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The global eradication of smallpox is viewed as one of the major achievements of twentieth century medicine. However, the history of inoculation against smallpox is much older. The technique of inoculating against the disease by using a small amount of bodily fluid from an infected person was well known in China and India for many centuries and had reached modern Turkey by the seventeenth century.

From: Library of Zhongguo zhongyi yanjiu yuan (China Academy for Traditional Chinese Medicine), Sun Shi yi’an (Doctor Sun’s Casebook)
By: Sun Qishun (Qing period, 1644-1911)
Published: 1817
Collection: Wellcome Images
Library reference no.: External ReferenceWang Shumin II 659, External ReferenceShen 13/1817 Qiu 659 and External Reference Vivienne Lo

The technique of inoculation against smallpox came late to Europe, where it was first promoted by Lady Wortley Montague who had seen women in the marketplace in Constantinople (Istanbul) practicing it and had her own children inoculated. Her espousal of the technique on returning to England caused controversy among her peers, many of whom argued that not only was deliberately infecting someone with a virus dangerous, but that attempts to prevent the disease were unchristian.

The Royal Society made extensive investigations into the novel technique. As Dr Rim Turkmani noted in her recent talk on Arabic in Britain, the Society consulted one of their fellows with first hand experience; the Ambassador of Tripoli, Cassam Aga. The response from the Ambassador, translated from the original Arabic and read to the Society in 1729, gives a brief overview of the technique: “If any one hath a mind to have his children inoculated, he arrives them to one that lies ill of the smallpox all the time when the pustules are come to full maturity. Then the surgeon makes an incision upon the back of his hand between the thumb & forefinger, and puts a little of the matter, squeezed out of one of the largest & fullest pustules into the wound. This done, the child’s hand is wrapt around with a handkerchief to keep it from the Air, and he is left to his liberty till the fever arising confines him to his Bed, which commonly happens at the end of three or four days. After that, by God’s permission, a few pustules of the smallpox break out upon the child.” He then recounts his own experience of being inoculated as a child, concluding that this practise is “so innocent, & so sure, that out of an hundred persons inoculated not two die, whereas on the contrary out of a hundred persons, that are infected with the smallpox in the natural way there die commonly about thirty”.

The origins of the technique in Constantinople are unclear. A 1713 report from Emanuel Timonius dated its introduction to about forty years previously and ascribed its introduction to ‘the Circassians Georgians and other Asiaticks’. On the other hand, the Ambassador’s account indicates that inoculation had been practiced for a longer period: “It is withall so ancient in the kingdoms of Tripoly, Tunis and Algier, that no body remembers its first rise, and it is generally practised not only by the inhabitants of the Towns but also by the wild Arabs.”

The Royal Society also monitored the progress of inoculation in England: Hans Sloane was present when the Royal Surgeon Claud Amyand administered infected matter to the young Princesses Amelia and Carolina in 1722. Amyand was clearly convinced of the efficacy of inoculation, as the next subject appearing on his list appears to be his own son. Others were less impressed, however. Volume 23 of the Classified Papers of the Society, into which statistics and case reports on inoculation were gathered contains a letter from the Mayor and Corporation of London explaining that the practice was being banned because it was thought to spread smallpox.

The technique would also prove a contentious issue in India. The first report of inoculation there reached the Society in 1731 in a letter preserved among the Royal Society’s papers in the British Library from Robert Coult giving an ‘account of the diseases in Bengal’ and by 1767 J Z Holwell was reporting widespread inoculation in Bengal. However, as in England the practice also tended to be regarded as a public health risk, and there were some attempts to suppress it under colonial rule.

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Snake venom is still a poison that is hard to combat and presents a real public health problem in tropical countries. Treatments are still often sought in naturally-occurring antidotes, as the focus of a recent book on the antivenomous properties of plants reveals. Snake venom, like other poisons, can also have medicinal properties. The early Royal Society collected accounts of snakes, samples of venom, and possible cures. One widely debated idea was that venom could be combated by the use of stones found in the heads of snakes. These stones were highly valued across the Indian Ocean and had begun to be brought back into Europe in the 1650’s by Jesuit missionaries [1].

One of the places where the Hooke folio provides a slightly different account to that of the Journal Book concerns these snake stones. The story begins with the minutes for the meeting of 20 May - a date on which the Journal Book records that the Society ‘did not sit’. The folio records that the stone had been brought to the East India Company to the Royal Society, who had received it from the King of Bantam as a present and were ‘unsure of its virtues’. One of the agents, a Mr Hublon, referred the Society to a translation of a Portuguese work printed in 1582. mentioning the medicinal properties of a stone found in the head of a snake, or ‘Piedra de Cobra de Mombasa’, which was thought to cure various ailments. Interestingly, although the Journal Book minutes for 27 May 1680, a date missing from the folio, mentions ‘Hublon’s stone’, it does not mention that the Company agents were present at the meeting, or refer to the Portuguese book. Dr Tison is recorded as giving an account that the dogs he had attempted to poison with snake venom did not become ill in the first place and that he had therefore abandoned the experiment - although he then added that he had tried one such stone on the hand of an unfortunate servant who had been bitten by a viper (it is not clear whether he encouraged the viper in this case!) This is in contrast to the folio which records in the draft reply to the Company - one of the sheets in the folio not in Hooke’s hand - that the two dogs given venom and nux vomica died despite the administration of the antidote, a passage that is missing from the copy of the letter in the Journal Book.
The Society’s draft reply to the EIC describes the use of the stone, found in ‘the province of Zanguobar (used to refer to the East Coast of Tanzania) in Africa’ and used there as a treatment for colic, in childbirth and against depression and in Europe and the East Indies as an antidote to poison. The description of how to prepare a medicine from the stone, ‘to rub it on a hard smooth stone till a cream comes of it’, is given, apparently derived from the use in Africa or the East Indies. The letter then contains an assurance that Francesco Redi ‘a virtuoso of Ferdinand grand Duke of Florence’ had not found the stone useful. The report of the Society’s own experiments, at first inserted in the middle of the letter, have been crossed out and moved to a tentative appendage in the draft in the Hooke folio, and omitted completely from the copy in the Journal Book. As well as providing an interesting example of the divergence between the folio and the official records, this incident illustrates firstly just how important it was to the East India Company to discover the medical properties of new vegetable, mineral and even animal substances. The agents of the Company were at the mercy of newly encountered diseases. European medicines were often powerless to combat these problems or did not survive the long journey to their destination. Those medicines that were found to be effective, such as the anti-malarial, ‘Jesuits’ bark’, were also a potential source of revenue for the Company. Secondly, it shows that the Royal Society was already becoming seen by this stage as a port of call for queries involving unfamiliar objects. Finally it shows why the Society often had to rely on the testimony of their network of contacts rather than their own experiments - although the records are unclear the attempt to poison the dogs seems to have failed in some way and such poison, as well as instructions on how to administer it, would have been scarce and the medical effects would have been difficult to gage - depressed dogs being still more scarce
Ironically, despite the complete failure of their own experiments, the reference to Redi may serve to reassert the Royal Society’s commitment to experimentation. Snakestones had become a mainstay in the debate between two rival natural philosophers in Italy: Athanasius Kirchner and Francesco Redi. While Kirchner was an advocate of the Aristolean philosophy and had close ties to the papacy and the College Romano, Redi, an fearsome opponent of Aristotle, was his rival at the Medici court. While Kirchner used a single trial to confirm, as he claimed, the reports of the missionaries of the stone effecting miraculous cures, Redi performed hundreds of experiments to support his claims that the stones were not effective against poison. The verdict of the Royal Society here therefore shows a more theoretical than practical commitment to experimentation. This did not diminish their interest in various types of poisons and their antidotes, however, the search for toxins derived from plant and animal matter continues throughout the early records of the Society [2].

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On a recent visit to the excellent Boerhaave Museum in Leiden I noticed several of the Royal Society’s members represented among its collection. For example, on display was a copy of John Flamsteed’s beautiful Atlas coelestis, published posthumously in 1729 by his wife and amanuensis Margaret. Most prominent, however, was the work of Antoni van Leeuwenhoek of Delft, who is credited, along with Robert Hooke with the discovery of micro-organisms, a process which, as Jenni noted in her earlier post, can be traced more clearly using the Hooke folio. Leeuwenhoek was elected a member of the Royal Society in 1680 and clearly relished this recognition of his achievements: a 1686 portrait by J. Verkolje shows the former shopkeeper leaning proudly on a copy of the Society’s charter. One of Leeuwenhoek’s letters, published in the Philosophical Transactions of 1708/9, discusses the circulation of blood in fishes, a topic on which he had first corresponded with the Society in 1688. His observations and sketches decisively proved the theory that had been first advanced by William Harvey in 1628. Leeuwenhoek’s finding was illustrated by an incredibly detailed drawing of the circulation in the tail of a tadpole in the Boerhaave Museum.

Given the growing acceptance in this period that the blood did flow around the body, two important topic of discussion for the Society arose: namely, was how this was achieved and what purpose it served. Hooke tried to demonstrate in a series of experiments of 1669 that the circulation of the blood was caused by the beating of the heart. During the next year, discussion of the circulation of the blood in animals prompted some comparisons with the ongoing microscopical observations of the pores in plants, some being described as shaped like tiny drawers or ‘letter boxes’. The Society discussed whether a similar system to the circulation of the blood operated with the movement of the sap in plants and trees, providing their nourishment from the roots, or whether ‘ambient air’ was responsible for sustaining the plant. These speculations may have encouraged the curator of plants, Grew, in his 1675 publication on the ‘Comparative anatomy of trunks’.

Some interesting ideas about the relationship of air to the circulation of the blood were also put forward by Hooke at a meeting of 1672, when during a discussion of the purpose of respiration he argued ‘that by the air something essentiall to life might be conveyed into the blood, and something that was noysome to it be discharged back into the air’. He suggested that in order to discover whether ‘there are not Valves in the arterys, by which the air may passe into the parts of the Blood’ a representation could be made by injecting wax into the arteries.

Both the discussion of valves and the suggestion of injecting wax to produce accurate anatomical models echo the work of a Dutch contemporary of Leeuwenhoek’s based in Leiden. Jan Swammerdam was a pioneer in both microscopy and anatomy and had, also in 1672, presented the Society with a uterus filled with wax so as to show its anatomical structure more clearly. Swammerdam and Leeuwenhoek both observed red blood cells, the latter reporting the presence of ‘globules’ in his microscopical observations. It would be some time before these ‘globules’ could be decisively connected with Hooke’s conjectures about the purpose of the blood’s circulation through the lungs. However, the circulation of ideas between London and Leiden, which also included De Graaf and Constantin Huygens - both of whom helped Leeuwenhoek in his translation of his works and letters - would prove influential in advancing the understanding of the mechanism and purpose of the circulation of the blood.

Image: L0013035 Credit: Wellcome Library, London Photomontage From: Arcana naturae, ope & beneficio exquistissimorum microscopiorum detecta By: Leeuwenhoek, Anthony van Published: C. Boutesteyn Leyden 1708 3 figures Collection: Rare Books Full Bibliographic Record Link to Wellcome Library Catalogue

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Acupuncture has been practiced in China, Japan and Korea for centuries and along with other ‘traditional’ or ‘complementary’ therapies remains a controversial topic in Western medicine. In the Hooke folio, an account of a meeting on the 18 January 1682 records the Royal Society discussing a letter from a Wilhem Ten Rhyne, from the factory of the Dutch East India Company (VOC) which asks that his manuscript on the use of acupuncture in Japan be published in English. The letter also describes the use of artemisia vulgaris, commonly known as mugwort, a herb used traditionally in Europe and America. In Oriental medicine it is known as moxa and is used in combination with acupuncture to stimulation circulation. The use of moxa to cure gout had also been discussed in a meeting of 1st August 1678, leading to a wider discussion about the effects of heat on the human body. This led to the observation that, like Chinese and Japanese doctors, Galen had paid more attention to the pulses in various parts of the body than was usual among surgeons of the day.

The Royal Society continued to debate the benefits of both moxa and acupuncture: a letter of 1692 from Wilhelm Ten Rhyne answers a list of queries about the specific uses of the techniques in Japan. These remedies had also been noted by Engelbert Kaempfer (1651-1716) in his ‘History of Japan, giving an account of the ancient and present state and government of that empire. . .To which is added, part of a journal of a voyage to Japan, made by the English in the year 1673’. Kaempfer’s manuscript was not published for almost a century acquired by the botanist and President of the Royal Society Hans Sloane who saw to the translation of the work by Johann Caspar Scheuchzer and its publication in 1727.

The benefits of ‘alternative’ or ‘complementary’ medicines are still hotly debated. While some claim that acupuncture essentially has a placebo effect, other research has suggested more tangible medical effects, most recently in treating Parkinson’s disease. The effects of artemisia vulgaris are a matter of continuing debate, some studies (for example the study of Cardini and Weixin published in JAMA in 1998) suggest it can assist in breach births by promoting fetal activity. A recent Royal Society policy paper on the issue stresses the importance of large scale randomised control trials in exploring the effects of types of therapies.

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Malaria is a major health problem and is thought to be responsible for about 18% of all deaths of children aged under five years in sub-Saharan Africa, or between 700 000 and 900 000 children each year, as well as aiding the spread of other diseases such as HIV/AIDS by weakening the immune system. Trials to develop an effective vaccine are ongoing. However, treatments using the anti-malarial properties of the bark of the chinconcha tree have been known for centuries, and used for many years against the disease until its active ingredient, quinine, began to be produced artificially.

The folio records a letter from the Royal Society’s prolific correspondent and later member Henri Justel, which mentions ‘Jesuits Bark’, the name being given to the bark of the Peruvian chinconcha tree. The letter does not survive, but the bark was not forgotten and together with numerous other substances it was boiled together with water, spirit of wine and white wine (RB. 6. 213, 1685) in Mr Pappin’s ‘digesting’ machine. Impressed, Pappin reported back that the bark lasted three or four time longer than bones before being reduced to a powder. There is no mention of the medical properties of the bark here, however, and the next reference to it in the Royal Society records occurs in the Philosophical Transactions of 1737/8. By this time the bark is clearly in demand: the author Dr Grey gives detailed information about the four different types of tree in Peru, their various effects and preparations, and reports that the drug enters Europe through Panama. He goes on to express concern that the exploitation by the Spanish will soon wipe out the local indigenous population who had been well aware of the anti-malarial properties of the plant well before the arrival of the colonisers, and that the bark will become scarce due to over-exploitation.

Anti-malarial drugs and the development of insecticides that kill the mosquitos carried the disease were of course a valuable tool in the exploration and final colonisation of Africa by European powers during the next century. This provided impetus for the identification of the parasite of the genus Plasmodium and the artificial production of quinine. Concerns like those expressed by Grey about the availability and intellectual property surrounding anti-malarial drugs still exist today. Problems with malaria prevention include the tendency for insects to develop resistance to insecticides like DDT, as well as their potentially negative environmental and health effects. The Royal Society has continued to engage with the problem of malaria: Hiliary Ranson is currently conducting research into the DNA of insecticide-resistant plasmodium in an attempt to evolve a method of blocking the process of development of resistance. Her research is demonstrated by this interactive tool. The recent winner of the Royal Society’s Pfizer Award, Dr Alex Nzila has taken a different approach: focusing on drug resistance in humans, he has shown that resistance can be reduced by combining an existing anticancer drug, methotrexate, with folic acid.

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