Author: Erica Sommerville

“Variola” may not sound like an intimidating name, but throughout history there was no name more feared. Daniel Koplow in his book, Smallpox: the Fight to Eradicate a Global Scourge, says about variola (better known to English speakers as smallpox), “Over a period of at least three millenia it was second to none in inflicting human pain, suffering and death. By some estimates, smallpox killed as many as 500 million people during the twentieth century alone.”¹ Allan Chase agrees, calling smallpox “the worst pestilence ever to afflict mankind.”² Once the reigning king, this virus has now been consigned to less than 600 samples in two laboratories on this planet and may eventually be condemned to intentional extinction. If nothing else, variola has a unique place in history.

The origin of the virus is unknown, but many who were smitten by it are not: Ramses V of Egypt (whose mummy bears the characteristic scarring of a smallpox victim), Elizabeth I of England, George Washington, as well as billions of people whose names never made it into the annals of history. The symptoms were obvious and the scars unmistakable. After around two weeks of incubation, it might feel like the flu with fever and aches, but a very few days later an unmistakable crop of “postules” (raised bumps under the skin that were hard to the touch) formed and inflicted more pain and discomfort on the sufferer for another couple of weeks. Many of the postules left unsightly scars on the face, neck, and extremities. No one who got the disease escaped without some scars. No one knew how to cure it. No one who was fortunate enough to survive it ever came down with it again.

Many doctors in many cultures had their methods of preventing it, but one method that seemed to work arose in the Asian and African cultures centuries before it was used in the West. These cultures discovered that induced cases were rarely as vicious as naturally acquired smallpox, and they also had a low fatality rate (1% compared with the naturally-occurring case rate of 30%). When it was introduced to the West, it was called “variolation” or “inoculation,” and it was greeted with suspicion and distrust. Westerners often chose not to practice it for several reasons, not the least of them being that it was still considered unsafe by many doctors. Since patients were typically given the disease through contact with an infected person’s blood or lymph, sometimes other diseases such as hepatitis and syphilis were passed on with it, causing severe complications.³ Also, during the course of their inoculation, patients could pass along full-blown cases of smallpox to their loved ones, so they had to be kept in strict quarantine, a measure that was not always successful. Still, it was used with much success in many cultures and was eventually adopted by many European countries and mandated by George Washington for the Continental Army in 1777.⁴

Many in the New England colonies viewed this practice as evil to the core. Writing in the 18th century, John Williams said, “I do seriously believe it’s a delusion of the Devil; and that there was never the like delusion in New-England since the time of the witchcraft at Salem.”⁵ Samuel Grainger wrote a letter to a friend attempting to dissuade him from accepting the practice and appealed to a variety of arguments. Hoping most of all to base his viewpoint on the Bible, he believed that smallpox was judgment from God, either for personal or national sin. He felt that the only means available afforded by the Bible for dealing with a pestilential disease was to repent of sin and reform one’s ways. Circumventing judgment by taking steps to prevent the disease only brought on further judgment from God. “Must the Supreme Providential Will become subservient to the becks and appointment of the human will, or must the human will say, the divine will be done,” he wrote⁶ . The fact that a person undergoing inoculation could pass along smallpox to his neighbors bothered him as well since we are commanded by the Bible to love our neighbors⁷.

Others defended the practice against these arguments with varying degrees of success. William Cooper wrote in 1721, “To bring sickness upon oneself for its own sake, is what no man in his right wits would do. But to make myself sick in such a way, as may probably serve my health, and save my life, and with such a design is certainly fitting and reasonable and therefore lawful.”⁸ Eventually, the attitude of another writer, James Jurin, put the controversy over inoculation in a striking light, “He [any physician] will consider, whether it will be for his reputation, where his friend and his patient shall put his life, or the lives of his children, into his hands, to amuse himself with theological disputes and scruples, whether it be lawful to save them. For if the practice of inoculation be really found to be a means of preserving life, it will not be easy to make the world believe, that it is criminal to use it.”⁹

It took a middle-aged country doctor in England to bring the king of infectious diseases to it knees. Edward Jenner of Berkeley, Glouchestershire had treated many patients throughout his medical career, and he would often treat sufferers of a disease called cowpox. Although it afflicted cows primarily, many milkmaids would contract the disease from the cows they milked. It always had more benign (although similar) manifestations than smallpox, and it was a well-known proverb of the milkmaids that those who got cowpox never got smallpox. Curious, Dr. Jenner, who had been variolated as a boy and therefore could not test it out on himself, took some lymph from a milkmaid’s infected hand and infected eight-year-old James Phipps with it on May 14th of 1796. In early July, he injected James with smallpox and waited. Nothing happened. He tried again a couple of weeks later, but the boy was immune to the virus. Jenner surmised that cowpox was related to smallpox and provides crossimmunity, that is, immunity against both itself and its related viruses, to the person who recovers from it. He called his process “vaccination” from the Latin word “vacca” or “cow.” The medical fields of vaccination and immunology developed out of that single discovery – and so did the death of smallpox.¹⁰

The news of Jenner’s discovery swept Europe where, for instance, Bavaria made obligatory vaccination the law in 1807¹¹. Many nations’ militaries followed suit, though the nations themselves did not because of many who mistrusted the practice. Vaccination was much less expensive than variolation. Beyond being safer for the patients, it was much cheaper and safer for others around them than variolation. Some practitioners of variolation were displeased with these advantages because they were bad for business, and vaccination did not earn as much for them. Some doctors honestly feared for the safety of those being vaccinated because of the rare side effects or complications from the procedure. Others who were heavily involved in the sanitation and public reform movements thought that smallpox could be controlled by increased sanitation, thus making vaccination unnecessary. Still others, like Reverend Thomas Robert Malthus, thought that smallpox was God’s means of keeping the unworthy poor from overrunning the earth’s population, and thus it should not be diminished by such measures.¹²

Slowly the method of vaccination was refined. It must be remembered that vaccination was invented and implemented long before any nation had strict controls on medical products and procedures. Also, the workings of the disease and of the human immune system were largely unknown when this practice was discovered, thus making true knowledge of how to improve it much more difficult. For many patients early on, the process was done by arm-to-arm contact, but this brought with it the same risks of contamination for other diseases, such as hepatitis and syphilis, that inoculation had¹³. Soon the vaccine was taken from bovine sources instead to prevent contamination. When it was discovered that glycerin inhibited the propagation of all kinds of bacteria, it was added to vaccines in order to prevent many bacterial contaminants.¹⁴ The current vaccine stocked by the World Health Organization is made from “pulp scraped from vaccine-infected animal skin, mainly calf and sheep, with phenol added to a concentration sufficient to kill bacteria but not so high as to inactivate the vaccinia virus.”

With aggressive use, the vaccine quickly tapered off the number of cases throughout the world. In 1948, the United Nations created the World Health Organization (WHO). Early on, it focused its attention on smallpox. Global involvement was considered key in the process of fully stopping this dread disease – as long as there was one place where the virus lived on, anyone who traveled there would be at risk and large- scale vaccination programs would have to continue indefinitely. However, if there were a means of controlling and eventually wiping out the virus’ potential hosts all over the world, humanity could perhaps rest easy at last.

Daniel Koplow points out the wisdom of the coordinators of this effort. Instead of attempting to vaccinate every single person on the globe, the strategy involved quick identification of outbreak sites and vaccination in those immediate areas to prevent further spread. Three things about the nature of the disease aided the eradication campaign. First, everyone who had the virus showed outward signs, making it easier to find outbreaks of the virus. Second, the virus has no non-human carriers, so only where human beings were stricken with it could they find the virus. Also, they did not have to worry about fleas, rats, or other animals carrying it, as happened with the bubonic plague. Third, many nations instituted obligatory vaccination programs for their citizens thus doing the work for the WHO volunteers. Efforts were astonishingly successful in places like West Africa, one of the hotbeds of smallpox in the world, which was declared to be completely free of smallpox within less than four years after the campaign’s work began there¹⁵. The last case of naturally-occurring smallpox was found in Somalia in 1979. Aaron Chase adds “The total cost to all the world’s nations of the World Health Organization smallpox eradication program came to only 300 million, or far less than the going price of a half-dozen F-16 or equivalent fighter-bombers.”¹⁶ It took a great deal of global coordination, trial and error, and scientific exploration to beat smallpox, but vaccination – the most inexpensive and safe of all medical procedures – made it possible.

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References

1. Daniel A. Koplow Smallpox: the Fight to Eradicate a Global Scourge University of California Press, Berkeley, CA 2003, p. 1
2. Allan Chase Magic Shots: a Human and Scientific Account of the Long and Continuing Struggle to Eradicate Infectious Diseases by Vaccination, William Morrow and Company, New York, NY, 1982, p. 51
3. Ibid., p. 74
4. Daniel A. Koplow, p.18
5. John Williams “An Answer to a Late Pamphlet, intitled, ‘A Letter to a Friend in the Country, Attempting a Solution of the Scruples and Objections of a Consciencious or Religious Nature, Commonly Made Against the New Way of Receiving the Smallpox’ ” Early American Imprints. First Series, no. 2407 Readex Microprint (New York), 1985, p. 4
6. Samuel Grainger “The Imposition of Inoculation as a Duty Religiously Considered in a Leter[sic] to a Gentleman in the Country inclin’d to Admit It” Early American Imprints. First Series, no. 2222 Readex Microprint (New York), 1985, p.12
7. Ibid., p.25
8. William Cooper “A Letter to a Friend in the Country, Attempting a Solution of the Scruples and Objections of a Conscientious or Religious Nature, Commonly Made Against the New Way of Receiving the Small-pox.” Early American Imprints. First Series, no. 2247 Readex Microprint (New York), 1985, p.3
9. James Jurin An Account of the Success of Inoculation the Small Pox in Great Britain: with a Comparison but MisCarriages in that Practice, and the Mortality of the Natural Small-pox 2nd edition. Printed for J. Peele (London), 1724, p. 4
10. Allan Chase, p. 42-46
11. Ibid. p. 62
12. Ibid. p. 72-3
13. Daniel Hopkins The Greatest Killer: Smallpox in History, with a New Introduction University of Chicago Press (Chicago), 2002, p. 85
14. Fenner, F. Smallpox and its Eradication World Health Organization, (Genva) 1988 ( Available online)
15. Ibid. p. 23
16. Ibid. p. 82

Erica A. Sommerville is not a medical doctor but a college student. She does not dispense medical advice. Her aim is to educate the public about scientific issues. Please consult a board-certified medical doctor before making any medical decisions for yourself or your family.

Infantile Paralysis. This sinister name was given to a disease which was virtually unheard-of before the late 19th century, but which began terrorizing developing countries and swept across the world. Many believe it has existed for centuries. In Trial by Fury: the Polio Vaccine Controversy, Aaron Klein includes a picture of a mural in Egypt which some believe shows an early victim of the disease – a priest with a withered leg.¹ Other theories as to its origin abound, but its imprint is undeniable in the histories of Western countries (and eventually the world) throughout the 20th century. This disease is now better known as poliomyelitis.

The long-standing scientific explanation for the sudden spike in polio case levels in the early 1900s states that increased sanitation actually encouraged the spread of the disease. In the “dirtier” days of the past, many were exposed to the virus throughout their lives and they developed immunity to it because they were exposed to small amounts without getting paralytic cases of it². In addition, some of the mother’s antibodies against polio were passed on to her infant (through breast milk) so that infants were protected during the earliest months of their lives. Since most of the community was immune, when someone did get paralytic polio, it did not spread very far until the chain of immunity was broken in developing countries. As better sanitation practices provided cleaner water, among other things, many in the population were no longer immunized through low-level exposure. Now epidemics arose at alarming rates, particularly during the summer months when more children were likely to be in close proximity to each other (and the virus) for long periods of time. The World Health Organization’s Global Polio Eradication Initiative has estimated that there were 50 million worldwide paralytic polio survivors in the 20th century alone³.

The workings of polio as a disease were not known for many years. Slowly, scientists began to learn that the virus enters through the mouth and travels to the intestines where it begins to multiply for anywhere from 4-35 days. “The initial symptoms include fever, fatigue, headaches, vomiting, constipation (or less commonly diarrhea), stiffness in the neck, and pain in the limbs.”⁴ From the intestines, the virus moves to the bloodstream and eventually invades the central nervous system through nerve fibers. It begins to destroy the motor neurons, thus immobilizing muscles and causing the characteristic paralysis of severe cases. Usually the paralysis only affects the legs, but for some it causes quadriplegia and even death by asphyxiation when the paralysis affects the portions of the brain that control breathing. Researchers today know that only 1 in 200 cases is paralytic and 5-10% of paralytic cases result in death. However, there is still no cure for the disease; it can only be prevented⁵. Those who do contract it can be given physical therapy, but little else can be done for them.⁶

When the disease was first recognized, the medical community had no idea how to handle it. Of those who contracted the disease, not all got severe cases of it. A few had temporary paralysis but for most who experienced any kind of paralysis, it was permanent. The iron lung (an artificial means of respiratory support) and leg and arm braces became symbols of the disease’s more severe effects and the valiant efforts to aid in the suffering. Doctors were unsure of how to treat it and tried any number of things. One famous woman, Sister Elizabeth Kenny, began a clinic and treated patients by placing heat packs on their atrophied muscles and slowly working patients up to increased levels of mobility, attempting to wean them from the use of the iron lung. Many treatments were painful, and the suffering of those children stirred the hearts of researches and housewives alike. In the United States, the National Foundation for Infantile Paralysis, otherwise known as the March of Dimes, began a massive campaign to raise funds not only for sufferers and their families (who lived before the time of medical insurance), but more importantly to find a cure.

Early vaccination attempts in the 1930s were disastrous – either the vaccines were too weak to sustain immunity or they were so strong that they induced full-blown polio. At first, researchers did not know that there were three different (but closely related) viruses that caused the disease, and several vaccines came out that protected against one but not all of those viruses. Two researches in the early 1950s emerged with competing ideas of which kind of vaccine would work. Jonas Salk insisted that a killed vaccine, which used killed samples of the three major types of the poliovirus, was safe and effective. Alfred Sabin insisted that a live attenuated vaccine (which means that the virus injected is alive but a weakened form of the poliovirus) was the only one that could induce lasting immunity.

The March of Dimes funded them both, and it became a sort of race to see who would succeed first. Jonas Salk took an early lead and perfected his vaccine in 1952. He first tried it out on residents of a rehabilitation hospital for polio victims in order to see if the vaccine did, indeed, increase the antibodies in the blood against all three types of poliovirus. This seemed a safe testing ground since all of the patients had been exposed to the virus, but not all had been exposed to all three strains, thus the results offered him some idea of the vaccine’s effectiveness. When that was successful, he vaccinated his entire laboratory, himself, and his family and began testing the vaccine on other uninfected children. Finally, he decided to try a large-scale trial of the vaccine in 1954. Dr. Thomas Francis, an epidemiologist at the University of Michigan agreed to supervise the national field trial. He insisted that it be conducted as a double-blind, placebo-controlled trial. Half of the children received the vaccine and half did not, and neither the doctors, the patients, nor Salk himself knew which child got which. All of the records and later surveillance information about each child was shipped to him at the Vaccine Evaluation Center he created in Ann Arbor, Michigan. The results of this, the largest field trial in the history of the United States in which 1.8 million children participated, were released in spring of 1955: the group of children who got the vaccine were significantly less likely to contract polio than were the group of children who did not get the vaccine. In addition, the incidence of diseases not related to polio were the same between the two groups of children. As a result, the vaccine was licensed in time for the summer of 1955.⁷ Immediately, the number of polio cases in the United States plummeted (see graph in “Vaccines are Incredibly Effective at Preventing Disease”).

Not long afterward, Alfred Sabin refined his live attenuated formula, but he could not test the vaccine in the United States since so many had already been immunized using Salk’s vaccine, so he went instead to Russia to find new case subjects. Since vaccination had not begun there, polio was still raging. There (and in Singapore, Eastern Europe and Mexico), he vaccinated 4,500,000 people. There were very few side effects, and the vaccine was highly effective. After a few more tests, the United States licensed the vaccine for use in 1961, and it quickly replaced the Salk formula until 1999. Soon after licensure in the United States, the Sabin formula was proven to have caused extremely rare cases of paralytic polio⁸. Since at that point, the threat of wild poliovirus was much greater than the threat of Vaccine Associated Paralytic Polio (VAPP), authorities continued to administrate it. By 1999, the United States had been free of wild polio for many years and the problem of VAPP was deemed to be more problematic than continuing with the Sabin formula. Since the Salk formula has no history of VAPP, it is considered safer for the general public and almost as effective⁹, so that is what we use today in the United States.

Eventually, most countries switched over to the Sabin formula, and it is still the vaccine of choice for the World Health Organization’s Global Polio Eradication Initiative for several reasons. Not only does this vaccine, now called the Oral Polio Vaccine (OPV), provide antibody immunity from all three strains of poliovirus, but it also creates a local immunity in the intestines, the most important site for the multiplication of the virus in its early stages. Another advantage is its oral distribution which reduces the need for trained health professionals to administer it. It is very inexpensive, with each dose costing around $0.08 (US). Lastly, the OPV-vaccinated person sheds the attenuated virus through his stool, and in areas of poorer hygiene, this means that others around him will be immunized as well. The person vaccinated with the killed virus vaccine (IPV) can still be infected with polio and have it multiply in his gut since IPV does not provide that local immunity. This has become a concern of the eradication program, since circulating vaccine-derived poliovirus can still cause polio in areas where polio is no longer endemic (meaning no longer indigenous to the area). For this reason, the WHO has recommended that countries use OPV for outbreaks especially and that routine vaccination continues to be practiced until global eradication of the virus is confirmed¹⁰. The history of polio in this country and abroad is very different from those of many other diseases.

Because sanitation reduces a population’s immunity to the disease, it first began in the very places that were equipped to fight it – developing countries with the scientific and financial means to research and develop a vaccine. Yet politics and science had to work hand-in-hand to overcome the disease, and since the two have often clashed, it was not an easy battle. Now, a little over a century after the first epidemics cropped up, the world is very nearly polio free, thanks to mass vaccination. Perhaps this disease will someday be as powerless to harm as it was for so many centuries before it was recognized.

References

1. Aaron E. Klein Trial by Fury: the Polio Vaccine Controversy Scribner (New York, NY) 1972, p. xiv (picture)
2. Center for Disease Control (CDC) “Polio Vaccines” (Available online)
3. Global Polio Eradication Initiative (GPEI) “News and Documents: Fact sheet and FAQ” ( Available online )
4. Global Polio Eradication Initiative (GPEI) “Background: The Disease and Virus” ( Available online )
5. GPEI, News
6. GPEI, Disease
7. Aaron E. Klein, pp. 79-80
8. Ibid., pp. 149-151
9. CDC, p. 4
10. Global Polio Eradication Initiative “Post Eradication Recommendations” ( Available online )

Erica A. Sommerville is not a medical doctor but a college student. She does not dispense medical advice. Her aim is to educate the public about scientific issues. Please consult a board-certified medical doctor before making any medical decisions for yourself or your family.

The history of rubella in the United States gives another excellent example of how disease rates plummet when vaccination occurs. The following graph shows rubella cases from 1966 (the first year rubella was a nationally notifiable disease) to 2001:¹

Notice that the incidence of rubella did not begin to fall until the vaccine was licensed in 1969. The greatest decrease came after the second (combination) vaccine, the MMR, was licensed. Notice also that the decrease in the rubella rate started in about 1970. Remember from the previous graphs of polio and measles that the significant decrease in the measles rate started in 1964, while the significant decrease in the polio rate started in 1955. This makes it obvious that improved sanitation is not the reason that these diseases declined. If improved sanitation were the explanation, the diseases should all decline at roughly the same time, not spread out over a period of 15 years!

The trend that I have shown for polio, measles, and rubella exists in other countries for other diseases as well. For example, the UK’s department of health has tracked the case rates (and death rates) of many diseases in the UK. Their data also show the dramatic efficacy of vaccines. Click on the links to see the dramatic decline in these diseases in the UK, thanks to immunization:

Diphtheria Rate plummeted in 1944, just after diphtheria immunization was introduced

Measles Rate plummeted in 1968, just after measles immunization was introduced

The conclusion should be clear – disease rates plummet once vaccination is introduced.

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References

1. Morbidity and Mortality Weekly Report, Volume 42:#53 (1994),p. 95 Volume 50:#53 (2003), p. 119

Dr. Wile and Erica A. Sommerville are not medical doctors. Dr. Wile is a nuclear chemist, and Miss Sommerville is a college student. As a result, they do not dispense medical advice. They simply educate the public about scientific issues. Please consult a board-certified medical doctor before making any medical decisions for yourself or your family.