Inside Story

Lady Mary’s experiment, and other infectious stories

Historian Simon Schama spent the pandemic researching smallpox, cholera and plague

Frank Bowden Books 18 August 2023 1979 words

Unlikely influencer: Lady Mary Wortley Montagu and her son Edward, with attendants, in Constantinople c. 1717, as depicted by Jean Baptiste Vanmour. Alamy

Some global events enter into collective memory and others don’t. More people died from the influenza pandemic that began in the last year of the Great War than from the fighting; yet the war is a central part of Australian memory in a way the Spanish flu is not. In recent years the world has experienced a real and common peril — the coronavirus known as Covid-19 — but what will we remember of its enormous toll?

I have been thinking (and writing) about the prospect of emerging pandemics for most of my professional life. I started my career as an infectious diseases physician in the 1980s just as HIV was emerging and have seen Lyme disease, hepatitis C, SARS, MERS, H5N1, Ebola, Nipah, hantavirus, bat lyssavirus and monkeypox (to name a few) appear and recede. I thought the next pandemic would be a bird influenza that had been “humanised,” but wiser observers saw the risk of a coronavirus with the right genetic profile.

Although border closures formed part of existing control plans, I didn’t believe that any liberal democracy would close itself off from the world, and the state border closures in my own country were unthinkable — until they happened. I did expect mass gatherings to be cancelled but never imagined entire populations confined to their homes.

Yet just three and a half years after its sudden appearance, I skim academic articles about the virus and altogether avoid general media coverage. This may be an adaptive response to trauma, and a sign that we trust that the technocracy and polity have learned enough to mitigate the effects of the next inevitable event. Or is it something else?

In his new book Foreign Bodies, historian Simon Schama shows how eighteenth- and nineteenth-century authorities, scientists and societies dealt with large-scale outbreaks of smallpox, cholera and plague. Each case shows the “immemorial conflict between ‘is’ and ‘ought,’” Schama writes,

between short-term power plays and long-term security… between the cult of individualism and the urgencies of common interest… between native instinct and hard-earned knowledge. If it is a happy answer you want to the question as to which will prevail, it is probably best not to ask an historian.

Foreign Bodies opens, appropriately in this age of wilful intellectual amnesia, with the French philosopher Voltaire, who nearly died of smallpox in 1723. Because it is the only infectious disease that has been eradicated from the planet, we have no contemporary experience of the terror it inflicted on local populations when it appeared. But smallpox not only killed a significant proportion of any group of people it infected but usually left survivors scarred and disfigured.

Voltaire was contemptuous of how doctors treated the disease in France. In his Letters Concerning the English Nation (1733) he cites the use of inoculation in Britain as an example of that country’s modernity. What he may not have known is that inoculation had only recently, and indeed reluctantly, been introduced from the East.

Smallpox inoculation was very different from the vaccination that came later. It involved pricking smallpox pustules on an infected individual and transferring the extracted fluid into a healthy subject — usually by making a number of superficial pricks of the skin with the contaminated needle. The vast majority of inoculated subjects suffered only a mild to moderate attack of smallpox, although occasionally they died. We still don’t know why inoculation produced a less severe disease than “naturally” acquired infection.

Britain’s adoption of inoculation, patchy and fragile as it was, was driven by an unlikely eighteenth-century influencer. Before she returned from Constantinople to England in 1718, Lady Mary Wortley Montagu, wife of the English ambassador to an Ottoman sultan, had access to a female world closed to her husband. She had been struck by the absence of smallpox scarring in the women she met socially and observed in harems.

Montagu — who had herself been disfigured by an attack of smallpox — learned that the disease’s effects were minimised by the local practice of inoculation. She brought this knowledge back to London and convinced an English surgeon to inoculate her son. The practice was slow to catch on, but Montagu’s political connections meant that Caroline, Princess of Wales, became aware of her advocacy and had her two daughters inoculated. Even Catherine the Great eventually followed suit.

At this distance, the medical profession’s resistance to inoculation isn’t surprising, but it is ironic, considering that medics at the time lacked effective treatments for almost any disease. When the English profession did adopt inoculation, doctors couldn’t help but combine it with mercury, antimony and other useless (and even dangerous) but popular medications. Lady Mary despaired of this meddling, wishing that the protocol would stick to that of the East.

Schama touches on the trope of wise folk remedies versus mainstream medicine in recounting Lady Mary’s story, but he is always aware of the risk of lionising success after the event. Effective treatments have a survival advantage, dangerous ones disappear — eventually.

On balance, inoculation was a useful and relatively safe procedure. But it was supplanted when Edward Jenner introduced vaccination in 1796. Others had already observed that milkmaids, who rarely contracted smallpox, had almost always been infected with a trivial infection known as cowpox (or vaccinia in Latin). Jenner was not the first to infect patients with cowpox to prevent smallpox, but he formalised the procedure and promoted its widespread use.

In this case, the close relation of the viruses that caused cowpox and smallpox provided a serendipitous protective cross-immunity. But nature doesn’t provide many similar serendipities. It would be ninety years before Louis Pasteur developed the next human vaccine, in his case against rabies. Although viruses had still not been identified as a cause of disease, he “passaged” the infectious material through generations of rabbits, eventually producing an attenuated or “live” vaccine designed to provoke a protective immune response without causing the disease itself.

The first acknowledged recipient of Pasteur’s vaccine was a nine-year-old boy, Joseph Meister, who had recently been bitten by a rabid dog. As Schama points out, the usual triumphalist history of the discovery is complicated somewhat when we learn that two subjects had received the vaccine prior to Meister, and one of them had died.

Three exciting decades of microbiological discovery followed Robert Koch’s identification of the anthrax bacillus in 1876. The bacterial causes of many of the important epidemic infectious diseases — plague, tuberculosis, cholera and salmonella, to name a few — were elucidated in short order. Because it isn’t easy to prove that a germ actually causes a disease, Koch postulated the criteria that needed to be met.

It is here, in the context of a persisting uncertainty about the true cause of epidemics, that Schama introduces the unlikely character of Adrien Proust, the father of Marcel. Proust the elder, a public health physician in late-nineteenth-century France, advocated an international body to coordinate responses to epidemics and promote the very new science of vaccination. Representing France at a conference on cholera in Constantinople, Proust had heard the Ottoman Sultan Abdulaziz discussing the health risks for home countries of those returning from the Haj — a topic that remains germane today.

Cholera epidemics were widespread in Europe at the time, and international politics and professional differences were hampering control. Schama argues that while the British were motivated partly by mercantile interests anxious to keep ports open, a medico-philosophical argument was also in play.

The latter reflected one of the key moments in the history of infectious diseases: London-based physician John Snow’s discovery in 1854 that contaminated drinking water was responsible for cholera outbreaks. The British set about applying an engineering approach to cholera control — building sewers to separate waste and drinking water and protect potable water at its source — and it worked. But that experience encouraged British health authorities to fixate on cleanliness, above all else, as the way to healthiness. They saw the new vaccines as a distraction from the main game of carbolic acid and better drains.

The bulk of the second part of Foreign Bodies is taken up with the life of Waldemar Haffkine, the Russian-born microbiologist who developed vaccines against cholera and plague in the late nineteenth century. Haffkine, an obscure figure in the history of bacteriology who deserves better recognition, was hampered from the start by the fact that he was not a medical practitioner. Schama effortlessly places him in the scientific and social domains of the time, illustrating the inherent mistrust he faced both as a Jew and as a non-medico. (Pasteur was not a physician either, but his hagiography was unassailable by then.)

Most of the action takes place in the British Raj, where it soon becomes apparent that the outsider Haffkine’s vaccine rollouts relied more on local Indian support than on his colleagues in the British-run Indian Medical Service. Those vaccines probably saved an order of magnitude more lives than the British-sanctioned sector closures and slum clearances, but Haffkine suffered a blow in 1902 when nineteen people died as a result of a tetanus-contaminated vial of plague vaccine. Although he was exonerated five years later by an inquiry helmed by three giants of microbiology, his career had collapsed. Still only forty-two, he undertook no further significant work of discovery.

Haffkine would marvel at the new RNA technologies and the speed and scale of modern vaccine production, but he would understand the fundamentals of what has been hailed as a miracle of modern science. But this industrial-scale achievement has to be balanced with the more mundane (and at times uncivil) public health debates that preceded the availability of the Covid vaccines.

Uncertainty about something as basic as how SARS-CoV-2 is transmitted lingered longer than the time it took to produce the first vaccine. Masks were recommended after the virus was found to sometimes be carried on the air (airborne transmission, that is) not just in the air (droplet transmission). A proven means of preventing respiratory infections, hand hygiene, was adopted early by everyone but quickly dropped away when mask mandates came into force. You probably need both to prevent transmission and it is interesting to note that the vast majority of Australians’ infections occurred after masks disappeared and hand hygiene waned.

The web of life is a fragile gossamer. Subtle, undetectable disruptions in one part of the chain can lead to unexpected downstream consequences. Almost all new human infections are caused by pathogens that were once harmlessly confined to the animal world. The movement from animal to human is happening principally because of habitat loss, an increasing reliance on overcrowded food production and, sometimes, local tastes for exotic meats from undomesticated animals.

Foreign Bodies opens with the words attributed to Pliny the Elder — in the end, all history is natural history — and Schama finishes with the story of the decline of the horseshoe crab. Unchanged by evolution over millions of years, the crab’s blood has been used in recent decades to test for the presence of a specific contaminant in vaccine vials. Climate change and overharvesting have dramatically reduced the crabs’ numbers and pharmaceutical companies have struggled to find a more sustainable alternative at a time when safe vaccine production is an international industrial priority.

This is an unusual but beautifully written book. Schama admits it was not the one he was planning to write when the pandemic began. It is a mixture of personal observations of North American nature, modern political commentary, microbiological exposition, historical analysis, anecdote and biographical diversion. Occasionally, present-day issues jarringly appear in the midst of a prolonged historical narrative, and I wonder if Haffkine deserves as much space as he gets. But these are quibbles and I am grateful to Simon Schama for painlessly curing me of my Covid-19 avoidance disorder. •

Foreign Bodies: Pandemics, Vaccines and the Health of Nations
By Simon Schama | Simon & Schuster | $59.99 | 480 pages