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Crawford and Stokes: key figures in combating yellow fever

09 November 2020

In the first of a three-part series on public health and infectious disease, we introduce the biographies of doctor John Crawford (1746–1813) and bacteriologist Adrian Stokes (1887–1927), key figures in understanding the transmission of, and developing early treatment for, yellow fever.

Biographies introduced by Turlough O'Riordan, DIB

In 1979 the WHO announced the eradication of smallpox, a disease that had killed over 300 million humans in the twentieth century. It was perhaps the organisation's greatest achievement since its founding in 1948. However the battle against infectious diseases continues today.

Identifying and understanding the aetiology – the underlying cause –  of any disease is key to developing any treatment. Clinical research informs analysis of the mode of transmission of an infectious disease. Once understood in a human context, methods to inhibit transmission can be developed. Ideally a vaccine, or failing that a prophylactic, can be deployed to inhibit transmission.

Yellow fever, a viral disease affecting the kidneys and liver, is – like malaria – transmitted by mosquito. Yellow fever’s rising incidence in recent decades, despite the availability of effective vaccines, has left over one billion people susceptible to infection, mostly living in tropical regions of Africa and South America. As recently as 2013 yellow fever killed 45,000 people.

Two DIB lives – once central to the disease's identification, another to the development of an effective vaccine – are illustrative of the history of the infectious disease. Doctor John Crawford (1746–1813), before service in the East India Company, and later in the Caribbean, settled in Baltimore, Maryland. Long interested in entomology, Crawford was the first to suggest a connection between the spread of yellow fever and insects. He was also one of two doctors who first introduced vaccination against smallpox to the USA.

The bacteriologist Adrian Stokes (1887–1927) travelled to Nigeria in the 1920s, part of an international team of experts assembled to combat yellow fever. Stokes established the disease, a virus, could be transmitted from monkeys to humans by mosquitos. Developing a curative serum from the blood of infected monkeys, Stokes himself succumbed to the disease – contracted from abrasions on his hands becoming infected with the disease during his experiments. As he approached death he asked that his own experience of the disease be observed scientifically.

John Crawford (1746–1813)

by Linde Lunney

Crawford, John (1746–1813), doctor, medical publisher, and public benefactor, was born 3 May 1746 at Ballytromery near Crumlin, Co. Antrim, second son among six children of Thomas Crawford (d. 1782), presbyterian minister and farmer, and Anne Crawford (née Mackay). His elder brother was William Crawford (d. 1800), a prominent presbyterian minister; Adair Crawford, a doctor and chemist, and Alexander Crawford, a doctor and United Irishman, and were younger brothers, and they had two sisters. Thomas Crawford senior was himself son and grandson of presbyterian divines noted in their day; he was minister in Crumlin from 1724 until his death, and farmed the congregational farm. Anne Crawford was the aunt of the novelist Elizabeth Hamilton (d. 1816) and of Charles Hamilton, an orientalist (d. 1792).

John Crawford was educated locally, perhaps by his father; he is said to have attended lectures at TCD from about the age of 17, but an assertion that he graduated there is unconfirmed. He was probably apprenticed to a Dublin doctor, and between 1772 and 1774 he was surgeon on board the East India Company ship Marquis of Rockingham on voyages to Bombay and Bengal; he seems also to have visited China and St Helena. In 1772 he published an account of a liver disease fatal in hot climates, which may have been beriberi. He possibly visited Ireland around 1778; around that time he married Mary, daughter of John O'Donnell and Barbara O'Donnell (née Anderson) of Trough, on the border of Co. Clare and Co. Limerick. It is possible that he met her through knowing her brothers in the East India Company: John O'Donnell (d. p. 1805?) had an adventurous career in the east before becoming a very prominent merchant in Baltimore, Maryland, and Henry Anderson O'Donnell (b. 1758) married a Persian princess.

Crawford and his wife went to Barbados, on his appointment as surgeon to the hospital there. When a hurricane in 1780 devastated the island, Crawford could have made a great deal of money from his surviving supplies of food and medicine, but instead gave them away to those in need. His health broke down due to overwork and exposure, and in 1782 he and his wife and two small children travelled to England on furlough, but his wife died on the voyage. Crawford was forced to leave his children behind in England when he returned to Barbados in 1786. In 1790 he became surgeon-major in Demerara, then a Dutch colony, and in 1794, on a visit to Europe, he took his MD in the Dutch university of Leiden; the university of St Andrews had granted him the degree of MD in 1791.

John O'Donnell, Crawford's brother-in-law, suggested that he and his children should settle in Baltimore, Maryland, and in 1796 he moved there. He found himself among ‘more of the branches of the families amidst of which I was born than I have ever seen since I left my native country’ (quoted in Wilson (1942)), and was made most welcome. He was friendly with the famous doctor Benjamin Rush, and established a good practice. He enthusiastically studied the natural history of his new environment, as he had done in the tropics; he had a wide knowledge of botany and entomology. Even before 1794, when he discussed his ideas with the medical faculty in Leiden, he had come to the conclusion that insects at various stages of their life-cycles could be vectors of diseases in humans. This had been suggested in outline by earlier authors, but a theory of the role of ‘animalculae’ in the spread of disease had never found any backing, as it was contrary to the then generally accepted doctrine that fevers and agues resulted from exposure to miasma (the very name of malaria still expresses this long-held idea) or from simple contagion. Crawford was first to suggest that insects were involved in the spread of yellow fever. Other medical men poured scorn on his novel ideas, and his practice and reputation suffered.

In 1804 Crawford started publishing a weekly magazine, the Companion and Weekly Miscellany, using the pseudonym of Edward Easy, and in 1806 transferred the editorship to his daughter Eliza, who thus became the second woman editor in the United States. In this weekly, retitled The Observer and Repertory . . ., he published during 1806–7 his ‘Theory and application to the treatment of disease’. Some notice was taken of his ideas, but he found no adherents. Even in 1811, when he planned a course of lectures on the cause and treatment of diseases, he was not hopeful of convincing his opponents. He wrote to Benjamin Rush that ‘my situation can not be made worse by it . . . My contemporaries may not thank me for the attempt; I know they will not: my great aim is to do good, and I leave the issue to him from whom I have received what I have’ (quoted in Wilson), and in the published version of the only lecture that is known to have been delivered he pledged that as long as ‘life and health remain, I shall devote myself strictly to the performance of my duty’. A number of palliative and curative measures for use in epidemic diseases, involving inter alia rigorous hygiene of the sickroom, were suggested by Crawford on the basis of his theory; some are now established as routine medical practice, though his opposition to any idea of contagion as a means of infection vitiates a few of his recommendations.

As well as his importance as a pioneer of a theory of insect-borne disease, Crawford is recognised as one of the two doctors who first introduced vaccination against smallpox into America. In the summer of 1800, at the same time as Benjamin Waterhouse was also experimenting with cowpox, Crawford received vaccine from London, and apparently successfully vaccinated at least one person. He published nothing on his vaccination work, but rejoiced in 1807 that smallpox had been rendered nearly harmless by the new technique. Crawford was involved with other projects to benefit his fellow citizens in Baltimore: he was one of the founders of Baltimore Library (1798) and of a Society for the Promotion of Useful Knowledge in the city (1800). He helped to establish a dispensary in Baltimore (1801) and a state penitentiary, and suggested improvements in training military and naval medical men. He was consulting physician to the Baltimore hospital, an examiner in the Baltimore medical faculty, and briefly (1812) held a lectureship in natural history in Baltimore Medical College. He was prominent in the city's Hibernian Society, and was grand master of the Masonic order in Maryland in every year but one from 1801 until his death, which took place on 9 May 1813. He was buried with Masonic honours in Westminster presbyterian graveyard in Baltimore; James McHenry (1753–1816), also a doctor, a Mason, and from Co. Antrim, is buried in the same place. Crawford's valuable and important library was bought by the University of Maryland at auction in 1813; the first major book purchase of that institution, it forms the nucleus of what is now known as the Health Sciences and Human Services Library.

His daughter, Eliza, survived him; she had led an adventurous life, having travelled to France as companion to Elizabeth Patterson (1785–1879), first wife of Jérôme Bonaparte (1784–1860). She married first Henry Anderson, probably a relative, then left him and married secondly Maximilian Godefroy, a noted architect. Crawford lived with them from their marriage (1799) until his death. He and his daughter are described by Elizabeth McCalmont (née Barklie) of Larne, Co. Antrim, in memoirs published by Francis J. Bigger. Crawford's son seems to have trained in medicine in London, but may have died of consumption before his father.

Adrian Stokes (1887–1927)

by David Murphy

Stokes, Adrian (1887–1927), physician and bacteriologist, was born 9 February 1887 at Lausanne, Switzerland, third son of Henry John Stokes (1842–1920), of the Indian civil service, and his wife Mary Anne (d. 1924), daughter of William MacDoughall of Howth, Co. Dublin. His grandfather was Whitley Stokes, regius professor of medicine at TCD; Sir William Stokes, the eminent surgeon, was his uncle. His aunt was Margaret McNair Stokes, the noted archaeologist. He attended the St Stephen's Green School, where he won the John Robertson medal for an English essay (1904). Entering TCD in 1905, he studied history in his first year before turning to medicine. A distinguished student, he obtained first-class honours and a senior moderatorship and won the Bank's prize. He published an article, ‘Rare abnormality in the heart and great vessels’, in the Journal of Anatomy while still a student, and was secretary of the Dublin University Biological Association, maintaining connections with the association in later years. Graduating MB and B.Ch. in 1910, he subsequently graduated MD (1911).

He worked as a demonstrator at TCD and became a fellow of the Royal College of Surgeons in Ireland in 1912. In the same year he won the TCD travelling prize but turned it down, maintaining that his nearest rival was more worthy of the award. He studied bacteriology at St Mary's Hospital in London, and in 1913 won the travelling prize again. On this occasion he took up the award and went to New York, where he studied at the Rockefeller Institute. Returning to Dublin, he worked as assistant to Alexander Charles O'Sullivan (1858–1924), professor of pathology at TCD.

At the outbreak of the first world war he volunteered for service and was commissioned as a lieutenant in the RAMC on 11 August 1914. Posted to France in September 1914, he helped combat an outbreak of typhoid fever in the Guards regiments in the early months of the war. Shocked by the number of wounded men suffering from tetanus, he pestered his superior officers for a supply of anti-tetanus serum and then made a tour of dressing stations and field ambulances with his motorcycle and sidecar, treating the wounded. In this way he introduced the first mobile laboratory into the BEF. He also introduced the nasal catheter for the treatment of those suffering from the effects of gas. In 1916 he identified and eradicated an outbreak of spirochaetal jaundice in the British trenches, publishing his findings in the British Medical Journal (1916) and the Lancet (1917). Mentioned in despatches, he was awarded the DSO (1918) and an OBE (1919). He was also made a chevalier of the Belgian Order of the Crown (1918).

In 1919 he was appointed professor of bacteriology and preventative medicine at TCD and also as assistant physician to the Royal City of Dublin and Adelaide Hospitals. Due to his experience with spirochaetal jaundice, he was asked by the Rockefeller Yellow Fever Commission to travel to Nigeria in 1920 to work with their medical mission. There were no cases of yellow fever in Nigeria at the time and the mission was a failure. In 1922 he was appointed as Sir William Dunn professor of pathology at London University and was attached to Guy's Hospital, becoming a member of the Royal College of Physicians in London in 1924. Popular with his students, he soon established a reputation for encouraging students to undertake their own research, while also helping them with their publications. Taking leave from his teaching position, he went to Lagos in 1927 to work with the Rockefeller Yellow Fever Commission and soon established that the disease was a virus and that it could be passed from monkeys to humans by mosquitoes. Following a series of live animal experiments, he also began to develop a serum from the blood of convalescent monkeys. On 15 September 1927 he became ill with yellow fever, having contracted the disease through abrasions on his hands, and insisted that mosquitoes be allowed to feed on him to see if yellow fever could then be passed on to monkeys. He also left instructions that a full autopsy be carried out after his death in order to provide new information and specimens. He died on 19 September 1927 and was buried in the Ikogi cemetery. The work that this mission in Lagos carried out eventually led to the development of a yellow-fever vaccine. He never married.

Sources for Crawford

F. J. Bigger, The Magees of Belfast and Dublin, printers (1916), 33; Dictionary of American biography (1928–58); John Rathbone Oliver, ‘An unpublished autograph letter from Dr John Crawford (1746–1813) to General William Henry Winder (1775–1824)’, Bulletin of the Institute of the History of Medicine, iv (1930), 145–51; Julia E. Wilson, ‘An early Baltimore physician and his medical library’, Annals of Medical History, 3rd series, iv (1942), 63–80; Burke, A genealogical and heraldic history of the landed gentry of Ireland (4th edition, 1958), 186, 533; Davis Coakley, Irish masters of medicine (1992), 47–54; American national biography (1999); ‘John Crawford 1746–1813’ (website of Health Sciences and Human Services Library, University of Maryland, www.hshsl.umaryland.edu/resources/historical/crawford/, accessed Oct. 2020)

Sources for Stokes

Times (London), 22, 26 Sept. 1927; British Medical Journal (1927), 615–18; N. Paul Hudson, ‘Adrian Stokes and yellow fever’, Transactions of the Royal Society of Tropical Medicine and Hygiene, lx (1966), 170–74; WWW; Burke, IFR (1976), 1055–6; J. B. Lyons, Brief lives of Irish doctors (1978), 148–9; Davis Coakley, Irish masters of medicine (1992)

Image: 'Yellow Fever mosquito' by John Tann is licensed with CC BY 2.0

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