Defeating the Ministers of Death

by David Isaacs

  There were two reasons why smallpox was so important to Lady Mary. In 1713, her 20-year-old brother had died from the disease, leaving two young children. Lady Mary herself had caught smallpox at age 26 and it had left her face permanently scarred (although by all accounts this did not impede her love life).

  In 1716, her husband was appointed as the British ambassador to Turkey, and the couple lived in Istanbul for two years. Lady Montagu defied custom and befriended Ottoman women, visiting them in their homes, going to Turkish baths with them, and sometimes wearing Turkish costume. She learned a great deal about Turkish life and customs, and wrote letters home. These earned her some renown when they were published as Letters from Turkey.

  In one of these letters she wrote to a friend:

  The small-pox so fatal and so general amongst us, is here entirely harmless by the invention of ingrafting, which is the term they give it. There is a set of old women who perform the operation. People make parties for this purpose . . . the old woman comes with a nutshell full of the matter of the best sort of smallpox.

  She went on to describe how the old woman opened up four or five veins ‘with a large needle and puts into the vein as much matter as can lay upon the head of her needle, and after that binds up the little wound’. She concluded: ‘Every year thousands undergo this operation; they take the small-pox here by way of diversion, as they take the waters in other countries.’

  While in Turkey, Mary insisted that the embassy surgeon, Charles Maitland, variolate her six-year-old son, Edward, fearing he would suffer the same fate as his uncle. She did not get her daughter Mary variolated, thinking she was too young at only one month old. The Montagu family physician was the very same Dr Emanuele Timoni who had informed the Royal Society about variolation. Dr Timoni probably advised and helped Dr Maitland, although any assistance he provided has not been recorded.

  When Lady Mary returned to England in 1719 she promoted variolation in her writings, but it was often dismissed as an oriental folk remedy. In 1721, when a smallpox epidemic hit London, Lady Mary asked Charles Maitland to variolate her daughter Mary, now three years old. This was the first time the procedure had been performed in England. Maitland had retired to Hertford and was nervous. He asked for three members of the Royal Society to act as witnesses before he variolated Mary in both arms. One of them, Dr James Keith, had lost all but one of his own children to smallpox, and was so impressed that he asked Maitland to immunise his surviving six-year-old son. Little Mary and Dr Keith’s son both survived, and the news spread among the medical profession. The younger Mary would later marry Lord Bute, who became prime minister.

  Lady Mary had influential friends, most notably Caroline, Princess of Wales, who was intelligent and interested in science. Princess Caroline spoke positively of variolation to her husband and the royal physicians, who were soon won over. Variolation had the royal seal of approval.

  The royal couple were keen to publicise the technique and asked if six condemned prisoners in Newgate Prison could be offered the choice between variolation and execution. Unsurprisingly, the prisoners all chose variolation. Dr Maitland variolated three men and three women aged 19 to 36 in April 1721. Three physicians closely observed the prisoners, who all survived the treatment and were set free that September.

  One of the prisoners, 19-year-old Elizabeth Harrison, was subsequently used as a human guinea-pig. She was taken to Maitland’s home in Hertford, where a smallpox epidemic was raging. There she nursed a smallpox patient in the local Christ’s Hospital, and lay in the same bed as a 10-year-old boy with smallpox every night for six weeks without contracting the disease. Though it’s unclear whether Elizabeth had any choice in the matter, it was the strongest proof yet of the effectiveness of variolation.

  The dilemma of omission (not immunising and risking the disease) versus commission (committing to accept the risk of the immunisation) was one faced by Benjamin Franklin (1706–1790), who wrote in his autobiography:

  In 1736 I lost one of my sons, a fine boy of four years old, by the smallpox taken in the common way. I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it; my example showing that the regret may be the same either way, and that, therefore, the safer should be chosen.

  Benjamin Franklin was an extraordinarily talented man, renowned as a scientist, inventor and politician. He and his brothers were strong defenders of freedom of speech and published their own newspaper. In the 1720s the Franklin brothers had written in their newspaper criticising the practice of variolation for its potential to harm. It was tragically ironic, therefore, that smallpox came to Philadelphia in 1736 and killed Benjamin Franklin’s beloved son Frankie.

  In contrast, the great United States president John Adams had been variolated as a child, but his wife Abigail and children had not. During a smallpox epidemic in 1776, they decided that the risk of variolation was lower than the risk of catching smallpox. Abigail and her four children travelled 16 kilometres to Boston, to be inoculated by an expert, Dr Thomas Bullfinch. Purging by vomiting for a week beforehand was thought to enhance variolation, so Dr Bullfinch prescribed an emetic. Abigail’s variolation was uneventful, but 11-year-old Nabby developed pustules and fevers, and her body ached terribly. John, aged nine, was fine, but the inoculation had to be repeated on six-year-old Charles and four-year-old Thomas, as in their cases the lack of a scar indicated the first inoculation hadn’t worked. Charles was delirious for two days and took weeks to recover. But at the end of it all they were immune and the American public’s faith in variolation grew. John Adams once famously said: ‘Facts are stubborn things; and whatever may be our wishes, our inclinations, or the dictates of our passions, they cannot alter the state of facts and evidence.’

  Vaccination

  Variolation rapidly fell from favour when Dr Edward Jenner developed a safer and highly effective alternative called vaccination in England at the end of the 18th century. Jenner would never have developed his vaccine if it had not been for his observations of people who had been variolated, so we owe a debt to all those who practised and publicised variolation.

  The names are confusing. The word ‘variolation’ comes from variola, the Latin name for the smallpox virus (varius means ‘spotted’). Vacca means ‘cow’ in Latin, and the word ‘vaccine’ derives from a famous paper Jenner wrote about cowpox, a disease of cows’ udders caused by the cowpox virus, which is related to but different from the much more dangerous smallpox virus. Jenner called cowpox variolae vaccinae. Subsequently the virus causing cowpox was identified, and was named vaccinia virus. From this name the word ‘vaccination’ was later coined by Louis Pasteur in honour of Jenner.

  Edward Jenner was a country doctor, equivalent to a latter-day general practitioner, who worked in rural Gloucestershire. He was a careful observer and experimenter and gained the distinction of being made a Fellow of the Royal Society (FRS) in 1788. Interestingly, his FRS was awarded not for his world-changing work on vaccination, but for explaining why the young baby cuckoo has a special groove in its back. (The cuckoo’s mother lays her single egg in another bird’s nest; the cuckoo hatches first and uses the groove to eject the other bird’s eggs.) Being an FRS allowed Jenner to present his work on cowpox to the Royal Society, which gave him scientific credibility and gave his work much more clout.

  Jenner had witnessed the way smallpox could kill and maim his patients and was a keen proponent of variolation. His parents had had Jenner himself successfully variolated in 1757, aged eight, which might have influenced his enthusiasm for the practice. Jenner variolated a large number of people in his parish. Most of them developed a mild dose of smallpox, although some got severe smallpox. A third group, Jenner observed, displayed a local reaction at the site of variolation but did not develop a rash at all. From his records, Jenner was able to determine that these peopl
e had all previously had cowpox. Some were milkmaids; others had caught the disease from milkmaids. Jenner knew the folklore that milkmaids were characteristically unmarked by smallpox scars. The traditional English poem ‘Where Are You Going, My Pretty Maid?’ may be an illustration of this. A man courting a milkmaid asks:

  ‘Where are you going, my pretty maid?’

  ‘I’m going to market, sir,’ she said.

  ‘What is your fortune, my pretty maid?’

  ‘My face is my fortune, sir,’ she said.

  ‘Then I cannot marry you, my pretty maid.’

  ‘Nobody asked you, sir,’ she said.

  She has attitude, but no money.

  Jenner postulated that milkmaids did not get smallpox because they had previously been infected with cowpox, which they almost universally caught from the cows they milked. The cowpox usually started on their hands, from touching the udders of infected animals, and could spread up their arms but not usually further, and they did not become ill. Some locals even reputedly infected themselves with cowpox to prevent smallpox.

  Jenner did not know that both diseases were caused by viruses, nor that the viruses were related. But he did note that the appearance of the pockmarks of cowpox resembled a mild dose of smallpox, and he postulated that infection with cowpox could promote immunity against further cowpox and also against smallpox.

  This was revolutionary thinking. In 1796 Jenner performed a famous experiment that would horrify a modern-day ethics committee. He lanced some cowpox pustules (fluid-filled blisters) on the hand of a milkmaid, Sarah Nelmes, sucked up the fluid and injected it into two small cuts he made in the arm of an eight-year-old boy, James Phipps. Jenner wrote of his experiment on James:

  On the seventh day he complained of uneasiness in the axilla [armpit] and on the ninth he became a little chilly, lost his appetite, and had a slight headache. During the whole of this day he was perceptibly indisposed, and spent the night with some degree of restlessness, but on the day following he was perfectly well.

  Six weeks later, Jenner inoculated James with material taken from a smallpox victim to see if James would fall ill. Fortunately the boy did not contract smallpox; the cowpox had rendered him immune. What was more, Jenner injected poor James with smallpox material more than 20 more times to make sure the immunity was long term. Edward Jenner was a thorough man, although his concern seems to have been more for the validity of his research than for the fate of wee James.

  James Phipps was the son of a poor labourer who worked as Jenner’s gardener, so Jenner might reasonably be accused of exploitation. However, he was generous in his gratitude: years later, Edward Jenner gave Phipps, his wife and two children a free lease on a cottage. When Edward Jenner died, James Phipps went to his funeral.

  Ethics can be defined as how we believe we ought to behave. We should hesitate before using current concepts of what is and is not considered ethical to condemn historical behaviour. Was Jenner’s vaccination of eight-year-old James Phipps, the child of his poverty-stricken gardener, ethical? Even if Jenner informed Mr and Mrs Phipps of the possible risks, the power imbalance is problematic. Did the Phippses fear that Mr Phipps might no longer be employed if they did not consent to the experiment? It seems unlikely that the cottage lease Jenner later gifted to the Phippses was offered at the time of the experiment, but what if Jenner offered other inducements of which we are not aware? Nowadays inducements to participate in research would raise ethical hackles, particularly if they were excessive.

  A utilitarian can point to the good outcome for the Phipps family, and the even better outcome for the world: the experiment would lead to a vaccine that prevented millions of deaths. But ethicists are concerned about what we should do with ‘tainted information’ – data obtained through unethical research – and ponder whether such data should ever be used for ethical and beneficial results. This is not to say that Jenner’s experiment was indeed unethical. However, Dr Jenner would never be able to persuade a modern research ethics committee that it was ethical to vaccinate a child before trying the vaccine on many adults first and without knowing a great deal more about the likely risks and benefits.

  Jenner was not the first person to vaccinate people using cowpox. There are reliable reports of others performing similar procedures in the previous 25 years in England and Germany, including a Dorset farmer called Benjamin Jesty, who successfully gave cowpox to his wife and two children during a 1774 smallpox epidemic. Jenner was probably well aware of Jesty’s experience. But even if he was not the first person to give cowpox to a child, he deserves the plaudits because he formally showed that cowpox had rendered James Phipps immune by deliberately exposing James to smallpox. Furthermore, Jenner was not satisfied with the single case of James Phipps, but tested his theory by transmitting the cowpox from person to person by inoculation.

  In 1798, Jenner reported his findings on 23 subjects to a sceptical Royal Society. His paper was called An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Discovered in Some of the Western Counties of England Particularly Glouchestershire [sic], and Known by the Name of ‘Cowpox’. The Royal Society recognised its importance, and so did the global scientific community: Jenner’s paper was immediately translated into six languages and his technique of vaccination rapidly adopted throughout much of the Western world.

  Nevertheless, the concept of inoculating healthy individuals with cowpox alarmed large sections of the British public. The satirist James Gillray was quick to ridicule the practice, publishing an amusing cartoon showing cow features growing out of the bodies of people being vaccinated by Jenner. Undeterred, Jenner continued to work on cowpox vaccine and publicise its use.

  Catherine the Great of Russia gave the first Russian child to receive cowpox vaccine the nickname ‘Vaccinov’, and had the State pay for his education. Vaccines reached Newfoundland in 1800, and three years later, mass vaccination programs were started in the Spanish colonies in the Americas and the Philippines. In 1813, the United States Congress passed an Act to ensure safe smallpox vaccine supply to the American public, and in 1832 it established a vaccination program for Native Americans.

  In 1803, five years after Jenner published his seminal paper, an Australian assistant surgeon, John Savage, inoculated orphans with the cowpox vaccine. New South Wales doctors needed a human supply of cowpox and there was no means of refrigeration, so they kept the cowpox vaccine alive by using a needle to transfer infectious material, which they wrongly called ‘lymph’, from one vaccinated person’s arm to another’s. A year later, Savage and another colonial surgeon, Thomas Jamison, wrote in a letter to the Sydney Gazette of 3 June 1804: ‘It is our decided opinion, that the Cow Pox is completely established in this Colony.’

  Some physicians used vaccinated children as their source of cowpox. Dr Alex Cook, a Parramatta surgeon, wrote to the Sydney Morning Herald in 1843:

  I took a well formed scab, after falling off a child’s arm that I had vaccinated, rolled it up in a clean piece of paper and put it into a well-corked vial. Last week I took the same scab, (after it had been in the vial for upwards of six months), made it into a pulp with a little warm water . . . and to my great satisfaction it produced the vaccine pustule as well defined as if the lymph had been ever so recently procured.

  Vaccine supply was also maintained by using a truly captive population: the women of the Female Factory in Parramatta. This was the only convict establishment with enough unvaccinated subjects to allow continuous propagation of cowpox.

  In 1841, New South Wales Governor George Gipps heard that Mauritius was in the throes of a virulent smallpox epidemic. Governor Gipps offered the colonists free vaccination ‘to avert the calamities which must necessarily follow if the smallpox is introduced into the Colony, and to keep up a constant supply of vaccine lymph’. Doctors were told to charge a shilling for vaccination, which would be returned if the parents brought their child back with a scab that proved the vaccine had taken.

  Gip
ps asked Dr JV Thompson, the Deputy Inspector General of Hospitals, to ensure there was adequate cowpox vaccine to protect the colony. Dr Thompson sent a letter in response. The letter sat in the archives of the New South Wales State Records Authority for 169 years until, on 24 November 2010, a senior archivist, Janette Pelosi, was looking through some papers and saw a small pink parcel pinned to a letter. The letter was titled ‘Respecting Vaccine Virus’ and had been written on 17 May 1841. The accompanying package contained cowpox vaccine material wedged between two sealed microscope slides, a common way of transporting specimens at the time.

  Concerned that the virus might still be infectious, Ms Pelosi rang New South Wales Health. The package was transported breathlessly and with some publicity to the local public health unit to see if it contained viable cowpox or even smallpox. Fortunately it did not.

  The historic specimen is now held at Westmead Hospital, almost next door to Cumberland Hospital, the site of the old Female Factory. The Children’s Hospital at Westmead, where I work, is wedged between the two hospitals, like the cowpox specimen wedged between two microscope slides.

  A year after that discovery, in 2011, the Virginia Historical Society in the United States held an intriguingly named ‘Bizarre Bits’ exhibition. The Washington Post advert noted the contents included ‘an infant’s smallpox scab’. This was actually a cowpox scab to be used for vaccination, enclosed in plastic and pinned to a letter written by a local Richmond man to his father in Charlottesville in 1876. An alert reader notified the US Centers for Disease Control and, to the bemusement of visitors, an emergency team arrived at the exhibition clad in gowns, masks, caps and gloves, to bag and remove the offending letter and scab. The press played up the drama. Tests showed no live virus remained.