Smallpox

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Smallpox
Classification & external resources

A child infected with smallpox
ICD-10	B03.
ICD-9	050
DiseasesDB	12219
MedlinePlus	001356
eMedicine	emerg/885
MeSH	D012899

Variola virus (Smallpox)
Virus classification
Group: Group I (dsDNA) Family: Poxviridae Genus: Orthopoxvirus Species: Variola vera

Smallpox (also known by the Latin names Variola or Variola vera) is a highly contagious disease unique to humans.^[1] Smallpox is caused by either of two virus variants named Variola major and Variola minor. V. major, the deadlier form, has a mortality rate of 3–35%, while V. minor causes a milder form of disease called alastrim and kills ~1% of its victims.^[2][1] Long-term side-effects for survivors include the characteristic skin scars. Occasional side effects include blindness due to corneal ulcerations and infertility in male survivors.

Smallpox was responsible for an estimated 300–500 million deaths in the 20th century. As recently as 1967, the World Health Organization (WHO) estimated that 15 million people contracted the disease and that two million died in that year.^[3] After successful vaccination campaigns throughout the 19th and 20th centuries, the World Health Organization (WHO) certified the eradication of smallpox in 1979.^[4]

Contents 1 Vaccine 2 Infection 2.1 Hemorrhagic smallpox 2.2 Eurasia 2.3 The Americas 2.4 Inoculation 2.5 Vaccination 2.6 Eradication 2.7 Post-eradication 2.8 Biological weapon 3 Famous victims 4 See also 5 References 5.1 Further reading 6 External links 6.1 Disease information 6.2 Images 6.3 Smallpox in history

[edit] Vaccine

Main article: Smallpox vaccine

Edward Jenner is credited with producing the smallpox vaccine using cowpox fluid (hence the word vaccination is derived from the Latin vacca, cow); his first vaccination occurred on May 14, 1796. However, the first European recorded as vaccinating against smallpox was Benjamin Jesty, a farmer. Jesty noted the common knowledge that dairymaids who had previously contracted the less severe cowpox never suffered with smallpox, even after nursing ill family members. During the smallpox outbreak in the summer of 1774, Jesty inoculated his wife and her children. Jesty's wife became ill but recovered with treatment. The method of variolation, however, originated in Asia long before this time; reports from colonizers may have inspired the subsequent development of the vaccine in Europe.

The practice of vaccination against smallpox spread quickly in Europe and then to North America. Prior to Jenner's cowpox vaccine, many New England settlers were inoculated by means of making small incisions in the arms of the healthy patient, scraping a pustule from a smallpox victim, and spreading the pus in the arm incisions. The inoculated patients were often sick for weeks but generally recovered. Prior to 1776, Abigail Adams from Massachusetts wrote to her husband John Adams (then in Congress in Philadelphia) that she was taking their children to Boston to be inoculated, after a severe outbreak near their rural home had killed entire neighboring families. The first smallpox vaccination in North America occurred on June 2, 1800 by Dr. John Clinch in Trinity, Newfoundland.^[5] National laws requiring vaccination began appearing as early as 1805.

The last case of wild smallpox occurred on October 26, 1977. One last victim was claimed by the disease in the UK in September 1978, when Janet Parker, a photographer in the University of Birmingham Medical School, contracted the disease and died. A research project on smallpox was being conducted in the building at the time, though the exact route by which Mrs. Parker became infected was never fully elucidated.

Cultures of the virus are kept by the Centers for Disease Control and Prevention (CDC) in the United States and at the Institute of Virus Preparations in Siberia, Russia. (While scientists certified it eradicated in December 1979, WHO formally ratified this on 8 May 1980 in resolution WHA33.3) Smallpox vaccinations were discontinued in most countries in the 1970s as the morbidity and mortality of vaccination by then exceeded the risk of infection by a disease extinct in the wild. Nonetheless, after the 2001 anthrax attacks took place in the United States, concerns about smallpox have resurfaced as a possible agent for bioterrorism.^[1] As a result, there has been increased concern about the availability of vaccine stocks. Moreover, George W. Bush has ordered all American military personnel to be vaccinated against smallpox and has implemented a voluntary program for vaccinating emergency medical personnel.

[edit] Infection

Smallpox is highly infectious, although less so than chickenpox. Unlike chickenpox, smallpox is not notably infectious in the prodromal period—viral shedding is usually delayed until the appearance of the rash. Smallpox is transmitted primarily through prolonged social contact or direct contact with infected body fluids or contaminated objects such as bedding or clothes. Infection in the natural disease will be via the lungs.

The incubation period between contraction and the first obvious symptoms of the disease is around 12 days. In the initial growth phase the virus seems to move from cell to cell, but around the 12th day, lysis of many infected cells occurs and the virus is found in the bloodstream in large numbers. The initial or prodromal symptoms are similar to other viral diseases such as influenza and the common cold: fevers, muscle pain, stomach aches, etc. The digestive tract is commonly involved, leading to vomiting. Most people become prostrated at this stage.

Smallpox virus preferentially attacks skin cells, and by days 12–15, smallpox infection becomes obvious. The attack on skin cells causes the characteristic pimples associated with the disease. The pimples tend to erupt first in the mouth, then on the arms and the hands, and later on the rest of the body. At this point the pimples, called macules, are usually still fairly small. This is the stage at which the victim is most contagious.

By days 15–16 the condition worsens, and at this point the disease can take two very different courses, depending on whether it is ordinary or hemorrhagic smallpox. The most common type is classic ordinary smallpox, in which the pimples grow into vesicles and then fill up with pus, turning them into pustules. Ordinary smallpox generally takes one of two basic courses. In discrete ordinary smallpox, the pustules stand out on the skin separately. There is a greater chance of surviving this form. In confluent ordinary smallpox, the blisters merge together into sheets which begin to detach the outer layers of skin from the underlying flesh. This form is usually fatal. If the patient survives the course of the disease, the pustules deflate in time (the duration is variable), and start to dry up, usually beginning on day 28. Eventually the pustules completely dry and start to flake off. Once all of the pustules flake off, the patient is considered cured, and is no longer contagious.

To distinguish between chickenpox and smallpox in the field, an examination of the patient's palms and soles is necessary. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size. Smallpox pustules are all very nearly the same size: the virus moves in more uniform stages than does chickenpox.

[edit] Hemorrhagic smallpox

In the other form of Variola major smallpox, known as hemorrhagic smallpox, a mortality of 96 percent has been reported.^[6] An entirely different set of symptoms starts to develop. The skin does not blister, but remains smooth. Instead, bleeding occurs under the skin, making the skin look charred and black (this is known as black pox). The eyes also hemorrhage, making the whites of the eyes turn deep red (and, if the victim lives long enough, eventually black). At the same time, bleeding begins in the organs. Death may occur from bleeding (fatal loss of blood or by other causes such as brain hemorrhage), or from loss of fluid. The entry of other infectious organisms, since the skin and intestine are no longer a barrier, can also lead to multi-organ failure. This form of smallpox occurs in anywhere from 3–25% of fatal cases (depending on the virulence of the smallpox strain).

The historical modes of death are similar to those in burns, with catastrophic losses of fluid, protein and electrolytes beyond the capacity of the body to replace or assimilate, and fulminating sepsis, both due to the removal of the barrier between the internal milieu and outside world. Supportive treatments have improved since the last large smallpox epidemics, but it would be grossly optimistic to imagine that, even with a small number of patients, the most intensive modern treatment would ensure survival, even where the damage is predominantly only in the skin. A reduction in the severity of the disease by raising immunity is likely to make a large difference in numbers reaching the threshold of death, and supportive treatment a small one in elevating that threshold.

[edit] Eurasia

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Historical epidemics and pandemics are believed by some historians to have been early outbreaks of smallpox. But contemporary records are not detailed enough to make a definite diagnosis at this distance.

Some people ^[Who?] believe smallpox was the sixth plague of the Old Testament of the Bible recorded in the book of Exodus 9:8-12, "...festering boils on people and animals through the land." However, smallpox infection is unique to humans, contradicting this premise.

The Plague of Athens devastated the city of Athens in 430 BC, killing around a third of the population, according to Thucydides. Historians have long considered this an example of the disease plague, but more recent examination of the reported symptoms led some scholars to believe the cause could have been measles, smallpox, typhus, or a viral hemorrhagic fever (like Ebola).

The Antonine Plague that swept through the Roman Empire and Italy in 165–180 is also thought to be either smallpox or measles. A second major outbreak of disease in the Empire, known as the Plague of Cyprian (251–266), was also either smallpox or measles.

The next major epidemic believed to be smallpox occurred in India. The exact date is unknown. Around A.D. 400, an Indian medical book recorded a disease marked by pustules, saying "the pustules are red, yellow, and white and they are accompanied by burning pain … the skin seems studded with grains of rice." The Indian epidemic was thought to be punishment from a god, and the survivors created a goddess, Sitala, as the anthropomorphic personification of the disease.^[7][8][9] Smallpox was thus regarded as possession by Sitala. In Hinduism the goddess Sitala both causes and cures high fever, rashes, hot flashes and pustules. All of these are symptoms of smallpox.

Smallpox did not enter Western Europe until about 581. Most of the details about the epidemic that followed are lost, probably due to the scarcity of surviving written records of early medieval society.

[edit] The Americas

Documented Smallpox Epidemics in the New World[10]
Year	Location	Description
1520-1527	Mexico, Central America, South America	Smallpox kills millions of native inhabitants of Mexico. Unintentionally introduced at Veracruz with the arrival of Panfilo de Narvaez on April 23, 1520[citation needed] and was credited with the victory of Cortes over the Aztec empire at Tenochtitlan (present-day Mexico City) in 1521. Kills the Inca ruler, Huayna Capac, and 200,000 others and destroys the Incan Empire.
1617-1619	North America northern east coast	Killed 90% of the Massachusetts Bay Indians
1674	Cherokee Tribe	Death count unknown. Population in 1674 about 50,000. After 1729, 1738, and 1753 smallpox epidemics their population was only 25,000 when they were forced to Oklahoma on the Trail Of Tears
1692	Boston, MA
1702-1703	St. Lawrence Valley, NY
1721	Boston, MA
1736	Pennsylvania
1738	South Carolina
1754-1767	North East U.S. and South East Canada	"Smallpox was probably first used as a biological weapon during the French and Indian Wars of 1754-1767 when British forces in North America distributed blankets that had been used by smallpox patients among them to Native Americans collaborating with the French."[11]
1770s	West Coast of North America	Kills out 30% of the West Coast Native Americans
1781-1783	Great Lakes
1830s	Alaska	Reduced Dena'ina Athabaskan population in Cook Inlet region of southcentral Alaska by half.[12] Smallpox also devastated Yup'ik Eskimo populations in western Alaska.
1860-1861	Pennsylvania
1865-1873	Philadelphia, PA, New York, Boston, MA and New Orleans, LA	Same period of time, in Washington DC, Baltimore, MD, Memphis, TN Cholera and a series of recurring epidemics of Typhus, Scarlet Fever and Yellow Fever
1877	Los Angeles, CA

After first contacts with Europeans and Africans, some believe that the death of 90 to 95 percent of the native population of the New World was caused by Old World diseases[4]. It is suspected that smallpox was the chief culprit and responsible for killing nearly all of the native inhabitants of the Americas. For more than two hundred years, this disease affected all new world populations without intentional European transmission, from contact in the early 1500s to until possibly as early as the French and Indian Wars (1754-1767).^[11]

In 1519 Hernán Cortés landed on the shores of what is now Mexico and was then the Aztec empire. In 1520 another group of Spanish came from Cuba and landed in Mexico. Among them was an African slave who had smallpox. When Cortés heard about the other group, he went and defeated them. In this contact, one of Cortés's men contracted the disease. When Cortés returned to Tenochtitlan, he brought the disease with him.

Soon, the Aztecs rose up in rebellion against Cortés. Outnumbered, the Spanish were forced to flee. In the fighting, the Spanish soldier carrying smallpox died. After the battle, the Aztecs contracted the virus from the invaders' bodies.^{[citation needed]} Cortes would not return to the capital until August 1521. In the meantime smallpox devastated the Aztec population. It killed most of the Aztec army, the emperor, and 25% of the overall population.^{[citation needed]} A Spanish priest left this description: "As the Indians did not know the remedy of the disease…they died in heaps, like bedbugs. In many places it happened that everyone in a house died and, as it was impossible to bury the great number of dead, they pulled down the houses over them so that their homes become their tombs."^{[citation needed]} On Cortés's return, he found the Aztec army’s chain of command in ruins. The soldiers who lived were still weak from the disease. Cortés then easily defeated the Aztecs and entered Tenochtitlán, where he found that smallpox had killed more Aztecs than had the cannons.^{[citation needed]} The Spaniards said that they could not walk through the streets without stepping on the bodies of smallpox victims.^{[citation needed]}

The effects of smallpox on Tahuantinsuyu (or the Inca empire) were even more devastating. Beginning in Colombia, smallpox spread rapidly before the Spanish invaders first arrived in the empire. The spread was probably aided by the efficient Inca road system. Within months, the disease had killed the Sapa Inca Huayna Capac, his successor, and most of the other leaders. Two of his surviving sons warred for power and, after a bloody and costly war, Atahualpa become the new Sapa Inca. As Atahualpa was returning to the capital Cuzco, Francisco Pizarro arrived and through a series of deceits captured the young leader and his best general. Within a few years smallpox claimed between 60% and 90% of the Inca population^{[citation needed]}, with other waves of European disease weakening them further. However, some historians^{[attribution needed]} think a serious native disease called Bartonellosis may have been responsible for some outbreaks of illness.^{[citation needed]}

Even after the two mighty empires of the Americas were defeated by the virus, smallpox continued its march of death. In 1633 in Plymouth, Massachusetts, the Native Americans were struck by the virus. As it had done elsewhere, the virus wiped out entire population groups of Native Americans. It reached Lake Ontario in 1636, and the lands of the Iroquois by 1679, killing millions. The worst sequence of smallpox attacks took place in Boston, Massachusetts. From 1636 to 1698, Boston endured six epidemics. In 1721, the most severe epidemic occurred. The entire population fled the city, bringing the virus to the rest of the Thirteen Colonies. In the late 1770s, during the American Revolutionary War, smallpox returned once more and killed an estimated 125,000 people.^[13]

[edit] Inoculation

By that time, a preventive treatment for smallpox had finally arrived. It was a process called inoculation, also known as insufflation or variolation. Inoculation was not a sudden innovation, as it is known to have been practiced in India as early as 1000 BC.^[14] The Indians rubbed pus into the skin lesions. The Chinese blew powdered smallpox scabs up the noses of the healthy after discovery, by a Buddhist nun, that this inoculated non-immune people. The patients would then develop a mild case of the disease and from then on were immune to it. This technique is known as variolation and although variolation had a 0.5-2% mortality rate, this was considerably less than the 20-30% mortality rate of the disease itself. The process spread to Turkey where Lady Mary Wortley Montagu, wife of the British ambassador, learned of it from Emmanuel Timoni (ca. 1670–1718), a doctor affiliated with the British Embassy in Istanbul.^[2] She had the procedure performed on her son and daughter, aged 5 and 4 respectively. They both recovered quickly and the procedure was hailed as a success and reported to the Royal Society in England. Timoni, from the University of Padova, Italy and a member of the Royal Society of London since 1703, published “an account, or history, of the procuring the smallpox by incision” in December 1713 in the Philosophical Transactions. His work was published again in 1714 in Leipzig and was followed by those of Pylarino (1715), Leduc (1722), and Maitland (1722).

In 1721, an epidemic of smallpox hit London and left the British Royal Family in fear.^[2] Reading of Lady Wortley Montagu’s efforts, they wanted to use inoculation on themselves. Doctors told them that it was a dangerous procedure, so they decided to try it on other people first. The test subjects they used were condemned prisoners. The doctors inoculated the prisoners and all of them recovered in a couple of weeks. So assured, the British royal family inoculated themselves and reassured the English people that it was safe.

But inoculation still had its critics. Prominent among them were religious preachers who claimed that smallpox was God’s way of punishing people and that inoculation was a tool of Satan.^{[citation needed]} This resistance only encouraged Montagu and the others to work even harder. By 1723 inoculations were extremely common in England, but even scientific opposition (such as the Fellow of the Royal College of Physicians Pierce Dod) continued for some time.

In 1721, Onesimus was the slave of a Boston preacher when smallpox came to Boston via a ship arriving from Barbados.^[15] His owner, Cotton Mather asked his slave if he ever had smallpox. Onesimus said, “Yes and no,” and explained a technique from his homeland in Africa, thought to be in Sudan. He explained that pus from an infected person was deliberately rubbed into a scratch or cut of a non-infected person, and when successful, the person had immunity. This remedy from an African slave was the precursor to inoculations. Cotton Mather, the son of a former Harvard University dean, was waging a campaign of his own to promote the process, although religious resistance to inoculation was very strong. At one point, Cotton Mather was in danger from a crowd that wanted to hang him. After six patients died from the procedure, he was called a murderer. But, when the population of Boston returned after the end of a smallpox epidemic in 1722, he was an instant hero. Out of the population of Boston, 7% had died from smallpox. Out of the 300 people that chose to inoculate themselves, only 2% died. In 1750, the English magazine, Gentleman's Magazine, reprinted a 1725 pamphlet that argued in support of smallpox inoculations. By 1774, it was considered odd not to choose inoculation. Onesimus was later freed by Mather, not for his knowledge and help in combating smallpox, but because Mather considered him to be disobedient.

Even though inoculation was a powerful method of controlling smallpox, it was far from perfect. Inoculation caused a mild case of smallpox which resulted in death in about 2% of the cases. It was also difficult to administer. Sick patients had to be locked away to prevent them from transmitting the disease to others. Thus George Washington initially hesitated to have his Revolutionary War troops inoculated during a smallpox outbreak in February 1777, writing, “should We inoculate generally, the Enemy, knowing it, will certainly take Advantage of our Situation;” but the virulence of the outbreak soon prompted him to order inoculation for all troops and recruits who had not had the disease.^[16]

In 1757, a young boy in England was inoculated by David Jenner. The boy suffered from the disease for an entire month and recovered completely.

[edit] Vaccination

At the age of thirteen, Jenner was apprenticed to Dr. Ludlow in Sodbury. He observed that people who caught cowpox while working with cows were known not to catch smallpox. He assumed a causal connection. The idea was not taken up by Dr. Ludlow at that time. After Jenner returned from medical school in London, a smallpox epidemic struck his home town of Berkeley, England. He advised the local cow workers to be inoculated. The farmers told him that cowpox prevented smallpox. This confirmed his childhood suspicion, and he studied cowpox further, presenting a paper on it to his local medical society.

Perhaps there was already an informal public understanding of some connection between disease resistance and working with cows. The “beautiful milkmaid” seems to have been a frequent image in the art and literature of this period. But we know for a fact: In the years following 1770 there were at least six people in England and Germany (Sevel, Jensen, Jesty 1774, Rendall, Plett 1791), who tested successfully the possibility of using the cowpox vaccine as an immunisation for smallpox in humans. In 1796 Sarah Nelmes, a local milkmaid, contracted cowpox and went to Jenner for treatment. Jenner took the opportunity to test his theory. He inoculated James Phipps, the eight-year-old son of his gardener, not with smallpox but with cowpox. After an extremely weak bout of cowpox, James recovered. Jenner then tried to infect James with smallpox but nothing happened—the boy was immune to smallpox.

Jenner reported his observations to the Royal Society. Further work was suggested, and Jenner published a series of 23 cases, including his son Edward, none suffered severely from smallpox. Two years later a society to oppose vaccination had been established in Boston, Massachusetts^{[citation needed]} — an indication of rapid spread and deep interest. By 1800 Jenner’s work had been published in all of the major European languages. The process was performed all over Europe and the United States. The death rate was close to zero with the process, which became known as vaccination and was continued to around 1974 in the UK. A typical death rate at that time was roughly one per million, making vaccination against smallpox with vaccinia the most dangerous immunisation widely provided in modern times.^{[citation needed]}

The Balmis Expedition (1803) carried the vaccine to Spanish America, the Philippines and China under commission of the Spanish Crown.

Some years before Dr. Jenner, Benjamin Jesty, a farmer at Yetminster in Dorset (he later moved to and is buried at Worth Matravers) is recorded as observing the two milkmaids living with his family to have been immune to smallpox and then inoculating his family with cowpox to protect them from smallpox. This was done in 1774 and can be found with Crookshank's History and Pathology of Vaccination, London 1889, vol. 1, p.110ff. But the question of who first initiated smallpox inoculation/vaccination can not be answered properly, as there is in the sources the exact date and time only for the predecessor Plett (1791), but not for Sevel, Jensen and Rendall. Louis T. Wright,^[17] an African-American and Harvard medical school graduate (1915), introduced intradermal vaccination for smallpox for the soldiers while serving in the Army during WWI.^[18]

[edit] Eradication

“	The annihilation of smallpox—the dreadful scourge of the human race—will be the final result of vaccination.	”
—Edward Jenner (1749–1823)

Jenner's dream was ultimately achieved. Since Jenner demonstrated the effectiveness of cowpox to protect humans from smallpox circa 1796, various attempts were made to eliminate smallpox. In 1842, England banned inoculation, later progressing to mandatory vaccination instead. In the United States, from 1843 to 1855 first Massachusetts, and then other states required vaccination. This alteration in the relationship of State to citizen was not universally approved.^[19] Protests notwithstanding, coordinated efforts against smallpox went on, and the disease continued to diminish in the wealthy countries. In poorer countries, vaccines and the necessary infrastructure were less affordable and available.

In 1958 the Soviet Union called for the eradication of smallpox from the planet. At that point, 2 million people were dying every year. In 1967, an international team was formed under the leadership of an American, Donald Henderson. To eradicate smallpox, each outbreak had to be stopped from spreading, by isolation of cases and vaccination of everyone who lived close by. This process is known as ring vaccination. The key to this strategy was surveillance and containment. Surveillance can be best defined as the monitoring of cases in a community. The initial problem the WHO team faced was inadequate reporting of smallpox cases, as many cases did not come to the attention of the authorities.

The fact that man is the only reservoir for smallpox infection played a significant role in WHO deciding to eradicate smallpox. There are many other pox viruses in nature, including monkeypox. However, none appears to be of public health significance. In addition, smallpox carriers did not exist.

WHO established a network of consultants who assisted countries in setting up surveillance and containment activities.

Eradicating smallpox required huge effort and concentration of manpower. In India and Bangladesh, religion and civil strife along with natural disasters became obstacles. In fear of offending the goddess associated with the disease, many Hindus refused the vaccine. In some countries, such as the Sudan, civil war threatened to interfere with eradication attempts. Clearly, health teams placed themselves in great danger by working in war-torn areas. Surprisingly, none of the team members were hurt in the process.

Natural events also impeded the vaccination team’s efforts. The monsoon rains burst dams and dikes. The rain and flooding forced people to flee, once again allowing smallpox to spread. This outbreak took the team a whole year to stop.

The last major European outbreak of smallpox was the 1972 outbreak of smallpox in Yugoslavia. After a pilgrim returned from the Middle East, where he had contracted the virus, an epidemic infected 175 people, causing 35 deaths. Authorities declared martial law, enforced quarantine, and undertook massive revaccination of the population, enlisting the help of the WHO and Donald Henderson. In two months, the outbreak was over. Prior to this, there had been a smallpox outbreak on May-July of 1963 in Stockholm, Sweden, brought from the Far East by a Swedish sailor; this had been dealt with by quarantine measures and vaccination of local population.^[20]

The last naturally occurring case of Variola Minor was diagnosed in Somalia on a cook named Ali Maow Maalin on October 26, 1977. The last naturally occurring case of the more deadly Variola Major had been detected in October 1975 in a two-year-old Bangladesh girl, Rahima Banu. In the final tally, US$300 million had been applied to the eradication program.

[edit] Post-eradication

In 1978, there was evidently an escape of smallpox from containment in a research laboratory in Birmingham, England. A medical photographer, Janet Parker, died from the disease itself, and the Professor responsible for the unit, Professor Henry Bedson, killed himself. In light of this accident, all known stocks of smallpox were destroyed, except the stocks at the United States Center for Disease Control (CDC) and the Russian Vector State Research Center of Virology and Biotechnology in Siberia, where a regiment of troops guards it. Under such tight control, smallpox would, it was thought, never be let out again. Even though the destruction of virus stocks was ordered in 1993, 1994, 1995, and 1996^{[citation needed]}, they have not yet been destroyed, since a number of researchers still wish to retain the stocks for scientific purposes.

It is possible that an isolated case might have occurred during the '80s, in the Indian state of Sikkim.^{[citation needed]}

In March 2003 smallpox scabs were found tucked inside an envelope in a book on Civil War medicine in Santa Fe, New Mexico.^[21] The envelope was labeled as containing the scabs and listed the names of the patients that were vaccinated with them. Assuming the contents could be dangerous, the librarian who found them did not open the envelope. The scabs ended up with employees from the National Centers for Disease Control, who responded quickly once informed of the discovery. The discovery raised concerns that smallpox DNA could be extracted from these and other scabs and used for a biological attack. Even with Variola sequenced, assembling a virus from scratch remains challenging.

[edit] Biological weapon

A production line to manufacture smallpox on an industrial scale was launched in the small Siberian town of Koltsovo in 1990.^[22] The development of genetically altered strains of smallpox was presumably conducted in Vector Institute in Russia under leadership of Dr. Sergei Netyosov in the middle of the 1980s, according to Kenneth Alibek, although this has never been proven due to the classified nature of the program^[22]

[edit] Famous victims

Famous victims of this disease include Date Masamune of Japan (who lost an eye to the disease), Ramesses V,^[23] the Shunzhi Emperor and Tongzhi Emperor of China (official history), Mary II of England, Louis XV of France (who himself succeeded his great-grandfather through a series of deaths of smallpox or measles among those first in the succession line), Maximilian III Joseph, Elector of Bavaria and Peter II of Russia. Henry VIII's fourth wife, Anne of Cleves, survived the disease but was scarred by it, as was Henry VIII's daughter, Elizabeth I of England in 1562, as was his sister Margaret, Queen of Scotland. Mary Queen of Scots contracted the disease as a child but had no scarring, Guru Har Krishan 8th Guru of the Sikhs in 1664, Peter III of Russia in 1744 and Abraham Lincoln in 1863. Joseph Stalin, who was badly scarred by the disease early in life, often had photographs retouched to make his pockmarks less apparent.

[edit] See also

• Biological warfare
• Vaccination
• Vaccinia
• Virus
• Population history of American indigenous peoples

[edit] References

[edit] Further reading

[edit] External links

[edit] Disease information

• Smallpox Fact Sheet from the CDC
• Smallpox summary by AFIP (Armed Forces Institute of Pathology)
• Bioterrorism Category A Agents—Information Resources
• Smallpox Biosafety The Genetic Engineering of Smallpox: WHO’s Retreat from the Eradication of Smallpox Virus
• CDC.gov—‘Bioterrorism Agents > Smallpox Info for Specific Groups: What Everyone Should Know,’ CDC
• Smallpox as a potential WMD.

[edit] Images

• Photographs of smallpox patients
• Smallpox Images and Diagnosis Synopsis

[edit] Smallpox in history

• WHO.int—‘Smallpox: Historical significance,’ World Health Organization (WHO)
• Inoculation for the Small-Pox defended—1750 article from Gentleman's Magazine
• Why Blame Smallpox? Small pox in ancient Peru
• History of Smallpox in South Asia
• Small pox history in India