Posts Tagged ‘History’

Chasing Jenner’s Vaccine

Wednesday, November 16th, 2011

Edward Jenner Cowpox virus (CPXV) is one of the earliest described members of the genus Orthopoxvirus (OPV). Historically, researchers referred to the ailment known as cowpox and even suggested that it could provide immunity against smallpox. It was Edward Jenner’s publications in 1798 and 1799 which provided the first scientific description of vaccination by detailing the efficacy of CPXV “scarification” in inducing protective immunity against challenge with variola (smallpox) virus (VARV). The common name “cowpox virus” refers to the association with pustular lesions on the teats of cows and historic zoonotic transmission of this disease to humans (milkers) through contact with infected cows. Human infections are generally mild and self-limiting with localized skin lesions healing after 3–4 weeks, however, systemic involvement and fatal outcome have been reported in immunocompromised individuals.

New analysis shows that the smallpox vaccine is known to have originated in the United Kingdom, however the vaccine strains were most closely allied to CPXV isolates from Russia and from Finland. The most likely scenario is that most of the commercially produced smallpox vaccines were not made from the original Jenner strain, but instead from isolates found in other regions of Europe.


Chasing Jenner’s Vaccine: Revisiting Cowpox Virus Classification. (2011) PLoS ONE 6(8): e23086. doi:10.1371/journal.pone.0023086
Cowpox virus (CPXV) is described as the source of the first vaccine used to prevent the onset and spread of an infectious disease. It is one of the earliest described members of the genus Orthopoxvirus, which includes the viruses that cause smallpox and monkeypox in humans. Both the historic and current literature describe “cowpox” as a disease with a single etiologic agent. Genotypic data presented herein indicate that CPXV is not a single species, but a composite of several (up to 5) species that can infect cows, humans, and other animals. The practice of naming agents after the host in which the resultant disease manifests obfuscates the true taxonomic relationships of “cowpox” isolates. These data support the elevation of as many as four new species within the traditional “cowpox” group and suggest that both wild and modern vaccine strains of Vaccinia virus are most closely related to CPXV of continental Europe rather than the United Kingdom, the homeland of the vaccine.

Fabulous Measles Timeline

Sunday, April 3rd, 2011

From History of Vaccines:

Measles timeline

Lessons from plague

Wednesday, March 30th, 2011

Microbiology Today Since ancient times, Yersinia pestis has wreaked havoc on the human population. In this article in Microbiology Today (pdf) Petra Oyston asks what can the transmission and evolution of this unusual pathogen teach us about how we might prepare for future emergent pathogens?

Cycles of plague have swept across the world in three documented pandemics. The first pandemic is known as the Justinian Plague (AD 541–544). The plague arrived in Egypt from Ethiopia, and then spread through North Africa, Europe, Arabia, and Central and Southern Asia. Epidemics spread in 8- to 12-year cycles, often repeatedly infecting the same areas. The second pandemic started in the 14th century, spreading from the steppes of Central Asia westward along trade routes. The plague then spread northwards in Europe, killing an estimated 40% of the population and earning it the name the Black Death. The third pandemic appears to have originated in the Chinese province of Yunnan in 1855, spreading due to war and troop movements to the southern coast, reaching Hong Kong in 1894. Maritime routes allowed the global spread of infection, and the Americas were infected for the first time; stable enzootic foci were established on every major continent with the exception of Australia. The vestigial remnants of the third pandemic persist to the present day, although the numbers of cases are much reduced, largely due to effective public health measures and the introduction of antibiotics.


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The bugs that ate history

Friday, November 5th, 2010

Leonardo da Vincis Atlantic Codex Since the beginning of mankind, human beings have strived to pass on their thoughts and knowledge to other people and to future generations. In this respect, the cultural role played by paper has been immense: paper is used for drawings, books, archival documents, photographs, prints, and so forth. Paper was first made in China around 105 AD, and its history can be roughly divided into two major periods: before the 19th century, when paper was made by hand, cellulose from linen and cotton rags was used as the raw material; from the 19th century onwards, when paper was machine-made from wood pulp, paper has contained several other components in addition to cellulose; these include lignin, hemicellulose and pectin. Furthermore, paper is often coated with sizes (the sizing of paper is a process that renders the sheets impervious to ink) such as gelatine, or with minerals, pigments and other substances to impart desirable properties. Libraries, archives and museums preserve paper material, and such material is at risk of deterioration and needs to be protected from physicochemical and biological agents. In many cases, microbial processes have been implicated in paper deterioration.

Scripta manent? Assessing microbial risk to paper heritage. Trends in Microbiol. Oct 22 2010
Paper, like all other cultural heritage materials, degrades over time, but conservation slows down the rate of its deterioration. There is a long history of cooperation between microbiologists and conservators of libraries and archival materials, but current approaches addressing paper deterioration need urgent reassessment to take full advantage of modern microbiological methodologies. This article discusses what we believe are the current priority research areas in assessing microbial risk to paper heritage, and reports studies on a 13th century Italian manuscript and on Leonardo da Vinci’s Atlantic Codex which illustrate the problems and challenges encountered when dealing with microbial investigations of paper artworks. The potential of using a more advanced microbiological approach is highlighted.


Distinct clones of Yersinia pestis caused the Black Death

Monday, November 1st, 2010

Several historical epidemic waves of plague have been attributed to Yersinia pestis, the etiologic agent of modern plague. The most famous of these was the second pandemic which was active in Europe from AD 1347 until 1750, and began with the ‘Black Death’. The most informative method to establish the etiological nature of these ancient infections should be the analysis of ancient DNA, but the results of this method have been controversial. By combining ancient DNA analyses and protein-specific detection, this paper demonstrates that Y. pestis caused the Black Death. Furthermore, they show that at least two variants of Y. pestis spread over Europe during the second pandemic. The analysis of up to 20 diagnostic markers reveals that the two variants evolved near the time that phylogenetic branches 1 and 2 separated and may no longer exist. These results resolve a long-standing debate about the etiology of the Black Death and provide key information about the evolution of the plague bacillus and the spread of the disease during the Middle Ages.

Distinct Clones of Yersinia pestis Caused the Black Death. PLoS Pathog 6(10): e1001134. doi:10.1371/journal.ppat.1001134
From AD 1347 to AD 1353, the Black Death killed tens of millions of people in Europe, leaving misery and devastation in its wake, with successive epidemics ravaging the continent until the 18th century. The etiology of this disease has remained highly controversial, ranging from claims based on genetics and the historical descriptions of symptoms that it was caused by Yersinia pestis to conclusions that it must have been caused by other pathogens. It has also been disputed whether plague had the same etiology in northern and southern Europe. Here we identified DNA and protein signatures specific for Y. pestis in human skeletons from mass graves in northern, central and southern Europe that were associated archaeologically with the Black Death and subsequent resurgences. We confirm that Y. pestis caused the Black Death and later epidemics on the entire European continent over the course of four centuries. Furthermore, on the basis of 17 single nucleotide polymorphisms plus the absence of a deletion in glpD gene, our aDNA results identified two previously unknown but related clades of Y. pestis associated with distinct medieval mass graves. These findings suggest that plague was imported to Europe on two or more occasions, each following a distinct route. These two clades are ancestral to modern isolates of Y. pestis biovars Orientalis and Medievalis. Our results clarify the etiology of the Black Death and provide a paradigm for a detailed historical reconstruction of the infection routes followed by this disease.


Where do viruses come from?

Friday, September 17th, 2010

the fertile crescent Measles is a common infection in children and is spread by the respiratory route, but where did the virus come from? The disease is characterized by a prodromal (initial) illness of fever, coryza, cough, and conjunctivitis followed by appearance of a generalized maculopapular rash. Measles virus (MeV) infects approximately 30 million people annually, with a mortality of 197,000, mainly in developing countries. In the prevaccine era, more than 90% of 15-year-old children had a history of measles. Measles remains a major cause of mortality in children, particularly in areas with inadequate vaccination and medical care.

MeV infection can confer lifelong immunity, and there is no animal reservoir or evidence of latent or common persistent infection except for a rare condition called subacute sclerosing panencephalitis (SSPE). Therefore, maintenance of MeV in a population requires constant supply of susceptible individuals. If the population is too small to establish continuous transmission, the virus can be eliminated. Mathematical analysis shows that an immunologically-naïve population of 250,000-500,000 is needed to maintain MeV. This is approximately the population of the earliest urban civilizations in ancient Middle Eastern river valleys around 3000-2500 BCE. Historically, the first scientific description of measles-like syndrome was provided by Abu Becr, known as Rhazes, in the 9th century. However, smallpox was accurately described by Galen in the 2nd second century whereas measles was not. Epidemics identified as measles were recorded in the 11th and 12th centuries.

MeV is a member of the genus Morbillivirus, which belongs to the family Paramyxoviridae. In addition to MeV, Morbillivirus includes dolphin and porpoise morbillivirus, canine distemper virus, phocid distemper virus, peste des petits ruminants virus, and rinderpest virus (RPV). Genetically and antigenetically, MeV is most closely related to RPV, which is a pathogen of cattle. MeV is assumed to have evolved in an environment where cattle and humans lived in close proximity. MeV probably evolved after commencement of livestock farming in the early centers of civilization in the Middle East. The speculation agrees with the mathematical analysis mentioned above.

Molecular clock analysis can estimate the age of ancestors in evolutionary history by phylogenetic patterns. The basic approach to estimating molecular dates is to measure the genetic distance between species and use a calibration rate (the number of genetic changes expected per unit time) to convert the genetic distance to time. Pomeroy et al. showed that “Time to the Most Recent Common Ancestor” of the current MeV circulating worldwide is recent, i.e., within the last century (around 1943). Nevertheless, the time when MeV was introduced to human populations has not been investigated. In this study, the researchers performed molecular clock analysis on MeV to determine the time of divergence from RPV, suggesting that MeV emerged in humans in the 11th to 12th centuries.

Origin of measles virus: divergence from rinderpest virus between the 11th and 12th centuries. Virology Journal 2010, (7):52 doi:10.1186/1743-422X-7-52
Measles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genus Morbillivirus and is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV. We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 – 6.5×10-4 substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20th century. And, divergence between MeV and RPV occurred around the 11th to 12th centuries. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age. MeV may have originated from virus of non-human species and caused emerging infectious diseases around the 11th to 12th centuries. In such cases, investigating measles would give important information about the course of emerging infectious diseases.


Killing a Killer: What Next for Smallpox?

Monday, February 1st, 2010

Smallpox Should we destroy the remaining laboratory stocks of smallpox virus?

Now that the 20th century has passed into the domain of history books, we can retrospectively begin to assess the relative contributions that the many advances in the realm of infectious disease have actually made to public health in general. At the top of this virtuous list will surely be the discovery of antibiotics in the 1930s and the use of vaccination to eradicate smallpox as an extant human disease in the 1960s and 1970s. As clearly pointed out in a recent book by D. A. Henderson, one of the leaders of the global smallpox eradication program, this task of ridding Homo sapiens from the curse of this ancestral disease was neither easy nor without controversy. In fact, the history of the many consequences of smallpox on humankind reads like a long litany of human misery and calamitous events, but is juxtaposed with the more noble accomplishments that began with the discovery of vaccination by Jenner in 1798 and culminated with the World Health Organization (WHO) certifying the world free of smallpox in 1980. With this singular accomplishment, as many as 60–100 million individuals who would have been predicted to die of smallpox have been spared from a truly gruesome death. Nevertheless, the narrative of smallpox did not stop with its eradication as a pandemic human disease. Instead, we find ourselves still wrestling with an issue that intermingles public health policy, philosophy, national security, and bioterrorism, and affects our perceptions of research ethics with extreme pathogens in general. It boils down to a not-so-simple question: What exactly should the Victor do with the Vanquished?

Killing a Killer: What Next for Smallpox? 2010 PLoS Pathog 6(1): e1000727. doi:10.1371/journal.ppat.1000727


Dance till you can’t dance no more

Friday, January 22nd, 2010

dance In 1518, one of the strangest epidemics in recorded history struck the city of Strasbourg. Hundreds of people were seized by an irresistible urge to dance, hop and leap into the air. In houses, halls and public spaces, as fear paralyzed the city and the members of the elite despaired, the dancing continued with mindless intensity. Seldom pausing to eat, drink or rest, many of them danced for days or even weeks. And before long, the chronicles agree, dozens were dying from exhaustion. What was it that could have impelled as many as 400 people to dance, in some cases to death?

Medieval dancing epidemics were not unrelated events: they were linked both in time and space. Every one of the ten or so outbreaks between the late 1300s and 1518 happened along the Rhine and Mosel rivers. In 1374, for instance, the crazed dance gradually spread out from an epicentre around Aachen, Liege and Maastricht to neighbouring towns such as Ghent, Utrecht, Metz, Trier and, eventually, Strasbourg. Moreover, outbreaks of compulsive dancing virtually always struck in or close to places affected by earlier outbreaks. Maastricht, Trier, Zurich and Strasbourg each experienced two or more episodes. There are also several reports of compulsive dancing after 1518. All of these, crucially, took place close to the Rhine, and all but one within a short ride of Strasbourg itself.

How can we explain this striking epidemiological picture? One suggestion is that wild dancing formed part of the ecstatic ritual of a heretical sect, an energetic counterpart of the flagellant’s cult. There are two main difficulties with this theory. First, in lucid moments the dancers implored bystanders and priests to come to their aid. There is absolutely no evidence that the dancers wanted to dance. On the contrary, they expressed fear and desperation. Second, the authorities consistently saw the afflicted not as heretics but as the victims of diabolical possession or divine curse, and treated them accordingly. The dancers were subject to exorcisms or sent on pilgrimages. Never were they hauled before the inquisition.

Other authors have sought a chemical or biological origin for the dancing mania, and the chief contender has been ergot, a mould that grows on the stalks of damp rye. While seductively simple, this hypothesis is untenable. The chemicals contained in ergot do not allow for sustained dancing. They can certainly trigger violent convulsions and delusions, but not coordinated movements that last for days. Yet while the dancers were free from ergot, they almost certainly were delirious. Only in an altered state of consciousness could they have tolerated such extreme fatigue and the searing pain of sore, swollen and bleeding feet. Moreover, witnesses consistently spoke of the victims as being entranced, seeing terrifying visions and behaving with wild, crazy abandon. So what could have plunged hundreds of people into trances so deep that remorseless dancing became possible? Psychologists, neurologists and anthropologists have identified severe psychological distress as a factor increasing the likelihood of an individual entering an altered state. It is unlikely to be a coincidence, therefore, that in the year 1518 many people in Strasbourg were experiencing truly exceptional levels of hunger and mental anguish.

In a spin: the mysterious dancing epidemic of 1518. Endeavour. 2008 32(3): 117-121. doi: 10.1016/j.endeavour.2008.05.001

The Tomb of the Shroud

Thursday, December 17th, 2009

bone A new article in the open-access journal PLoS ONE presents scientific research conducted on “The Tomb of the Shroud” – a tomb found in Jerusalem dating back to the time of Jesus. This rock-hewn burial cave belongs to a cemetery known as Akeldama or “Field of Blood” as described in the Bible (Matthew 27:3-8; Acts 1:19), and located in the lower Hinnom Valley in Jerusalem. In comparison to more than 70 other tombs in the Akeldama area, this particular tomb is unique as it contains remnants of a burial shroud and evidence of leprosy (Hansen’s disease) and tuberculosis in the shrouded male remains therein. This is the oldest known case of leprosy with confirmed dates and molecular evidence. Some of the other individuals in this multi-chambered tomb showed signs of tuberculosis, and ancient human DNA was detected to piece together the family relationships.

No other first century tomb from Jerusalem had ever been examined by molecular methods. The discovery of the presence of Mycobacterium tuberculosis and Mycobacterium leprae in the individuals buried within the “Tomb of the Shroud” is significant in understanding the geographical and temporal distribution of tuberculosis and leprosy in antiquity. This research has evidenced that molecular pathology clearly adds a new dimension to the archaeological exploration of disease in ancient times. The successful genetic analyses of unique archaeological sites such as “Tomb of the Shroud” pose great promise for future investigations into host-pathogen relationships and evolution, geographic distribution, and epidemiology of disease and social health in antiquity.

Molecular Exploration of the First-Century Tomb of the Shroud in Akeldama, Jerusalem. 2009 PLoS ONE 4(12): e8319. doi:10.1371/journal.pone.0008319
The Tomb of the Shroud is a first-century C.E. tomb discovered in Akeldama, Jerusalem, Israel that had been illegally entered and looted. The investigation of this tomb by an interdisciplinary team of researchers began in 2000. More than twenty stone ossuaries for collecting human bones were found, along with textiles from a burial shroud, hair and skeletal remains. The research presented here focuses on genetic analysis of the bioarchaeological remains from the tomb using mitochondrial DNA to examine familial relationships of the individuals within the tomb and molecular screening for the presence of disease. There are three mitochondrial haplotypes shared between a number of the remains analyzed suggesting a possible family tomb. There were two pathogens genetically detected within the collection of osteological samples, these were Mycobacterium tuberculosis and Mycobacterium leprae. The Tomb of the Shroud is one of very few examples of a preserved shrouded human burial and the only example of a plaster sealed loculus with remains genetically confirmed to have belonged to a shrouded male individual that suffered from tuberculosis and leprosy dating to the firstcentury C.E. This is the earliest case of leprosy with a confirmed date in which M. leprae DNA was detected.