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In 1976, due to an outbreak of influenza at Fort Dix, New Jersey, the United States set a precedent in immunology by attempting to vaccinate the entire population of the country against the possibility of a swine-type Influenza A epidemic. While a great many people were successfully immunized in a very short period of time, the National Influenza Immunization Program (NIIP) quickly became recognized as a failure, one reason being that the feared epidemic never surfaced at all. But this massive undertaking deserves more analysis than just a simple repudiation. For example, all evidence linked to the pathology, microbiology, and historical cycle of influenza and the outbreak at Fort Dix suggests that the reactions of the scientists and other personnel involved in the NIIP were correct. However, one must also acknowledge the many complications and misjudgments that plagued the program after its initiation, from biological difficulties, logistical problems, to tensions with the media. The swine flu is a historical event that needs to be evaluated, regarding both its successes and its failures, so that lessons can be learned for future immunization programs.
While influenza, or the “flu”, is not commonly recognized as an extremely lethal disease, the pathology of influenza, and especially of the kind found at Fort Dix, does suggest that an immunization program was a reasonable course to take in 1976. In the public’s mind, influenza is often not seen as a specific disease, using interchangeable names for it like “flu”, “gripe”, and “virus”. (Silverstein: 1) However, influenza is very different from an everyday low fever or “stomach flu”. It is a respiratory infection, connected with a fever, coughing, and muscle aches, which often lasts a few days in duration.
While the disease itself is usually harmless, it can lead to exposure of the lungs to viral or bacterial pneumonia, which can prove fatal, especially for the very young, elderly, or infirm. (Silverstein: 13) There are three types of influenza, depending on their activity: type A, which is usually the cause of outbreaks; type B, which is linked to sporadic cases, and type C, which rarely causes disease reactions. (Silverstein: 54) The virus which causes influenza enters the host through the respiratory tract, and binds itself to epithelial cells. The virus causes the cell to engulf it by endocytosis, and then fuses to the wall of the endocytic vesicle, injecting the contents of the virus into the cytosol of the cell. The RNA of the virus enter the nucleus of the cell, and spur the creation of new copies of the genes. These genes, as well as new viral proteins that are created in the cell, leave the cell as fresh viruses, budding off the plasma membrane of the cell.
While Scientists still do not know a great deal about the communicability of influenza, they do know that it can be spread by human-to-human contact, and has some airborne stability. (Silverstein: 59) Specifically, the characteristics of the influenza at Fort Dix was extremely discouraging. First of all, it was very similar to the 1918 swine influenza A pandemic, which turned out to be one of the most lethal outbreaks of disease in recorded history, and one victim had already died. Also, while usually this disease is caused by exposure to pigs, it was obvious that this was the first time since the earlier pandemic that it was being spread by people. (Silverstein: 23) While influenza is usually not deadly in itself, the scientists in 1976 were right to assume that the virus was a serious threat.
The biological similarity between the influenza at Fort Dix and the swine flu of 1918 was one of the biggest factors in determining the course of action to be taken at that point. The influenza virus is globular in shape, and is approximately 100 nanometers in diameter. The sheath of the virus is made up of a lipid bilayer, taken from the plasma membrane of the original host. Within the central core of this bilayer are located about 3000 matrix proteins (which differ depending on the type of the influenza), and 8 RNA genes. The surface membrane is spiked with protein molecules of two kinds: about 500 hemagglutinin (“H”) and 100 neuraminidase (“N”) molecules. Hemagglutinin molecules appear as pointed spikes, which are used to bind the virus to a cell and inject contents into it. Neuraminidase appear as blunt spikes, and possesses specialized enzymes which cause the infected cell to release the new viruses. (Silverstein: 50-52 and <u>Flu</u>) <p>
The influenza virus is relatively unique in its ability to change its H and N molecules, called antigenic shift. For example, the swine flu of 1918 was named H1N1, while a later strain of influenza which was found to have changed its hemagglutinin molecules was named H2N1, and an even later influenza was found to have changed both its surface molecules (double antigenic shift), and was named H2N2. Scientists believe that these changes are due to the recombination of influenza viruses from different sources, such as if an influenza from a swine was mixed with an influenza from a person, which could create an new strain that has swine-type hemagglutinin and human-type neuraminidase. (Silverstein: 55-56) Spot mutations on the viral RNA, or missence mutations, also occur and are thought to cause slight changes in the make-up of the influenza virus, or antigenic drift. (<u>Flu</u>) It has been observed that an antigenic shift usually occurs after a number of years, after the population has built up immunities to the old strain. It is common for a major outbreak to occur after a shift, and even more likely after a double shift, because the antibodies in the population are useless against these new forms of disease. Missence mutations usually cause smaller epidemics, since the change in the virus is not so great. It has also been found that older strains of influenza are likely to return to a population once the antibodies against them have mostly died out. (Silverstein: 55, 62 and Flu) What was particularly alarming about the influenza at Fort Dix was that not only was it a double antigenic shift, but it was a shift back to H1N1, the cause of the 1918 pandemic. (Silverstein: 55) The biological make-up of the swine flu was evidence enough to take precautions against a major outbreak.<p>
The influenza virus’ shifts created a cycle of virility of the disease, one that also pointed to the possibilities of a major outbreak in 1976. Owing to its constant adaptation and re-emergence, there is much reason why influenza is called “The last great plague”, since it is basically impossible to come up with a lasting solution to it. (Silverstein: 9) While influenza has been recorded since the 15th century, the number of years between major world outbreaks (or pandemics) has decreased in the last century, due to increased and faster intercontinental travel, which accelerates the build-up of immunity to a given influenza strain. (Silverstein: 11) It has been hypothesized that the cycle has now stratified into 11-year periods between major antigenic shift pandemics. Within these periods occur smaller epidemics (centralized outbreaks), linked to an antigenic drift. (Silverstein: 18-19) It is also suggested that the strains recycle themselves in about 50 years, long enough so that most of the original immunities have died out in a population. (Silverstein: 55) This model appears to function well, since there were exactly 11 years between the pandemics of 1946, 1957, and 1968, as well as the fact that the 1957 disease was similar to the 1889 disease, and the 1968 disease was similar to that of 1900. (Silverstein: 57) Using this model, the next year for a major pandemic would be fairly close to 1976, and the next strain up for recycling would likely be the swine flu of 1918.
Looking at the pathological, microbiological, as well as historical evidence surrounding the Fort Dix outbreak, it is not difficult to see why those in charge in 1976 decided that action had to be taken. It is also important to note, however, how they decided what action this was going to be. There are a few possibilities of drugs that can be taken to fight influenza. Examples of these are Amantadine, which blocks the shift of pH in the infected cell which triggers the release of the RNA into the cytosol; Zanamivir, which blocks the neuraminidase and inhibits the release of the viruses (though this drug was not even around in 1976); and antibiotics, which do not affect the flu, but can help against secondary bacterial infections. There are very few drugs that can be taken, however, because it is difficult to find a drug which affects the processes of the virus which does not also hurt the cell (Flu) Vaccines, which trigger the body’s production of antibodies without actually causing the disease, are usually more productive then drugs. While antibodies created against the core proteins of the influenza virus do not create an ineffective immunity, the antibodies created against hemagglutinin are extremely potent, and block the penetration of cells by the virus. Also, neuraminidase antibodies help to lessen the release of viruses from cells and the disease’s spread. (Silverstein: 52-54) Because of these reasons, the scientists in 1976 chose to create a vaccine against the swine flu. Another question surrounding the action to be taken involved whether to stockpile the vaccine after manufacturing it for the country, or immediately moving to immunization. It was decided to go ahead with immunization, because they had a good amount of time until the next flu season to organize the project, the threat of swine flu seemed real, and if they waited until influenza hit they would not have time to start the vaccinations before the disease set in. (Silverstein: 29-31) Another, though more personal reason for the decision to immunize was that it gave the scientists, like those at the Center for Disease Control (CDC) who were heading up the project, an opportunity to demonstrate to the public the value of immunizations. (Silverstein: 38)
To truly understand the National Influenza Immunization program, it is necessary to look at the operation itself. The preparation of the vaccine was similar to previous vaccine productions, except it was to a much larger scale – about 200 million doses. (Silverstein: 105) To create the vaccine, the scientists inject the appropriate strain of influenza (and possibly another strain to increase growth) into embryonated eggs, which create a culture for the viruses. The multiplied viruses are separated from the yolk and rendered noninfectious by formaldehyde. The potency of this vaccine is measured in the amount which the vaccine, using its hemagglutinin, clumps together blood cells (agglutination), and is recorded in terms of chick cell agglutination (CCA). Since the vaccine can be somewhat toxic, causing sore arms and fevers, it is important to find the right balance of efficacy (immune response) and safety for the vaccine, by either reducing the virus amount or using split-virus vaccine, which is made up of further purified viruses. (Silverstein: 61) After massive field tests, it was decided that 200 CCA units was very effective for most of the population (85% had at least 40 “units” of hemagglutinin antibody, the accepted amount), and caused few side effects. (Silverstein: 82) Once the appropriate vaccine was determined, four manufacturers went into production of the substance, and the vaccination procedures were organized. The high-risk groups for the disease (elderly and infirm) would be vaccinated first, in nursing homes and health departments. Then the rest of the population would be reached through the schools, factories, medical centers, and shopping centers. (Silverstein: 108) To speed up the process, jet guns would be used for the injections instead of syringes. (Silverstein: 80) Not only this, but an informed consent authorization would be required for all participants, so that the vaccination of every person, as well as track outbreaks of the flu, could be monitored. (Silverstein: 78) Despite all the planning, NIIP began three months late, and only vaccinated 24% of the population before the program was terminated. (Silverstein: 113) And while the feared swine flu pandemic failed to surface, this was just one example of the many complications which surrounded the program.
One major difficulty in the immunization program involved the fact that the biological results of the vaccine did not always go as planned. For example, while the organizers expected two doses of vaccine from each egg that was used for incubation, the eggs only yielded one dose, drastically setting back the timetable for production. (Silverstein: 79) Also, while the vaccine produced the desired hemagglutinin antibody, the neuraminidase antibody was not created. This was probably due to the inactivation of this protein in the virus in treatment or production. While this antibody was not as necessary as that of hemagglutinin, it was still important in stopping the spread of the disease. (Silverstein: 84) Not only this, but the field trials demonstrated that, while the vaccine worked well for adults, it did not work well in these doses for young adults and children. (Silverstein: 83) This problem was not fully resolved until the vaccinations had already begun, when it was decided that children ages 3-18 should get two doses of split virus vaccine, four weeks apart. Unfortunately, there were only 4 million doses of split-virus left for 57 million children. (Silverstein: 112) To make matters worse, while the swine flu influenza never surfaced, the original influenza of the time, Victoria, did appear this season. This disease could not be confronted, however, since all the vaccine for this strain had been mixed with the new vaccine, and by this point the president had called a moratorium of all influenza vaccinations. It was only after the moratorium was lifted for the mixed swine and Victoria vaccine that the original influenza could be combated. (Silverstein: 126) It was obvious that one can not always count on Nature to be as effective apartner as one would hope.
A major biological complication to the immunization campaign was its connection to Guillain-Barréacute; Syndrome (GBS). For the most part, the vaccination went more smoothly than even expected, with less than the predicted side effects and deaths. (Silverstein: 116) However, it was discovered that the vaccinations could be a factor in an increased number of cases of GBS. GBS is a rare paralytic disease, similar to polio, which causes an onset of polyneuritis, or tingling and weakness of the extremities and then some extent of paralysis. While most recover in the following months, there is a 5% fatality rate (mostly due to secondary respiratory disease or pneumonia), and 10% remain paralyzed to some extent. GBS is thought to result from an immunopathological reaction to an foreign agent in the body. (Silverstein: 117 and Laitin) While it was difficult to know for certain if the vaccines were causing GBS, since there were few prior statistics of GBS incidences to compare it with, there was enough evidence to suggest that this was the case. Preliminary calculations estimated that while there were 0.7 cases of GBS per million of non-vaccines at this time, there were 8.3 cases per million in vaccines. Not only this, but those non-vaccines which developed GBS were much more likely to have been sick prior to the syndrome than those who were vaccines, suggesting that the vaccine contained the trigger effect that usually would not have been present in healthy individuals. (Laitin ) While the vaccination program did not create an epidemic of GBS, this was enough to shut down the already flailing NIIP, which ended on December 16, 1976. (Silverstein: 119) This date was not the end of the troubles between the NIIP and the GBS, however, since the 500 cases of the syndrome and 25 deaths cost the government (who had agreed to take liability of the program) millions of dollars, not to mention a serious blow to its image. (Silverstein: 127 and
If the scientific complications of the NIIP were not enough, the media only helped to make the situation worse. First of all, while the program received broad support at its inception, the press was quick to criticize the program once no new incidents of swine flu appeared in the months after the Fort Dix affair, and emphasized the criticisms of people such as Albert Sabin, known for his polio vaccinations, who originally supported the project, but later pushed for a stockpiling of the vaccination. (Silverstein: 85-6) The press did more than just discourage the immunization plan, for they also helped to push the program forward. In August, when the NIIP appeared likely to never get off the ground, an outbreak of a particularly lethal strain of pneumonia occurred at the Pennsylvania State Convention of the American Legion, killing 29 of 182 cases. While it was later discovered that the disease, called Legionnaire’s Disease, was caused by a relatively unknown bacteria, and was in no way connected to swine flu, the press had already played its part. Immediately, despite no evidence to support the claim, the connection was made in the media between the Legionnaires’ Disease and swine flu. This was enough public agitation to push necessary legislation through congress, allowing the NIIP to go forward. While the press had helped to save the immunization program, it had done so using extravagant claims, and it might have proved useful if the NIIP had not survived at all. (Silverstein: 98-99, 106) Another example of sensationalism in the media occurred when a few days after the beginning of the immunization program three elderly people died at a vaccination station. Once again, while there was no evidence that the deaths were related to the vaccine, the press quickly exaggerated the story, creating an imagined “body-count” of vaccine victims. The hysteria that followed caused nine states to close down their immunization programs until the CDC announced decisively that the deaths were in no way connected to the vaccination. (Silverstein: 110-111) Judging from these incidents, it is not surprising that the press acted little differently when the actual connection between GBS and the vaccine was discovered. While the press can be slighted for its sensationalist portrayals of the immunization program, the leaders of the program should also be held responsible, for not creating a better relationship with the media, and not using this source as a way to educate the public about the program and influenza.
What made all of these difficulties more troublesome at the time was the inability of the program to adapt to new situations and obstacles. When the outbreak was announced, the responsibility of facing the threat quickly moved up the political hierarchy, until President Gerald Ford himself announced the instigation of the NIIP. By this time, however, the threat of the pandemic had been exaggerated, in part to serve political purposes. (Silverstein: 42-43) While the prestige of the presidency helped gather momentum for the project, it also complicated matters, since because the President had taken control of the undertaking, no one beneath him could take initiative and re-organize the plans to face unexpected obstacles. (Silverstein: 47) Another problem with the logistics of the NIIP was that its planning was so overwhelmingly optimistic about the success of all the different facets of this immense endeavor that only in the best-case scenario would all go as planned. If the organizers had instead planned for the worst, they very well might have been able to deal with the many difficulties that occurred in a more suitable manner. (Silverstein: 138) Not only this, there was no re-evaluation of the program at different stages of its progress. For example, once the decision had been made to go ahead with both the manufacturing of the vaccine and the immunization, there was no reconsideration of stockpiling the vaccine, even when the disease failed to appear in the months after the manufacturing. (Silverstein: 142) Because of these organizational difficulties, the NIIP was unable to adapt to challenges the occurred, and there were many such challenges. Aside from those already listed, the NIIP and the government also had to face the refusal of the of the American Insurance Association to insure the manufacturers of the influenza vaccine, since it was afraid of mass quantities of invalid lawsuits regarding the immunization. This dilemma threatened to kill the NIIP, and it took many months for Congress to accept liability for the vaccinations, having to pass special legislation to allow individuals to fail claims against the government. (Silverstein: 96-7, 106) Other predicaments which plagued the immunization program included the discovery that one of the manufacturers had made millions of the wrong kind of influenza vaccine, legal complications which stalled the organization of advertising for the campaign, and arguments over the form and content of the consent forms for the vaccination. (Silverstein: 79, 108-109) Because of the inadequacies of the logistics of the NIIP, these complications often set the entire program back weeks or months, and threatened the integrity of the undertaking altogether.<p>
This is not to say that the immunization program did not have its positive points. First of all, it would be ridiculous to renounce the NIIP because the swine flu never occurred. The program was a preventative action, in order to protect the population if the disease <i>did</i> occur, and things would have been a lot worse if swine flu had erupted and the government had done nothing to prepare for it. (Silverstein: 134) Also, despite the mistakes of those in charge of the project, and the negative publicity it received from the press, the NIIP was successful in vaccinating a large amount of the population in a very short time. This is proof that the people had made their own decisions about the benefits and risks of the program, and that the local health officials had adequately taken control of the program in their areas. (Silverstein: 115) And because of this vast undertaking, there is no question that the people had become more knowledgeable of immunization, for as one Senator explained, “We have raised the public’s awareness of the need to prevent disease from happening.” (Silverstein: 124) Also, for the most part, the surveillance system of the vaccinations was largely successful, in that it competently kept track of every individual vaccinated, carefully watched for outbreaks of the swine flu, and was able to monitor adverse side effects to the immunization. (Laitlin) In fact, because the syndrome’s increase was so slight, the connection between GBS and the influenza vaccinations probably would never have been noticed if not for the scrutiny of the surveillance system. (Silverstein: 121) Because of the information that this system gathered, as well as the increased scientific and public interest in influenza at the time, the NIIP has undoubtedly helped to further knowledge of the influenza disease, as well as contribute to the fields of microbiology and epidemiology in general. (Laitlin)
With such a massive undertaking as the National Influenza Immunization Campaign of 1976, it is normal to try to identify heroes and villains among those who were involved in the endeavor. However, it is not possible to do so. The immunization campaign had its strong points and its weak points, and the people who organized the project made both good decisions and mistakes. The scientists and the politicians who evaluated the Fort Dix were right to take the most cautious reaction they could, because all of the pathological, microbiological, and historical evidence they had at the time strongly suggested that a dangerous pandemic could occur. But while many of the unforeseen difficulties which arose to complicate the NIIP can not be blamed on the organizers of the immunization campaign, they should be held responsible for not creating a more adaptable program that could deal with these occurrences. The NIIP must be evaluated for its drawbacks and its successes, so that people will not just see this as an unfortunate historical event, but can use it to help further immunization and disease-fighting programs in the future.
- The “Flu”. Online. 17 Feb. 1999. Available: www.ultranet.com/~jkimball/BiologyPages/I/Influenza.html
- Laitlin, Elissa A. and Elise M. Pelletier. “The Influenza A/New Jersey(Swine Flu) Vaccine and Guillain-Barréacute; Syndrome: The Arguments for Causal Association.” Drugs and Devices Line, 1997. Online. 15 Feb. 1999. Available: www.hsph.harvard.edu/Organizations/ddil/swieflu.html
- Silverstein, Arthur M. Pure Politics and Impure Science: The Swine Flu Affair. Baltimore and London: The John Hopkins University Press, 1981.
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