The Snow series is an educational course. We hope you will recognise our efforts by donating to TTE or becoming a paying subscriber, as writing the series took a lot of time and effort.

In this lecture, we examine the main objections and alternative explanations for Snow’s findings and show how he dealt with them. Let’s start with miasmata.

The 1855 General Health Board (GHB) report on the Golden Square outbreak (see Lecture 18) contained this paragraph written by Dr Fraser and colleagues on page 162:

So it was effluvia which caused the outbreak; case closed.

In 1856, Snow published a short paper in The Lancet called On the supposed influence of offensive trades on mortality.

Using rates per 10 thousand inhabitants available from the 1851 census, he demonstrated that the so-called offensive trades, those whose activities created offensive smells like tanners and slaughterhouses, had a very low death rate.

Next, he took on Farr’s pyramid (see also Lecture 4)

Here, Farr had spotted a possible confounder: those who died in great numbers lived near or on the river, which was, of course, the lowest part of urban London. Snow had pointed to the data time and time again; seafarers, longshoremen and those who used river water to drink were most at risk. Farr interpreted the closeness to the Thames as a source of miasmata, hence of disease. 

And then there was the point that refuse, and foul smells were present all over London, so why would the mortality be differential if miasmata were the cause?

The highest parts of London were most distant from the river and likely to drink cleaner water unless they were a widowed 59-year-old, fond of the Broad Street water, who dispatched her butler on a cart twice a week to fill up bottles of Broad Street water (see Lecture 14).

Repeatedly using a logical process called induction, he showed the association between water and cholera and then went one step further. He described several cases of transmission from contact, especially whenever people came into contact with clothes stained with the faeces of the cases. These were rice water white and sometimes not as identifiable as physiological waste.

He had already discounted meteorological variables, social class, and ascertainment bias in his great experiment. The same logic applied to the Golden Square outbreak:

“...whilst the presumed contamination of the water of the Broad Street pump with the evacuation of cholera patients afford an exact explanation of the fearful outbreak of cholera in St James’s parish, there is no other circumstance which offers any explanation at all, whatever hypothesis of the nature and cause of the malady be adopted. Many persons were inclined to attribute the severity of the malady in this locality to the very circumstances to which many people attribute the comparative immunity of the city of London from the same disease, viz., to the drains of the neighbourhood having being distributed and put in order about half a year previously. Mr Bazalgette, however pointed out… that the streets in which the new sewers had been made suffered less than the others; and a reference to the map will show this is correct for I recollect that the streets in which the sewers had been repaired about February last were Brewer Street, Little Pulteney Street and Dean Street, Soho. Many of the non medical public were disposed to attribute the outbreak of cholera to the supposed existence of a pit in which persons dying from the plague had been buried two centuries ago….the situation of the pit is said to be Little Marlborough Street, just out of the area in which the chief mortality occurred. With regard to the effluvia from the sewers passing into the streets and houses, that is a fault common to most parts of London and other towns. There is nothing peculiar in the sewers or drainage of the limited spot in which the outbreak occurred; and Saffron Hill and other localities which suffer much more from ill odours have been very lightly visited by cholera.” 

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Snow explained the incubation period, the infectious dose required to make someone ill and had chemically tested the suspect water himself, finding a high concentration of chloride which he interpreted as a high likelihood of the presence of organic matter. He has associated exposure with disease and lack of exposure with the absence of disease, probably randomly or quasi-randomly allocated to dwellings in the same street.

He demonstrated the importance of visual inspection, follow-up, and investigation of outliers like the widow of Hampstead (Lecture 14) and the gentleman from Brighton. This was a gentleman who came from Brighton, dined in Wardour Street, near Broad Street, returned home and died. His data were as robust as he could find, and his theory fitted in and explained most of the contemporary events, as shown in his review from Moscow to India to London. He had identified the portal of entry into England (the Baltic Fleet and the 1848 index case from Hamburg) and worked out that inhaled vapours would not cause a predominantly gastrointestinal set of symptoms. His theory was firmly grounded on the pathophysiological aspects of cholera: how could inhalation cause lethal gastroenteritis in the space of a few hours or days?

Most of all, he was able to distinguish the epidemiological modes of communication, the propagated source and the point source. The theory fitted most facts, although he did not know the nature of the “morbid poison”. The General Health Board’s investigators, Dr Thomson and Mr Rainey (see Lecture 18), visualised it, but Pacini made the connection.

On the mode of communication of cholera. London, J. Churchill, 1849, 31 pp., (MCC1); the medical establishment dismissed Snow’s first attempt at formulating an integrated and coherent theory. However, Snow’s Mode of Communication of Cholera. Second Edition (MCC2) drew a few important critiques. 

One of the most accurate and fair critics of Snow’s MCC2 was Edmund Parkes. Parkes was singularly well placed to discuss cholera transmission as he had witnessed hundreds of cases in his army service in India, written a lot about the topic and was a rising star of the medical establishment. Snow cited Parkes’s work as he had investigated the 1848 Horsleydown outbreak on behalf of the newly-created General Board of Health and concluded that it was due to effluvia. Parkes was also to serve in the Dardanelles with Florence Nightingale and witness many more cases of the disease in Crimean War soldiers. A historian reckons he wrote his critique of Snow’s work just before deploying to the Dardanelles. Like most “Anglo-Indian” physicians, Parkes had turned from a contagionist into an anticontagonist and then a contingent contagionist (see Lecture 4). 

Edmund Alexander Parkes (1819-1876) (image courtesy of Wikimedia)

Parkes moved several objections to Snow’s work, which we have to consider in the historical context and knowledge of the time, not with our contemporary understanding.

Parkes most vital point was that as Snow did not have sub-district level data for the exposure of the water provision in his “great natural experiment” in South London for the area in blue on his map (that was served by both companies), he could not be sure that his aggregate data was correct. Thus, Snow’s “experiment” remained speculative, although Parkes was careful not to dismiss the dirty water hypothesis as so many of his fellow miasmatists had done.

He was also critical of other weaknesses in Snow’s analysis, like the absence of excavation evidence of communication between the Broad Street well and cesspool or other obvious sources of contamination, Snow’s negative inspection of the water from the pump and his inability to explain the many instances in which exposure did not bring disease.

This was a recurrent criticism of Snow’s work and constituted the basis for the so-called Milroy objection. Dr Gavin Milroy (1805-1886) had investigated the 1849 Albion Terrace outbreak on behalf of the GHB and firmly concluded that it was due to rotting garbage, the main open sewer running near the houses and nuisances arising from privies (see Lecture 9). Snow had countered these objections in MCC 2 (page 29) pointing out that the conditions applied to all houses in the row, not just to those in which cholera cases had arisen. His contemporaries, however, were convinced that he had still not responded to the Milroy objection: not everyone exposed to dirty water had developed cholera. 

Snow was well aware of the points which were cleared up (with one exception) soon after the publication of MCC2 - leading our contemporary Tom Koch to accuse Snow of rushing to print before all the facts were known. Indeed, Snow republished the South London mortality once the sub-district water distribution became public knowledge because of Sir John Simon’s 1855 report.

Snow also missed the reputed index case, which the Reverend Whitehead identified (see upcoming Lecture 18).

Kerbstone marker on the site of the Broad Street pump (now Broadwick Street).

CONTEMPORARY THEMES

Modern-day miasmatists hold on to their credo but do not expose their beliefs to the kind of refutation that Snow’s did. They contend that SARS-CoV-2 is mostly aerosol-borne, but the evidence they provide in this era of molecular epidemiology is thin. Fomite transmission offers a more convincing mode of communication. Miasmatists rely on laboratory challenge studies, which have scarce generalizability while criticising the results of randomised trials for the same reason. 

Their attacks are not as courteous as Professor Parkes', Drs Fraser’s, or Milroy’s but more reminiscent of The Lancet’s review of MCC2 (see Lecture 17).

Parkes’s and Milroy’s observation that Snow could not explain the many well-recorded instances of exposure to dirty water and the absence of disease still stands today for respiratory viruses.

In the most contrived of experiments, challenge studies (See also Lecture 10), carried out in quarantined volunteers, a variable number of recipients manifest signs of disease. Sometimes, transmission does not happen within households or between couples sharing the same bed.

In lecture 4, we have seen the competing Victorian-era theories on the origins and transmission of agents. In today’s post-COVID polarised setting, would eminent people like Parkes, Farr and Simon, women like Nightingale and bodies like the Royal College of Physicians be willing to initiate investigations and gradually change their deeply held views based on evidence and experience?

Parkes was an excellent example, migrating from contagionist to anticontagionist to contingent contagionist views on the basis of experience and thought.

Ackernecht (see also Lecture 4), summing up the weaknesses of the two opposed camps, wrote thus:

These facts have yet to be explained to this day, and germ theory, far from casting light on these strange occurrences, has been unthinkingly followed or used to conveniently ignore its partial explanatory value. 

Some who have observed and studied acute respiratory infections for a lifetime have even concluded that they are not infectious.

Share Trust the Evidence

Readings:

Snow J. On the mode of communication of cholera. London, J. Churchill, 1849, 31 pp. (MCC1) Available as a drill through here.

Parkes EA. Mode of communication of cholera by John Snow, MD: second edition - London, 1855, pp 162. Int J Epidemiol. 2013 Dec;42(6):1543-52. doi: 10.1093/ije/dyt193. 

Nobody loves a critic: Edmund A Parkes and John Snow's cholera. Int J Epidemiol. 2013 Dec;42(6):1553-9. doi: 10.1093/ije/dyt194. 

Edmund Alexander Parkes, John Snow and the miasma controversy. Int J Epidemiol. 2013 Dec;42(6):1562-5. doi: 10.1093/ije/dyt212. 

Confronting unexpected results: Edmund Parkes reviews John Snow. Int J Epidemiol. 2013 Dec;42(6):1559-62. doi: 10.1093/ije/dyt195. 

Anticontagionism between 1821 and 1867: The Fielding H. Garrison Lecture. 1948. Int J Epidemiol. 2009 Feb;38(1):7-21. doi: 10.1093/ije/dyn254. 

Hope-Simpson, R.E. (1958) The Epidemiology of Non-Infectious Diseases. Journal of the Royal Society of Health, 78, 593-599.