FROM THE JAMES LIND LIBRARY Thomas Nettleton and the dawn of quantitative assessments of the effects of medical interventions

Arthur Boylston Centre for Editing Lives and Letters, Queen Mary University College, E1 4NS E-mail: [email protected]

DECLARATIONS Thomas Nettleton (1683–1742) was one of the first, whom, John Keith, a physician, immediately asked possibly the first, to use quantitative assessments Maitland to inoculate his sole surviving son. Competing interests of the effects of medical interventions. Prior to Impressed by the mild inoculated smallpox and None declared establishing a medical practice in Halifax, West complete recovery of the two children, a group

Funding Yorkshire, Nettleton had been educated at of physicians approached King George I with a Bradford Grammar School, and had studied medi- request to expand this initial experience by experi- None cine at Edinburgh and Leyden, where he was menting on condemned prisoners. After being Ethical approval awarded his Doctorate of Medicine. In December promised a complete pardon for their crimes, six Not applicable 1721, during an epidemic of smallpox in West prisoners confined at Newgate agreed to be inocu- Yorkshire and frustrated by the lack of any effec- lated. In August 1721, observed by several mem- Guarantor tive therapy for the disease, Nettleton began to use bers of the Royal Family, various apothecaries, AB , which at the time was known as inocu- surgeons, and Fellows of the Royal Society and lation. Variolation to immunize people against College of Physicians, Maitland variolated the six Contributorship smallpox was introduced into Europe and North prisoners. Five of them developed mild, distinct AB is the sole America in 1721.1–3 However, there was uncer- smallpox; one did not develop any pustules and contributor tainty and debate about whether it did more good subsequently admitted that he had had smallpox Acknowledgements than harm. To address this uncertainty, Nettleton six months before. In February 1722, Maitland Additional material collected statistics on the mortality associated with published his account of the Newgate experi- naturally-acquired smallpox and compared these ment,8 and conducted two further trials on parish for this article is with mortality following variolation. He commu- orphans.1 available from the nicated his findings in a series of letters and a Maitland’s early trials of variolation in Britain James Lind Library pamphlet published in 1722 and 1723.4–7 were intended to demonstrate its relative safety website (www. and the mild resulting smallpox, and they led to a jameslindlibrary.org), decision in April 1722 to inoculate two daughters where it was Early clinical trials of variolation of the Prince of Wales, the future George II. originally published in Britain Although the princesses suffered no ill-effects, news of two deaths following variolation in Britain The practice of variolation in Europe begins with and others in Boston led to an intense debate about its importation from the Middle East by a Scottish the safety and advisability of the procedure. surgeon, Charles Maitland, who accompanied Lady Mary Wortley Montague, her diplomat hus- band and their children to Constantinople.1 Lady Recognition of the need to Mary discovered that variolation was widely prac- compare mortality following tised in Turkey and that it was considered safe and inoculated and ‘natural’ smallpox effective in preventing fatal smallpox. She had her in large populations son inoculated by an ancient Greek practitioner, assisted by Maitland. Just before the princesses had been inoculated, In April 1721, back in England, Maitland was a letter from Thomas Nettleton to William asked by Lady Mary to inoculate her daughter. Whitaker – a friend in London – revealed that he Maitland agreed, but insisted on observers, one of had inoculated over 40 individuals in the parish of

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Halifax, with no deaths and only a few cases of contradictions in Wagstaffe’s article. While citing severe disease.4 Nettleton’s letter was read to the Nettleton’s initial findings,5 Arbuthnot also used Royal Society on 17 May 1722, and a correspon- the Bills of Mortality of London and figures for the dence ensued between Nettleton and James Jurin, Polish city of Breslaw to arrive at an estimate that the mathematically-inclined secretary of the Royal about one in 10 of all people over the age of 1 year Society. Nettleton informed Jurin that he had died of smallpox. However, his calculations were encountered vigorous local opposition to inocula- based on assumptions about the lack of mortality tion, but that he believed that objections would from smallpox among the very young and also on melt away after inoculation had been ‘set in its true the number of cases of smallpox that there were in Light’.4 Jurin invited him to submit his letter London each year. to Whitaker for publication in the Philosophical On 16 December 1722, Nettleton sent Jurin Transactions, and asked for any further experience another letter, and this seems to have triggered of inoculation that Nettleton might have. the latter’s subsequent attempts to quantitate the On 16 June 1722, Nettleton wrote to Jurin: effects of inoculation:6

‘Sir, I doubt not that when you have collected a ‘. Inoculation which is so vehemently opposed by sufficient Number of Observations for it, you will many and countenanced by very few. It is to me be able to demonstrate, That the Hazard of the perfectly indifferent as to any private interest of my Method is very inconsiderable in proportion to that own whether the Thing is received or exploded but . in the ordinary way by accidental Contagion In I must own that I am strongly possest of an order to satisfy myself, what Proportion the number Opinion that it will in time prove to be of very great of those who die of smallpox might bear to the whole Service to Mankind & as it is Experience princi- number that is seized with the Distemper I have pally that must determine whether it will be so or made some enquiry hereabouts.’ not. You will excuse my freedom in communicat- He had collected the outcomes of 1245 patients ing to you some observations I have had the with natural smallpox and found that 270 had Opportunity to make regarding the Matter. died, ‘nearly 22 out of every hundred’. At the time There are two propositions advanced by the Nettleton had inoculated 55 individuals with no Favourers of the Practice concerning which the deaths.5 Publick seems to require more full Satisfaction. However, news of the deaths following inocula- That the Distemper raised by Inoculation is really tion in Britain and Boston led to controversy. the Small Pox & That it is more mild and favour- 6 William Wagstaffe MD, FRS, physician to St able & far less mortal that the Natural Sort.’ Bartholomew’s Hospital, attacked the practice on Nettleton dealt with the first proposition by several, sometimes contradictory, grounds.9 On giving a number of reasons why he believed that the one hand, he argued that the disease that the disease transmitted by inoculation was identi- appeared in inoculated patients was not true cal to the mild form of natural smallpox that every smallpox, while on the other hand he said that doctor had observed. As far as the second proposi- inoculation was dangerous because it would tion was concerned – that is, that inoculated small- spread the disease; and while arguing that inocu- pox was ‘less mortal’ than naturally acquired lation should be banned, he also insisted that more smallpox, he wrote: experience was needed before it could be evalu- ated. Nevertheless, one of his charges was signifi- ‘The truth of this I suppose can only be found by cant: he complained that inoculation had not been making a Comparison in so far as our Experience given a fair trial because he claimed that almost all will extend.’ those who had been inoculated were children and that their mortality from natural smallpox was He then gave figures for the mortality of only 1%. He also complained that different inocu- natural smallpox in several towns and parishes lators used different techniques and, therefore, across the north of England revealing that 636 of their results could not be compared. 3405 patients (19%) had died. None of the 60 On 25 September 1722, John Arbuthnot10 pub- patients that he had inoculated had succumbed. lished a booklet in which he pointed out the many He continued:

336 J R Soc Med 2010: 103: 335–339. DOI 10.1258/jrsm.2010.10k005 Downloaded from jrs.sagepub.com at The Royal Society of Medicine Library on October 14, 2014 Thomas Nettleton and the dawn of quantitative assessments of the effects of medical interventions

‘I am very sensible You will require a great Number ‘Whenever any shall happen to miscarry under this of Observations before you can draw any certain Operation, that will indeed be very unfortunate & Conclusions.’6 ill, but in this Case you will have recourse to the Merchant’s Logick state the Accounts of Profit and Nettleton’s letter was read to the Royal Society Loss to find on which side the Balance Lyes . and on 21 December 1722, and Jurin wrote acknowl- form a Judgement accordingly.’ edging Nettleton’s valuable observations.7 He revealed that he had been thinking along similar Jurin explained his undertaking in a first ac- lines but, like Arbuthnot, he had attempted to count of the information he had received following calculate the mortality of natural smallpox from his appeal for data:12 the Bills of Mortality collected from London ‘This Controversy, though drawn out in many parishes. Jurin acknowledged that these figures Particulars, seems principally to turn upon the two were difficult to interpret, in part because following Points: they took no account of early childhood deaths. Nettleton’s direct approach was clearly superior. (1) Whether the Distemper given by Inoculation be On 17 January 1723,11 Jurin read his own paper, effectual Security for the Patient, against his citing Nettleton and information from a few other having the Small Pox afterwards in the natural inoculators.1,12 His paper was mostly well re- Way. ceived, but it was criticized by Isaac Massey,13 (2) Whether the Hazard of Inoculation be consider- apothecary to Christ’s Hospital, and the uncle of ably less than that of Natural Small Pox. Edmund Massey who had preached a famous anti- If these two points were effectually settled there inoculation sermon in 1722. Massey’s point was would, I suppose, be an end of the Dispute, at least that the comparison between inoculated and natu- among Physicians. For if either of them be fairly ral smallpox was unfair because many patients determin’d in the Negative the Practice of Inocula- with natural smallpox might have survived if they tion must on all Hands be given up. And on the had been given the same medical support as those other Hand, if the Test of Experience should plainly who were inoculated. Also many patients with declare for the affirmative Side of both these Ques- natural smallpox who had died were unwell from tions, I doubt not that every Gentleman, who has other diseases whereas inoculated individuals the Honour to serve his Country in the Capacity of were usually in good health. Massey suggested a Physician will have Integrity and Humanity that: enough to declare himself honestly and openly in ‘. not above One in Forty that have the Small Favour of the Practice. At least he will consider Pox, would die of that Distemper, if treated with whether it will be for his Reputation when his equal Care with those that are inoculated: but to Friend and Patient shall put his Life or the Lives of form a just Comparison, and calculate right in his Children into his Hands, to amuse himself with this Case, the Circumstances of the Patients, Theological Disputes and Scruples, whether it be must and ought to be as near as may be on a lawful to save them. For if the Practice of Inocula- Par.’13 tion be really found to be a Means of preserving Life, it will not be easy to make the World believe However, the generally enthusiastic response to that it is criminal to use it.’ Jurin’s paper led him to appeal for information through an advertisement placed in the Philosophi- Jurin showed that 2351 patients out of 14,559 cal Transactions.1 Over 120 letters were received by with natural smallpox had died (16%), while only the Royal Society, where the originals are available nine of 440 individuals successfully inoculated had in the archives (Royal Society Archives CP XXIII. succumbed (2%). In his analysis of the information, Inoculation Papers). The replies to this appeal Jurin sensibly decided to count all deaths follow- formed the basis for the quantitative assessment of ing inoculation as due to inoculation, regardless of the benefits of inoculation subsequently published the opinions of observers of individual cases about by Jurin.3 the cause of death. This dealt with possible ob- Nettleton replied with a direct statement of the server bias in deciding whether a death was really value of quantification:7 due to inoculated smallpox. Jurin also avoided

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another potential pitfall by counting only deaths, interested in applying mathematics to medicine in thereby avoiding subjective debates about the de- the wake of ’s book Philosophiae gree of severity of individual cases. Finally, Jurin Naturalis Principia Mathematica (The Mathematical acknowledged that, before it would be possible to Principles of Natural Philosophy). know for certain that inoculation always conferred In 1729 Nettleton published a book entitled immunity to smallpox, it would: Some Thoughts Concerning Virtue and Happiness,15 which was subsequently retitled A Treatise on ‘require a considerable time and a much greater Virtue and Happiness. The book ran through at least Number of Experiments than have yet been made.’ seven editions, the last of which appeared in 1766, Thus it was that the correspondence between 24 years after Nettleton’s death. Thomas Nettleton and James Jurin during the On 9 January 1742, Thomas Nettleton died in winter of 1722–1723 led to judgements about the Dewsbury (where he had been born in 1683), and effects of variolation being based not on impres- he was buried in the churchyard there three days sions from a few cases or indirect arguments from later. His grave and memorial stone have been lost; past figures, but rather on comparisons of unam- but his pioneering contribution to the dawning of biguous outcomes (deaths) among large numbers quantitative evaluation of the effects of medical of inoculated people, and among others who had treatments deserves to be remembered. contracted smallpox naturally. The dates of the various letters between References Nettleton and Jurin indicate that the idea of collect- 1 Miller G. The adoption of inoculation for smallpox in England ing mortality data was Nettleton’s alone. He began and France. Philadelphia, PA: University of Pennsylvania his study before June 1722. Nettleton’s analyses are Press; 1957 2 Rusnock A. Vital accounts: quantifying health and population the earliest examples so far identified of the use of in eighteenth century England and France. Cambridge: numerical methods to assess the effects of any Cambridge University Press; 2002 medical intervention. 3 Huth EJ. Quantitative evidence for judgments on the efficacy of inoculation for the prevention of smallpox: Nettleton continued to correspond with Jurin England and New England in the 1700s. The James Lind until the secretary resigned his post at the Royal Library 2005 Society in 1727. They discussed individual cases, 4 Nettleton T. An account of inoculating the Small Pox; in a letter to Dr William Whitaker. London: S Palmer for helped refute reports that some of Nettleton’s J Batley, at the Dove in Pater-Noster Row; 1722 inoculated patients had died, and collated further 5 Nettleton T. A Letter from the same Learned and data from Yorkshire. Nettleton also sent Jurin vari- Ingenious Gentleman, concerning his further Progress in inoculating the Small Pox. Philosophic Transactions of the ous reports of meteorological phenomena which Royal Society of London 1722/23;32:49–52 were of particular interest to the Royal Society. 6 Nettleton T. Part of a letter from Dr Nettleton, Physician at Halifax. To Dr Jurin RS Secr. Concerning the inoculation of the Small Pox, and the mortality of that distemper in the natural way. Philosophical Transactions 1722;32:209–12 What may have led Nettleton to 7 Rusnock A. The Correspondence of James Jurin (1684–1750) use quantitative methods to Physician and Secretary to the Royal Society. Amsterdam: Editions Rodopi BV; 1996 assess the effects of medical 8 Maitland C. Mr Maitland’s account of inoculating the Small treatment? Pox. London: Printed by J Downing and sold by J Roberts at the Oxford Arms in Warwick Lane; 1722 9 Wagstaffe W. A Letter to Dr Friend Shewing the Danger and Nettleton may have been motivated to begin Uncertainty of Inoculating the Smallpox. London: Printed his studies by an interest in mathematics. He is for Samuel Butler next Bernard’s Inn in Holborn; 1722 reported to have taught mathematics to ‘blind 10 Arbuthnot J. Mr Maitland’s Account of Inoculating the Smallpox Vindicated from Dr Wagstaffe’s Misrepresentations Professor Saunderson who soon outstripped his of that Practice; with some remarks on Mr Massey’s Sermon. tutor’.14 Saunderson was an almost exact contem- London: Printed and Sold by J Peele, at Lock’s Head in porary of Nettleton’s and had lost both his sight Paternoster Row; 1722 11 Jurin J. A letter to the Learned Caleb Cotesworth M.D. and his eyes to smallpox during infancy (Oxford Containing a comparison between the mortality of the natural Dictionary of National Biography online edition) small pox and that given by inoculation. London: W and J He later became the fourth Lucasian Professor of Innys at the Prince’s Arms at the West End of St. Paul’s Churchyard; 1723 Mathematics at Cambridge. Perhaps Nettleton, 12 Jurin J. An account of the success of inoculating the Small like Jurin, was one of the physicians who became Pox in Great Britain with a comparison between the

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miscarriages of that practice, and the mortality of the mortality of natural and inoculated small pox. 2nd edn. natural Small Pox. London: J Peele at Locke’s Head in London: W Meadows; 1723 Pater-Noster Row; 1724 14 Crabtree J. A Concise History of the Parish and Vicarage of 13 Massey I. A short and plain account of inoculation. With Halifax, in the Country of York. Halifax: Hartley and some remarks on the main argument made use of to Walker; 1836 recommend that practice, by Mr Maitland and others. To 15 Nettleton T. Some thoughts concerning virtue and happiness which is added, a letter to the learned James Jurin, MDRS in a letter to a clergyman. London: Jer Batley; 1729. [Final Secr Col Reg Med Lond Soc. In answer to his letter to the version: A Treatise on Virtue and Happiness. Glasgow: learned Dr. Cotesworth, and his comparison between the James Knox; 1766]

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