lennie Weinrib) – A good-natured but dim-witted horse who works for Ludicrous Lion.
 * Tick Tock (performed by Andy Ratoucheff, voiced by Lennie Weinrib) – A mobile alarm clock that warns the good characters when Witchiepoo is coming and informs them of various other dangers.
 * Grandfather Clock (voiced by Walker Edmiston) – A mobile grandfather clock who is married to Grandmother Clock.
 * Grandmother Clock (voiced by Joan Gerber) – A mobile grandmother clock who is married to Grandfather Clock.
 * Miss Wristwatch (voiced by Joan Gerber impersonating Zsa Zsa Gabor) – A glamorous rich mobile human-sized wristwatch.
 * Hippie Ants - A group of ants that would try to have free candy from Pop Lolly.
 * The Boyds - A bunch of birds that serve as Living Island's residential band. The Boyds are based on The Byrds.
 * Lady Boyd (performed by Sharon Baird, voiced by Joan Gerber) – A blue bird who is the lead singer of The Boyds. She was often seen singing the end theme to this show.
 * Shirlee Pufnstuf (performed by Sharon Baird, voiced by Joan Gerber impersonating a younger Shirley Temple) – A dragon who is H.R. Pufnstuf's sister and a famous actress.
 * Max von Toadenoff the Great (voiced by Lennie Weinrib) – A monocled toad who works as a film director. Max von Toadenoff the Great is based on Erich von Stroheim, but named for Akim Tamiroff.
 * The Good Trees – Several walking, talking trees who always help out H.R. Pufnstuf and the good guys. In the film Pufnstuf, the song "Living Island" described them as the "Hippie Trees of Peace and Love". They consist of:
 * Hippie Tree (voiced by Lennie Weinrib) – A tree with sunglasses and dreadlocks who often speaks in hippie slang.
 * Madame Willow (voiced by Joan Gerber) – Also known as the Dowager Tree, Madame Willow is an older, elitist female tree with a lorgnette.
 * Chief Redwood (voiced by Walker Edmiston) – Also known as the Indian Tree, Chief Redwood dons a feathered headdress and speaks in the fashion of a stereotypical melodramatic Native American.
 * There is an older, male tree who may or may not be the husband of Madame Willow.
 * There is another female tree whose lips are always in the shape of an "O".
 * There is a baby tree.
 * The Evil Trees – Three trees on Witchiepoo's side that speak in a Transylvanian accent.
 * Evil Tree #1 – (voiced by Lennie Weinrib impersonating Béla Lugosi) – The leader of the Evil Trees.
 * Evil Tree #2 (voiced by Walker Edminston impersonating Peter Lorre) –.
 * Evil Tree #3 (voiced by Lennie Weinrib) – A tree that always speaks in rhyme.
 * The Mushrooms – A group of talking mushrooms on Witchiepoo's side that turn whoever touches them into mushrooms. The mushroom leader smokes a cigar and speaks like James Cagney.
 * The Crustaceans – They are shown in several episodes as well as the closing theme song, some crab-like characters who are never named or introduced. There is a family of them, much like the living clocks and the living trees. They almost never say anything, but one of them has a couple of brief lines in "The Almost Election of Witchiepoo."
 * Witchiepoo's Castle – A talking, living entity that is home to Witchiepoo and her minions. There is also a door inside the castle that is a separate living entity as well as living pillars.
 * Dr. Blinky's House – A broken down house, propped up with crutches with a bandage on one side and an ice pack atop its chimney. It suffers from explosive sneezing that it has no control over. This usually sends Pufnstuf and friends running for cover, although it has been occasionally used to thwart Witchiepoo's plans enough for her to tell the house to cover its door when it sneezes. It houses several other inanimate talking characters such as fireplace (who speaks like Edward G. Robinson), a test tube (voiced by Walker Edmiston) and a candle (voiced by Walker Edmiston). There is a talking human skull (who speaks like Boris Karloff) and a few talking books, one of which is named Charlie (voiced by Lennie Weinrib). Charlie's brother, an evil black book of spells, is kept on Witchiepoo's nightstand.
 * The Winds – The Winds of Living Island are often called upon by H.R. Pufnstuf to blow Witchiepoo out of the sky. They consist of the North Wind (voiced by Walker Edmiston in a shivering voice), the South Wind (voiced by Joan Gerber in a southern belle voice), the East Wind (voiced by Walker Edmiston in a Chinese accent), and the West Wind (voiced by Lennie Weinrib impersonating John Wayne).

Production
After creating costumes for characters in the live-action portion of The Banana Splits Adventure Hour, Sid and Marty Krofft were asked to develop their own Saturday morning children's series for NBC. The plot was recycled from Kaleidoscope, a live puppet show the Kroffts had staged in the Coca-Cola pavilion of the HemisFair '68 World's Fair. It included several key characters from this show, such as Luther the dragon and a silly witch. Other ideas were cultivated from Sid's life. As a child, he had charged friends buttons, not pennies, to view puppet shows in his back yard; buttons were standard currency on Living Island. Sid and Marty had toured with their puppets as the opening act for Judy Garland, and they based Judy the Frog on her. Ludicrous Lion bears more than a passing resemblance to Irving, the eponymous lion in a pilot they had made in 1957 called Here's Irving.

Sid's friend Lionel Bart asked him to view a rough cut of the movie adaptation of Oliver! Sid took notice of young actor Jack Wild and immediately decided that he was the kid whom he wanted to play the lead in his television series. Only two actresses auditioned to play Witchiepoo. The first was then-unknown Penny Marshall. Stage veteran Billie Hayes came in next, set into a maniacal cackle and hopped up on a desk. She was given the part on the spot.

For Marty Krofft, the production was a particular headache. Marty accepted guardianship of Jack Wild while the teenage boy was in the United States filming the show. He later described bringing Wild into his home as a mistake, considering that he already had his hands full with two young daughters.

Like most children's television shows of the era, H.R. Pufnstuf contained a laugh track, the inclusion of which the Kroffts were initially against. Sid Krofft commented "We were sort of against that, but Si Rose — being in sitcoms — he felt that when the show was put together that the children would not know when to laugh." Marty Krofft added "the bottom line — it's sad — you gotta tell them when it's funny. And the laugh track, (Si) was right. It was necessary, as much as we were always looking to have a real laugh track, a real audience. In comedies, if you don't have them (laugh track), you're in big trouble, because if you don't hear a laugh track, it's not funny. And that's the way the audience (at home) was programmed to view these shows."

H.R. Pufnstuf appeared in a segment of Sigmund and the Sea Monsters, and along with Witchiepoo in the Lidsville episode "Have I Got a Girl For Hoo Doo", where Hoo Doo conjures Pufnstuf as Witchiepoo's date for a witches' dance. The Krofft Superstar Hour also involved characters in two segments The Lost Island (which H.R. Pufnstuf was in) and Horror Hotel (in which Witchiepoo, Orson Vulture, Seymour Spider, and Stupid Bat are featured with Hoodoo). The Kroffts also loaned out the character, with Hayes reprising her role, for The Paul Lynde Halloween Special, in which she appears as the sister of the Wicked Witch of the West (portrayed by Margaret Hamilton).

Theme song
The show's theme song, titled "H.R. Pufnstuf", was written by Les Szarvas but is also credited to Paul Simon. Simon's credit was added when he successfully sued The Kroffts, claiming that the theme too closely mimicked his song "The 59th Street Bridge Song (Feelin' Groovy)". He is credited as the song's co-writer in TeeVee Tunes's Television's Greatest Hits Volume 5: In Living Color.

A cover of the show's theme song, performed by The Murmurs, is included on the 1995 tribute album Saturday Morning: Cartoons' Greatest Hits, produced by Ralph Sall for MCA Records.

Episodes
''All episodes were directed by Hollingsworth Morse and written by Lennie Weinrib and Paul Harrison. (Robert Ridolphi also co-wrote Episode 1 "The Magic Path".) ''

Cast

 * Jack Wild – Jimmy
 * Billie Hayes – Wilhelmina W. Witchiepoo

Voice characterizations

 * Lennie Weinrib – H.R. Pufnstuf, Bela Lugosi Tree, Dr. Blinky's Talking Book, Stupid Bat, Pop Lolly, West Wind, Akim Toadenoff the Great, Orson Vulture, Polka Dotted Horse, Hippie Tree, Alarm Clock, Jimmy as Movie Villain
 * Walker Edmiston – Dr. Blinky, Peter Lorre Tree, Dr. Blinky's Candle, East Wind, Grandfather Clock, North Wind, Chief Redwood, Dr. Blinky's Test Tube, Ludicrous Lion, Seymour Spider
 * Joan Gerber – Freddy the Flute, Grandmother Clock, Judy the Frog, Madame Willow, South Wind, Lady Boyd, Shirley Pufnstuf

Film
While the television series was still in production, the Kroffts were approached to do a film adaptation. A joint venture between Universal Pictures and the show's sponsor Kellogg's Cereal, the 1970 film retained most of the cast and crew from the series and featured guest appearances by Cass Elliot as Witch Hazel and Martha Raye as Boss Witch. The movie was finally released on VHS in 2001 by Universal Home Video as part of its Universal Treasures Collection and on DVD on May 19, 2009. The film also included Googy Gopher, Orville Pelican, and Boss Witch's chauffeur Heinrich Rat, who were exclusive to the movie. A difference in the film is that the characters that had been voiced by Lennie Weinrib were each voiced by Allan Melvin and Don Messick.

The Kroffts have long had plans for a new H.R. Pufnstuf film. Sony first attempted a remake in 2000, but dropped the project. Eight years later, Sony again announced development on the project, but there has been no news since.

Tours
A number of stage show tours were run in the United States starring the characters from the show. The most prominent of these was "H.R. Pufnstuf & The Brady Kids Live at the Hollywood Bowl", which was performed and recorded in 1973. This performance was released on VHS in 1997.

In 1970, H.R. Pufnstuf was featured in a float at the Rose Parade in Pasadena, featuring the cast from the show.

An elaborate H.R. Pufnstuf puppet show was featured at The Sid and Marty Krofft Puppet Theater at Six Flags Over Mid-Missouri in 1971. H.R. Pufnstuf and his pals Cling and Clang also made life-size appearances at the park. A section of the 1971 Six Flags Over Mid-Missouri map shows the location of the theater near entrance to the park's Sky-Way Ride.

Home media releases
In 2004, Rhino Entertainment/Rhino Retrovision released H.R. Pufnstuf: The Complete Series, featuring all 17 episodes on three discs, remastered and uncut, accompanied by interviews with Sid & Marty Krofft, Billie Hayes, and Jack Wild. Pufnstuf, a major motion picture released in 1970, was also released on May 19, 2009, by Universal Studios. SMK and Vivendi Entertainment has obtained the home video rights to the series and released the complete series on January 11, 2011. Two versions of the release exist; one is a traditional complete series set, while the other is a collector's set, featuring a bobble-head of H.R. Pufnstuf. The series is also available in Digital media format at iTunes Store.

In the United Kingdom, during 1986, Channel 5 Video released the opening three episodes of the television series on VHS.

McDonaldland lawsuit
The show was the subject of a successful U.S. federal lawsuit brought by the Kroffts against the fast food restaurant McDonald's, whose McDonaldland characters were found to have infringed the show's copyright. The case, Sid & Marty Krofft Television Productions Inc. v. McDonald's Corp., 562 F.2d 1157, was decided by the U.S. Court of Appeals for the Ninth Circuit in 1977.

Claims of drug references
The Krofft brothers have responded in several interviews to popular beliefs that subtle recreational drug references exist in the show. For example, the title character's name Pufnstuf has been interpreted as a reference to smoking hand-rolled (H.R.) marijuana (puffin' stuff);    Marty Krofft has said the initials H.R. actually stand for "Royal Highness" backwards. The show's theme song lyric "he can't do a little, 'cause he can't do enough" has been read as referring to the addictive nature of drugs. Pufnstuf has quotes like "Whoa, dude!" and other "hippie" slang words. Lennie Weinrib, the show's head writer and the voice of Pufnstuf, has said, "I think fans gave it a kind of mysterious code-like meaning, like 'Ah, was Pufnstuf puffing stuff? Like grass?' Was it psychedelic? Was it drug oriented? Not to us, it wasn't." In a 2000 interview, Marty Krofft answered the question by saying, "The Krofft look has a lot of color, but there were no drug connotations in the show." He addressed the topic at length in an interview with the St. Louis Post-Dispatch in 2004, in response to the question, "OK, let's get this right out in the open. Is H.R. Pufnstuf just one giant drug reference?":

"We've heard that for 35 years. We did not intentionally do anything related to drugs in the story. People thought we were on drugs. You can't do good television while on drugs. People never believe you when you say that, but you can't. The shows were very bright and spacey looking. They may have lent themselves to that culture at the time, but we didn't ascribe that meaning to them, and I can't speak to what adults were doing when they were watching the shows. We just set out to make a quality children's program."

Authors of books on the show and its contemporaries, however, have not always accepted the Kroffts' alternative explanations for apparent references to drugs. David Martindale, author of Pufnstuf & Other Stuff, maintains that the Kroffts' desire to attract an audience who are now parents of impressionable children pushes them to downplay the double entendres: "But to deny it, the shows lose some of their mystique. The Kroffts prefer to remain playfully vague." Martindale said in another interview that he fully believes Marty Krofft's insistence that he did not use drugs, especially given that Marty's focus was that of a businessman, but Martindale describes Sid Krofft as "a big kid" and "a hippy", saying, "His comment when I told him we were going to do this book was—and I quote—'Oh, far out.' He says these shows didn't come from smoking just a little pot, and you could say, 'Oh, yeah. It comes from smoking a lot of pot.' But I think he was very deliberately doing double meanings so the show could amuse people on different levels."

Kevin Burke, co-author of Saturday Morning Fever: Growing Up with Cartoon Culture, argues that the "consistency of thought" in the rumors of drug references has a basis, although his co-author and brother Timothy Burke, a history professor at Swarthmore College, insists "human beings are capable of achieving hallucinatory heights without chemical assistance." Contradicting his own position, Marty Krofft has neither admitted nor hinted in occasional interviews that the references were made knowingly; in one case, a writer reported that when pressed as to the connotation of "lids" in the title Lidsville, "Well, maybe we just had a good sense of humor", Krofft said, laughing. His comments to another interviewer were more direct; in a Times Union profile whose author observed, "Watching the shows today, it's hard to imagine a show with more wink-and-nod allusions to pot culture, short of something featuring characters named Spliffy and Bong-O", Krofft conceded that the show's title had been an intentional marijuana reference, as had Lidsville, but "that was just a prank to see if they could get them past clueless NBC executives".

Parodies and tributes

 * H.R. Pufnstuf appears in the eighth episode of the first-season of CHiPs, titled "Green Thumb Burglars", with his voice reprised by Lennie Weinrib. He is pulled over by Ponch (Erik Estrada) and Jon (Larry Wilcox) on one of Los Angeles' numerous freeways. Though he was referred to by name, while Jon maintained a sense of decorum about the actor inside the Pufnstuf suit, he let the good Mayor Pufnstuf off with a warning. Ponch later declared himself a "big overgrown kid", in reference to the kids' show.
 * One of the most notable parodies of H.R. Pufnstuf was "The Altered State of Druggachusetts", a segment on the HBO comedy series Mr. Show with Bob and David. The sketch consists of a failed television pilot for a kids' show introduced by "Sam and Criminy Craffft" (portrayed by Bob Odenkirk and David Cross). The show itself is similar to H.R. Pufnstuf, with drug references made humorously overt. Instead of a talking flute, the boy carries a talking bong, and all of the residents in Druggachusetts take or are living incarnations of various drugs.
 * Nike made a skateboarding shoe for their SB Dunk line named after the show, with the colors of the shoe resembling those of Pufnstuf.
 * Todd Kauffman, animator and director of the Total Drama series, initially made a pitch for an animated adaption of H.R. Pufnstuf in 2005 complete with an animated opening sequence with the theme song covered and performed by Finger Eleven, but option rights costs led the project to be disbanded. Kauffman however, was later inquired to do the cover for the DVD release, "Sid & Marty Kroffts Saturday Morning Hits".
 * H.R. Pufnstuf appears in the fifth episode of season 3 of My Name Is Earl titled "Creative Writing". In a fantasy sequence based on a story written by Randy (Ethan Suplee), H.R. Pufnstuf is the sidekick to Randy's secret agent character.
 * In 2016, H.R. Pufnstuf, Cling, Clang, and Freddy the Flute appear in a crossover episode of Mutt & Stuff titled "H.R. Pufnstuf Comes to Mutt & Stuff!" with H.R. Pufnstuf voiced by Randy Credico with Mary Karcz providing the in-suit performance and Donna Kimball providing the face performance, Freddy the Flute performed by Kimball, and Cling and Clang performed by Arturo Gil and Joseph S. Griffo. H.R. Pufnstuf is depicted as the uncle of Stuff.
 * In 2017, professor of religion Jeffrey Kripal wrote in his book Secret Body of the show's impact on his young life. "Disturbing," he recalled. "Who wrote this stuff? And puff'n on what stuff?"
 * In 2018, reference to H.R. Pufnstuf is made in Season 2 of the Amazon Original show Goliath. In the show, criminal billionaire Tom Wyatt (Mark Duplass) recreates his own erotic memories/fantasies from his childhood while the intro to H.R. Pufnstuf is playing on the TV. Duplass' character on the show is fixated on individuals, male and female, who have lost their limbs. While having ties to the "La Mano Cartel" on the show, the head of the cartel, removes limbs, heads, etc., and sends these people to Wyatt to use in his fantasies. Each time before Duplass' character reverts to his fantasies, he says "H.R. Pufnstuf, who's your friend when things get rough?"

title: H.R. Pufnstuf


text:
Edward MacLysaght

Edgeworth Lysaght, later Edward Anthony Edgeworth Lysaght, and from 1920 Edward MacLysaght (Éamonn Mac Giolla Iasachta; 6 November 1887 – 4 March 1986) was a genealogist of twentieth-century Ireland. His numerous books on Irish surnames built upon the work of Rev. Patrick Woulfe's Irish Names and Surnames (1923).

Early life and education
Edgeworth Lysaght was born at Flax Bourton, Somerset (near Bristol), to Sidney Royse Lysaght, of Irish origin, a director of the family iron and steel firm John Lysaght and Co. and a writer of novels and poetry, and Katherine (died 1953), daughter of Joseph Clarke, of Waddington, Lincolnshire. Lysaght's grandfather, Thomas Royse Lysaght, was an architect, and his great-grandfather, William Lysaght, a small landowner distantly connected with the Barons Lisle. Lysaght was named "Edgeworth Lysaght" after his father's friend, the economist Francis Ysidro Edgeworth; "Edward" was added at baptism, and he was called "Ned". "Anthony" was added at confirmation. He lost the sight in one eye after a childhood accident.

Lysaght was educated at Nash House preparatory school, Bristol, and at Rugby School, where he was unhappy, his parents' frequent absence due to his father's business responsibilities necessitating travel to South America, South Africa, and Australia contributing to this. He was a contemporary there of Rupert Brooke, whose father was Lysaght's housemaster. Eighteen months after leaving Rugby, on the advice of Francis Edgeworth, he then went to Corpus Christi College, Oxford, to study law, but, having on his own account "had a wild time as part of the smart set" and anticipating rustication after a drunken incident, he left after three terms.

Life in Ireland
Lysaght took up residence in a caravan at Lahinch, County Clare, Ireland, where he had previously holidayed and become friendly with local people. His father, himself strongly connected to his Irish boyhood and wanting to establish himself as a "country gentleman", recognized his son's enthusiasm for Ireland and in 1909 bought a 600-acre estate at Tuamgraney, at which Lysaght would farm until 1913, introducing an electrical generator and other forms of modernization including the development of a limekiln, nursery, and school where young men of means could learn the basics of farming. This was the beginning of a metamorphosis for Lysaght; although of English upbringing, he disliked the local gentry, considering them "layabout rentiers", and preferred to make friendships amongst employees and his neighbours.

He sought to replace his English accent with a Clare one, and eschewed his lack of religion (despite an Anglican upbringing) of a few years before in favour of Roman Catholicism, and became involved in the Gaelic League. An integral factor in Lysaght's reinvention was his relationship with Mabel ("Maureen") Pattison; five years his senior, they had met when Lysaght spent a period at a Dublin hospital. She was born and raised in South Africa, her father a civil servant there, but had an Irish family including a local postmistress. Lysaght's family sought to avoid what they considered an unsuitable marriage, sending Lysaght and his brother Patrick on a world tour taking in Ceylon and Japan, but they were nevertheless married at the Brompton Oratory on 4 September 1913. They had two children. Mabel introduced him to friends in the Arts Club, and Lysaght entered Dublin literary society; his "somewhat overdone" attempts to "give himself a new, more Irish identity" were noticed by acquaintances. Lysaght's father invested £300 in Maunsell's publishers, who produced Lysaght's book of poems Irish eclogues. As of the early 1930s, he served on the General Committee of the Munster Agricultural Society. He and Mabel later divorced in South Africa. Lysaght remarried to Mary Cuneen. He had three children with his second wife.

By 1915 Lysaght's command of Irish had improved dramatically, and in that year he founded the Nua-Ghaeltacht at Raheen, County Clare.

He was an independent delegate to the 1917–1918 Irish Convention in which he opposed John Redmond's compromise on Home Rule. By 1918 his involvement in all aspects of the Irish independence movement had deepened greatly. Although not known if he was actually a member of the Irish Republican Army (IRA), he was very active in the Irish War of Independence as a supporter, financially and otherwise, of the East Clare Brigade of the IRA.

In 1919, he published a largely autobiographical novel entitled The Gael. In 1920, Lysaght, along with others of the name, changed his name to "MacLysaght", "so as to emphasise its Gaelic origin".

His Raheen office served as a meeting place for the Volunteers and guns, documents and ammunition were stored there. However, the war led to a sharp decline in the fortunes of his farm. The execution of close friends such as Conor Clune of Quin in November 1920 and the subsequent devastating raids on his farm resulted in his playing a far more active role in Sinn Féin as a loyal supporter of the new TD for Clare, Éamon de Valera. For this, he was imprisoned following his return from Britain as part of a Sinn Féin delegation which was publicising the Black and Tans atrocities.

Later life
MacLysaght was elected to the Free State Seanad Éireann in 1922. He was appointed Inspector for the Irish Manuscripts Commission in 1938. MacLysaght was elected to the Royal Irish Academy in 1942 and in the same year was awarded a D.Litt. He was appointed Chief Herald of Ireland in 1943 and served in this post until 1954. MacLysaght served as Keeper of Manuscripts at the National Library of Ireland from 1948 to 1954 and was Chairman of the Irish Manuscripts Commission from 1956 to 1973.

Death
MacLysaght died on 4 March 1986, aged 98, and was interred in the graveyard of St. Cronan's Church, Tuamgraney.

Works

 * Irish Life in the Seventeenth Century (1939)
 * The Surnames of Ireland
 * Supplement to Irish Families
 * More Irish Families
 * More Irish Families incorporating Supplement to Irish Families
 * The Gael (1919)
 * Cursaí Thomáis (1927)
 * Changing Times (1978)
 * Changing Times (1978)

title: Edward MacLysaght


text:
Ned Flanders

Nedward "Ned" Flanders Jr., commonly referred to by his surname, is a fictional character in the animated television series The Simpsons, voiced by Harry Shearer and first appearing in the series premiere episode "Simpsons Roasting on an Open Fire." He is the good-natured, cheery next-door neighbor to the Simpson family and is generally loathed by Homer Simpson, though there are numerous instances where the two are portrayed as good friends. A scrupulous and devout Evangelical Christian, he is among the friendliest and most compassionate of Springfield's residents and is generally considered a pillar of the Springfield community.

He was one of the first characters outside the immediate Simpson family to appear on the show, and has since been central to several episodes, the first being season two's "Dead Putting Society". As the series progressed, Flanders's religious fanaticism increased immensely, prompting the coining of the term "Flanderization". His last name comes from Flanders Street in Portland, Oregon, the hometown of Simpsons creator Matt Groening.

Creation

Ned Flanders, who was designed by Rich Moore, first appeared in the season one episode "Simpsons Roasting on an Open Fire". The episode was the series premiere, but not the first episode produced. The first episode in which Flanders and his family were prominent is season two's "Dead Putting Society", which also contained the first appearance of Maude and Rod Flanders. The character was named after Flanders Street in Portland, Oregon, the hometown of Simpsons creator Matt Groening. Groening described the inspiration for Flanders as "just a guy who was truly nice, that Homer had no justifiable reason to loathe, but then did". It was not until after the first few episodes that it was decided Flanders would be a faithful Christian. Mike Scully noted that Flanders is "everything Homer would love to be, although he'll never admit it". Flanders had been meant to be just a neighbor that Homer was jealous of, but Harry Shearer used "such a sweet voice" and Flanders was broadened to become a Christian and a sweet guy that someone would prefer to live next to over Homer. Flanders is known for his nonsensical jabbering, such as "Hi-diddly-ho, neighborino" (meaning "Hi, neighbor"). His first use of the word "diddly" was in "The Call of the Simpsons".

Development
Ned Flanders' religion was not mentioned in his first few appearances and in the first few seasons he was only mildly religious and his primary role was to be so "cloyingly perfect as to annoy and shame the Simpsons", whereas Homer Simpson has always hated Ned Flanders and always tries to undermine him. There has been a consistent effort among the show's writers to make him not just a "goody good and an unsympathetic person". In the later seasons, Flanders has become more of a caricature of the Christian right, and his role as a "perfect neighbor" has been lessened. For example, in some recent episodes Flanders has appeared to show rather prejudiced attitudes towards women, non-whites, homosexuals and people of religions other than Christianity. Though he only ever showed homophobic signs in non-canon episodes, notably "Frinkenstein" where he says "I'm running to find a cure for homosexuality".

Ned's store the Leftorium first appeared in "When Flanders Failed". It was suggested by George Meyer, who had had a friend who had owned a left-handed specialty store which failed.

There have been at least two occasions where Ned was not voiced by Harry Shearer. In "Bart of Darkness", Flanders's high pitched scream was performed by Tress MacNeille and in "Homer to the Max", Flanders comments about cartoons being easily able to change voice actors and on that occasion he was voiced by Karl Wiedergott.

The Adventures of Ned Flanders
The Adventures of Ned Flanders was a "series" of shorts starring Flanders, but only one episode, "Love that God", was produced. It appears at the end of the fourth season episode "The Front" because the episode was too short and the producers had already tried "every trick in the book" to lengthen it. Although the episode was scripted by Adam I. Lapidus, "Love That God" was written by Mike Reiss, Al Jean and Sam Simon. In the 34-second-long segment, which comes complete with its own theme song, Ned walks into Rod and Todd's room as they are praying and tells them it is time for church. He is upset when Todd replies that they are not going, until Todd reminds him it is Saturday, and Ned laughs at his mistake.

Most fans were confused by the short, but Bill Oakley and several other writers loved it so much that they wanted to do more. Later, Oakley and Josh Weinstein decided to produce an entire episode that was nothing but loosely associated shorts, which became the season seven episode "22 Short Films About Springfield". The Flanders/Lovejoy segment of that episode was written by David X. Cohen. "22 Short Films about Springfield" in turn inspired the Futurama episode "Three Hundred Big Boys".

Role in The Simpsons
Ned is very honest and sincere in carrying out the Christian doctrines of charity, kindness, and compassion. He is frequently shown doing volunteer work, and is rigorously honest and upright, even going so far as to spend an entire day tracking down a Leftorium customer in order to give him the extra change that he had forgotten to hand over.

In "Homer's Triple Bypass", he donates a kidney and a lung out of the goodness of his heart to whoever needs them first. He also is a good neighbor to the Simpsons, regularly offering his assistance. Ned's dogged friendship inspires the loyalty of others; when his Leftorium shop appeared on the verge of bankruptcy shortly after it opened, Homer arranged a bailout with the help of many people in Springfield. Despite a meek outward appearance, Ned hides an exceptionally well-toned physique.

The Simpsons' good neighbor
In the early years of The Simpsons, Homer Simpson generally loathed Ned, because Ned's family, job, health and self-discipline are of higher quality than he could ever hope to attain himself. Homer is often shown "borrowing" (stealing) items from Flanders, such as a weather vane, a camcorder, a diploma, a toothbrush and an air conditioning unit. Even the Simpsons' couch came from "the curb outside Flanders' house". Homer has since come to have a love-hate relationship with Ned, sometimes being his best friend, partly due to Ned's selfless tolerance of him, and other times treating Ned with complete disregard. Homer seems to genuinely care for Ned, despite still expressing and often acting on feelings of loathing. Nowadays Homer seems to regard Ned as more of a nuisance. An early running joke was that Marge considers Flanders to be a perfect neighbor, and usually sides with him instead of her husband, which always enrages Homer. In "Left Behind," Homer succinctly states, "[Flanders] makes me feel so damn guilty!"

Religiosity
Ned Flanders is a genuinely well-meaning good-natured person and is one of the few in Springfield to whom that description applies. Firmly religious, he can be timid and something of a pushover. He is a Republican and a devout Evangelical Christian who strictly follows the Bible literally and is easily shocked when challenged on any point of dogma. This causes frequent calls to Reverend Lovejoy, even over minuscule things, to the point that Lovejoy has stopped caring and has even suggested that Flanders try a different religion. This was a running joke in the early seasons, but has been used less in the later episodes. In the eighth season, the episode "In Marge We Trust" would examine the relationship between Lovejoy and Flanders, and shows the history of their relationship and how Lovejoy became increasingly uninterested in Flanders' problems. Flanders is shown to have a room in his house filled with memorabilia of The Beatles. He claims that this is because they were "bigger than Jesus".

Family and job
Ned is a widower, having been married to the equally religious Maude. They had two children together; the sheltered and naïve Rod and Todd Flanders. In the eleventh season episode "Alone Again, Natura-Diddily", Maude died an untimely death in a freak accident involving a T-shirt cannon, leaving Flanders alone and grieving. While still married to Maude, Ned married Ginger, while on a drunken bender in Las Vegas. Ginger came to live with Ned and his sons for a brief period following Maude's death in a later episode, but she quickly grew tired of the Flanders' sickly-sweet personalities and fled. Despite his outward nerdishness, Flanders has also been connected romantically with a beautiful Christian-rock singer, Rachel Jordan, movie star Sara Sloane and eventually marrying local teacher Edna Krabappel until she died as well.

Ned got his diploma from Oral Roberts University in an unspecified field and worked as a salesman in the pharmaceuticals industry for the bulk of his adult life. Having saved much of his earnings, Flanders decided to quit his job and invested his family's life savings into a store in the Springfield mall called the Leftorium specializing in products for left-handed people. In the fifth season episode, "Sweet Seymour Skinner's Baadasssss Song", Superintendent Chalmers fires Ned Flanders, who has become principal after Skinner being sacked, only because he freely expresses his religious views in the school. However in the Season 29 episode "Left Behind", owing to declining sales, the Leftorium had been downsized from an outlet to a kiosk, eventually going out of business alongside the Sears outlet at Springfield Mall. Leaving Flanders unemployed, he returned to Springfield Elementary School, finding a new job as Bart Simpson's new teacher and substituting the void left by his deceased second wife Edna Krabappel, as well as honoring her life dream. Flanders remained Bart's teacher until the Season 33 episode "My Octopus and a Teacher", at which point the role was assumed by Rayshelle Peyton.

In the episode "Hurricane Neddy" a flashback to 30 years earlier shows Ned as a young child, despite the fact that in the episode "Viva Ned Flanders" he says to the church congregation that he was actually 60 years old, attributing his youthful appearance to his conformity to the "three Cs"—"clean living, chewing thoroughly, and a daily dose of vitamin church". Ned grew up in New York City and was the son of "freaky beatniks" who did not discipline Ned (as they did not think it was right) and let him run wild. Eventually they took him to Dr. Foster, a psychiatrist, who put the young Ned through the University of Minnesota Spankalogical Protocol, which involved eight months of continuous spanking. The treatment worked so well that it rendered Flanders unable to express any anger at all and resulted in his trademark nonsensical jabbering at moments when he was particularly close to losing his temper, causing Ned to unknowingly repress his anger.

Reception
Although in more recent seasons Flanders has become a caricature of the Christian right, he is still a favorite of many Christian viewers. Rowan Williams, a former archbishop of Canterbury, is a confessed Simpsons fan, and is reportedly a Flanders fan. Ned's "unbearable piousness" has been described as The Simpsons' sharpest critique of organized religion: "The show's implicit argument seems to be that humorless obsessives like Ned have hijacked religious institutions, removing them from the center of society to a place where only those who know their brides of Beth Chedruharazzeb from their wells of Zohassadar can seek solace." Steve Goddard of the website Ship of Fools said, "Ned is an innocent abroad in a world of cynicism and compromise. We love him because we know what it's like to be classed as a nerd – and to come out smiling at the end of it." The February 5, 2001 edition of Billy Graham's Christianity Today, titled Saint Flanders, featured Flanders, along with Homer and Marge, on the cover and described him as "the most visible evangelical to many Americans."

Cultural impact
Flanders has been described as "The United States' most well-known evangelical". According to Christianity Today in 2001, "on American college and high school campuses, the name most associated with the word Christian—other than Jesus—is not the Pope or Mother Teresa or even Billy Graham. Instead, it's a goofy-looking guy named Ned Flanders on the animated sitcom known as The Simpsons. The mustache, thick glasses, green sweater, and irrepressibly cheerful demeanor of Ned Flanders, Homer Simpson's next-door neighbor, have made him an indelible figure, the evangelical known most intimately to nonevangelicals." In 2001 and 2002, the Greenbelt Festival, a British Christian music and arts fest, held a special "Ned Flanders Night". The 2001 event featured a look-alike contest, as well as the tribute band "Ned Zeppelin". It was held in a 500-seat venue that was filled to capacity, and an extra 1500 people were turned away at the door. A second event was held in 2002, with Ned Zeppelin reappearing. In 2017, after then-president Donald Trump insulted anchor Mika Brzezinski on Twitter, Orrin Hatch responded and said, "Every once in a while you get a dipsy-doodle," as Ned Flanders' term. In 2019, Trevor Noah on The Daily Show compared Mike Pence to Flanders when discussing the Ukraine scandal. Aaron Stonehouse, Western Australia's first Liberal Democrat MP, made a comparison between the McGowan government and Ned Flanders' wife, Maude Flanders, a devout Christian who died after being knocked off a grandstand in a T-shirt cannon accident on The Simpsons. In 2022, Relevant claimed that Flanders was "unapologetically not cool" as a Christian, but overall "decent".

Professional ice hockey goaltender Peter Budaj was known for having Ned Flanders painted on his mask during his hockey career. Another tribute band, Okilly Dokilly, plays heavy metal music. In 2018, MadeinTYO released a rap song about Flanders. The Ned Flanders Crossing, a pedestrian and bicycle bridge over Interstate 405 in Portland, Oregon, was named for the character in 2021. It connects two sections of Northwest Flanders Street, for whom the character is named.

Flanderization
Flanders' significant evolution of his Christian fanaticism has led to the term dubbed "Flanderization", which refers to the increasingly exaggerated characterization of any character throughout a TV or a film series. The specific case of Flanders attracts special attention. Debate exists over whether Flanders is a consistently flanderized character or whether he later returned to a more complex, dynamic portrayal. The appropriateness of the term "flanderization" has also been disputed, as many characters in The Simpsons have undergone the caricaturizing process, and Flanders himself may not be the most extreme case. Flanders' shifting portrayal has also been controversial as representative of a shift in media portrayals of religious people. As both the primary representative of Christianity on The Simpsons and as one of the most significant Christian fictional characters in the real world, the simplification of Flanders as a character has been the subject of criticism, study, and reinterpretation.

Merchandise
Flanders has been included in The Simpsons merchandise. In 2008, the Flanders' Book of Faith, part of the Simpsons Library of Wisdom, was released by HarperCollins. The book takes a look at Flanders' life and his ever enduring faith. In 2021, Flanders got a sneaker line from Adidas.

title: Ned Flanders