Smallpox Vaccine:

Does It Work?

Randall Neustaedter OMD

      The debate over use of the smallpox vaccine has focused on the risks of side effects and deaths caused by the vaccine, as well as the problems associated with the vaccine’s outmoded technology, but these discussions have ignored questions about the vaccine’s effectiveness. Authorities insist that smallpox vaccine was responsible for eradication of one of humanity’s greatest scourges (WHO, 1980). It may therefore come as a tremendous surprise that throughout the nearly 200-year history of smallpox vaccination thoughtful physicians and a veritable army of citizens doubted that the vaccine worked at all.

      Four factors have contributed to skepticism of smallpox vaccine’s effectiveness. First is the dubious notion that lesions from cowpox, a disease of cattle, could prevent smallpox, a related but different human disease. Second, during the nineteenth century, which preceded modern bacteriology and the age of refrigeration, it was impossible to know exactly what was in any given dose of vaccine. Third, the reported increase of smallpox disease in communities following the introduction of vaccination seemed to contradict the claims of vaccination proponents. A fourth disturbing fact is the total absence of any carefully controlled efficacy studies of the smallpox vaccine. 

 Does cowpox prevent smallpox?

      The idea for a smallpox vaccine obtained from cowpox lesions arose from a superstition among milkmaids in England. Those maids who purportedly contracted cowpox pustules on their hands from the udders of cows were subsequently immune to smallpox. Or at least so went the story. Cowpox is a rare, benign disease of cows in Great Britain. It causes bluish lesions on the cow’s udder, but few other symptoms. In humans it may cause these same symptoms on the hands and a flu-like illness. Today the disease is extremely rare. Horses would get a similar disease, known as grease, or horsepox, which is now extinct. The early vaccines were prepared from both cows and horses during animal epidemics. It was only during the late nineteenth century that cowpox was artificially inoculated onto the skin of calves and harvested for vaccine, and not until the eradication campaign of 1967 that a reliable preparation of the cultured virus existed. Prior to that time the potency of any particular vaccine preparation was unknown.

      When a cattle breeder named Benjamin Jesty supposedly found himself immune to smallpox after having contracted cowpox from his own cows, he decided to inoculate his entire family with cowpox lesions. This was in 1774. Such a procedure was well known to the populace, since the practice of inoculation with the actual smallpox virus had been popular in England since the 1740s, with often deadly results. Twenty years after Jesty and others experimented on themselves with cowpox inoculations, Edward Jenner, a notorious self-promoter, went a step further. He inoculated a child with cowpox and then injected the child with a deadly dose of smallpox. Luckily, the child did not die. This experiment led Jenner to publicize his theory of vaccination in 1796, which quickly became an accepted, and required, practice without any scientific experimentation or medical studies to prove the vaccine’s effectiveness.

      Despite the initial widespread popularity of vaccination, no one actually proved that the cowpox vaccine prevented smallpox, and many critics insisted that the vaccine did not work. Physicians were especially skeptical about the ability of cowpox to prevent smallpox, even if the populace was quick to adopt a variety of superstitions to prevent diseases. Jenner’s proof consisted of locating farmers who had previously contracted cowpox and never came down with smallpox. Then he inoculated them with material from smallpox lesions to see if the vaccine would produce a reaction. When it did not he claimed this proved his theory. However, it only proved that these farmers did have antibodies and resistance to smallpox, which they could have acquired from previous exposure to the disease. Not everyone exposed will suffer the consequences of obvious infections. Physicians came forward with hundreds of cases where an individual farmer had contracted cowpox from cows, but later developed smallpox nonetheless. Jenner dismissed these claims out of hand. Perhaps the medical profession’s terrible experience using inoculation with material from an actual smallpox lesion and subsequent deaths created a situation where authorities felt desperate to adopt a safer alternative. As it turned out the death rate caused by cowpox vaccination was lower than results with the previous smallpox inoculation. Cowpox was clearly a safer substance, and hopes ran high that it would work. It was only after the vaccination campaign was in full swing that the dangers of the new vaccine came to light, and its failings became widely broadcast.  

What is in that vial?

      Early doubts about the vaccine’s efficacy focused on its questionable source. It was hard for anyone to imagine that pustular lesions from a cow’s udder could prevent disease in humans. There was a natural and understandable aversion to applying such noxious material to one’s skin. Jenner attempted to use material from horses’ infections, the now extinct disease known as horse grease. When this was poorly accepted he reverted back to the use of material from cows. In fact the new cowpox vaccination often did transfer other contagious and deadly diseases to recipients, especially syphilis, leprosy, and tuberculosis. The populations of England and continental Europe were well acquainted with the extreme danger of using vaccine prepared from the actual smallpox disease (variolation), which was outlawed in England in 1840, and they were loathe to accept any other form of inoculation with diseased material. Vaccination was often forced upon a population that would otherwise judiciously refuse it.

      The transfer of a secondary disease is not unique to smallpox vaccination. During the modern era, several diseases have been transferred to vaccine recipients including a monkey virus that has caused innumerable cases of cancer, even 40 years later, from a contaminated polio vaccine given in the 1960s, stealth viruses that cause chronic fatigue syndrome, and possibly the AIDS virus through a live polio vaccine campaign in the Congo (Neustaedter, 2002).

      Live vaccines are grown on animal tissues or animal cell cultures. Because of the possibility of contamination from these tissues, vaccines always carry the potential of infecting recipients with these contaminating organisms. Modern vaccines are screened as carefully as possible, but manufacturers can only find the organisms for which the tests were designed. Other contaminating viruses will not be detected. Even modern vaccines contain viruses from chickens and other animals that could potentially cause disease in humans. Monkey viruses contained in vaccines were considered unable to infect humans until the SV40 virus (the fortieth simian virus identified) was found to cause cancer in vaccine recipients and their children. Older vaccines had less stringent manufacturing and testing procedures. In June 2002, Aventis Pasteur, a French vaccine manufacturer, donated a cache of 85 million doses of smallpox vaccine produced in the 1960s to the US government. It is possible that this vaccine could be tainted with any number of contaminating viruses and bacteria unknown at the time of production. Consumers would do well to question the manufacturing date of any smallpox vaccine before allowing its use.

Post-vaccine epidemics

      During the nineteenth and early twentieth centuries, when smallpox epidemics ran rampant, the introduction of smallpox vaccination was often followed by an increased incidence of the disease. Many vaccine critics accused the smallpox vaccine of precipitating these epidemics. A disastrous smallpox epidemic occurred in England during the period 1871-1873 at a time when the compulsory smallpox vaccination law had resulted in nearly universal coverage. A Royal Commission was appointed in 1889 to investigate the history of vaccination in the United Kingdom. Evidence mounted that smallpox epidemics increased dramatically after 1854, the year the compulsory vaccination law went into effect. In the London epidemic of 1857-1859, there were more than 14,000 deaths; in the 1863-1865 outbreak 20,000 deaths; and from 1871 to 1873 all of Europe was swept by the worst smallpox epidemic in recorded history. In England and Wales alone, 45,000 people died of smallpox at a time when, according to official estimates, 97 percent of the population had been vaccinated.

      When Japan started compulsory vaccination against smallpox in 1872 the disease steadily increased each year. In 1892 more than 165,000 cases occurred with 30,000 deaths in a completely vaccinated population. During the same time period Australia had no compulsory vaccination laws, and only three deaths occurred from smallpox over a 15-year period.

      Germany adopted a compulsory vaccination law in 1834, and rigorously enforced re-vaccinations. Yet during the period 1871-1872 there were 125,000 deaths from smallpox. In Berlin itself 17,000 cases of smallpox occurred among the vaccinated population, of whom 2,240 were under ten years of age, and of these vaccinated children 736 died.

      In the Philippines, global public health measures were instituted when the United States began its occupation to establish a self-reliant government in the early 1900s. The incidence of smallpox steadily declined and the compulsory vaccine campaign was credited with this dramatic reduction. However, in the years 1917 to 1919, the Philippines experienced the worst epidemic of smallpox in the country’s history with over 160,000 cases and over 70,000 deaths in a completely vaccinated population. Over 43,000 deaths from smallpox occurred in 1919 alone. The entire population of the Philippines at the time was only 11 million.

      Vaccine failures of this magnitude may have several causes. The vaccine used could have been defective. During that period it was difficult to verify what the vaccine actually contained. The vaccine could have been contaminated with smallpox virus and actually caused epidemics. Or vaccine critics may have been correct in asserting that Jenner’s cowpox vaccine, which is essentially the same vaccine used today, simply did not work to prevent smallpox.

Studies of vaccine effectiveness

       It is undeniable that vaccination with vaccinia virus (originally from cowpox) produces antibodies to vaccinia. Over 95 percent of those receiving vaccine for the first time will develop antibodies at a titer of 1:10 or greater. However, authorities are uncertain what level of antibodies are necessary to protect against smallpox infection (CDC, 1991). In fact, it has never been proven that the vaccine is effective against smallpox at all. Some smallpox experts have admitted that vaccination will modify the disease and prevent deaths, but not prevent the disease.

      Donald A. Henderson, MD, the world’s leading authority on smallpox, has lamented the paucity of smallpox vaccine studies. “Reliable data are surprisingly sparse as to the efficacy and durability of protection afforded by vaccination” (Henderson, 1988).

      Despite the lack of efficacy studies, vaccine promoters have consistently made claims that the smallpox vaccine works incredibly well. In his book about the defeat of smallpox, Joel Shurkin, a science reporter, makes the bold assertion that, “Vaccination with cowpox virus does confer immunity to smallpox and does so safely and easily and with almost 100 percent effectiveness” (Shurkin, 1979). These types of sweeping and grandiose claims remained unquestioned despite the absence of corroborating scientific studies.

      The World Health Organization declared in 1979 that smallpox was eliminated from the world through its intense vaccination campaign begun in 1967. However, these campaigners conducted few studies of vaccine efficacy. They merely documented the decrease in smallpox disease. Other diseases have also disappeared from the world. The bubonic plague (or Black Death) killed 25 million people in Europe during the years 1347 to 1352, one third of Europe’s population. Yet the plague has faded into distant memory without the aid of vaccines. Typhoid and yellow fever disappeared from North America as a result of modern sanitation measures prior to vaccine development for these diseases. Smallpox may have disappeared for the same reason.

      A variant of the smallpox virus may still be alive and active in the world, causing human disease and deaths. The claim that smallpox has been eliminated is contradicted by numerous reports of pox virus transmission in Africa today. This disease has been named human monkeypox because the virus resembles a pox virus found in captive monkeys in 1958 (Mukinda et al., 1996). Human monkeypox exists in rainforest villages of central and western Africa, where it is readily transferred through person-to-person contact. It causes the same symptoms as smallpox, and differs from smallpox virus only in its protein structure, a difference of a few nucleotide sequences. Up until the 1960s it was not possible to differentiate the various pox viruses, but since that time cases that would have been labeled as smallpox are now labeled monkeypox or camelpox depending on their DNA structure.

      Several outbreaks of human monkeypox have occurred since the virus was first isolated from humans in 1959 (Gipsen, 1976). In 1996, 71 cases were reported in the Katako-Kombe area in Zaire with four deaths. In one small village of 346 inhabitants, 42 cases were reported, including three deaths (WHO, 1996). By December of 1997 more than 500 cases of monkeypox were reported in Zaire. It is possible that smallpox has made a comeback in this remote part of the world. Apparently vaccination with the vaccinia virus does not protect against monkeypox, since 92 out of 94 children with facial scarring caused by monkeypox also had scars typical of smallpox vaccination (Arita & Henderson, 1976).

      Three types of studies have been conducted to evaluate the effectiveness of smallpox vaccination. The first is a simple record of the incidence of smallpox disease and deaths in a population before and after the onset of compulsory vaccination. The second is a record of the number of deaths caused by smallpox in the vaccinated compared to the unvaccinated individuals in an epidemic. And the third is accomplished by purposefully exposing vaccinated individuals to smallpox.

      (1) Studies of smallpox incidence

      The primary type of study conducted to prove the effectiveness of smallpox vaccine compared the incidence of disease before and after introduction of compulsory vaccination in a specific population. However, this type of study is fraught with many problems. An episodic disease such as smallpox will wax and wane year by year, making it difficult to compare statistics over any short period of time. Alfred Wallace eloquently addressed this problem in a pamphlet discussing the statistical evidence regarding smallpox incidence.

In 1796 more than 4,000 per million died of small-pox in London, while in the next year there were only about 800, and the following year (1798) over 3,000. Again, in 1870 less than 100 per million died of it, while in 1871 there were about 300, and in 1872 about 2,500. Thus the figures go increasing and decreasing so suddenly and so irregularly, that by taking only a few years at one period, and a few at another, you can show an increase or a decrease according to what you wish to prove (Wallace, 1904).

Wallace advised analyzing statistics over long periods of time and using large populations. A study of smallpox incidence in Sweden did review statistics for a period of more than one hundred years before and after compulsory vaccination. During the period between 1774 and 1801, prior to vaccination, the death rate from smallpox was 1,973 per million population in Sweden. After vaccination was introduced, 1802-1816, the death rate was 479 per million. Following compulsory vaccination begun in 1817 until 1879 the death rate was 181 (Shurkin, 1979).

      This decline in smallpox in Sweden seems impressive, but other factors besides vaccination may have contributed to the statistics. Such a steady decline in infectious disease incidence could also correspond to improved sanitation and other public health measures. Vaccine critics suggest that any review should also examine the incidence of other contagious diseases to see if they follow the same pattern as a disease for which there is a vaccine available.

      In Great Britain the incidence of life-threatening childhood diseases steadily decreased during the era prior to vaccines and antibiotics. The following chart gives figures for the death rate in children (birth to 15 years) for several contagious diseases in the pre-vaccine era. Each of these diseases decreased 88 to 99 percent during this period. The decline was generally attributed to improvements in living conditions and sanitation (McBean, 1957).

Death-rate per million children (Ages, between birth and 15 years.)

      During the smallpox era, epidemics would come and go, striking with relentless force in some years and remaining absolutely quiescent in others. When smallpox died down, vaccine enthusiasts claimed victory over the smallpox threat. When smallpox incidence increased they would blame a deficiency in vaccination or revaccination.

      The history of smallpox in Egypt is a case in point. Compulsory smallpox vaccination was instituted in 1890, but coverage was never complete. During an epidemic in 1919 a total of 7,895 cases of smallpox occurred, followed by 3,004 in 1920. More than 5.5 million people were vaccinated during that epidemic. Then in 1921 the number of smallpox cases declined to 92. The League of Nations Monthly Report of October 15, 1929 attributed this remarkable drop in smallpox to the renewed vaccintion efforts. Five years later another epidemic struck. In 1926 a total of 2,677 smallpox cases occurred with 544 deaths, despite the previous vaccine campaign. This time more than 14.6 million doses of vaccine were supposedly administered (in a population of less than 14 million people). Then in 1930 the League of Nations announced that the incidence of smallpox had been reduced to only 14 cases. Smallpox was declared nearly eradicated. However, in 1932 another smallpox epidemic struck in Egypt, despite continued compulsory vaccination of all children. By 1934 the toll of cases had reached 7,650 with 1,373 deaths. This variable incidence of smallpox from year to year was typical at the time, and the nearly universal vaccination of the population in Egypt was a dismal failure.

     (2) Vaccinated vs. unvaccinated

      Smallpox occurs in completely vaccinated populations, and childhood deaths from smallpox have occurred in communities where 100 percent of children were recently vaccinated, but controlled studies comparing the vaccinated and unvaccinated are notoriously absent. Three reports in the modern era provide some comparison of smallpox disease among people previously vaccinated vs. those unvaccinated.

      An unsettling report was tucked away in the British Medical Journal of 1828, which showed that the fatality rate among people with smallpox who had been previously vaccinated was significantly higher than from smallpox that occurred in the unvaccinated. This was true for smallpox in people over 15 years of age during the years 1923 through 1926 in Great Britain. ”In a total for these years of 11,019 cases, 4,010 occurred among the vaccinated with 13 deaths – a fatality rate of 0.3 percent – and 6,915 occurred among the unvaccinated with 4 deaths – a fatality rate of 0.06 percent. That is to say, the fatality rate among vaccinated cases was five times as great as among unvaccinated cases” (Garrow, 1928). No satisfactory answer could be found for this apparent discrepancy in the smallpox vaccine proponent’s claims for reduced mortality. One respondent noted that Germany had a much higher vaccination rate than England, but a higher mortality rate from smallpox, suggesting that the vaccine increased the death rate (Parry, 1928).

      A careful review of all smallpox cases occurring in North America and Europe during the period between 1950 and 1971 did show that those who had been previously vaccinated had a lower fatality rate than those who had never been vaccinated. Of the 680 smallpox victims during that period, 79 had never received vaccine and 41 of them died (52 percent). Of the 70 people with smallpox who were vaccinated in the previous 10 years, only one died (1.4 percent). Those people vaccinated over 20 years prior to exposure only had a fatality rate of 11 percent. Interestingly, the number of smallpox victims who had never received vaccine (79 total cases) was nearly equivalent to the number of cases with a history of vaccination in the previous 10 years (Mack, 1972).

      The results of that study suggest that smallpox vaccine does significantly reduce the death rate from acquired smallpox, though it did not prevent the disease in those people. This lone survey of smallpox cases is often cited as proof that the vaccine reduces fatalities from smallpox.

      Smallpox vaccination is certainly not a guarantee against contracting the disease. During an epidemic in India (in 1953) 80 percent of people with smallpox had a history of at least one vaccination, and 50 percent had been vaccinated two or three times (Kempe, 1960). None of the smallpox cases had been vaccinated in the previous 12 months. As a result of this apparent vaccine failure, the author recommended yearly smallpox vaccinations during periods of epidemics.

      In both of these reports, vaccination following soon after exposure to smallpox did not prevent the disease or deaths. In the European study, there was a 30 percent death rate among those people who received the vaccine shortly after exposure. In the Indian study, between 10 and 40 percent of people who received vaccine within four days of exposure contracted smallpox nonetheless.

      (3) Exposing the vaccinated to smallpox

      Probably the most disturbing and bizarre aspect of the vaccination fervor was an experimental method carried out by early vaccine enthusiasts. Physicians would deliberately expose recently vaccinated children to smallpox in order to assess whether the vaccine was protective. Perhaps they justified this experiment by rationalizing the lives it could potentially save, but putting a child’s life at risk in a medical experiment defies the Hippocratic Oath and all ethical guidelines.

      Edward Jenner was the first to conduct such an experiment. On May 14, 1796 Jenner took pus from a cowpox sore on the hand of a milkmaid and inserted it into scratches he had made on the arm of an eight-year-old boy. The boy developed flu-like symptoms as expected. Six weeks later, Jenner took pus from a smallpox lesion and similarly inserted this into new scratches to determine if the boy would acquire smallpox. Nothing happened, and Jenner assumed the boy was now immune to smallpox. This experiment launched his lucrative career in the vaccine business.

      Six years later, Benjamin Waterhouse, a Boston physician, conducted an appalling experiment on 32 children. On August 16, 1802 Waterhouse vaccinated 19 boys from the poorhouse in Boston. Several months later he inoculated 12 of these boys with material from an active smallpox lesion. None of them acquired smallpox. In order to prove that the smallpox material was truly viable, he inoculated two other boys who had no known prior exposure with the same material. Both boys developed typically violent cases of smallpox. For his final act, Waterhouse took pus from the smallpox lesions of these two boys and inoculated all the original 19 subjects again. He placed them in the same room with the two suffering from smallpox and they all resided together for 20 days. None of the group came down with smallpox. Based on the reputation he gained from this experiment, Waterhouse then attempted to establish a monopoly on vaccine production and sales in Boston, personally attacking the vaccines of other physicians as spurious. His domination of the vaccine market ultimately failed (Blake, 1957; Shurkin, 1979).

Summary

      Smallpox vaccine was violently opposed during the first century following its invention, and its failure rate during epidemics of completely vaccinated populations did not contribute to public confidence. Early vaccines were notoriously unreliable because of production problems, lack of refrigeration, and nonsterile techniques that spread other fatal diseases through the vaccine serum and needles. The dangers of adverse reactions, the spread of disease through vaccination, and the ineffectiveness in preventing epidemics made the vaccine seem undesirable.

      Contamination of vaccines with viruses and bacteria is still a problem in the modern age, and the most recent studies of smallpox vaccine effectiveness are not reassuring. There is abundant evidence that vaccination does not prevent smallpox. Epidemics have occurred in completely vaccinated populations. Individual smallpox cases occur just as readily in the vaccinated as the unvaccinated, and contrary to official pronouncements, giving smallpox vaccine soon after exposure does not prevent the disease. One study, however, did suggest that the vaccine may reduce the incidence of deaths from smallpox.

      Although public health officials continue to heap accolades upon the success of vaccination in wiping out the disease, there is little evidence to justify the claim that the vaccine has any effect on disease incidence. Unfortunately, there is no way for anyone to re-evaluate whether the vaccine acts preventively since smallpox disease no longer exists.

References

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