Because of its indiscriminate killing power smallpox was universally feared, perhaps even more so than bubonic plague. Both diseases brought their own kind of terror but bubonic plague, which was known as the Black Death, was episodic, invading Europe in waves over the centuries while smallpox was a perennial enemy, a threat that never abated. Like bubonic plague, smallpox too had its own epithet. It was known as the ‘speckled monster’ because of the way it spotted its victims’ bodies with pustules or pox that left deep, permanent scars when they healed. It is these pox which gave the disease its name. Around the end of the fifteenth century the term ‘small pockes’ was first used to distinguish this disease from syphilis—another dreaded disease. (Syphilis was called the ‘great pockes’ because the infected pustules that erupted on the skin of its victims were much larger.[4])
In 1800, the historian Thomas Macauley graphically described the horror that was smallpox, the fear that it engendered in individuals and the devastation it visited upon Edward Jenner’s society:
Smallpox was always present, filling the churchyard with corpses, tormenting with constant fear all whom it had not yet stricken, leaving on those whose lives it spared the hideous traces of its power, turning the babe into a changeling at which the mother shuddered, and making the eyes and cheeks of the betrothed maiden objects of horror to the lover.[5]It was this formidable enemy that Edward Jenner challenged with his intellect but medical knowledge in Jenner’s time was very limited in comparison to the 21st century. Although there were enormous changes in the way medicine was practised in the 1700s, there were crucial gaps in scientific knowledge which prevented progress, the most significant of which is something that seems so fundamental today—that micro-organisms cause disease. It was unlikely that a cure for infectious diseases such as smallpox and bubonic plague could be found if science was unable to provide an understanding of their cause.
The prevailing belief was that diseases could result from physiological dysfunction and so investigations into the chemical and material structure of the body through post-mortems became a way for doctors to expand their knowledge of anatomy and pathology. In the eighteenth century, for the first time, doctors were being formally educated and trained in hospitals and were acquiring certified qualifications in their profession.[6] But hospitals then were vastly different to the high-tech institutions they are today and procedures were carried out with no understanding of infection and its transmission.
When Edward Jenner developed the first vaccine he was unaware of the existence of micro-organisms and that smallpox, the highly contagious human disease, was caused by a virus one-millionth of a millimetre in size that can multiply only within human cells. To many intellectual minds in the eighteenth century, such an idea would have been both fanciful and preposterous. In keeping with the climate of enquiry prevalent in Jenner’s era, however, the theory that smallpox arose from innate seeds that were present in all humans or was the result of unfavourable environmental conditions was questioned, and the view that smallpox was a specific disease that could be attributed to a specific material cause became current. Despite this step forward in medical knowledge identifying the real cause would be impossible until the end of the nineteenth century when Louis Pasteur proved his ‘Germ Theory of Disease’ and it became widely accepted that micro-organisms cause disease.
Today the smallpox virus is called the ‘variola’ virus, coming from the Latin word varius, meaning ‘stained’, or from varus, meaning ‘mark on the skin’, signifying the rash and disfiguring scars that are hallmarks of the disease . There are two strains of the virus: variola major, which has severe symptoms and a very high mortality rate (sometimes as high as 100 percent); and variola minor, which as its name implies is much less severe, with a mortality rate of less than 2 per cent.
In the same way that there was uncertainty about the cause of smallpox, for many centuries there was also uncertainty about how people caught it. Smallpox is spread through droplet infection—in lay terms, coughs and sneezes. Breathing in just a few particles of the virus is all it takes to become infected. The virus enters the body through the lungs, passes through the respiratory tract and enters the bloodstream, eventually spreading to the internal organs and the skin. With variola major it takes twelve to fourteen days for symptoms (which are nothing short of gruesome) to appear. It begins with a fever and then a splitting headache and backache, an inability to stand and delirium. Nausea and vomiting are also common.
After two to four days, the fever eases and a rash appears. The rash is the result of the virus replicating in the skin. After several more days, pustules or pox form. The pustules contain a cloudy fluid and they cover the body, are excruciatingly painful and can spread to the throat, the eyes and the anus. In some cases the rash merges and can peel off the body in black sheets.[7] Although death usually occurs between day eleven and day fifteen of the rash, some people die before it has fully developed because of blood poisoning, secondary infections or internal bleeding. If a person survives, over a period of three to four weeks the pustules form crusts which actually contain the virus. The crusts then shrink, dry up and eventually fall off leaving deep scars.
A FAR-REACHING DISEASE WITH A LONG HISTORY
So how did a country doctor during a period in which medical knowledge and technological ability were limited, come to develop a vaccine for this horrifying disease without fully understanding the science behind his discovery?
The story begins with Edward Jenner’s childhood. Born on 17 May 1749 in the small market town of Berkeley in Gloucestershire, Edward Jenner was the third of eight children born to the vicar of Berkeley, the Reverend James Stephen Jenner, and Sarah Jenner. When Edward was five years old his parents died and he was cared for by his eldest sister Mary until he was sent to boarding school. It was there, during a smallpox epidemic, that Edward was first confronted by the many horrors associated with smallpox that were part and parcel of life in the era in which he lived. His experience, however, would prove instrumental in providing both motivation and means in his later work.
Edward Jenner was only eight years old, away from home and family, when he was subjected to a medical procedure that was known as variolation. For him it was a horrendous experience, one he would never forget. Variolation provided the only hope of protection from smallpox. It involved deliberately infecting healthy people with smallpox in the hope that they would contract a less severe case and, as a result, would not catch it again. Healthy children and adults were exposed to various forms of material from people who had experienced fairly mild cases of smallpox. Fluid from pustules or ground-up scabs were inserted into the nose or rubbed into a cut made in the skin. As only a small number of people who were variolated developed a fatal case of smallpox, for many the chance of salvation far outweighed the risk of death.
The ordeal that Edward went through when he was variolated we would now consider tantamount to abuse. First he had to be bled. Bleeding was a common but potentially dangerous medical treatment that involved cutting the veins or using leeches to suck out blood. Edward then had to fast and purge over a period of six weeks, which left him weak, emaciated and at his very young age utterly afraid. After this brutal ordeal Edward was variolated and locked in a stable with other boys who were desperately ill with smallpox, and left there until the disease had run its course.[8]
There are three things to be grateful for: Edward Jenner did not catch smallpox; he had witnessed at close quarters a disease that had visited its unique horror on many societies for thousands of years; and he had experienced variolation first-hand. The practice had reached England just some 30 years before this event. Until then, during smallpox epidemics very little could be done to stop the spread of the disease. Apart from individuals praying and fasting the only public measure available was to round up those who were symptomatic and isolate them in foul places called ‘pest houses’ or on derelict ships languishing in harbours. All in vain, of course. Once symptoms were in evidence it
was too late.
Because there was no understanding of microbiology and hence the nature of infectious diseases, smallpox reigned unchecked for millennia. The theory is that it started as a rodent virus that jumped to humans in agricultural settlements in north-eastern Africa as long ago as 10,000BC. There is evidence that smallpox was known in ancient Egypt. Mummies dated as belonging to the eighteenth to twentieth Dynasties, 1570 to 1085BC, have marks that are consistent with smallpox scars and this includes the well-preserved mummy of the pharaoh, Ramses V, who died in 1157BC.[9]
The first smallpox epidemic ever recorded occurred in 1350BC during a war between the Egyptians and the Hittites. Egyptian prisoners were carriers of the disease which decimated the Hittite soldiers and citizens and killed their king, Suppiluliumas I, perhaps hastening the decline of the civilisation. Egyptian merchants also became unwitting carriers and smallpox began its slow but deadly journey to the rest of the world. Literary records place it in the Mediterranean area and in China in the third century AD.
Smallpox was the indomitable enemy of empires and a furtive assassin that changed the line of succession of ruling families in Europe and Asia. Around 180AD smallpox attacked the Roman Empire. In the epidemic, called the Plague of Antonine, as many as 7 million people may have been killed, a massive number for ancient times. Roman legions returning from a military campaign against Parthia brought the disease with them from Armenia. The rate at which smallpox spread—10,000 infections per day—gives some idea of its apocalyptic power.[10] The Roman population was decimated, and so great were the losses amongst the army that Emperor Marcus Aurelius, who soon succumbed to the disease himself, began relying on paid mercenaries to protect the empire from incursions by Goths and Vandals. The mercenaries began to exploit Rome’s weakness and historians see this as marking the end of Rome’s golden age, ushering in the beginning of the decline of the Roman Empire.
Smallpox took up residence in all corners of the globe. In Asia, the king of Burma died from smallpox in 1368 and the king and queen of Ceylon (modern-day Sri Lanka) and all of their sons succumbed in 1582. In Europe, smallpox had an exhaustive and impressive list of victims. It altered the succession of the British royal family. Queen Anne was the last monarch of the House of Stuart because in 1700 her heir, Prince William, died of smallpox at the age of eleven. In the 50 years before Edward Jenner’s birth in 1749, the Japanese emperor Higashiyama, the Austrian emperor Joseph I, King Louis I of Spain, Tsar Peter II of Russia and Queen Ulrika Eleanora of Sweden all lost their lives to smallpox.[11]
Smallpox, the speckled monster, was carried to the Americas, the New World, during the voyages of discovery where it killed many more Aztecs and indigenous North Americans than were killed by invading colonisers. Within 100 years of the Spanish conquistadors arriving in Mexico in 1518, the indigenous population of 25 million had contracted to 1.6 million, principally due to smallpox. In 1520 the Aztec emperor, Ciutláhuac, became one of the multitudes of victims.
The abhorrent slave trade also contributed to the introduction of smallpox in the Americas because many slaves came from regions of Africa where smallpox was endemic. On the eastern coast of what became the United States, smallpox had disastrous consequences for the original population. It was here that one of the first deplorable acts of biological warfare took place. In 1763 the leader of the British forces suggested grinding smallpox scabs into blankets that were to be distributed to Indian tribes, a practice that a century later was used by the American government in what could be interpreted as a deliberate act of genocide.[12]
It is ironic that the knowledge that smallpox material could be used to pass on the disease would eventually form part of the theoretical framework for its ultimate defeat. Also critical was the knowledge that those who survived smallpox did not succumb a second time. This view was present in many societies and was borne out by experience.
The Greek historian Thucydides made such an observation during a smallpox epidemic that hit Athens in 430BC. Early in the tenth century AD, a Persian physician and philosopher, Abu Bakr Muhammad Ibn Zakariya al-Razi, known as Rhazes, wrote DeVariolis et Morbillis Commentaries, a medical description of smallpox. In it he explained that smallpox survivors did not develop the disease again and also concluded that smallpox could be transmitted from person to person. In 1734, Voltaire in his Philosophical Letters noted that people known as the Circassians (Circassia is an historical region near the Black Sea) had observed that out of 1000 people ‘hardly one was attacked twice by full-blown smallpox’. Three or four might experience a mild recurrence but ‘one never truly has that illness twice in life’.[13]
Over time, the combined knowledge that smallpox material from one person could be used to infect another and that those who survived smallpox did not get the disease again brought about the practice of variolation. For centuries before Edward Jenner experienced it, variolation had been practised without any sound medical evidence as to why it worked. In India where it had been used from around 1000AD the most common method was to apply scabs or pus to the scratched skin of a healthy person. In China pox or scab material rubbed on a cotton pad was inserted into the nose or blown into the nostrils through a tube.[14] The Chinese also made pills from dried fleas taken from cows, an early hint that fleas played some part in the disease.
In the mid 1600s travelling merchants introduced variolation to the Ottoman Empire where it became frequently practised. Many women in the Turkish sultan’s harem in Istanbul had been variolated during childhood on parts of their bodies where scars would not be seen.[15] Reports describing the method of variolation used in Turkey reached England in the early 1700s when smallpox was running rampant. Members of the Royal Society of London, the esteemed and prestigious national academy of science that had been founded in 1660, became aware of the practice but it was not immediately embraced by physicians.
It was an English aristocrat, a woman, Lady Mary Wortley Montague, who is credited with introducing variolation to England and western Europe where it was also called inoculation. Lady Mary had experienced the scourge first-hand in 1715. Once a reputed beauty, her face was ravaged by the speckled monster which had also robbed her of her brother. In 1717 Lady Mary’s husband, Edward Wortley Montague was appointed as ambassador to Turkey and within two weeks of arriving, Lady Mary wrote to her friend Sarah Chiswell, describing how variolation, which she called ‘ingrafting’, was used at the Ottoman court.[16] Material from the pustules of people who had contracted a mild case of smallpox was introduced to the healthy through scratches or a puncture made on the arm.
Convinced that the method was a way to protect her children, in March 1718 Lady Montague instructed the embassy surgeon, Charles Maitland, to variolate her five-year-old son. When she returned to London in April 1721, Lady Montague had her four-year-old daughter variolated by Dr Maitland in the presence of physicians appointed to the English royal court, including the king’s physician, Sir Hans Sloane. Consequently members of the English royal family became interested in the possibility of saving their own children through variolation.
Charles Maitland was granted a Royal Licence to conduct a trial, which he carried out on six prisoners at Newgate Prison on 9 August 1721. The ethics of this may be questionable from a 21st-century perspective but the prisoners were promised a full pardon if they submitted. All six survived variolation and were released. One prisoner was then exposed directly to smallpox and proved to be immune. After the next successful trial, which Maitland carried out on six children from a charitable institution in London, the Princess of Wales allowed her two daughters to be treated.[17] The actions of Lady Mary had saved more children than her own but sadly her friend, Sarah, with whom she had shared her discovery, died from smallpox a few years later.
Not surprisingly, with a royal imprimatur, variolation soon gained general acceptance but it was not foolproof. Two to 3 per cent of people who were variolated died because success depended on physicians identifying a mild strain of smallpox and s
ome people were inadvertently infected with other life-threatening illnesses such as tuberculosis or syphilis. An even greater risk was that those who were inoculated with a virulent strain, apart from losing their own lives, were potentially the source of new smallpox epidemics. However, mortality rates were ten times lower amongst those who caught smallpox from variolation than those who caught it naturally. In 1722 James Jurin, a physician and secretary to the Royal Society, conducted one of the first medical statistical surveys and found that the mortality rate in non-variolated children was 1 in 14 but for the inoculated, it was 1 in 91.[18]
In the Americas variolation found powerful supporters as well. Benjamin Franklin, whose son died of smallpox in 1736, also carried out a statistical study to assess the effectiveness of the procedure and promoted it enthusiastically. In 1766, during the War of Independence, American soldiers under George Washington were unable to wrest Quebec from the English because a smallpox epidemic halved their troop numbers. British troops on the other hand had been variolated and did not succumb. Being a witness to the success of variolation, George Washington made the practice mandatory for all his soldiers.
By the time Edward Jenner was born in 1749 variolation was widespread throughout England. As an indication of how enormous the social and economic repercussions of smallpox were, the London Smallpox and Inoculation Hospital, dedicated to the treatment and prevention of smallpox, had been established. In both England and Europe doctors began variolating on a large scale and many built up lucrative businesses. During the 1750s when the young Edward suffered his ordeal many of the nobility of Europe were ensuring that their children were given a chance to escape smallpox. Empress Marie-Therese of Austria and her children and grandchildren were variolated as was King Louis XVI of France and his children, and Catherine II of Russia and her son.[19] Variolation remained the only defence against smallpox until Jenner’s vaccine became an accepted replacement in the mid nineteenth century.
Smallpox, Syphilis and Salvation Page 2