Natural Smallpox Research Articles

Kant and the smallpox inoculation

Smallpox was an endemic, very contagious disease which caused a high mortality rate during the age of enlightenment. In order to counter act this epidemic, smallpox inoculation was developed. This technique consisted in the inoculation of infected pus taken from a sick person into a healthy one in order to prevent the risks of natural smallpox infection. It was in this context that a German doctor in charge of inoculation wrote to Kant twice in 1799, and again in 1800, to ask him if inoculation was morally permissible. Kant wrote a draft of an answer, but it was never completed or published during his lifetime. These drafts provide elements of an answer that he nevertheless refused to give explicitly in the Doctrine of Virtue (1797) where the question of the morality of inoculation remained unanswered.

Functional epitopes and neutralizing antibodies of vaccinia virus

Smallpox is an infectious disease caused by the variola virus, and it has a high mortality rate. Historically it has broken out in many countries and it was a great threat to human health. Smallpox was declared eradicated in 1980, and Many countries stopped nation-wide smallpox vaccinations at that time. In recent years the potential threat of bioterrorism using smallpox has led to resumed research on the treatment and prevention of smallpox. Effective ways of preventing and treating smallpox infection have been reported, including vaccination, chemical drugs, neutralizing antibodies, and clinical symptomatic therapies. Antibody treatments include anti-sera, murine monoclonal antibodies, and engineered humanized or human antibodies. Engineered antibodies are homologous, safe, and effective. The development of humanized and genetically engineered antibodies against variola virus via molecular biology and bioinformatics is therefore a potentially fruitful prospect with respect to field application. Natural smallpox virus is inaccessible, therefore most research about prevention and/or treatment of smallpox were done using vaccinia virus, which is much safer and highly homologous to smallpox. Herein we summarize vaccinia virus epitope information reported to date, and discuss neutralizing antibodies with potential value for field application.

Smallpox good and bad: evolution of popular perceptions of the personification of the disease in the Urals in the 19th — early 20th century

In this paper, elaboration of the image of smallpox in popular perception, which manifested itself in connec-tion with the organization of smallpox vaccination by the Russian government, is examined. In the context of the cultural dominance of the ruling class over the people and paternalistic attitude towards it, promulgation of the vaccination is a unique phenomenon for the early 19th century Russia, when the “amount at stake” forced the authorities to appeal to their subjects. It provides an opportunity to analyze the symbols generated by the domi-nant ideology and their perception by traditional consciousness. Propaganda started by means of sermons by the clergy. Numerous Exhortations emphasized contraposition of the benefits of the vaccinated smallpox and the harm of the natural smallpox. The verbal channel of the agitation was supported by a visual one — publication of ”popular prints”. Analysis of the plots in nine images from D.A. Rovinsky’s collection showed that corporeality was recognized as the main means of the visual agitation. Through the image of human body, health and beauty of persons vaccinated against smallpox was transmitted, as well as deformity and hideousness of those who went through the natural smallpox. Having absorbed the dualism of the pro-government propaganda, popular con-sciousness went to create an alternative version of perceptions of the infection and vaccination. By applying the binary oppositions ’friend-foe’ and ’sacred-profane’, people made an important change in their own system of values: unlike other epidemics, such a particularly dangerous infection as smallpox had changed its place in the traditional worldview. It stopped being associated with plague and death and became recognized as being “one’s own” and ”godsent”. Therefore, it should not be opposed but should be accepted with gratitude as a ”gift of God”. Intercultural communications on the subject of smallpox vaccination are not only a vivid illustration of the ambigu-ous impact of the dominant ideology on a folk culture; the emergence of socially and culturally differentiated im-ages of smallpox, having drawn a new demarcation line between the scholarly and folk cultures, deepened the rift in the Russian society, as well as introduced additional difficulties in the process of immunoprophylaxis and made it difficult to identify and treat the smallpox patients.

40 Years without Smallpox

The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

40 лет без оспы

The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

The introduction of vaccination practice in the Orenburg Region in the early XIX century

The purpose of this work is to research the process of introduction of smallpox prevention in the Orenburg Region in the early 19th century. The author focuses the main attention on the organization and activity of subsidiary medical institutions smallpox committees. The author shows the role of Free Economic Society, doctors, clergy, civil people in the development of smallpox prevention in the region. Based on the analysis of historical sources which are represented in the state archive of the Orenburg Region (fund 6 the offices of Orenburg military governor) the author makes an attempt to detect the main cause of civil resistance in the region. The author used chronological, historical, retrospective and inquiry learning methods. The conducted research showed that in the 19th century in the Orenburg province there was a system of vaccine prevention of smallpox among the population despite the difficult sanitary and epidemiologic situation, lack of medical institutions and shortage of qualified medical personnel. The formation of this process started in the early XIX century. Thus, effective activities of the state and public organizations during this period let to lower the general illness rate and death rates from natural smallpox among the population in the Orenburg province.

“The Practice of Conveying and Suffering the Small-pox”: Inoculation as a Means of Spiritual Conversion in Cotton Mather’s Angel of Bethesda

“The Practice of Conveying and Suffering the Small-pox”: Inoculation as a Means of Spiritual Conversion in Cotton Mather’s Angel of Bethesda Lucas Hardy (bio) You may see (said they) what hee is by his Diseases! —Cotton Mather, The Diary, 1692 Smallpox arrived for the sixth time in the city of Boston in late April of 1721.1 Reacting to the outbreak in his diary, Cotton Mather—the eminent Puritan theologian and first proponent of inoculation in America—wrote, “The grievous Calamity of the Small-pox has now entered the Town. The practice of conveying and suffering the Small-pox by Inoculation, has never been used in America…But how many lives might be saved by it, if it were practiced? I will procure a Consult of our Physicians, and lay the matter before them.”2 If his first remark about smallpox was an apparently scientific one, Mather’s second comment, which came just two days later, looked entirely ministerial. He noted, again in his diary, “The Entrance of the Smallpox into the Town must awaken in me several Tempers and Actions of Piety relating to myself, besides a Variety of Duty to the People.”3 Throughout the nearly yearlong epidemic, Mather oscillated between his interest in medicine and his deeply-entrenched sense of Protestant ethics to determine the proper course of action in assisting the community with the outbreak. Since the middle of the twentieth century, medical historians have paid special attention to the scientific impact of Mather’s work on inoculation. Otho T. Beall, Jr. and Richard H. Shryock, for instance, in Cotton Mather: First Significant Figure in American Medicine (1954), were the first to show in a book-length study the importance of Mather’s role in the [End Page 61] smallpox epidemic. They asserted that “the history of immunology, with all its ultimate values in overcoming infectious diseases, began…in the Boston of 1721.”4 Three decades later, Arthur M. Silverstein, in A History of Immunology (1989), argued that Mather “not only advanced a theory of acquired immunity in natural smallpox infection but also explained…why variolation [or inoculation] is effective in inducing lasting immunity.”5 More recently, Ed Cohen, in A Body Worth Defending: Immunity, Biopolitics, and the Apotheosis of the Modern Body (2009) has suggested that “the first person to adapt the notion of ‘self-defense’ to a medical context, thereby foreshadowing what we now call immunity, is the most iconic and bombastic of American Protestants, Cotton Mather.”6 While these studies have positioned Mather as a progressive scientist on the verge of discovering concepts that would become theories of contagion and acquired immunity well over a century after the 1721 outbreak, their tendency to follow the scientific legacy of inoculation has overlooked the fact that Mather viewed the procedure chiefly as a method for obtaining resistance to the pathogenic force of innate sin. In this regard, inoculation served as the very “action of piety” and “duty to the people” he mentioned in his diary.7 This essay proves that Mather viewed inoculation not just as a medical procedure but, more accurately, as a new scientific means for inducing spiritual conversion. For the Puritans, the ultimate purpose of conversion was to produce the assurance that God had bestowed saving grace upon the repentant. Early in the twentieth century, Perry Miller explained that this process began within each person by some contact with a conversionary “means.” “Conversion,” Miller writes, “is an event in nature, and as in other natural events, the process of regeneration is initiated by an external object from which the senses derive a phantasm, exactly as in any other act of apprehension.”8 The experience Miller describes began with the convert capturing a sensation, but it quickly became an intellectual operation wherein she sought to interpret the spiritual meaning of both the stimulus and the sensation. Inoculation, then, promoted such a conversion in two specific ways. First, it kindled a weak form of smallpox in the patient and produced symptoms that could be read for signs of healing in both the body and the soul. Second, and of most importance to Cotton Mather, was the idea that it induced a prescribed...

‘Defying providence’: a salutary new look at the history of smallpox

Arthur W Boylston, Defying Providence. Smallpox and the forgotten medical revolution. Charleston, SC: CreateSpace, 2012; 282 pp. ISBN 978-1478232452 ‘Defying Providence tells the story of the many men and women who wrestled with their consciences to turn inoculation from a primitive folk practice into the most powerful weapon against smallpox in the 18th century.’ (p.10) Until the 18th century, the outcome of a smallpox infection was fated by providence. Between 10% and 20% of the infected died and, among the survivors, many remained stigmatized in their flesh and appearance for the rest of their lives. Plague had been public enemy number one of the 17th century. When its cyclic and deadly recurrences began to ebb, smallpox became the new scourge, a disease that killed princes and peasants alike. Lady Montague, who had had her children inoculated against smallpox in Turkey in 1718, popularized the technique in England. Still, it was a risky practice responsible for some deaths. Was inoculation more dangerous than a natural smallpox infection? Opinions were split until mortality among the inoculated and that of the naturally infected was compared. Inoculation reduced mortality by a factor of 10 in the 1720s, both in the UK and in North America. With this information the practice amplified. Many country doctors adopted it. In 1768, one of them noticed that some people working in farms did not have the usual clinical reactions following a smallpox inoculation. They seemed resistant. Many farm workers had previously contracted cowpox. This news spread among doctors, not among milkmaids. Could artificial inoculation of cowpox confer immunity against smallpox? Jenner’s brilliant idea led to the vaccine revolution, and finally the end of smallpox: ‘without inoculation the cowpox effect could not have been discovered. There was no folk tradition.’ The myth remains that the beautiful complexion of milkmaids spared from the disfiguring effects of smallpox ignited Jenner’s imagination, but it was likely the resistance to inoculation among farmers that opened the door to ‘vaccines’. A less-known aspect of the forgotten medical revolution of the 18th century is its impact on the American Revolution. General George Washington gave the landmark mandate to inoculate the colonial army. In America, the colonial and the English armies were not equally susceptible to smallpox. Most English soldiers were immune from previous infection or inoculation, while Washington’s troops, highly susceptible, were killed 10 times more by the disease than from combat. In 1777, surmounting defiance from state and army hierarchy, the Congress approved the plan to systematically inoculate its soldiers. The act was implemented during the next two consecutive years. ‘Thereafter,’ writes Boylston, ‘the threat to the revolution from smallpox was over. Inoculation became as much a part of soldiering as a musket […] Americans would have certainly lost the revolution without it because most American colonists had had little previous exposure to the virus, and therefore no immunity to it. When smallpox spread through susceptible soldiers, the force always disintegrated.’ (p.212). Still, inoculation had already weathered excessive hindrances; delays in inoculating the troops preparing to reach Quebec resulted in Canada remaining British. The style in Defying Providence is scholarly in its precision, paying attention to details, and citing primary sources extensively. But Boylston also has an undeniable ability for storytelling and suspense building. The result reads like a brilliant tale in which the practice of inoculation, after helping modern medicine forge its first research and conceptual tools, was later denigrated as dangerous and unacceptable when the public health preference shifted to vaccination. Smallpox was the main health scourge when the conditions for a science of epidemics (an epidemiology) began to exist. Boylston can therefore trace in these illustrious decades of the 18th century the early manifestations of comparative studies, ancestors of controlled trials, and of what came to be known as evidence-based or evidence-informed medicine. Defying Providence is a precious book about ‘one of medicine’s finest hours’, at the crossroad of the history of diseases, of medicine, and of epidemiology.

43. Global warming and expanding the range of feral conditions in Yakutia – The coldest region of the North-East Asia

In Yakutia, there has long been a number of natural foci of infectious human and animal diseases such as tularemia, anthrax, rabies, brucellosis, leptospirosis and others. The circulation of pathogens in nature is closely connected with the peculiarities of natural ecosystems and their animal populations, especially the mass species of birds and mammals and their ecto-and endoparasites. Global warming has caused the expansion to the north of the range of many species of birds and their ectoparasites from the southern parts of the Asia–Pacific region. There was the possibility of the spread causative agent of avian influenza H5N1 dangerous to humans, in-line with those observed in recent decades, global warming and the expansion of the range of animal-carriers and custodians of infectious agents are expanding the range of feral diseases such as rabies, brucellosis,and encephalitis, stable foci of new diseases, including pseudotuberculosis, have appeared in our region. With further advancement of the classical forms of rabies in South Yakutia in the central and northern areas of the Arctic, the counter-propagation form of rabies may occur to the south, with the genetic restructuring of their agents as a result of recombination of genes and new mutations. Melting of permafrost soils and an irrigation of territories can promote “awakening” of the centres, previously widespread in the region, of a malignant anthrax and natural smallpox. There is concern has about the recently established detection of viable, including spore-forming, micro-organisms in the remains of the mammoth fauna of the natural burial sites in the Late Pleistocene permafrost sediments over time. The latter indicates that there is potential for the release of pathogens from the surface of especially dangerous infections from that era (epidemiological echo). Previously, Somov (1974), who worked many years in Chukotka and other regions of the Russian Far East, put forward a hypothesis on the preservation of psychrophilic pathogens infections at low temperatures of the environment in saprophytic state that only if it enters the human body become virulent. In this regard, we suggested in 1980 that “the further development of the northern territories may appear natural foci of new, perhaps previously unknown infectious diseases”. Thus, global warming contributes to increased incidence of especially dangerous infections by expanding the range of animal carriers and disseminators of infection due to possible preservation at low temperatures in the state of saprophytic pathogens in the active state.

Zabdiel Boylston's evaluation of inoculation against smallpox

Variolation, known in the 18th century as inoculation, was introduced almost simultaneously in Boston and London in the early 1720s.1 A furious debate followed. Among the issues were the religious implications of interfering with divine providence; the legality of spreading a potentially fatal infection; whether the disease induced really was smallpox; whether it was safer than natural smallpox; and whether inoculation induced immunity. Thomas Nettleton, a Yorkshire physician and inoculator, suggested in a letter sent in 1722 to James Jurin, Secretary of the Royal Society, that the best way to answer the safety and efficacy question was to make a comparison between the mortality of smallpox and the mortality among those inoculated.2,3 He submitted 3405 cases of natural smallpox, of which 636 died, whereas there had been no deaths among the 60 patients he had inoculated. Jurin took up the suggestion and advertised for information from anyone with experience of natural smallpox or variolation.4 To simplify the investigation and avoid arguments about subjective issues such as the severity of an individual case he only recorded death or survival. His correspondents revealed that the operation was practised throughout England and that the operators ranged from fully licensed physicians to surgeons, apothecaries and lay women.5 Jurin published annual summaries of his correspondence between 1724 and 1727.6–10 Table 1 shows the data presented by Boylston13 and Jurin,9 analysed using a simple χ2 analysis. The mortality among inoculees was similar on both sides of the Atlantic, but while natural smallpox was associated with a higher death rate than inoculation in both places, the relative increase in the rate was 8 in Boston and 6.9 in England. This apparently similar effectiveness was present despite differences in the operators and the exact method of inoculation. Table 1 Fatality of natural and inoculated smallpox This very early use of mathematical evidence in favour of inoculated smallpox over the natural disease influenced the adoption of variolation both in England and in the colonies. In 1731 David Hartley, now remembered as the father of psychology,14 used these figures to argue for general inoculation in the town of Bury St Edmunds because it would save about 600 lives.15 In 1730, when smallpox reappeared in Boston, Boylston republished his book and several of the town's doctors, including William Douglass, his old nemesis, now offered variolation to their patients.16 The published evidence was taken so seriously that opponents of variolation tried to argue that the figures were biased.4,17 They complained that inoculators regularly excluded pregnant women and those in ill health, and that they were treating a healthier population than those who suffered the natural disease. The title of Boylston's book – An historical account of the smallpox inoculated in New England upon all sorts of persons, whites, blacks, and of all ages and constitution – may represent a reply to these criticisms. The efficacy and relative safety of inoculation compared with natural disease was accepted both in England and in the North American colonies. It was used in Philadelphia in 1735 and Charleston, South Carolina in 1738 when epidemic smallpox appeared. By the middle of the 18th century John Adams and Thomas Jefferson had been inoculated and the Royal College of Physicians had endorsed the practice as safe and beneficial.4,18

Identification of Vaccinia CD8 + T-Cell Epitopes Conserved among Vaccinia and Variola Viruses Restricted by Common MHC Class I Molecules, HLA-A2 or HLA-B7

Immunization with vaccinia virus results in long-lasting protection against smallpox and is an approach that has been successfully used to eliminate natural smallpox infections worldwide. Today, vaccinia virus is very important not only as a vaccine virus to protect human against smallpox, but also as an expression vector for immunization against other infectious diseases, such as HIV and cancer. In this article, we identify three new vaccinia human CD8 + T-cell epitopes conserved among vaccinia and variola viruses restricted by HLA-A2, HLA-B7, or HLA-B*3502, which belongs to the HLA-B7 supertype. Identification of these CD8 + T-cell epitopes restricted by common HLA alleles will help to quantitate human CD8 + T-cell responses to licensed and experimental smallpox vaccines and to vaccinia virus vectors. CD8 + T-cell responses specific to these epitopes can also be used to quantitate cellular immune responses, especially with new smallpox vaccines that do not induce a “take,” such as the modified vaccinia virus Ankara strain. Combined with previous reports by us and others, these results show that there are some vaccinia viral proteins containing multiple epitopes restricted by different MHC molecules of humans and mice.

MSJAMA. The physicians' dilemma in the 18th-century French smallpox debate.

MSJAMA. The physicians' dilemma in the 18th-century French smallpox debate.

Quantitation of CD8+ T cell responses to newly identified HLA-A*0201-restricted T cell epitopes conserved among vaccinia and variola (smallpox) viruses.

Immunization with vaccinia virus resulted in long-lasting protection against smallpox and was the approach used to eliminate natural smallpox infections worldwide. Due to the concern about the potential use of smallpox virus as a bioweapon, smallpox vaccination is currently being reintroduced. Severe complications from vaccination were associated with congenital or acquired T cell deficiencies, but not with congenital agammaglobulinemia, suggesting the importance of T cell immunity in recovery from infection. In this report, we identified two CD8+ T cell epitopes restricted by the most common human major histocompatibility complex (MHC) class I allele, HLA-A*0201. Both epitopes are highly conserved in vaccinia and variola viruses. The frequency of vaccinia-specific CD8+ T cell responses to these epitopes measured by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay and HLA/peptide tetramer staining peaked 2 wk after primary immunization and then declined, but were still detectable 1 to 3 yr after primary immunization. 2 wk after immunization, IFN-γ–producing cells specific to these two epitopes were 14% of total vaccinia virus-specific IFN-γ–producing cells in one donor, 35% in the second donor, and 6% in the third donor. This information will be useful for studies of human T cell memory and for the design and analyses of the immunogenicity of experimental vaccinia vaccines.

Dr. James Latham (c. 1734-1799): pioneer inoculator in Canada.

Dr. James Latham, British military surgeon and inoculator, was the first known person to have practised inoculation for smallpox in Canada. He came to Canada with his regiment in July 1768 and undertook inoculation in Quebec and Montreal in the years 1768–70 and again in 1786. His efforts were recorded in the Québec Gazette and have been liberally quoted by various authorities on the history of medicine in Canada. But to date little has been known of his life or subsequent career. Recent work has re-assessed the role of inoculation in reducing the incidence of smallpox in the 18th century. In an age where smallpox was considerable inevitable, inoculation with live smallpox matter could reduce the mortality from the disease from one in six deaths from natural smallpox to one in fifty deaths for those inoculated.

Increased sensitivity of albino mice to natural smallpox virus after whole-body γ-ray irradiation

Increased sensitivity of albino mice to natural smallpox virus after whole-body γ-ray irradiation

View of the Natural Small-Pox, &c

View of the Natural Small-Pox, &c

VI. A letter to the learned Dr. Caleb Cotesworth, F. R. S. of the College of Physicians, London, and Physician to St. Thomas's Hospital; containing a comparison between the danger of the natural small pox, and of that given by inoculation

Sir, The sincere and disinterested Regard for the Good of Mankind, Which you have always manifested, as well in your extensive private Practice, as in that publick Post, Which you have so long and so Usefully fill'd, must affect you, I am sure, with a great and sensible Concern for the Destruction made among us by that terrible Calamity the Small Pox.